NO JUDUL

1. Active smoking and

risk of breast cancer
in a Danish nurse
cohort study
Active smoking and
survival following
breast cancer among
African American and
non-African American
women in the Carolina
Breast Cancer Study.
Cancer Causes Control
Alcohol consumption
and cigarette smoking
in combination: A
predictor of
contralateral breast
cancer risk in the
WECARE study
Alcohol, Physical
Activity, Smoking, and
Breast Cancer
Subtypes in a Large,
Nested Case-Control
Study from the
Norwegian Breast
Cancer Screening
Program.
Ambient Air Pollution
and Chronic Bronchitis
in a Cohort of U.S.
Women
Are Jordanian primary
healthcare
practitioners fulfilling
their potential in
cancer prevention and
community health?
Findings from a cross-
sectional survey.
Association between
lifetime exposure to
passive smoking and
risk of breast cancer
subtypes defined by
hormone receptor
status among non-
smoking Caucasian
women.
The association
between smoking and
breast cancer
characteristics and
outcome
Association of
Cytochrome CYP1A1
Gene Polymorphisms
and Tobacco Smoking
With the Risk of Breast
Cancer in Women
From Iraq
Associations between
obesity, smoking and
lymph node status at
breast cancer
diagnosis in the
Prostate, Lung,
Colorectal and Ovarian
(PLCO) Cancer
Screening Trial
Associations of Coffee
Drinking and Cancer
Mortality in the Cancer
Prevention Study-II
Breast cancer and
exposure to tobacco
smoke during
potential windows of
susceptibility
Breast tumor DNA
methylation patterns
associated with
smoking in the
Carolina Breast Cancer
Study.
Can statistic
adjustment of OR
minimize the potential
confounding bias for
meta-analysis of case-
control study? A
secondary data
analysis
Cell-Free DNA from
Ascites and Pleural
Effusions: Molecular
Insights into Genomic
Aberrations and
Disease Biology.
Cigarette Smoke
Regulates Calcium-
Independent
Phospholipase A2
Metabolic Pathways in
Breast Cancer.
Clinical characteristics,
classification and
surgical treatment of
periductal mastitis
Current smoking is
associated with a
larger waist
circumference and a
more androgenic
profile in young
healthy women from
high-risk breast cancer
families.
Development and
Psychometric
Evaluation of the Lung
Cancer Screening
Health Belief Scales
Differential
Association of the
Lifestyle-Related Risk
Factors Smoking and
Obesity with Triple
Negative Breast
Cancer in a Brazilian
Population
Distinct
epidemiological
profiles associated
with inflammatory
breast cancer (IBC): A
comprehensive
analysis of the IBC
registry at The
University of Texas MD
Anderson Cancer
Center.
Effects of a parallel-
arm randomized
controlled weight loss
pilot study on
biological and
psychosocial
parameters of
overweight and obese
breast cancer
survivors. Pilot and
feasibility studies
Environmental
Tobacco Smoke
Exposure and Survival
Following Breast
Cancer
Estimating the Risks of
Breast Cancer
Radiotherapy:
Evidence From
Modern Radiation
Doses to the Lungs
and Heart and From
Previous Randomized
Trials
Estrogen Repression
of MicroRNAs Is
Associated with High
Guanine Content in
the Terminal Loop
Sequences of Their
Precursor
Exposure to
Secondhand Smoke
and Risk of Cancer in
Never Smokers: A
Meta-Analysis of
Epidemiologic Studies
Expression profile of
Oct-4 lung cancer-
specific marker prior
and subsequent to a
salirasib treatment
regime.
First-degree relatives
of cancer patients: a
target group for
primary prevention? A
cross-sectional study
Geographical and
socioeconomic
differences in uptake
of Pap test and
mammography in
Italy: results from the
National Health
Interview Survey
Health-related
behaviors and
mortality outcomes in
women diagnosed
with ductal carcinoma
in situ
Hypermutation and
microsatellite
instability in
gastrointestinal
cancers.
Impact of tobacco
smoking on the risk of
developing 25
different cancers in the
UK: a retrospective
study of 422,010
patients followed for
up to 30 years
Incidence and risk
factors of
postoperative
pneumonia following
cancer surgery in adult
patients with selected
solid cancer: results of
"Cancer POP" study.
Incidental
extravascular findings
in computed
tomographic
angiography for
planning or
monitoring
endovascular aortic
aneurysm repair:
Smoker patients,
increased lung cancer
prevalence?
Inherited lung cancer
syndromes targeting
never smokers.
Leucocytes telomere
length and breast
cancer risk/
susceptibility: A case-
control study.
Lung cancer screening
with low-dose CT: a
world-wide view.
Mammographic
density, blood
telomere length and
lipid peroxidation.
Mechanistic evidence
that benzo[a]pyrene
promotes an
inflammatory
microenvironment that
drives the metastatic
potential of human
mammary cells
Modeling Variables
With a Spike at Zero:
Examples and Practical
Recommendations.
The most important
questions in cancer
research and clinical
oncology : Question 1.
Could the vertical
transmission of human
papilloma virus (HPV)
infection account for
the cause,
characteristics, and
epidemiology of HPV-
positive
oropharyngeal
carcinoma, non-
smoking East Asian
female lung
adenocarcinoma,
and/or East Asian
triple-negative breast
carcinoma?
Nicotine associated
breast cancer in
smokers is mediated
through high level of
EZH2 expression which
can be reversed by
methyltransferase
inhibitor DZNepA
Nicotine reduces
effectiveness of
doxorubicin
chemotherapy and
promotes
CD44(+)CD24(-)
cancer stem cells in
MCF-7 cell
populations.
Nicotine-enhanced
stemness and
epithelial-
mesenchymal
transition of human
umbilical cord
mesenchymal stem
cells promote tumor
formation and growth
in nude mice.
Nipple sparing
mastectomy
techniques: a literature
review and an
inframammary
technique.
Nipple-sparing
mastectomies: Clinical
outcomes from a
single academic
institution.
Oral bisphosphonate
use and lung cancer
incidence among
postmenopausal
women
Outdoor Light at Night
and Breast Cancer
Incidence in the
Nurses' Health Study II
Periodontal Disease
and Incident Cancer
Risk among
Postmenopausal
Women: Results from
the Women's Health
Initiative Observational
Cohort.
Pleiotropy of genetic
variants on obesity
and smoking
phenotypes: Results
from the Oncoarray
Project of The
International Lung
Cancer Consortium.
Pooled analysis of
active cigarette
smoking and invasive
breast cancer risk in 14
cohort studies
A possible dual effect
of cigarette smoking
on the risk of
postmenopausal
breast cancer
Postdiagnosis
Changes in Cigarette
Smoking and Survival
Following Breast
Cancer
Post-diagnosis social
networks, and lifestyle
and treatment factors
in the After Breast
Cancer Pooling
Project.
Psychooncology
Posttreatment
trajectories of physical
activity in breast
cancer survivors.
Cancer
Recent insights into
cigarette smoking as a
lifestyle risk factor for
breast cancer.
Reduced ovarian
reserve in young early
breast cancer patients:
preliminary data from
a prospective cohort
trial
Response to Conner et
al. Re: "Cigarette
Smoking and Breast
Cancer Risk in
Hispanic and Non-
Hispanic White
Women: The Breast
Cancer Health
Disparities Study".
Risk factors for
common cancers
among patients at
Kamuzu Central
Hospital in Lilongwe,
Malawi: A
retrospective cohort
study.
The Role of
Nitrosamine (NNK) in
Breast Cancer
Carcinogenesi
Selenium and breast
cancer risk: A
prospective nested
case-control study on
serum selenium levels,
smoking habits and
overweight.
Should Nonsmokers
Be Excluded from Early
Lung Cancer Screening
with Low-Dose Spiral
Computed
Tomography?
Community-Based
Practice in Shanghai
Sistas Inspiring Sistas
Through Activity and
Support (SISTAS):
Study Design and
Demographics of
Participants
The Sister Study
Cohort: Baseline
Methods and
Participant
Characteristics.
moking and mortality
in women diagnosed
with breast cancer-a
systematic review with
meta-analysis based
on 400,944 breast
cancer cases.
Smoking and risk of
breast cancer in the
Generations Study
cohort
The Surgical Impact of
E-Cigarettes: A Case
Report and Review of
the Current Literature.
Survival after
recurrence of stage I-
III breast, colorectal, or
lung cancer.
Tobacco-Specific
Carcinogens Induce
Hypermethylation,
DNA Adducts, and
DNA Damage in
Bladder Cancer
Prosthetic Breast
Reconstruction after
Mastectomy with or
without Prior
Postmastectomy
Radiotherapy
(Andersen, Jorgensen et al. 2017, Ao, Zhou et al. 2017, Carter-Harris, Slaven et al. 2017, Cohen, Burgos-
Aceves et al. 2017, Connor, Baumgartner et al. 2017, Conway, Edmiston et al. 2017, Dull, Conant et al.
2017, Ellingjord-Dale, Vos et al. 2017, Erdmann, Harrington et al. 2017, Fracol, Dorfman et al. 2017,
Gankhuyag, Lee et al. 2017, Gapstur, Anderson et al. 2017, Gaudet, Carter et al. 2017, Goldvaser, Gal et
al. 2017, Hassett, Uno et al. 2017, Husain, Nykin et al. 2017, James, Bertrand et al. 2017, Jeronimo and
Weller 2017, Jin, Thaiparambil et al. 2017, Jones, Schoemaker et al. 2017, Kispert and McHowat 2017,
Kispert, Schwartz et al. 2017, Knight, Fan et al. 2017, Kroenke, Michael et al. 2017, Lam, Hsieh et al.
2017, Liu, Nie et al. 2017, Lorenz, Jenkner et al. 2017, Lucas, Levine et al. 2017, Luo, Zheng et al. 2017,
Mazzei, Guerrini et al. 2017, Moses, Mwafongo et al. 2017, Nwizu, Marshall et al. 2017, Obeidat,
Habashneh et al. 2017, Parada, Bradshaw et al. 2017, Parada, Bradshaw et al. 2017, Parada, Sun et al.
2017, Sandler, Hodgson et al. 2017, Sandsveden and Manjer 2017, Sollie and Bille 2017, Strumylaite,
Kregzdyte et al. 2017, Taylor, Correa et al. 2017, van den Brandt 2017, Veal, Hart et al. 2017, Wang,
Moon et al. 2017, Wee and Poh 2017, Wenners, Grambach et al. 2017, White, D'Aloisio et al. 2017, Yuza,
Nagahashi et al. 2017, Arikawa, Kaufman et al. 2018, Ashikari, Kelemen et al. 2018, Bevel, Babatunde et
al. 2018, Ellberg, Olsson et al. 2018, Fouad, Ueno et al. 2018, Haug, Riedel et al. 2018, Hooper, Young et
al. 2018, Jacob, Freyn et al. 2018, Jung, Moon et al. 2018, Kim, Ko et al. 2018, Kumari, Das et al. 2018, Li,
Zhang et al. 2018, Malik, David et al. 2018, Naif, Al-Obaide et al. 2018, Pavanello, Varesco et al. 2018,
Petrelli, Giorgi Rossi et al. 2018, Pinsky 2018, Smith, Mullooly et al. 2018, Tao, Chen et al. 2018, Tousimis
and Haslinger 2018, Turker Sener, Guven et al. 2018, Yamamoto, Yatabe et al. 2018, Zhang, Zhou et al.
2018)

Andersen, Z. J., et al. (2017). "Active smoking and risk of breast cancer in a Danish nurse cohort study."
BMC Cancer 17(1): 556.
BACKGROUND: No scientific consensus has been reached on whether active tobacco smoking
causes breast cancer. We examine the association between active smoking and breast cancer
risk in Denmark, which has some of the highest smoking and breast cancer rates in women
worldwide. METHODS: We used the data from a nationwide Danish Nurse Cohort on 21,867
female nurses (age > 44 years) who at recruitment in 1993 or 1999 reported information on
smoking status, onset, duration, and intensity, as well as breast cancer risk factors. We obtained
data on incidence of breast cancer from Danish Cancer Registry until 2013, and used Cox
regression models to analyze the association between smoking and breast cancer. RESULTS: Of
21,831 women (mean age 53.2 years) 1162 developed breast cancer during 15.7 years of follow-
up. 33.7% of nurses were current and 30.0% former smokers at cohort baseline. Compared to
never smokers, we found increased risk of breast cancer of 18% in ever (hazard ratio and 95%
confidence interval: 1.18; 1.04-1.34) and 27% in current (1.27; 1.11-1.46) smokers. We detected
a dose-response relationship with smoking intensity with the highest breast cancer risk in
women smoking >15 g/day (1.31; 1.11-1.56) or >20 pack-years (1.32; 1.12-1.55). Parous women
who smoked heavily (>10 pack-years) before first childbirth had the highest risk of breast cancer
(1.58; 1.20-2.10). Association between smoking and breast cancer was not modified by
menopausal status, obesity, alcohol or hormone therapy use, and seemed to be limited to the
estrogen receptor positive breast cancer subtype. CONCLUSIONS: Active smoking increases risk
of breast cancer, with smoking before first birth being the most relevant exposure window.
Ao, X., et al. (2017). "Expression profile of Oct-4 lung cancer-specific marker prior and subsequent to a
salirasib treatment regime." Oncol Lett 14(5): 5145-5148.
Lung cancer is one of the leading types of cancer that lead to mortalities in the male and female
populations. The existing lung cancer-specific markers are not able to accurately predict the
condition of the disease, and the response of these markers can vary under various pathological
conditions. The ability for tumors to regenerate following treatment can be more aggressive,
and this may be due to the remaining lung cancer-specific stem cells, which are resistant to
chemotherapeutic drugs. Evaluating cancer stem cells under various pathological conditions, as
well as prior and subsequent to treatment, can help to increase the understanding of the
underlying mechanisms. In the present study, a mouse model with initial and advanced forms of
lung cancer was developed using tobacco smoke carcinogen. It was observed from tissue
sections that there were many actively dividing cells spread throughout the mouse lung tissue
with the initial stages of lung cancer, and these cells aggregated in advanced stages of lung
cancer. Furthermore, immunohistochemical staining indicated that there was an increased
number of octamer-binding protein 4 (Oct-4)-positive cells present in mouse tissues with
advanced stages of the disease compared with tissues without lung cancer or at the initial stages
of disease. The cancer stem cell population following salirasib treatment was also investigated in
two groups. The mice in the early treatment group were administered with salirasib following 1
month of tumor growth, and the delayed treatment group was treated following 2 months of
tumor growth. The number of cancer stem cells was markedly reduced in the early treatment
group. However, salirasib failed to have any observable effect in the delayed treatment group.
Cancer stem cells were analyzed using the marker Oct-4 to improve an understanding of the
proliferative ability of cancer stem cells under various pathological conditions, which may lead
to the development of novel cancer therapeutics.

Arikawa, A. Y., et al. (2018). "Effects of a parallel-arm randomized controlled weight loss pilot study on
biological and psychosocial parameters of overweight and obese breast cancer survivors." Pilot
Feasibility Stud 4: 17.
BACKGROUND: Weight gain often occurs after breast cancer (BC) diagnosis and obesity along
with sedentary behavior are associated with increased risk of BC recurrence and mortality. The
primary objective of this study was to determine whether a significant weight loss, of
approximately 10%, would lead to beneficial changes in biomarkers associated with cancer
and/or cancer recurrence, and quality of life (QOL) in overweight and obese BC survivors.
METHODS: This parallel-arm study took place in Minneapolis, Minnesota, from January 2009
until March 2010. Participants were overweight and obese postmenopausal BC survivors who
had completed treatment at least 3 months prior to enrollment and who did not smoke.
Twenty-one BC survivors were randomized, via a random number generator computer software,
to a 1000-calorie deficit feeding and exercise intervention (CR) or a weight management
counseling intervention (WM) for 12 weeks followed by a 6-week follow-up. Body weight,
biomarkers, and QOL were measured at baseline, weeks 6, 12, and 18. Body composition and
fitness level were measured at only two time points. RESULTS: Twenty-one women were
enrolled into the study and 20 completed all time points. Weight loss occurred with both
interventions. Body weight in CR changed from 85.5 (95% confidence interval (CI) 77, 94) kg to
76.7 (95% CI 68.1, 85.2) kg, whereas in WM it changed from 98.3 (95% CI 89.8, 106.8) kg to 93.2
(95% CI 84.6, 101.7) kg. Fitness in CR changed from 4.9 (95% CI 4, 5.8) to 6.3 (95% CI 5.4, 7.2). CR
led to lower plasma levels of leptin, F2-isoprostanes, and CRP. Quality of life seemed to improve
 with both interventions, while sleep quality decreased only in CR. CONCLUSIONS: Overweight
and obese BC survivors were able to adhere to a strict diet and exercise program, which
significantly decreased body weight, increased fitness level, and improved biomarkers and QOL.
However, the strict dietary intervention in CR seemed to decrease participants' sleep quality and
social relationships. Future larger randomized controlled trials should focus on behavioral
modification and personalized nutrition counseling to help breast cancer survivors achieve a
sustainable weight loss and fitness level. TRIAL REGISTRATION: ClinicalTrials.gov identifier:
NCT02940470.

Ashikari, A. Y., et al. (2018). "Nipple sparing mastectomy techniques: a literature review and an
inframammary technique." Gland Surg 7(3): 273-287.
Nipple sparing mastectomy (NSM) has quickly become an accepted technique for patients with
selected cancers and for risk reducing surgery. Much of its surgical acceptance over the last
decade has been based on the low risk of nipple areolar complex (NAC) occurrence in breast
cancer patients. Improved patient satisfaction due to improved cosmetic outcomes with
reconstruction have also driven its popularity. We reviewed current English journals to
determine the NSM techniques which achieve the lowest complications, best outcomes, and
best patient satisfaction. We researched studies showing reductions in complications with
improved surgical techniques and patient selection which have been implicated in improved
results. In the studies reviewed, incision placement, away from the nipple, resulted in the lowest
rates of ischemic nipple complications and the best cosmetic outcomes. The effect of other
factors such as surgeon experience and thickness of skin flap development were more difficult
to prove. Leaving a 2-3 mm rim of tissue around the nipple bundle was shown to help preserve
the nipple vascularity. Lower complication rates with improved outcomes and patient
satisfaction were reported in the literature in patients with B or smaller cup sizes, non-smokers,
and patients with lower body mass index (BMI). Incision placement, away from the nipple, with
preservation of a 2-3 mm rim of tissue around the nipple bundle along with careful patient
selection were the most significant variables reviewed which helped to lower complications
rates of NSM. Coordinated surgical planning with the breast and plastic surgeons to determine
the best surgical approach for each individual patient is necessary to obtain the best results.
Although short-term oncologic follow-up seems to be acceptable, longer follow-up will still be
needed to define the best breast cancer surgical candidates for the nipple sparing approach.

Bevel, M., et al. (2018). "Sistas Inspiring Sistas Through Activity and Support (SISTAS): Study Design and
Demographics of Participants." Ethn Dis 28(2): 75-84.
Introduction: Recruiting racial, ethnic, and other underserved minorities into conventional clinic-
based and other trials is known to be challenging. The Sistas Inspiring Sistas Through Activity and
Support (SISTAS) Program was a one-year randomized controlled trial (RCT) to promote physical
activity and healthy eating among AA women in SC to reduce inflammatory biomarkers, which
are linked to increased breast cancer (BrCa) risk and mortality. This study describes the
development, recruitment, and implementation of the SISTAS clinical trial and provides baseline
characteristics of the study participants. Methods: SISTAS was developed using community-
based participatory research (CBPR) approaches. At baseline, study participants completed
assessments and underwent clinical measurements and blood draws to measure C-reactive
protein (CRP) and interleukin-6 (IL-6). Participants randomized to the intervention received 12
 weekly classes followed by nine monthly booster sessions. Post-intervention measurements
were assessed at 12-week and 12-month follow-ups. Results: We recruited a total of 337
women who tended to: be middle-aged (mean age 48.2 years); have some college education; be
employed full-time; have Medicare as their primary insurance; be non-smokers; and perceive
their personal health as good. On average, the women were pre-hypertensive at baseline (mean
systolic blood pressure = 133.9 mm Hg; mean diastolic blood pressure = 84.0 mm Hg) and
morbidly obese (mean BMI >40.0 kg/m(2)); the mean fat mass and fat-free mass among
participants were 106.4 lb and 121.0 lb, respectively. Conclusion: The SISTAS RCT addresses
some of the gaps in the literature with respect to CBPR interventions targeting AA women, such
as implementing diet and physical activity in CBPR-based studies to decrease BrCa risk.

Carter-Harris, L., et al. (2017). "Development and Psychometric Evaluation of the Lung Cancer Screening
Health Belief Scales." Cancer Nurs 40(3): 237-244.
BACKGROUND: Lung cancer screening is a recent recommendation for long-term smokers.
Understanding individual health beliefs about screening is a critical component in future efforts
to facilitate patient-provider conversations about screening participation. OBJECTIVE: The aim of
this study was to describe the development and psychometric testing of 4 new scales to
measure lung cancer screening health beliefs (perceived risk, perceived benefits, perceived
barriers, self-efficacy). METHODS: In phase I, 4 scales were developed from extensive literature
review, item modification from existing Breast and Colorectal Cancer Screening Health Belief
Scales, focus groups with long-term smokers, and evaluation/feedback from a panel of 10
content experts. In phase II, we conducted a survey of 497 long-term smokers to assess the final
scales' reliability and validity. RESULTS: Phase I: content validity was established with the
content expert panel. Phase II: internal consistency reliability of the scales was supported with
Cronbach's alpha's ranging from .88 to .92. Construct validity was established with confirmatory
factor analysis and testing for differences between screeners and nonscreeners in theoretically
proposed directions. CONCLUSIONS: Initial testing supports the scales are valid and reliable.
These new scales can help investigators identify long-term smokers more likely to screen for
lung cancer and are useful for the development and testing of behavioral interventions
regarding lung cancer screening. IMPLICATIONS FOR PRACTICE: Development of effective
interventions to enhance shared decision making about lung cancer screening between patients
and providers must first identify factors influencing the individual's screening participation.
Future efforts facilitating patient-provider conversations are better informed by understanding
the perspective of the individual making the decision.

Cohen, A., et al. (2017). "Estrogen Repression of MicroRNAs Is Associated with High Guanine Content in
the Terminal Loop Sequences of Their Precursors." Biomedicines 5(3).
Widespread microRNA (miRNA) repression is a phenomenon observed in mammals after
exposure to cigarette smoke and in many types of cancer. A comprehensive reduction in miRNA
expression after treatment with the hormone estrogen has also previously been described.
Here, we reveal a conserved association of miRNA downregulation after estrogen exposure in
zebrafish, mouse, and human breast cancer cell line, with a high guanine content in the terminal
loop sequences of their precursors, and offer a possible link between estrogen-related miRNA-
adducts formation and carcinogenesis. We also show common gene expression patterns shared
 by breast cancer tumors and estrogen-treated zebrafish, suggesting that this organism can be
used as a powerful model system for the study of human breast cancer.

Connor, A. E., et al. (2017). "Response to Conner et al. Re: "Cigarette Smoking and Breast Cancer Risk in
Hispanic and Non-Hispanic White Women: The Breast Cancer Health Disparities Study"." J Womens
Health (Larchmt) 26(1): 92-93.

Conway, K., et al. (2017). "Breast tumor DNA methylation patterns associated with smoking in the
Carolina Breast Cancer Study." Breast Cancer Res Treat 163(2): 349-361.
PURPOSE: Tobacco smoking is a risk factor in several cancers, yet its roles as a putative etiologic
exposure or poor prognostic factor in breast cancer are less clear. Altered DNA methylation
contributes to breast cancer development and may provide a mechanistic link between smoking
and gene expression changes leading to cancer development or progression. METHODS: Using a
cancer-focused array, we examined methylation at 933 CpGs in 517 invasive breast tumors in
the Carolina Breast Cancer Study to determine whether methylation patterns differ by exposure
to tobacco smoke. Multivariable generalized linear regression models were used to compare
tumor methylation profiles between smokers and never smokers, overall, or stratified on
hormone receptor (HR) status. RESULTS: Modest differences in CpG methylation were detected
at p < 0.05 in breast tumors from current or ever smokers compared with never smokers. In
stratified analyses, HR- tumors from smokers exhibited primarily hypomethylation compared
with tumors from never smokers; hypomethylation was similarly detected within the more
homogeneous basal-like subtype. Most current smoking-associated CpG loci exhibited
methylation levels in former smokers that were intermediate between those in current and
never smokers and exhibited progressive changes in methylation with increasing duration of
smoking. Among former smokers, restoration of methylation toward baseline (never smoking)
levels was observed with increasing time since quitting. Moreover, smoking-related
hypermethylation was stronger in HR+ breast tumors from blacks than in whites. CONCLUSIONS:
Our results suggest that breast tumor methylation patterns differ with tobacco smoke exposure;
however, additional studies are needed to confirm these findings.

Dull, B., et al. (2017). "Nipple-sparing mastectomies: Clinical outcomes from a single academic
institution." Mol Clin Oncol 6(5): 737-742.
Nipple-sparing mastectomies (NSMs) are increasingly used in the surgical treatment of patients
with breast cancer and for prevention of breast cancer. The present study was performed to
review the outcomes of patients undergoing NSMs at a single large university setting. A
retrospective chart review was performed on all patients undergoing NSMs from 2008-2014.
Charts were reviewed for demographic data and patient characteristics. Tumor and breast size,
cancer recurrence and complications were also evaluated. Descriptive statistics were utilized to
summarize the findings. From 2008-2014, 110 patients underwent 197 NSMs. The mean patient
age was 44.4 years (range, 20-77). The average body mass index was 24 (range, 18-47). Breast
weight was available for 106 specimens, with a mean weight of 475.5 g (range, 124.1-1,625.0 g).
Seventy-three NSMs were performed for cancer and 124 were performed prophylactically. The
mean tumor width was 1.38 cm (range, 0-6.0 cm), with an average nipple to tumor distance of
5.87 cm (range, 2.93-10.0 cm). Three (4%) patients required removal of the nipple areolar
complex (NAC) due to pathological extension of the tumor. A total of 34 (17.2%) complications
 occurred, including infections, hematomas and nipple necrosis, with 9 requiring removal of the
NAC and 13 requiring removal of the tissue expander or implant. Smokers had a 36.0% (9/25)
complication rate, compared with 14.5% (25/172) of nonsmokers (P<0.05). During follow-up,
one recurrence was noted, located on the chest wall. There were no recurrences in the NAC
group. Therefore, NSMs may safely be performed without compromising oncologic outcomes or
increasing complication rates in properly selected patients.

Ellberg, C., et al. (2018). "Current smoking is associated with a larger waist circumference and a more
androgenic profile in young healthy women from high-risk breast cancer families." Cancer Causes
Control 29(2): 243-251.
The purpose was to elucidate the interplay between current smoking, anthropometric
measurements, and endogenous hormone levels in women </= 40 years. Questionnaires on
lifestyle and reproductive factors were completed by 269 healthy women from high-risk breast
cancer families between 1996 and 2006 in Sweden. Blood samples for analyses of plasma
testosterone, estradiol, androstenedione, sex hormone-binding globulin, and body
measurements were obtained 5-10 days before predicted onset of the next menstrual period.
Women without smoking status, who were currently breastfeeding, or using hormonal
contraception other than combined oral contraceptives (OCs) were excluded (n = 27). Current
smokers (n = 57) had larger waist circumference (adjp = 0.004) and waist-to-hip ratio (WHR)
(adjp = 0.007) than non-smokers (n = 185). In non-OC users, adjusted mean androstenedione
levels were higher in current smokers compared with non-smokers (10.3 vs. 8.6 nmol/L; adjp =
0.0002). While in current OC users estradiol levels were higher in smokers compared with non-
smokers (22.5 vs. 17.4 pg/mL; adjp = 0.012). In multivariable models, WHR was associated with
both current smoking (adjp </= 0.016) and higher levels of androstenedione (adjp = 0.05) or
bioavailable testosterone (adjp = 0.001). Among non-OC users, a more androgenic profile was
observed in current smokers compared with non-smokers, but not in current OC users.
Irrespective of OC use, current smoking was associated with increased waist circumference.

Ellingjord-Dale, M., et al. (2017). "Alcohol, Physical Activity, Smoking, and Breast Cancer Subtypes in a
Large, Nested Case-Control Study from the Norwegian Breast Cancer Screening Program." Cancer
Epidemiol Biomarkers Prev 26(12): 1736-1744.
Background: To what extent alcohol, smoking, and physical activity are associated with the
various subtypes of breast cancer is not clear. We took advantage of a large population-based
screening cohort to determine whether these risk factors also increase the risk of the poor
prognosis subtypes.Methods: We conducted a matched case-control study nested within the
Norwegian Breast Cancer Screening Program during 2006-2014. A total of 4,402 breast cancer
cases with risk factor and receptor data were identified. Five controls were matched to each
case on year of birth and year of screening. Conditional logistic regression was used to estimate
ORs of breast cancer subtypes adjusted for potential confounders.Results: There were 2,761
luminal A-like, 709 luminal B-like HER2-negative, 367 luminal B-like HER2-positive, 204 HER2-
positive, and 361 triple-negative cancers. Current alcohol consumption was associated with
breast cancer risk overall [OR 1.26; 95% confidence interval (CI), 1.09-1.45] comparing 6+ glasses
a week to never drinkers. However, this risk increase was found only for luminal A-like breast
cancer. Smoking 20+ cigarettes a day was associated with an OR of 1.41 (95% CI, 1.06-1.89)
overall, with significant trends for luminal A-like and luminal B-like HER2-negative cancer.
 Current physical activity (4+ hours/week compared with none) was associated with 15%
decreased risk of luminal A-like cancer, but not clearly with other subtypes.Conclusions: In this
large study, alcohol, smoking, and physical activity were predominantly associated with luminal
A-like breast cancer.Impact: Alcohol, smoking, and physical activity were associated with luminal
A-like breast cancer subtype. Cancer Epidemiol Biomarkers Prev; 26(12); 1736-44. (c)2017 AACR.

Erdmann, N. J., et al. (2017). "Mammographic density, blood telomere length and lipid peroxidation." Sci
Rep 7(1): 5803.
Extensive mammographic density is a strong risk factor for breast cancer, but may also be an
indicator of biological age. In this study we examined whether mammographic density is related
to blood telomere length, a potential marker of susceptibility to age-related disease. We
measured mammographic density by a computer assisted method and blood telomere length
using a validated PCR method. Urinary malondialdehyde (MDA), a marker of lipid peroxidation,
was measured in 24 hour urine collections. In the 342 women examined telomere length was
negatively correlated with age, was lower in postmenopausal compared to premenopausal
women and in smokers compared to non-smokers, and was positively correlated with urinary
MDA. Telomere length was not associated with percent mammographic density or dense area,
before or after adjustment for risk factors and MDA. However, there was a significant
interaction between telomere length and MDA in their association with mammographic density.
At lower levels of MDA, mammographic density and telomere length were inversely associated;
while at high levels of MDA, there was evidence of a J-shaped association between
mammographic density and telomere length. Further work is need to replicate these results and
to examine the association of mammographic density with age-related chronic disease and
mortality.

Fouad, T. M., et al. (2018). "Distinct epidemiological profiles associated with inflammatory breast cancer
(IBC): A comprehensive analysis of the IBC registry at The University of Texas MD Anderson Cancer
Center." PLoS One 13(9): e0204372.
BACKGROUND: To date, studies on inflammatory breast cancer (IBC) lack comprehensive
epidemiological data. We analyzed detailed prospectively collected clinical and epidemiological
data from the IBC Registry at The University of Texas MD Anderson Cancer Center. METHODS:
Patients with IBC (n = 248) were consecutively diagnosed and prospectively enrolled between
November 2006 and April 2013. All patients were newly diagnosed and at least 18 years old.
Secondary IBC was excluded. Overall 160 variables were collected and evaluated including
sociodemographics, anthropometrics, tobacco and alcohol consumption, reproductive variables,
and family history data. RESULTS: Mean age at diagnosis was 51.6 (+/-11.5 SD) years, and the
majority of patients were White (77.8%). A mean BMI >/= 25 kg/m2, irrespective of menopausal
status, was observed in 80.2% of all patients, with 82.6% of African Americans being obese.
Approximately 42.2% of patients were ever smokers, and 91% reported ever being pregnant. A
history of breastfeeding was reported in 54% of patients, with significant differences between
ethnic groups in favor of White women (P<0.0001). Other reproductive factors such as use of
birth control pills & hormone replacement therapy were also more frequently associated with
White women compare to other ethnic groups (P < 0.05). In the multivariate Cox proportional
hazard analysis, African American or Hispanic ethnicity, not having breastfed, higher clinical
stage, and TNBC subtype were associated with shorter survival. CONCLUSION: Our data suggest
 that IBC is associated with distinct epidemiological profiles. This information could assist in
targeting patients with specific preventive strategies based on their modifiable behavioral
patterns.

Fracol, M., et al. (2017). "The Surgical Impact of E-Cigarettes: A Case Report and Review of the Current
Literature." Arch Plast Surg 44(6): 477-481.
We report a case of a 51 years old female with a 25 pack year smoking history who underwent
bilateral mastectomy and immediate tissue expander reconstruction for newly diagnosed right
breast cancer. The patient reported herself as a non-smoker despite significant e-cigarette use,
with resulting significant mastectomy skin flap necrosis and breast reconstruction failure. Little
is known about the physiologic effect of e-cigarettes on wound healing and tissue perfusion. To
this end, we provide an updated review of the impact of e-cigarettes on surgical outcomes.
PubMed, Ovid MEDLINE, and PRS GO were searched for the terms "e-cigarette", "electronic
cigarette", "e-cig", "electronic nicotine delivery system", "vaping", "surgery", "surgical", "peri-
operative", "operate", "operative", and "wound healing". Abstract review of all articles was
performed. 123 articles returned that contained both variants of e-cigarettes and surgery as
keywords. Of those, manual assessment returned three articles which were found to be relevant
to e-cigarette use in the surgical patient. No articles were found that compared perioperative
complications in e-cigarette versus traditional cigarette users in humans. In conclusion, our case
report depicts the potential dangers associated with e-cigarette use in the surgical patient.
There is a public misconception that e-cigarettes are healthier than traditional cigarettes and as
such their use may go unreported by patients. Early evidence suggests e-cigarettes may induce
some of the same physiologic changes as traditional cigarettes, and may have a significant
deleterious effect on wound healing.

Gankhuyag, N., et al. (2017). "The Role of Nitrosamine (NNK) in Breast Cancer Carcinogenesis." J
Mammary Gland Biol Neoplasia 22(3): 159-170.
Smoking cigarettes is one of the most concerning issues that leads to tobacco-related cancers
and can even result in death. Therefore, these issues should be addressed with a great sense of
urgency with low-cost and simple approaches. Over the past several years, the scientific
community has attempted to find solutions to overcome this issue. Thus, a large number of
excellent studies have been reported in this field, and summarizing these results and providing
important roadmaps for future studies is currently of great importance. Finding an outstanding
solution to address aforementioned issue would be of great value to the community and to the
social. Tobacco contains thousands of chemicals, and sixty-nine compounds have been
established as human carcinogens; specifically, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone
(NNK) is the strongest carcinogen among the tobacco-specific nitrosamines. Tobacco
carcinogens are also linked to mammary gland pathogenesis and increased risk of developing
many cancers, including breast cancer, the most common cancer in women worldwide. This
mini-review summarizes the role of NNK and the mechanisms of its receptor, nicotine
acetylcholine receptor (nAChR), signaling in breast cancer based on publications identified using
the keywords "secondhand smoke (SHS)", "Nitrosamines" and "breast cancer". Furthermore,
this review considers the risk of NNK to the public in an effort to reduce exposure to SHS in
women and their chances of developing breast cancer.
Gapstur, S. M., et al. (2017). "Associations of Coffee Drinking and Cancer Mortality in the Cancer
Prevention Study-II." Cancer Epidemiol Biomarkers Prev 26(10): 1477-1486.
Background: Associations of coffee consumption with cancer mortality are inconsistent for many
types of cancer, and confounding by smoking is an important concern.Methods: Cox
proportional hazards regression was used to estimate multivariable-adjusted HRs for coffee
consumption associated with death from all cancers combined and from specific cancer types
among 922,896 Cancer Prevention Study-II participants ages 28-94 years who completed a four-
page questionnaire and were cancer free at baseline in 1982.Results: During follow-up through
2012, there were 118,738 cancer-related deaths. There was a nonlinear association between
coffee consumption and all-cancer death among current smokers and former smokers and no
association among never smokers. Among nonsmokers, a 2 cup/day increase in coffee
consumption was inversely associated with death from colorectal [HR = 0.97; 95% confidence
interval (CI) 0.95-0.99], liver [HR = 0.92; 95% CI, 0.88-0.96], and female breast (HR = 0.97; 95%
CI, 0.94-0.99) cancers, and positively associated with esophageal cancer-related death (HR =
1.07; 95% CI, 1.02-1.12). For head and neck cancer, a nonlinear inverse association was
observed starting at 2-3 cups per day (HR = 0.72; 95% CI, 0.55-0.95), with similar associations
observed at higher levels of consumption.Conclusions: These findings are consistent with many
other studies that suggest coffee drinking is associated with a lower risk of colorectal, liver,
female breast, and head and neck cancer. The association of coffee consumption with higher
risk of esophageal cancer among nonsmokers in our study should be confirmed.Impact: These
results underscore the importance of assessing associations between coffee consumption and
cancer mortality by smoking status. Cancer Epidemiol Biomarkers Prev; 26(10); 1477-86. (c)2017
AACR.

Gaudet, M. M., et al. (2017). "Pooled analysis of active cigarette smoking and invasive breast cancer risk
in 14 cohort studies." Int J Epidemiol 46(3): 881-893.
Background: The 2014 US Surgeon General's report noted research gaps necessary to determine
a causal relationship between active cigarette smoking and invasive breast cancer risk, including
the role of alcohol consumption, timing of exposure, modification by menopausal status and
heterogeneity by oestrogen receptor (ER) status. Methods: To address these issues, we pooled
data from 14 cohort studies contributing 934 681 participants (36 060 invasive breast cancer
cases). Cox proportional hazard regression models were used to calculate multivariable-adjusted
hazard ratios (HRs) and 95% confidence intervals (CIs). Results: Smoking duration before first
birth was positively associated with risk ( P -value for trend = 2 x 10 -7 ) with the highest HR for
initiation >10 years before first birth (HR = 1.18, CI 1.12-1.24). Effect modification by current
alcohol consumption was evident for the association with smoking duration before first birth ( P
-value=2x10 -4 ); compared with never-smoking non-drinkers, initiation >10 years before first
birth was associated with risk in every category of alcohol intake, including non-drinkers (HR =
1.15, CI 1.04-1.28) and those who consumed at least three drinks per day (1.85, 1.55-2.21).
Associations with smoking before first birth were limited to risk of ER+ breast cancer ( P -value
for homogeneity=3x10 -3 ). Other smoking timing and duration characteristics were associated
with risk even after controlling for alcohol, but were not associated with risk in non-drinkers.
Effect modification by menopause was not evident. Conclusions: Smoking, particularly if
initiated before first birth, was modestly associated with ER+ breast cancer risk that was not
confounded by amount of adult alcohol intake. Possible links with breast cancer provide
additional motivation for young women to not initiate smoking.
Goldvaser, H., et al. (2017). "The association between smoking and breast cancer characteristics and
outcome." BMC Cancer 17(1): 624.
BACKGROUND: Smoking is associated with an increased incidence of hormone receptor positive
breast cancer. Data regarding worse breast cancer outcome in smokers are accumulating.
Current literature regarding the impact of smoking on breast cancer characteristics is limited.
We evaluated the impact of smoking on breast cancer characteristics and outcome. METHODS:
This was a retrospective single center study. All women diagnosed from 4/2005 through 3/2012
and treated in our institute for early, estrogen receptor positive, human epidermal growth
factor receptor 2 (HER2) negative breast cancer, whose tumors were sent for Oncotype DX
analysis were included. Medical records were reviewed for demographics, clinico-pathological
parameters, treatment and outcome. Data regarding smoking were retrieved according to
patients' history at the first visit in the oncology clinic. Patients were grouped and compared
according to smoking history (ever smokers vs. never smokers), smoking status (current vs.
former and never smokers) and smoking intensity (pack years >/=30 vs. the rest of the cohort).
Outcomes were adjusted in multivariate analyses and included age, menopausal status,
ethnicity, tumor size, nodal status and grade. RESULTS: A total of 662 women were included.
28.2% had a history of smoking, 16.6% were current smokers and 11.3% were heavy smokers.
Smoking had no impact on tumor size, nodal involvement and Oncotype DX recurrence score.
Angiolymphatic and perineural invasion rates were higher in current smokers than in the rest of
the cohort (10.4% vs. 5.1%, p = 0.045, 8.3% vs. 3.5%, p = 0.031, respectively). Smoking had no
other impact on histological characteristics. Five-year disease free survival and overall survival
rates were 95.7% and 98.5%, respectively. Smoking had no impact on outcomes. Adjusted
disease free survival and overall survival did not influence the results. CONCLUSIONS: Smoking
had no clinically significant influence on tumor characteristics and outcome among women with
estrogen receptor positive, HER2 negative, early breast cancer. As the study was limited to a
specific subgroup of the breast cancer population in this heterogeneous disease and since
smoking is a modifiable risk factor for the disease, further research is required to clarify the
possible impact of smoking on breast cancer.

Hassett, M. J., et al. (2017). "Survival after recurrence of stage I-III breast, colorectal, or lung cancer."
Cancer Epidemiol 49: 186-194.
BACKGROUND: The experiences of patients with recurrent cancer are assumed to reflect those
of patients with de novo stage IV disease; yet, little is truly known because most registries lack
recurrence status. Using two databases with excellent recurrence and death information, we
examined determinants of survival duration after recurrence of breast (BC), colorectal (CRC),
and lung cancers (LC). METHODS: Recurrence status was abstracted from the medical records of
patients who participated in the Cancer Care Outcomes Research and Surveillance study and
who received care at two Cancer Research Network sites-the Colorado and Northwest regions of
Kaiser Permanente. The analysis included 1653 patients who developed recurrence after
completing definitive therapy for stages I-III cancer. Multivariable modeling identified
independent determinants of survival duration after recurrence, controlling for other factors.
RESULTS: Through 60 months' average follow-up, survival after recurrence for BC, CRC, and LC
were 28.4, 23.1 and 16.1 months, respectively. Several factors were independently associated
with shorter survival for all three cancers, including higher initial stage (III vs. I: BC -9.9 months;
CRC -6.9 months; LC -7.4 months; P</=0.01). Factors associated with shorter survival for
 selected cancers included: distant/regional recurrence for BC and CRC; current/former smoker
for LC; high grade for CRC; and <4-year time-to-recurrence for BC. CONCLUSIONS: Initial stage
predicts survival duration after recurrence, whereas time-to-recurrence usually does not. The
impact of biologic characteristics (e.g., grade, hormone-receptor status) on survival duration
after recurrence needs further study. Predictors of survival duration after recurrence may help
facilitate patient decision-making.

Haug, U., et al. (2018). "First-degree relatives of cancer patients: a target group for primary prevention?
A cross-sectional study." Br J Cancer 118(9): 1255-1261.
BACKGROUND: Persons with a first-degree relative (FDR) with cancer are at increased cancer
risk. We investigated preventive behaviour, cancer risk perception and readiness to change an
unhealthy lifestyle in persons with and without an FDR with cancer. METHODS: Using an online
questionnaire, we conducted a cross-sectional study in Germany including persons (>/=35 years)
with an FDR with colorectal, lung, prostate, breast, stomach or cervical/uterine cancer (n = 621)
and persons without cancer in FDRs (n = 303). Quota sampling ensured similar age and sex
distributions in both groups. RESULTS: Unfavourable lifestyle factors were equally common in
both groups. The proportion perceiving an increased cancer risk significantly differed (p <
0.0001) with 4% among respondents without cancer in FDRs and 18% (colorectal cancer) to 30%
(stomach cancer) among cancer patients' relatives. The proportion of smokers ready to quit
smoking was significantly higher among those perceiving an increased vs. a lower cancer risk (64
vs. 46%, p = 0.04). There was a similar association for readiness to increase physical activity and
consumption of fruits/vegetables and to reduce alcohol consumption. CONCLUSIONS: Given the
increased risk perception and motivation to change an unhealthy lifestyle, our study provides a
strong rationale for research on the effectiveness of lifestyle interventions in cancer patients'
relatives.

Hooper, L. G., et al. (2018). "Ambient Air Pollution and Chronic Bronchitis in a Cohort of U.S. Women."
Environ Health Perspect 126(2): 027005.
BACKGROUND: Limited evidence links air pollution exposure to chronic cough and sputum
production. Few reports have investigated the association between long-term exposure to air
pollution and classically defined chronic bronchitis. OBJECTIVES: Our objective was to estimate
the association between long-term exposure to particulate matter (diameter <10 mum, PM10;
<2.5mum, PM2.5), nitrogen dioxide (NO2), and both incident and prevalent chronic bronchitis.
METHODS: We estimated annual average PM2.5, PM10, and NO2 concentrations using a
national land-use regression model with spatial smoothing at home addresses of participants in
a prospective nationwide U.S. cohort study of sisters of women with breast cancer. Incident
chronic bronchitis and prevalent chronic bronchitis, cough and phlegm, were assessed by
questionnaires. RESULTS: Among 47,357 individuals with complete data, 1,383 had prevalent
chronic bronchitis at baseline, and 647 incident cases occurred over 5.7-y average follow-up. No
associations with incident chronic bronchitis were observed. Prevalent chronic bronchitis was
associated with PM10 [adjusted odds ratio (aOR) per interquartile range (IQR) difference (5.8(
)mug/m(3))=1.07; 95% confidence interval (CI): 1.01, 1.13]. In never-smokers, PM2.5 was
associated with prevalent chronic bronchitis (aOR=1.18 per IQR difference; 95% CI: 1.04, 1.34),
and NO2 was associated with prevalent chronic bronchitis (aOR=1.10; 95% CI=1.01, 1.20), cough
(aOR=1.10; 95% CI: 1.05, 1.16), and phlegm (aOR=1.07; 95% CI: 1.01, 1.14); interaction p-values
 (nonsmokers vs. smokers) <0.05. CONCLUSIONS: PM10 exposure was related to chronic
bronchitis prevalence. Among never-smokers, PM2.5 and NO2 exposure was associated with
chronic bronchitis and component symptoms. Results may have policy ramifications for PM10
regulation by providing evidence for respiratory health effects related to long-term PM10
exposure. https://doi.org/10.1289/EHP2199.

Husain, H., et al. (2017). "Cell-Free DNA from Ascites and Pleural Effusions: Molecular Insights into
Genomic Aberrations and Disease Biology." Mol Cancer Ther 16(5): 948-955.
Collection of cell-free DNA (cfDNA) from the blood of individuals with cancer has permitted
noninvasive tumor genome analysis. Detection and characterization of cfDNA in ascites and
pleural effusions have not yet been reported. Herein, we analyzed cfDNA in the ascites and
pleural effusions from six individuals with metastatic cancer. In all cases, cfDNA copy number
variations (CNV) were discovered within the effusate. One individual had a relevant alteration
with a high copy amplification in EGFR in a never smoker with lung cancer, who showed only
MDM2 and CDK4 amplification in a prior tissue biopsy. Another subject with metastatic breast
cancer had cytology-positive ascites and an activating PIK3CA mutation identified in the tissue,
blood, and ascites collectively. This individual had tumor regression after the administration of
the mTOR inhibitor everolimus and had evidence of chromotripsis from chromosomal
rearrangements noted in the cell-free ascitic fluid. These results indicate that cfDNA from ascites
and pleural effusions may provide additional information not detected with tumor and plasma
cell-free DNA molecular characterization, and a context for important insights into tumor
biology and clonal dynamic change within primary tumor and metastatic deposits. Mol Cancer
Ther; 16(5); 948-55. (c)2017 AACR.

Jacob, L., et al. (2018). "Impact of tobacco smoking on the risk of developing 25 different cancers in the
UK: a retrospective study of 422,010 patients followed for up to 30 years." Oncotarget 9(25): 17420-
17429.
Background: The aim of this study was to analyze the impact of tobacco smoking on the risk of
developing 25 different cancers in patients followed for up to 30 years in general practices in the
UK. Methods: This study included all individuals with at least one visit to one of 196 general
practitioners' offices in the UK between January 1988 and December 2008 (index date). Only
individuals with documented smoking status were included. Smokers and non-smokers were
matched (1:1) by age, gender, index year, body mass index, and physician. The main outcome of
the study was the risk of cancer as a function of smoking status. Data regarding a total of 25
cancers were available for the present analysis. The risk of cancer was analyzed using Cox's
regression model. Results: The present retrospective study included 211,005 smokers and
211,005 non-smokers. The mean age was 36.5 years (SD = 12.5 years) in men and 34.3 years (SD
= 13.1 years) in women. There was a slightly positive association between smoking and any
cancer in both men (HR = 1.07) and women (HR = 1.03). Smoking was further found to be
positively associated with several cancers, such as liver cancer, bladder and kidney cancers,
pancreas cancer, and lymphoma. By contrast, the use of tobacco was negatively associated with
the risk of developing skin cancer, prostate cancer, multiple myeloma, endometrial carcinoma,
or breast cancer. Conclusions: Smoking increased the overall risk of cancer in primary care
practices in the UK. In addition, smoking was predominantly positively and less frequently
negatively associated with numerous specific cancers.
James, P., et al. (2017). "Outdoor Light at Night and Breast Cancer Incidence in the Nurses' Health Study
II." Environ Health Perspect 125(8): 087010.
BACKGROUND: Animal and epidemiologic studies suggest that exposure to light at night (LAN)
may disrupt circadian patterns and decrease nocturnal secretion of melatonin, which may
disturb estrogen regulation, leading to increased breast cancer risk. OBJECTIVES: We examined
the association between residential outdoor LAN and breast cancer incidence using data from
the nationwide U.S.-based Nurses' Health Study II cohort. METHODS: We followed 109,672
women from 1989 through 2013. Cumulative LAN exposure was estimated using time-varying
satellite data for a composite of persistent nighttime illumination at approximately 1 km(2) scale
for each residence during follow-up. Incident invasive breast cancer cases were confirmed by
medical record review. We used Cox proportional hazard models to calculate hazard ratios (HRs)
and 95% confidence intervals (CIs), adjusting for anthropometric, reproductive, lifestyle, and
socioeconomic risk factors. RESULTS: Over 2,187,425 person-years, we identified 3,549 incident
breast cancer cases. Based on a fully adjusted model, the estimated HR for incident breast
cancer with an interquartile range (IQR) (31.6 nW/cm(2)/sr) increase in cumulative average
outdoor LAN was 1.05 (95% CI: 1.00, 1.11). An association between LAN and breast cancer
appeared to be limited to women who were premenopausal at the time of a case [HR=1.07 (95%
CI: 1.01, 1.14) based on 1,973 cases vs. HR=1.00 (95% CI: 0.91, 1.09) based on 1,172 cases in
postmenopausal women; p-interaction=0.08]. The LAN-breast cancer association was observed
only in past and current smokers at the end of follow-up [HR=1.00 (95% CI: 0.94, 1.07) based on
2,215 cases in never smokers; HR=1.10 (95% CI: 1.01, 1.19) based on 1,034 cases in past smokers
vs. HR=1.21 (95% CI: 1.07, 1.37) for 300 cases in current smokers; p-interaction=0.08].
CONCLUSIONS: Although further work is required to confirm our results and to clarify potential
mechanisms, our findings suggest that exposure to residential outdoor light at night may
contribute to invasive breast cancer risk. https://doi.org/10.1289/EHP935.

Jeronimo, A. F. A. and M. Weller (2017). "Differential Association of the Lifestyle-Related Risk Factors
Smoking and Obesity with Triple Negative Breast Cancer in a Brazilian Population." Asian Pac J Cancer
Prev 18(6): 1585-1593.
Background: A longer lifespan and changing lifestyle-related and reproductive risk factors have
led to an increased incidence of breast cancer in Brazil. There have been few studies about
associations of specific risk factors with molecular subtypes of the disease. The aim of the
present study was to identify factors that modulate the risk of triple negative breast cancer.
Materials and Methods: A case-case analysis was performed. Data for 236 breast cancer
patients from two reference centres in North-eastern Brazil were applied to assess the
association of risk factors with triple negative breast cancer relative to the luminal A subtype.
Molecular subtypes were defined by expression status of hormone receptors and amplification
of HER2. Nominal logistic regression was used to estimate odds ratios and to generate a model
of independent variables. Results: Smoking and body mass index were differentially associated
with likelihood of triple negative breast cancer compared to the Luminal A subtype (p= 0.013; p=
0.004): Women who ever smoked some time in their lives were 4.016 (OR= 0.249; CI 95%: 0.09-
0.71) times less likely to have triple negative breast cancer. Obese and overweight patients,
respectively, were 4.489 (CI 95%: 1.32- 15.28) and 1.340 (CI 95%: 0.38- 4.69) times more likely to
have triple negative breast cancer. Conclusions: Case-case analysis with the Luminal A subtype
 as the reference group indicated that smoking and body mass index are differentially associated
with risk of triple negative breast cancer.

Jin, F., et al. (2017). "Tobacco-Specific Carcinogens Induce Hypermethylation, DNA Adducts, and DNA
Damage in Bladder Cancer." Cancer Prev Res (Phila) 10(10): 588-597.
Smoking is a major risk factor for the development of bladder cancer; however, the functional
consequences of the carcinogens in tobacco smoke and bladder cancer-associated metabolic
alterations remain poorly defined. We assessed the metabolic profiles in bladder cancer
smokers and non-smokers and identified the key alterations in their metabolism. LC/MS and
bioinformatic analysis were performed to determine the metabolome associated with bladder
cancer smokers and were further validated in cell line models. Smokers with bladder cancer
were found to have elevated levels of methylated metabolites, polycyclic aromatic
hydrocarbons, DNA adducts, and DNA damage. DNA methyltransferase 1 (DNMT1) expression
was significantly higher in smokers than non-smokers with bladder cancer. An integromics
approach, using multiple patient cohorts, revealed strong associations between smokers and
high-grade bladder cancer. In vitro exposure to the tobacco smoke carcinogens, 4-
(methylnitrosamino)-1-(3-pyridyl)-1-butanone and benzo[a]pyrene (BaP) led to increase in levels
of methylated metabolites, DNA adducts, and extensive DNA damage in bladder cancer cells.
Cotreatment of bladder cancer cells with these carcinogens and the methylation inhibitor 5-aza-
2'-deoxycytidine rewired the methylated metabolites, DNA adducts, and DNA damage. These
findings were confirmed through the isotopic-labeled metabolic flux analysis. Screens using
smoke-associated metabolites and DNA adducts could provide robust biomarkers and improve
individual risk prediction in bladder cancer smokers. Noninvasive predictive biomarkers that can
stratify the risk of developing bladder cancer in smokers could aid in early detection and
treatment. Cancer Prev Res; 10(10); 588-97. (c)2017 AACR.

Jones, M. E., et al. (2017). "Smoking and risk of breast cancer in the Generations Study cohort." Breast
Cancer Res 19(1): 118.
BACKGROUND: Plausible biological reasons exist regarding why smoking could affect breast
cancer risk, but epidemiological evidence is inconsistent. METHODS: We used serial
questionnaire information from the Generations Study cohort (United Kingdom) to estimate HRs
for breast cancer in relation to smoking adjusted for potentially confounding factors, including
alcohol intake. RESULTS: Among 102,927 women recruited 2003-2013, with an average of 7.7
years of follow-up, 1815 developed invasive breast cancer. The HR (reference group was never
smokers) was 1.14 (95% CI 1.03-1.25; P = 0.010) for ever smokers, 1.24 (95% CI 1.08-1.43; P =
0.002) for starting smoking at ages < 17 years, and 1.23 (1.07-1.41; P = 0.004) for starting
smoking 1-4 years after menarche. Breast cancer risk was not statistically associated with
interval from initiation of smoking to first birth (P-trend = 0.97). Women with a family history of
breast cancer (ever smoker vs never smoker HR 1.35; 95% CI 1.12-1.62; P = 0.002) had a
significantly larger HR in relation to ever smokers (P for interaction = 0.039) than women
without (ever smoker vs never smoker HR 1.07; 95% CI 0.96-1.20; P = 0.22). The interaction was
prominent for age at starting smoking (P = 0.003) and starting smoking relative to age at
menarche (P = 0.0001). CONCLUSIONS: Smoking was associated with a modest but significantly
increased risk of breast cancer, particularly among women who started smoking at adolescent
 or peri-menarcheal ages. The relative risk of breast cancer associated with smoking was greater
for women with a family history of the disease.

Jung, J., et al. (2018). "Incidence and risk factors of postoperative pneumonia following cancer surgery in
adult patients with selected solid cancer: results of "Cancer POP" study." Cancer Med 7(1): 261-269.
The aim of this study was to investigate the incidence and risk factors of postoperative
pneumonia (POP) within 1 year after cancer surgery in patients with the five most common
cancers (gastric, colorectal, lung, breast cancer, and hepatocellular carcinoma [HCC]) in South
Korea. This was a multicenter and retrospective cohort study performed at five nationwide
cancer centers. The number of cancer patients in each center was allocated by the proportion of
cancer surgery. Adult patients were randomly selected according to the allocated number,
among those who underwent cancer surgery from January to December 2014 within 6 months
after diagnosis of cancer. One-year cumulative incidence of POP was estimated using Kaplan-
Meier analysis. An univariable Cox's proportional hazard regression analysis was performed to
identify risk factors for POP development. As a multivariable analysis, confounders were
adjusted using multiple Cox's PH regression model. Among the total 2000 patients, the numbers
of patients with gastric cancer, colorectal cancer, lung cancer, breast cancer, and HCC were 497
(25%), 525 (26%), 277 (14%), 552 (28%), and 149 (7%), respectively. Overall, the 1-year
cumulative incidence of POP was 2.0% (95% CI, 1.4-2.6). The 1-year cumulative incidences in
each cancer were as follows: lung 8.0%, gastric 1.8%, colorectal 1.0%, HCC 0.7%, and breast
0.4%. In multivariable analysis, older age, higher Charlson comorbidity index (CCI) score, ulcer
disease, history of pneumonia, and smoking were related with POP development. In
conclusions, the 1-year cumulative incidence of POP in the five most common cancers was 2%.
Older age, higher CCI scores, smoker, ulcer disease, and previous pneumonia history increased
the risk of POP development in cancer patients.

Kim, A. S., et al. (2018). "Exposure to Secondhand Smoke and Risk of Cancer in Never Smokers: A Meta-
Analysis of Epidemiologic Studies." Int J Environ Res Public Health 15(9).
This is first meta-analysis to evaluate cancer risk associated with secondhand smoking across all
cancers. A literature search was conducted for articles published before June 2014 on Pubmed,
SCOPUS, Cochrane library, and CINAHL, and 40 articles on secondhand smoke and the
prevalence of cancer among never smokers were selected for final analysis as per the inclusion
criteria. Of the 40 articles, 27 were case-control studies and 13 were prospective cohort studies.
With respect to overall cancer risk, odds ratio (OR) involving never smokers with significant
exposure to secondhand smoke compared to never smokers without such exposure was 1.163
(95%CI 1.058(-)1.279). Subgroup meta-analyses by study design showed significant positive
associations for both case-control studies and prospective cohort studies (OR 1.165, 95%CI
1.029(-)1.320; and OR 1.160, 95%CI 1.002(-)1.343, respectively). The association was stronger in
the case of females (OR 1.253, 95%CI 1.142(-)1.374), lung cancer (OR 1.245, 95%CI 1.026(-
)1.511), and breast cancer (OR 1.235, 95%CI 1.102(-)1.385). Secondhand smoking may increase
the overall risk of cancer for never smokers, particularly lung and breast cancer, and especially
in women. Strict implementation of smoking cessation programs should be encouraged, not
only to reduce active smoking but also to limit exposure to secondhand smoke.
Kispert, S. and J. McHowat (2017). "Recent insights into cigarette smoking as a lifestyle risk factor for
breast cancer." Breast Cancer (Dove Med Press) 9: 127-132.
There have been many cohort studies published reviewing the epidemiological evidence that
links breast cancer to cigarette smoking, yet the underlying mechanisms are largely unknown
and research studies are few and incomplete. Although cohort studies are important in
establishing a connection between breast cancer and cigarette smoking, basic science research
is necessary to prove the relationship and to highlight potential interventions and drug targets
that can be used to manage the disease. This subject has been controversial for many decades;
however, there has been a recent resurgence in interest because of the widespread
acknowledgment of the role lifestyle choices play in cancer development and progression. This
review will detail the current statistics associated with cigarette smoking and discuss recent
cohort and basic research studies that highlight the association of cigarette smoking and breast
cancer initiation and progression.

Kispert, S., et al. (2017). "Cigarette Smoke Regulates Calcium-Independent Phospholipase A2 Metabolic
Pathways in Breast Cancer." Am J Pathol 187(8): 1855-1866.
Phospholipase A2 (PLA2)-dependent pathways are important in the regulation of cell
proliferation, differentiation, motility, and immune responses, and can be dysregulated during
tumor development and progression. We show herein, for the first time, that cigarette smoking
leads to an increase in platelet-activating factor (PAF) content and PAF receptor expression in
human breast cancer cells and tissue. PAF production could be abrogated in triple-negative
breast cancer cells by inhibition of calcium-independent PLA2 (iPLA2). We also demonstrate that
cigarette smoke induces the expression of cyclooxygenase-2 and microsomal prostaglandin E
synthase-1 and reduces 15-hydroxyprostaglandin dehydrogenase, resulting in prostaglandin E2
release in human breast cancer. Increased cyclooxygenase-2 expression and prostaglandin E2
release could be abrogated in metastatic breast cancer cells by inhibition of iPLA2. These studies
indicate that iPLA2-dependent metabolic pathways play an important role in tumor initiation or
progression in smokers, representing novel therapeutic targets for breast cancer patients who
smoke.

Knight, J. A., et al. (2017). "Alcohol consumption and cigarette smoking in combination: A predictor of
contralateral breast cancer risk in the WECARE study." Int J Cancer 141(5): 916-924.
Alcohol drinking and, to a lesser extent, cigarette smoking are risk factors for a first primary
breast cancer. Information on these behaviours at diagnosis may contribute to risk prediction of
contralateral breast cancer (CBC) and they are potentially modifiable. The WECARE Study is a
large population-based case-control study of women with breast cancer where cases (N = 1,521)
had asynchronous CBC and controls (N = 2,212), matched on survival time and other factors, had
unilateral breast cancer (UBC). Using multivariable conditional logistic regression to estimate
rate ratios (RR) and 95% confidence intervals (CI), we examined the risk of CBC in relation to
drinking and smoking history at and following first diagnosis. We adjusted for treatment, disease
characteristics and other factors. There was some evidence for an association between CBC risk
and current drinking or current smoking at the time of first breast cancer diagnosis, but the
increased risk occurred primarily among women exposed to both (RR = 1.62, 95% CI 1.24-2.11).
CBC risk was also elevated in women who both smoked and drank alcohol after diagnosis (RR =
1.54, 95% CI 1.18-1.99). In the subset of women with detailed information on amount
 consumed, smoking an average of >/=10 cigarettes per day following diagnosis was also
associated with increased CBC risk (RR = 1.50, 95% CI 1.08-2.08; p-trend = 0.03). Among women
with a diagnosis of breast cancer, information on current drinking and smoking could contribute
to the prediction of CBC risk. Women who both drink and smoke may represent a group who
merit targeted lifestyle intervention to modify their risk of CBC.

Kroenke, C. H., et al. (2017). "Post-diagnosis social networks, and lifestyle and treatment factors in the
After Breast Cancer Pooling Project." Psychooncology 26(4): 544-552.
OBJECTIVE: Larger social networks have been associated with better breast cancer survival. To
investigate potential mediators, we evaluated associations of social network size and diversity
with lifestyle and treatment factors associated with prognosis. METHODS: We included 9331
women from the After Breast Cancer Pooling Project who provided data on social networks
within approximately two years following diagnosis. A social network index was derived from
information about the presence of a spouse or intimate partner, religious ties, community
participation, friendship ties, and numbers of living relatives. Diversity was assessed as variety of
ties, independent of size. We used logistic regression to evaluate associations with outcomes
and evaluated whether effect estimates differed using meta-analytic techniques. RESULTS:
Associations were similar across cohorts though analyses of smoking and alcohol included US
cohorts only because of low prevalence of these behaviors in the Shanghai cohort. Socially
isolated women were more likely to be obese (OR = 1.21, 95% CI:1.03-1.42), have low physical
activity (<10 MET-hours/week, OR = 1.55, 95% CI:1.36-1.78), be current smokers (OR = 2.77,
95% CI:2.09-3.68), and have high alcohol intake (>/=15 g/d, OR = 1.23, 95% CI:1.00-1.51),
compared with socially integrated women. Among node positive cases from three cohorts,
socially isolated women were more likely not to receive chemotherapy (OR = 2.10, 95% CI:1.30-
3.39); associations differed in a fourth cohort. Other associations (nonsignificant) were
consistent with less intensive treatment in socially isolated women. Low social network diversity
was independently associated with more adverse lifestyle, but not clinical, factors.
CONCLUSIONS: Small, less diverse social networks measured post-diagnosis were associated
with more adverse lifestyle factors and less intensive cancer treatment. Copyright (c) 2016 John
Wiley & Sons, Ltd.

Kumari, K., et al. (2018). "Nicotine associated breast cancer in smokers is mediated through high level of
EZH2 expression which can be reversed by methyltransferase inhibitor DZNepA." Cell Death Dis 9(2):
152.
Recent studies show substantial growth-promoting properties of nicotine (NIC) in cancer, which
is a combined outcome of genetic and epigenetic alterations. However, the role of epigenetic
modifiers in response to NIC in breast cancer is less studied. In the present study, for the first
time we have shown NIC-induced enhanced EZH2 expression. Six pairs of smoking-associated
breast cancer patient tissues were analyzed. Samples from smoking breast cancer patients
showed distinguished enhanced EZH2 expression in comparison to non-smoking ones. The
upregulation in EZH2, which is due to NIC, was further confirmed in breast carcinoma cell lines
using 10 microM NIC, 1 microM DZNepA, and EZH2si. The upregulation of EZH2 was
concomitant with upregulation in Myc and alpha9-nAChR. The xenograft of breast cancer cells in
BALB/c nude mice in the presence or absence of NIC showed significantly higher tumor uptake
in the NIC injected group, which clearly demonstrates the effect of NIC in breast cancer
 progression. Interestingly, DZNepA considerably suppressed the NIC-mediated tumor growth.
CHIP-qPCR assay confirmed the increased Myc enrichment on EZH2 promoter upon NIC
treatment, thereby strengthening our findings that there exists an association between NIC,
Myc, and EZH2. Overall, the present study identifies a strong association between NIC and EZH2
particularly in the progression of breast cancer in smokers through a novel axis involving nAChR
and Myc. Moreover, the findings provide preliminary evidence suggesting potential of high level
of EZH2 expression as a prognostic marker in smoking-associated breast cancer.

Lam, T. C., et al. (2017). "Two-Stage Prosthetic Breast Reconstruction after Mastectomy with or without
Prior Postmastectomy Radiotherapy." Plast Reconstr Surg Glob Open 5(9): e1489.
BACKGROUND: Two-stage prosthetic breast reconstruction with initial insertion of a tissue
expander followed by an implant after a period of inflation is a well-established breast
reconstruction option. Most of the current literature concentrates on the immediate setting,
and there are only a few reports into delayed cases, especially after postmastectomy
radiotherapy (RT). We performed a retrospective review of our experience over a 12.5-year
period. METHODS: Between June 1998 and December 2010, a total of 671 patients received
prosthetic-only breast reconstruction. Of these, 170 (25.3%) underwent delayed 2-stage
prosthetic breast reconstruction after mastectomy for cancer. Patients were divided into group
A, no postmastectomy RT (n = 150), and group B, postmastectomy RT (n = 20). The primary
factor examined was the failure of the reconstruction from loss of prosthesis with or without
smoking. Other complications, as well as rates of revisional surgery were also recorded.
RESULTS: Expander or implant loss occurred in 3 of 150 patients in group A (2.0%) and 3 of 20
patients in group B (15%; P = 0.02). For nonsmokers, implant loss was 1.6% and 5.6%,
respectively (P = NS). Smoking was associated with 1 of the 3 losses in group A and 2 of the 3 in
group B (smokers, n = 2; P < 0.01). There was no significant difference in other complications
such as seromas or minor wound infections. CONCLUSIONS: Delayed 2-stage prosthetic breast
reconstruction has a low failure rate. It can also be successfully completed in selected patients
after postmastectomy RT, but care must be taken with patients who smoke.

Li, T., et al. (2018). "Nicotine-enhanced stemness and epithelial-mesenchymal transition of human
umbilical cord mesenchymal stem cells promote tumor formation and growth in nude mice." Oncotarget
9(1): 591-606.
Cigarette smoking is a well-known risk factor in the development and progression of malignant
diseases. Nicotine, the major constituent in cigarette smoke, has also shown negative effects on
stem cells. Mesenchymal stem cells (MSCs) have been widely demonstrated to migrate into
tumors and play key roles in cancer progression. However, the mechanisms by which nicotine
impacts MSCs and tumorigenesis of lung cancer are still undetermined. In this study we
investigated the effects of nicotine on human umbilical cord mesenchymal stem cells (hUC-
MSCs) and the impacts of nicotine-treated hUC-MSCs on tumor formation and progression. We
found that nicotine has a toxic effect on hUC-MSCs and changes the morphology, inhibits
proliferation and promotes apoptosis of hUC-MSCs in a dose-dependent manner. Nicotine-
treated hUC-MSCs produce higher level of IL-6. Moreover, nicotine promotes migration,
stemness and epithelial-mesenchymal transition (EMT) of hUC-MSCs by inhibiting E-cadherin
expression and upregulating mesenchymal markers such as N-cadherin and Vimentin, leading to
the induction of stem cell markers Sox2, Nanog, Sall4, Oct4 and CD44. Migration and
 proliferation of non-small cell lung cancer A549 cells and breast cancer MCF-7 cells are
promoted after their coculture with nicotine-treated hUC-MSCs in a cell-cell contact-
independent manner. Furthermore, nicotine-treated hUC-MSCs promote tumor formation and
growth of A549 cells in nude mice. These studies demonstrated that the enhanced stemness
and EMT of hUC-MSCs induced by nicotine are critical for the development of tobacco-related
cancers.

Liu, T., et al. (2017). "Can statistic adjustment of OR minimize the potential confounding bias for meta-
analysis of case-control study? A secondary data analysis." BMC Med Res Methodol 17(1): 179.
BACKGROUND: Different confounder adjustment strategies were used to estimate odds ratios
(ORs) in case-control study, i.e. how many confounders original studies adjusted and what the
variables are. This secondary data analysis is aimed to detect whether there are potential biases
caused by difference of confounding factor adjustment strategies in case-control study, and
whether such bias would impact the summary effect size of meta-analysis. METHODS: We
included all meta-analyses that focused on the association between breast cancer and passive
smoking among non-smoking women, as well as each original case-control studies included in
these meta-analyses. The relative deviations (RDs) of each original study were calculated to
detect how magnitude the adjustment would impact the estimation of ORs, compared with
crude ORs. At the same time, a scatter diagram was sketched to describe the distribution of
adjusted ORs with different number of adjusted confounders. RESULTS: Substantial
inconsistency existed in meta-analysis of case-control studies, which would influence the
precision of the summary effect size. First, mixed unadjusted and adjusted ORs were used to
combine individual OR in majority of meta-analysis. Second, original studies with different
adjustment strategies of confounders were combined, i.e. the number of adjusted confounders
and different factors being adjusted in each original study. Third, adjustment did not make the
effect size of original studies trend to constringency, which suggested that model fitting might
have failed to correct the systematic error caused by confounding. CONCLUSIONS: The
heterogeneity of confounder adjustment strategies in case-control studies may lead to further
bias for summary effect size in meta-analyses, especially for weak or medium associations so
that the direction of causal inference would be even reversed. Therefore, further
methodological researches are needed, referring to the assessment of confounder adjustment
strategies, as well as how to take this kind of bias into consideration when drawing conclusion
based on summary estimation of meta-analyses.

Lorenz, E., et al. (2017). "Modeling Variables With a Spike at Zero: Examples and Practical
Recommendations." Am J Epidemiol 185(8): 650-660.
In most epidemiologic studies and in clinical research generally, there are variables with a spike
at zero, namely variables for which a proportion of individuals have zero exposure (e.g., never
smokers) and among those exposed the variable has a continuous distribution. Different options
exist for modeling such variables, such as categorization where the nonexposed form the
reference group, or ignoring the spike by including the variable in the regression model with or
without some transformation or modeling procedures. It has been shown that such situations
can be analyzed by adding a binary indicator (exposed/nonexposed) to the regression model,
and a method based on fractional polynomials with which to estimate a suitable functional form
for the positive portion of the spike-at-zero variable distribution has been developed. In this
 paper, we compare different approaches using data from 3 case-control studies carried out in
Germany: the Mammary Carcinoma Risk Factor Investigation (MARIE), a breast cancer study
conducted in 2002-2005 (Flesch-Janys et al., Int J Cancer. 2008;123(4):933-941); the Rhein-
Neckar Larynx Study, a study of laryngeal cancer conducted in 1998-2000 (Dietz et al., Int J
Cancer. 2004;108(6):907-911); and a lung cancer study conducted in 1988-1993 (Jockel et al., Int
J Epidemiol. 1998;27(4):549-560). Strengths and limitations of different procedures are
demonstrated, and some recommendations for practical use are given.

Lucas, A. R., et al. (2017). "Posttreatment trajectories of physical activity in breast cancer survivors."
Cancer 123(14): 2773-2780.
BACKGROUND: Breast cancer survivors face a risk of disease recurrence and a higher risk of
developing comorbidities such as cardiovascular disease when compared with the general
population. Physical activity (PA) has been shown to reduce such risks. The current analyses
sought to identify: 1) unique patterns of PA among breast cancer survivors; and 2)
characteristics associated with the level of PA. METHODS: A total of 548 women reported PA
and sociodemographic, health-related, and psychosocial factors at 3 time points, 6 months
apart, after primary treatment of breast cancer. Cancer-related factors were obtained from
chart reviews. Finite mixture modeling was used to examine trajectory groups of moderate-
intensity to vigorous-intensity PA (MVPA) in the early posttreatment period. The authors then
examined the characteristics associated with trajectory group membership. RESULTS: Three
groups with distinct, stable patterns of PA were identified: the low MVPA (42.5% of patients),
medium MVPA (45.5% of patients), and high MVPA (12.0% of patients) groups. In a multivariable
setting, compared with more active breast cancer survivors, the least active group was found to
have a higher body mass index, were less likely to report alcohol consumption, were more likely
to smoke cigarettes, and had worse physical functioning and vitality scores. Cancer treatment-
related factors did not significantly predict group membership. CONCLUSIONS: A large
percentage of breast cancer survivors remain physically inactive after treatment, suggesting the
need for interventions to reduce morbidity and mortality in this population. Cancer
2017;123:2773-80. (c) 2017 American Cancer Society.

Luo, X., et al. (2017). "Should Nonsmokers Be Excluded from Early Lung Cancer Screening with Low-Dose
Spiral Computed Tomography? Community-Based Practice in Shanghai." Transl Oncol 10(4): 485-490.
OBJECTIVE: We investigated the efficacy of early lung cancer screening with low-dose spiral
computed tomography(LDCT) in both smokers and nonsmokers based on the current situation
of community health service, with integration of superior resources of medical institutions at all
levels in Shanghai. METHODS: From August 2013 to August 2014, we screened 11,332 (male
7144; female 4188) high-risk individuals in selected communities of Minhang, Shanghai City, for
early diagnosis of lung cancer with LDCT combined with multidisciplinary comprehensive
treatment pattern including minimally invasive surgery, exploring the medical service network
covering prevention, diagnosis, treatment, rehabilitation, and follow-up. RESULTS: Screening
resulted in a diagnosis of cancer in 29 participants. Of these participants, 27 had primary lung
cancer, 1 had lung metastatic cancer, and 1 had breast cancer. The detection rate of primary
lung cancer was 238.26 cases per 100,000 person-years among all the participants. Specifically,
the incidence of primary lung cancer was 336.97 cases per 100,000 person-years among the
nonsmoking participants, as compared with 159.06 cases per 100,000 person-years among the
 smoking participants (P=.054). Among the 27 primary lung cancers, 22 (81.48%) had stage 0 to I
lung cancer. CONCLUSION: Based on community health service, screening with LDCT could
improve the early diagnosis rate of lung cancer in both smokers and nonsmokers with feasibility
and validity, which could be applicable in qualified eligible medical centers and communities in
China. It is not reasonable to exclude nonsmokers from screening with LDCT.

Malik, D. E., et al. (2018). "Mechanistic evidence that benzo[a]pyrene promotes an inflammatory
microenvironment that drives the metastatic potential of human mammary cells." Arch Toxicol 92(10):
3223-3239.
Benzo[a]pyrene (B(a)P) is a major cancer-causing contaminant present in food such as cooked
meats and cereals, and is ubiquitous in the environment in smoke derived from the combustion
of organic material. Exposure to B(a)P is epidemiologically linked with the incidence of breast
cancer. Although B(a)P is recognized as a complete genotoxic carcinogen, thought to act
primarily via CYP-mediated metabolic activation to DNA-damaging species, there is also
evidence that B(a)P exposure elicits other biological responses that promote development of
the cancer phenotype. Here in mechanistic studies using human mammary cells MCF-7 and
MDA-MB-231, we have explored mechanisms whereby B(a)P (10(- 8) to 10(- 5)M) promotes
inflammation pathways via TNF-alpha and NFkappaB leading to IL-6 upregulation, microRNA
(Let7a, miR21 and miR29b) dysregulation and activation of VEGF. The miRNA dysregulation is
associated with altered expression of inflammation mediators and increased migration and
invasive potential of human mammary cancer cells. Our data suggest that mammary cell
exposure to B(a)P results in perturbation of inflammation mediators and dysregulation of
tumorigenic miRNAs, leading to an inflammation microenvironment that facilitates migration
and invasion of mammary epithelial cells. These properties of B(a)P, together with its well-
established metabolic activation to DNA-damaging species, offer mechanistic insights into its
carcinogenic mode of action.

Mazzei, M. A., et al. (2017). "Incidental extravascular findings in computed tomographic angiography for
planning or monitoring endovascular aortic aneurysm repair: Smoker patients, increased lung cancer
prevalence?" World J Radiol 9(7): 304-311.
AIM: To validate the feasibility of high resolution computed tomography (HRCT) of the lung prior
to computed tomography angiography (CTA) in assessing incidental thoracic findings during
endovascular aortic aneurysm repair (EVAR) planning or follow-up. METHODS: We conducted a
retrospective study among 181 patients (143 men, mean age 71 years, range 50-94) referred to
our centre for CTA EVAR planning or follow-up. HRCT and CTA were performed before or after 1
or 12 mo respectively to EVAR in all patients. All HRCT examinations were reviewed by two
radiologists with 15 and 8 years' experience in thoracic imaging. The results were compared
with histology, bronchoscopy or follow-up HRCT in 12, 8 and 82 nodules respectively. RESULTS:
There were a total of 102 suspected nodules in 92 HRCT examinations, with a mean of 1.79
nodules per patient and an average diameter of 9.2 mm (range 4-56 mm). Eighty-nine out of 181
HRCTs resulted negative for the presence of suspected nodules with a mean smoking history of
10 pack-years (p-y, range 5-18 p-y). Eighty-two out of 102 (76.4%) of the nodules met criteria for
computed tomography follow-up, to exclude the malignant evolution. Of the remaining 20
nodules, 10 out of 20 (50%) nodules, suspected for malignancy, underwent biopsy and then
surgical intervention that confirmed the neoplastic nature: 4 (20%) adenocarcinomas, 4 (20%)
 squamous cell carcinomas, 1 (5%) small cell lung cancer and 1 (5%) breast cancer metastasis); 8
out of 20 (40%) underwent bronchoscopy (8 pneumonia) and 2 out of 20 (10%) underwent
biopsy with the diagnosis of sarcoidosis. CONCLUSION: HRCT in EVAR planning and follow-up
allows to correctly identify patients requiring additional treatments, especially in case of lung
cancer.

Moses, A., et al. (2017). "Risk factors for common cancers among patients at Kamuzu Central Hospital in
Lilongwe, Malawi: A retrospective cohort study." Malawi Med J 29(2): 136-141.
BACKGROUND: Little is known about risk factors for different cancers in Malawi. This study
aimed to assess risk factors for and epidemiologic patterns of common cancers among patients
treated at Kamuzu Central Hospital (KCH) in Lilongwe, and to determine the prevalence of
Human Immunodeficiency Virus (HIV) infection in the same population. METHODS: We analysed
data from the hospital-based KCH cancer registry, from June 2009 to September 2012, including
data from a nested substudy on coinfections among cancer patients. Demographics and
behavioural variables, including smoking and alcohol use, were collected through personal
interviews with patients. We assessed HIV prevalence across cancer types. The distribution of
cancer types was reported overall and by gender. Logistic regression was used to assess risk
factors associated with common cancer types. RESULTS: Data from 504 registered cancer
patients were included-300 (59.5%) were female and 204 (40.5%) were male. Mean age was 49
years (standard deviation, SD = 16). There were 343 HIV-negative patients (71.2%), and 139
(28.8%) were HIV-positive. The commonest cancers were oesophageal (n = 172; 34.5%), cervical
(n = 109; 21.9%), and Kaposi's sarcoma (KS) (n = 52; 10.4%). Only 18% of cancer cases were
histologically confirmed. Patients with oesophageal cancer were likely to be older than 50 years
(odds ratio, OR = 2.22), male (OR = 1.47), and smokers (OR = 2.02). Kaposi's sarcoma patients
had the highest odds (OR = 54.4) of being HIV-positive and were also more likely to be male (OR
= 6.02) and smokers. Cervical cancer patients were more likely to be HIV-positive (OR = 2.2) and
less than 50 years of age. CONCLUSIONS: Age, smoking, and HIV are important risk factors for
the 3 commonest cancer types (oesophageal, KS, and cervical) at this teaching hospital in
Malawi. HIV is the single most important risk factor for Kaposi's sarcoma and cervical cancer.

Naif, H. M., et al. (2018). "Association of Cytochrome CYP1A1 Gene Polymorphisms and Tobacco
Smoking With the Risk of Breast Cancer in Women From Iraq." Front Public Health 6: 96.
Background: CYP1A1 gene polymorphisms and tobacco smoking are among several risk factors
for various types of cancers, but their influence on breast cancer remains controversial. We
analyzed the possible association of CYP1A1 gene polymorphisms and tobacco smoking-related
breast cancer in women from Iraq. Materials and methods: In this case-control study, gene
polymorphism of CYP1A1 gene (CYP1A1m1, T6235C and CYP1A1m2, A4889G) of 199
histologically verified breast cancer patients' and 160 cancer-free control women's specimens
were performed by using PCR-based restriction fragment length polymorphism. Results: Three
genotype frequencies (TT, TC, and CC) of CYP1A1m1T/C appeared in 16.1, 29.6, and 54.3% of
women with breast cancer, respectively, compared with 41.2, 40, and 18.8% in the control
group, respectively. CYP1A1m1 CC genotype and C allele were significantly associated with
increased risks for breast cancer in patients (54.3 and 69%, respectively) compared with controls
(18.8 and 39%, respectively). While the three genotype frequencies (AA, AG, and GG) of
CYP1A1m2A/G were detected in 20.1, 31.2, and 48.7% in patients compared with 46.3, 40.6,
 and 13.1% in controls, respectively. The frequency of GG genotypes and G allele was
significantly higher in patients (48.7 and 64%, respectively) than in the controls (13.1 and 33%,
respectively). Smoking women having either CC or GG genotypes showed a highly significant
association with increased risk of breast cancer [odds ratio (OR) = 1.607, 95% confidence
interval (CI) 0.91-1.64, p = 0.0001, and OR, 1.841, 95% CI, 0.88-1.67, p = 0.0001, respectively].
On the other hand, the T and A alleles of predominantly seen in healthy smoking women (83
and 85%, p = 0.0001, respectively). Conclusion: These findings indicated that both C and G
alleles of CYP1A1m1 and m2 were significantly associated with elevated risk of breast cancer in
Iraqi women, while the T and A alleles were predominantly seen in healthy controls which may
indicate their protective role. The C and G association with breast cancer incidence was more
prevalent among tobacco smoking patients. These polymorphisms may be used as biomarkers
of breast cancer in women from Iraq.

Nwizu, N. N., et al. (2017). "Periodontal Disease and Incident Cancer Risk among Postmenopausal
Women: Results from the Women's Health Initiative Observational Cohort." Cancer Epidemiol
Biomarkers Prev 26(8): 1255-1265.
Background: Periodontal pathogens have been isolated from precancerous and cancerous
lesions and also shown to promote a procarcinogenic microenvironment. Few studies have
examined periodontal disease as a risk factor for total cancer, and none have focused on older
women. We examined whether periodontal disease is associated with incident cancer among
postmenopausal women in the Women's Health Initiative Observational Study.Methods: Our
prospective cohort study comprised 65,869 women, ages 54 to 86 years. Periodontal disease
information was obtained via self-report questionnaires administered between 1999 and 2003,
whereas ascertainment of cancer outcomes occurred through September 2013, with a
maximum follow-up period of 15 years. Physician-adjudicated incident total cancers were the
main outcomes and site-specific cancers were secondary outcomes. HRs and 95% confidence
intervals (CI) were calculated using Cox proportional hazards regression. All analyses were
conducted two-sided.Results: During a mean follow-up of 8.32 years, 7,149 cancers were
identified. Periodontal disease history was associated with increased total cancer risk
(multivariable-adjusted HR, 1.14; 95% CI, 1.08-1.20); findings were similar in analyses limited to
34,097 never-smokers (HR, 1.12; 95% CI, 1.04-1.22). Associations were observed for breast (HR,
1.13; 95% CI, 1.03-1.23), lung (HR, 1.31; 95% CI, 1.14-1.51), esophagus (HR, 3.28; 95% CI, 1.64-
6.53), gallbladder (HR, 1.73; 95% CI, 1.01-2.95), and melanoma skin (HR, 1.23; 95% CI, 1.02-1.48)
cancers. Stomach cancer was borderline (HR, 1.58; 95% CI, 0.94-2.67).Conclusions: Periodontal
disease increases risk of total cancer among older women, irrespective of smoking, and certain
anatomic sites appear to be vulnerable. Impact: Our findings support the need for further
understanding of the effect of periodontal disease on cancer outcomes. Cancer Epidemiol
Biomarkers Prev; 26(8); 1255-65. (c)2017 AACR.

Obeidat, N. A., et al. (2017). "Are Jordanian primary healthcare practitioners fulfilling their potential in
cancer prevention and community health? Findings from a cross-sectional survey." BMJ Open 7(4):
e015269.
INTRODUCTION: Primary healthcare practitioners (PHCPs) can contribute to the control of
cancer by promoting healthy lifestyles to patients. Given the scarcity of data in the Middle East
on this subject, we sought to determine, through a cross-sectional survey, the status of healthy
 lifestyle promotion by PHCPs (physicians, nurses, midwives, nurse aids) in Jordan. METHODS:
Building on published studies, an Arabic questionnaire was developed to measure knowledge,
perceptions and practices of Jordanian PHCPs with regard to healthy lifestyle counselling. A
purposive sample of 20 clinics covering the main regions of Jordan was selected and all PHCPs
were asked to complete the questionnaire. RESULTS: 322 practitioners (32.3% physicians)
responded (a 75.1% response rate). 24.4% of PHCPs were current cigarette smokers (physicians
44.2%). Roughly 58% of physicians and 50% of non-physicians reported advising the majority of
patients to quit tobacco, but proportions were lower for providing other services (eg, asking
about frequency of tobacco use, inquiring about diet and exercise, providing evidence-based
guidance on quitting tobacco or improving diet and activity). Only 8% of the sample reported
collectively asking the majority of patients about smoking status, exercise and diet; and
providing evidence-based tips to improve these. Among physicians and non-physicians, 14.2%
and 40.4% were able to identify the lifestyle-related risk factors associated with breast,
colorectal and lung cancer. In multivariable analyses, confidence was the only significant
variable associated with provision of counselling on healthy lifestyles. CONCLUSIONS: Among
Jordanian PHCPs, primary prevention services are underprovided, and data suggest ample room
to improve PHCPs' skills and practices.

Parada, H., Jr., et al. (2017). "Environmental Tobacco Smoke Exposure and Survival Following Breast
Cancer." Cancer Epidemiol Biomarkers Prev 26(2): 278-280.
BACKGROUND: Environmental tobacco smoke (ETS) exposure is hypothesized to influence
survival after breast cancer, but few studies have examined this association. METHODS: A
population-based cohort of women (N = 1,508) diagnosed with first primary invasive or in situ
breast cancer in 1996 to 1997 was interviewed shortly after diagnosis and again approximately 5
years later to assess ETS exposure, and women were followed for more than 18 years using the
National Death Index; 597 deaths (237 associated with breast cancer) were identified.
Multivariable Cox regression was used to estimate adjusted HRs and 95% confidence intervals
(CI) for mortality among women with breast cancer as related to at-diagnosis and at-
/postdiagnosis changes in ETS exposure. RESULTS: There was little or no association between at-
diagnosis ETS exposure and all-cause (HR = 1.04; 95% CI, 0.78-1.40) or breast cancer-specific (HR
= 0.98; 95% CI, 0.63-1.52) mortality. Mortality was elevated among women who reported
cessation in postdiagnosis ETS exposure up to 1 year before the follow-up assessment, for all-
cause (HR = 1.81; 95% CI, 0.87-3.74) and breast cancer mortality (HR = 1.89; 95% CI, 0.68-5.24);
however, estimates were imprecise. CONCLUSIONS: We found little evidence of an association
between at-diagnosis ETS exposure and mortality after breast cancer. Postdiagnosis cessation of
ETS exposure was positively associated with mortality, although we could not rule out chance
and reverse causation as possible explanations. IMPACT: Exposure to ETS does not appear to
influence mortality after breast cancer. Cancer Epidemiol Biomarkers Prev; 26(2); 278-80.
(c)2016 AACR.

Parada, H., Jr., et al. (2017). "Postdiagnosis Changes in Cigarette Smoking and Survival Following Breast
Cancer." JNCI Cancer Spectr 1(1).
Background: The purpose of this study was to examine whether at-diagnosis smoking and
postdiagnosis changes in smoking within five years after breast cancer were associated with
long-term all-cause and breast cancer-specific mortality. Methods: A population-based cohort of
 1508 women diagnosed with first primary in situ or invasive breast cancer in 1996 to 1997 were
interviewed shortly after diagnosis and again approximately five years later to assess smoking
history. Participants were followed for vital status through December 31, 2014. After 18+ years
of follow-up, 597 deaths were identified, 237 of which were breast cancer related. Multivariable
Cox regression was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs).
Results: Compared with never smokers, risk of all-cause mortality was elevated among the 19%
of at-diagnosis smokers (HR=1.69, 95% CI=1.36 to 2.11), those who smoked 20 or more
cigarettes per day (HR=1.85, 95% CI=1.42 to 2.40), women who had smoked for 30 or more
years (HR=1.62, 95% CI=1.28 to 2.05), and women who had smoked 30 or more pack-years
(HR=1.82, 95% CI=1.39 to 2.37). Risk of all-cause mortality was further increased among the 8%
of women who were at-/post-diagnosis smokers (HR=2.30, 95% CI=1.56 to 3.39) but was
attenuated among the 11% women who quit smoking after diagnosis (HR=1.83, 95% CI=1.32 to
2.52). Compared with never smokers, breast cancer-specific mortality risk was elevated 60%
(HR=1.60, 95% CI=0.79 to 3.23) among at-/postdiagnosis current smokers, but the confidence
interval included the null value and elevated 175% (HR=2.75, 95% CI=1.26 to 5.99) when we
considered postdiagnosis cumulative pack-years. Conclusions: Smoking negatively impacts long-
term survival after breast cancer. Postdiagnosis cessation of smoking may reduce the risk of all-
cause mortality. Breast cancer survivors may benefit from aggressive smoking cessation
programs starting as early as the time of diagnosis.

Parada, H., Jr., et al. (2017). "Active smoking and survival following breast cancer among African
American and non-African American women in the Carolina Breast Cancer Study." Cancer Causes Control
28(9): 929-938.
PURPOSE: To examine racial differences in smoking rates at the time of breast cancer diagnosis
and subsequent survival among African American and non-African American women in the
Carolina Breast Cancer Study (Phases I/II), a large population-based North Carolina study.
METHODS: We interviewed 788 African American and 1,020 Caucasian/non-African American
women diagnosed with invasive breast cancer from 1993 to 2000, to assess smoking history.
After a median follow-up of 13.56 years, we identified 717 deaths using the National Death
Index; 427 were breast cancer-related. We used Cox regression to examine associations
between self-reported measures of smoking and breast cancer-specific survival within 5 years
and up to 18 years after diagnosis conditional on 5-year survival. We examined race and
estrogen receptor status as potential modifiers. RESULTS: Current (vs never) smoking was not
associated with 5-year survival; however, risk of 13 year conditional breast cancer-specific
mortality was elevated among women who were current smokers at diagnosis (HR 1.54, 95% CI
1.06-2.25), compared to never smokers. Although smoking rates were similar among African
American (22.0%) and non-African American (22.1%) women, risk of breast cancer-specific
mortality was elevated among African American (HR 1.69, 95% CI 1.00-2.85), but only weakly
elevated among non-African American (HR 1.22, 95% CI 0.70-2.14) current (vs. never) smokers
(P Interaction = 0.30). Risk of breast cancer-specific mortality was also elevated among current
(vs never) smokers diagnosed with ER(-) (HR 2.58, 95% CI 1.35-4.93), but not ER(+) (HR 1.11, 95%
CI 0.69-1.78) tumors (P Interaction = 0.17). CONCLUSIONS: Smoking may negatively impact long-
term survival following breast cancer. Racial differences in long-term survival, as related to
smoking, may be driven by ER status, rather than by differences in smoking patterns.
Pavanello, S., et al. (2018). "Leucocytes telomere length and breast cancer risk/ susceptibility: A case-
control study." PLoS One 13(5): e0197522.
BACKGROUND: Telomere length in peripheral blood leukocytes (PBL-TL) was proposed as a
biomarker of cancer risk. Recent scientific evidence suggested PBL-TL plays a diverse role in
different cancers. Inconsistent results were obtained on PBL-TL in relation to breast cancer risk
and specifically to the presence of BRCA1 and BRCA2 mutations. The aim of the present case-
control study was to analyse the correlation between family history of breast cancer or presence
of a BRCA mutation and PBL-TL in the hypothesis that TL is a modifier of cancer risk. METHODS:
PBL-TL was measured using the real-time quantitative PCR method in DNA for 142 cases and 239
controls. All the women enrolled were characterized for cancer family history. A subgroup of 48
women were classified for the presence of a BRCA mutation. PBL-TL were summarized as means
and standard deviations, and compared by standard analysis of variance. A multivariable
Generalised Linear Model was fitted to the data with PBL-TL as the dependent variable,
case/control status and presence of a BRCA/VUS mutation as factors, and age in 4 strata as a
covariate. RESULTS: Age was significantly associated with decreasing PBL-TL in controls (p =
0.01), but not in BC cases. The telomere length is shorter in cases than in controls after adjusting
for age. No effect on PBL-TL of BMI, smoke nor of the most common risk factors for breast
cancer was observed. No association between PBL-TL and family history was detected both in BC
cases and controls. In the multivariate model, no association was observed between BRCA
mutation and decreased PBL-TL. A statistically significant interaction (p = 0.031) between case-
control status and a BRCA-mutation/VUS was observed, but no effect was detected for the
interaction of cancer status and BRCA or VUS. CONCLUSION: Our study fails to provide support
to the hypothesis that PBL-TL is associated with the risk of hereditary BC, or that is a marker of
inherited mutations in BRCA genes.

Petrelli, A., et al. (2018). "Geographical and socioeconomic differences in uptake of Pap test and
mammography in Italy: results from the National Health Interview Survey." BMJ Open 8(9): e021653.
OBJECTIVE: The Italian National Health Service instituted cervical and breast cancer screening
programmes in 1999; the local health authorities have a mandate to implement these screening
programmes by inviting all women aged 25-64 years for a Pap test every 3 years (or for an
Human Papilloma Virus (HPV) test every 5 years) and women aged 50-69 years for a
mammography every 2 years. However, the implementation of screening programmes
throughout the country is still incomplete. This study aims to: (1) describe cervical and breast
cancer screening uptake and (2) evaluate geographical and individual socioeconomic difference
in screening uptake. METHODS: Data both from the Italian National Health Interview Survey
(NHIS) conducted by the National Institute of Statistics in 2012-2013 and from the Italian
National Centre for Screening Monitoring (INCSM) were used. The NHIS interviewed a national
representative random sample of 32 831 women aged 25-64 years and of 16 459 women aged
50-69 years. Logistic multilevel models were used to estimate the effect of socioeconomic
variables and behavioural factors (level 1) on screening uptake. Data on screening invitation
coverage at the regional level, taken from INCSM, were used as ecological (level 2) covariates.
RESULTS: Total 3-year Pap test and 2-year mammography uptake were 62.1% and 56.4%,
respectively; screening programmes accounted for 1/3 and 1/2 of total test uptake, respectively.
Strong geographical differences were observed. Uptake was associated with high educational
levels, healthy behaviours, being a former smoker and being Italian versus foreign national.
Differences in uptake between Italian regions were mostly explained by the invitation coverage
 to screening programmes. CONCLUSIONS: The uptake of both screening programmes in Italy is
still under acceptable levels. Screening programme implementation has the potential to reduce
the health inequalities gap between regions but only if uptake increases.

Pinsky, P. F. (2018). "Lung cancer screening with low-dose CT: a world-wide view." Transl Lung Cancer
Res 7(3): 234-242.
Lung cancer is the leading cause of cancer death worldwide, comprising almost 20% of all cancer
deaths. The concept of screening for lung cancer using low-dose computed tomography (LDCT)
dates back almost three decades. This paper reviews the randomized controlled trials and
demonstration projects carried out world-wide on LDCT lung cancer screening. Most research
has been carried out in North America, Europe and East Asia, regions where lung cancer
mortality rates are generally the highest. There are currently no organized national or regional
lung cancer screening programs with LDCT. A number of challenges exist to implementing such
programs, including the fact that LDCT lung cancer screening generally targets only high risk
ever-smokers, in contrast to screening programs for other cancers such as breast, cervical and
colorectal, which target entire populations based only on age and sex. While tobacco control
remains the most important tool in the long-term to decrease morbidity and mortality from lung
cancer, LDCT screening, appropriately carried out, has the potential to modestly decrease lung
cancer death rates for those countries whose overall resources and health care infrastructure
are adequate for the task.

Sandler, D. P., et al. (2017). "The Sister Study Cohort: Baseline Methods and Participant Characteristics."
Environ Health Perspect 125(12): 127003.
BACKGROUND: The Sister Study was designed to address gaps in the study of environment and
breast cancer by taking advantage of more frequent breast cancer diagnoses among women
with a sister history of breast cancer and the presumed enrichment of shared environmental
and genetic exposures. OBJECTIVE: The Sister Study sought a large cohort of women never
diagnosed with breast cancer but who had a sister (full or half) diagnosed with breast cancer.
METHODS: A multifaceted national effort employed novel strategies to recruit a diverse cohort,
and collected biological and environmental samples and extensive data on potential breast
cancer risk factors. RESULTS: The Sister Study enrolled 50,884 U.S. and Puerto Rican women 35-
74y of age (median 56 y). Although the majority were non-Hispanic white, well educated, and
economically well off, substantial numbers of harder-to-recruit women also enrolled
(race/ethnicity other than non-Hispanic white: 16%; no college degree: 35%; household income
<$50,000: 26%). Although all had a biologic sister with breast cancer, 16.5% had average or
lower risk of breast cancer according to the Breast Cancer Risk Assessment Tool (Gail score).
Most were postmenopausal (66%), parous with a first full-term pregnancy <30y of age (79%),
never-smokers (56%) with body mass indexes (BMIs) of <29.9( )kg/m(2) (70%). Few (5%)
reported any cancer prior to enrollment. CONCLUSIONS: The Sister Study is a unique cohort
designed to efficiently study environmental and genetic risk factors for breast cancer. Extensive
exposure data over the life-course and baseline specimens provide important opportunities for
studying breast cancer and other health outcomes in women. Collaborations are welcome.
https://doi.org/10.1289/EHP1923.
Sandsveden, M. and J. Manjer (2017). "Selenium and breast cancer risk: A prospective nested case-
control study on serum selenium levels, smoking habits and overweight." Int J Cancer 141(9): 1741-
1750.
Previous research has not been conclusive regarding the association between selenium (Se) and
breast cancer. This study was conducted to clarify if there is an association between
prediagnostic serum Se levels and breast cancer risk. A population based cohort, the Malmo Diet
and Cancer Study, was used and linked with the Swedish cancer registry up to 31 December
2013. Our study included 1,186 women with breast cancer and an equal number of controls.
Selenium levels were analysed from stored serum samples. The included individuals were
divided into quartiles based on Se value and we compared breast cancer cases with controls
using logistic regression yielding odds ratios (OR) with 95% confidence intervals. Serum Se was
also analysed as a continuous variable regarding breast cancer risk. The analyses were adjusted
for established risk factors and stratified on smoking status and body mass index (BMI). When
comparing the highest Se quartile with the lowest, the adjusted OR for breast cancer was 0.98
(0.75-1.26). With selenium as a continuous variable the adjusted OR was 1.00 (1.00-1.01) per 10
ng/ml. When comparing the highest with the lowest Se quartile in women with BMI > 25
kg/m(2) the adjusted OR was 0.77 (0.53-1.14). We conclude that it is unlikely that prediagnostic
serum selenium is overall associated with breast cancer risk and no modifying effect from BMI
or smoking was seen.

Smith, A., et al. (2018). "Associations between obesity, smoking and lymph node status at breast cancer
diagnosis in the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial." PLoS One 13(8):
e0202291.
INTRODUCTION: There is evidence suggesting that smoking and obesity prior to a breast cancer
diagnosis is associated with poorer outcomes. In this study, we investigate the associations
between smoking and obesity prior to a breast cancer diagnosis and the presence of lymph node
metastases at diagnosis. METHODS: Women with stage I-III breast cancer (n = 3,304) were
identified from the National Cancer Institute's Prostate, Lung, Colorectal and Ovarian Cancer
Screening Trial. Univariable and multivariable log-binomial models were used to estimate
relative risks (RR) and 95% confidence intervals (CIs) for associations between lymph node
positive breast cancer and; i) smoking, and ii) obesity prior to diagnosis. RESULTS: Pre-diagnostic
smoking/obesity was not associated with lymph node metastasis at diagnosis in multivariable
analyses; (RR 0.82, 95%CI 0.61, 1.10) and (RR 0.95, 95% CI 0.81, 1.12), respectively.
CONCLUSION: Obesity and smoking information was recorded a number of years prior to breast
cancer diagnosis, therefore these findings should to be replicated in a larger cohort of women,
with more detailed smoking and obesity information.

Sollie, M. and C. Bille (2017). "Smoking and mortality in women diagnosed with breast cancer-a
systematic review with meta-analysis based on 400,944 breast cancer cases." Gland Surg 6(4): 385-393.
BACKGROUND: It is evident that smoking is causing disease and increased mortality in general.
Recently published data are now suggesting that smoking might increase both the overall
mortality in women diagnosed with breast cancer but also increase their risk of dying from their
breast cancer. METHODS: A systematic review and meta-analysis on smoking status in women
diagnosed with breast cancer, their mortality rate and cause of death. Based on all cohort
studies published within the last ten years. RESULTS: Twelve studies met our inclusion criteria,
 and 400,944 women diagnosed with primary invasive breast cancer was included. Hazard ratio
(HR) for breast cancer associated death in former smokers was 1.02 (0.93, 1.12) and for current
smokers 1.28 (1.17, 1.41) when compared to never smokers. For all-cause death, the HR for
former smokers was 1.12 (1.04, 1.19), and for current smokers 1.52 (1.32, 1.76) when compared
to never smokers. CONCLUSIONS: This large systematic review and meta-analysis found a 28%
increase in breast cancer-associated mortality in those who were current smokers compared to
never smokers. The mortality in former smokers was equal to the one found in never smokers.
This indicates that breast cancer patients ceasing to smoke can lower their risk of dying from
their breast cancer disease dramatically, and possibly regain the risk of a never smoker.

Strumylaite, L., et al. (2017). "Association between lifetime exposure to passive smoking and risk of
breast cancer subtypes defined by hormone receptor status among non-smoking Caucasian women."
PLoS One 12(2): e0171198.
Tobacco smoking is inconsistently associated with breast cancer. Although some studies suggest
that breast cancer risk is related to passive smoking, little is known about the association with
breast cancer by tumor hormone receptor status. We aimed to explore the association between
lifetime passive smoking and risk of breast cancer subtypes defined by estrogen receptor and
progesterone receptor status among non-smoking Caucasian women. A hospital-based case-
control study was performed in 585 cases and 1170 controls aged 28-90 years. Information on
lifetime passive smoking and other factors was collected via a self-administered questionnaire.
Logistic regression was used for analyses restricted to the 449 cases and 930 controls who had
never smoked actively. All statistical tests were two-sided. Adjusted odds ratio of breast cancer
was 1.01 (95% confidence interval (CI): 0.72-1.41) in women who experienced exposure to
passive smoking at work, 1.88 (95% CI: 1.38-2.55) in women who had exposure at home, and
2.80 (95% CI: 1.84-4.25) in women who were exposed at home and at work, all compared with
never exposed regularly. Increased risk was associated with longer exposure: women exposed
</= 20 years and > 20 years had 1.27 (95% CI: 0.97-1.66) and 2.64 (95% CI: 1.87-3.74) times
higher risk of breast cancer compared with never exposed (Ptrend < 0.001). The association of
passive smoking with hormone receptor-positive breast cancer did not differ from that with
hormone receptor-negative breast cancer (Pheterogeneity > 0.05). There was evidence of
interaction between passive smoking intensity and menopausal status in both overall group (P =
0.02) and hormone receptor-positive breast cancer group (P < 0.05). In Caucasian women,
lifetime exposure to passive smoking is associated with the risk of breast cancer independent of
tumor hormone receptor status with the strongest association in postmenopausal women.

Tao, M. H., et al. (2018). "Oral bisphosphonate use and lung cancer incidence among postmenopausal
women." Ann Oncol 29(6): 1476-1485.
Background: Bisphosphonates are common medications for the treatment of osteoporosis in
older populations. Several studies, including the Women's Health Initiative (WHI), have found
inverse associations of bisphosphonate use with risk of breast and endometrial cancer, but little
is known about its association with other common malignancies. The objective of this study was
to evaluate the association of bisphosphonate use on the incidence of lung cancer in the WHI.
Patients and methods: The association between oral bisphosphonate use and lung cancer risk
was examined in 151 432 postmenopausal women enrolled into the WHI in 1993-1998. At
baseline and during follow-up, participants completed an inventory of regularly used
 medications including bisphosphonates. Results: After a mean follow-up of 13.3 years, 2511
women were diagnosed with incident lung cancer. There was no evidence of a difference in lung
cancer incidence between oral bisphosphonate users and never users (adjusted hazard ratio =
0.91; 95% confidence intervals, 0.80-1.04; P = 0.16). However, an inverse association was
observed among those who were never smokers (hazard ratio = 0.57, 95% confidence interval,
0.39-0.84; P < 0.01). Conclusion: In this large prospective cohort of postmenopausal women,
oral bisphosphonate use was associated with significantly lower lung cancer risk among never
smokers, suggesting bisphosphonates may have a protective effect against lung cancer.
Additional studies are needed to confirm our findings.

Taylor, C., et al. (2017). "Estimating the Risks of Breast Cancer Radiotherapy: Evidence From Modern
Radiation Doses to the Lungs and Heart and From Previous Randomized Trials." J Clin Oncol 35(15):
1641-1649.
Purpose Radiotherapy reduces the absolute risk of breast cancer mortality by a few percentage
points in suitable women but can cause a second cancer or heart disease decades later. We
estimated the absolute long-term risks of modern breast cancer radiotherapy. Methods First, a
systematic literature review was performed of lung and heart doses in breast cancer regimens
published during 2010 to 2015. Second, individual patient data meta-analyses of 40,781 women
randomly assigned to breast cancer radiotherapy versus no radiotherapy in 75 trials yielded rate
ratios (RRs) for second primary cancers and cause-specific mortality and excess RRs (ERRs) per
Gy for incident lung cancer and cardiac mortality. Smoking status was unavailable. Third, the
lung or heart ERRs per Gy in the trials and the 2010 to 2015 doses were combined and applied
to current smoker and nonsmoker lung cancer and cardiac mortality rates in population-based
data. Results Average doses from 647 regimens published during 2010 to 2015 were 5.7 Gy for
whole lung and 4.4 Gy for whole heart. The median year of irradiation was 2010 (interquartile
range [IQR], 2008 to 2011). Meta-analyses yielded lung cancer incidence >/= 10 years after
radiotherapy RR of 2.10 (95% CI, 1.48 to 2.98; P < .001) on the basis of 134 cancers, indicating
0.11 (95% CI, 0.05 to 0.20) ERR per Gy whole-lung dose. For cardiac mortality, RR was 1.30 (95%
CI, 1.15 to 1.46; P < .001) on the basis of 1,253 cardiac deaths. Detailed analyses indicated 0.04
(95% CI, 0.02 to 0.06) ERR per Gy whole-heart dose. Estimated absolute risks from modern
radiotherapy were as follows: lung cancer, approximately 4% for long-term continuing smokers
and 0.3% for nonsmokers; and cardiac mortality, approximately 1% for smokers and 0.3% for
nonsmokers. Conclusion For long-term smokers, the absolute risks of modern radiotherapy may
outweigh the benefits, yet for most nonsmokers (and ex-smokers), the benefits of radiotherapy
far outweigh the risks. Hence, smoking can determine the net effect of radiotherapy on
mortality, but smoking cessation substantially reduces radiotherapy risk.

Tousimis, E. and M. Haslinger (2018). "Overview of indications for nipple sparing mastectomy." Gland
Surg 7(3): 288-300.
The introduction of more targeted systemic therapies, better screening modalities with earlier
diagnosis and dramatically improved reconstructive techniques has allowed more minimally
invasive approaches to breast surgery. The recent introduction of nipple sparing mastectomy
(NSM) has dramatically improved the cosmetic outcomes and quality of life (QoL) for patients
undergoing mastectomy. This technique involves preservation of both the skin envelope
including the nipple areolar complex commonly through a barely visible inframammary skin
 incision followed by immediate breast reconstruction. An ideal candidate includes women with
small breasts, absence of ptosis, low BMI and not actively smoking. High risk patients include
those with radiation treatment, active smokers, macromastia, high BMI >30 kg/m(2), grade 2 or
3 ptosis and active smokers. There are several new techniques to approach complex high risk
patients which have expanded the candidates for NSM.

Turker Sener, L., et al. (2018). "Nicotine reduces effectiveness of doxorubicin chemotherapy and
promotes CD44(+)CD24(-) cancer stem cells in MCF-7 cell populations." Exp Ther Med 16(1): 21-28.
Breast cancer is the most common type of cancer in females and the second most common
cause of cancer mortality after lung cancer. Cancer stem cells represent a novel approach to
target cancer and reduce cancer recurrence and metastasis. Many patients with breast cancer
continue to smoke after receiving their diagnosis. Nicotine is a key factor in tobacco addiction
and also changes some cellular functions, such as activation of mitogenic pathways,
angiogenesis and cell proliferation. In the present study, the impact of nicotine was assessed in
a population of MCF-7 human breast cancer cells. Cluster of differentiation (CD)44(+)CD24(-)
cancer stem cell population of MCF-7 cells were evaluated using flow cytometry and scanning
electron microscopy. Chemoresistance effects of nicotine were demonstrated in these cells.
These findings demonstrated harmful effects of nicotine following metastasis of cancer, owing
to the chemoresistance produced through uninterrupted smoking, which may impact the
effectiveness of treatment.

van den Brandt, P. A. (2017). "A possible dual effect of cigarette smoking on the risk of postmenopausal
breast cancer." Eur J Epidemiol 32(8): 683-690.
Smoking seems modestly associated with breast cancer, but the potential dual effect of smoking
(with opposing properties: carcinogenic vs anti-estrogenic) is understudied. The relationship
between smoking before and after menopause and risk of postmenopausal breast cancer was
investigated in the Netherlands Cohort Study (NLCS). In the NLCS, 62,573 women aged 55-69
years provided information on smoking, dietary and other lifestyle habits in 1986. Follow-up for
cancer incidence until 2007 (20.3 years) consisted of record linkages with the Netherlands
Cancer Registry and the Dutch Pathology Registry PALGA. Multivariate case-cohort analyses
were based on 2526 incident breast cancer cases and 1816 subcohort members with complete
data on smoking. When smoking during pre- and postmenopausal periods was mutually
adjusted for, breast cancer risk was significantly positively associated with premenopausal
smoking pack-years, but inversely associated with postmenopausal smoking pack-years, both in
a dose-dependent manner. In continuous analyses, the hazard ratios (95% CI) were 1.35 (1.10-
1.65), and 0.47 (0.28-0.80) per increment of 20 premenopausal, and postmenopausal pack-
years, respectively. The interaction between pre- and postmenopausal pack-years in relation to
breast cancer risk was significant (P < 0.001). This study highlights the importance of
distinguishing and adjusting for smoking in different life periods, and suggests dual effects of
smoking on postmenopausal breast cancer risk.

Veal, C. T., et al. (2017). "Health-related behaviors and mortality outcomes in women diagnosed with
ductal carcinoma in situ." J Cancer Surviv 11(3): 320-328.
 PURPOSE: Women diagnosed with ductal carcinoma in situ (DCIS) of the breast are at greater
risk of dying from cardiovascular disease and other causes than from breast cancer, yet
associations between health-related behaviors and mortality outcomes after DCIS have not
been well studied. METHODS: We examined the association of body mass index, physical
activity, alcohol consumption, and smoking with mortality among 1925 women with DCIS in the
Wisconsin In Situ Cohort study. Behaviors were self-reported through baseline interviews and up
to three follow-up questionnaires. Cox proportional hazards regression was used to estimate
hazard ratios (HR) and 95% confidence intervals (CI) for mortality after DCIS, with adjustment for
patient sociodemographic, comorbidity, and treatment factors. RESULTS: Over a mean of 6.7
years of follow-up, 196 deaths occurred. All-cause mortality was elevated among women who
were current smokers 1 year prior to diagnosis (HR = 2.17 [95% CI 1.48, 3.18] vs. never smokers)
and reduced among women with greater physical activity levels prior to diagnosis (HR = 0.55
[95% CI: 0.35, 0.87] for >/=5 h per week vs. no activity). Moderate levels of post-diagnosis
physical activity were associated with reduced all-cause mortality (HR = 0.31 [95% CI 0.14, 0.68]
for 2-5 h per week vs. no activity). Cancer-specific mortality was elevated among smokers and
cardiovascular disease mortality decreased with increasing physical activity levels.
CONCLUSIONS: There are numerous associations between health-related behaviors and
mortality outcomes after a DCIS diagnosis. IMPLICATIONS FOR CANCER SURVIVORS: Women
diagnosed with DCIS should be aware that their health-related behaviors are associated with
mortality outcomes.

Wang, T., et al. (2017). "Pleiotropy of genetic variants on obesity and smoking phenotypes: Results from
the Oncoarray Project of The International Lung Cancer Consortium." PLoS One 12(9): e0185660.
Obesity and cigarette smoking are correlated through complex relationships. Common genetic
causes may contribute to these correlations. In this study, we selected 241 loci potentially
associated with body mass index (BMI) based on the Genetic Investigation of ANthropometric
Traits (GIANT) consortium data and calculated a BMI genetic risk score (BMI-GRS) for 17,037
individuals of European descent from the Oncoarray Project of the International Lung Cancer
Consortium (ILCCO). Smokers had a significantly higher BMI-GRS than never-smokers (p = 0.016
and 0.010 before and after adjustment for BMI, respectively). The BMI-GRS was also positively
correlated with pack-years of smoking (p<0.001) in smokers. Based on causal network inference
analyses, seven and five of 241 SNPs were classified to pleiotropic models for BMI/smoking
status and BMI/pack-years, respectively. Among them, three and four SNPs associated with
smoking status and pack-years (p<0.05), respectively, were followed up in the ever-smoking
data of the Tobacco, Alcohol and Genetics (TAG) consortium. Among these seven candidate
SNPs, one SNP (rs11030104, BDNF) achieved statistical significance after Bonferroni correction
for multiple testing, and three suggestive SNPs (rs13021737, TMEM18; rs11583200, ELAVL4; and
rs6990042, SGCZ) achieved a nominal statistical significance. Our results suggest that there is a
common genetic component between BMI and smoking, and pleiotropy analysis can be useful
to identify novel genetic loci of complex phenotypes.

Wee, J. T. and S. S. Poh (2017). "The most important questions in cancer research and clinical oncology :
Question 1. Could the vertical transmission of human papilloma virus (HPV) infection account for the
cause, characteristics, and epidemiology of HPV-positive oropharyngeal carcinoma, non-smoking East
Asian female lung adenocarcinoma, and/or East Asian triple-negative breast carcinoma?" Chin J Cancer
36(1): 13.
 Specific research foci: (1) Mouse models of gamma-herpes virus-68 (gammaHV-68) and
polyomavirus (PyV) infections during neonatal versus adult life. (2) For human papilloma virus
(HPV)-positive oropharyngeal carcinoma (OPC)-(a) Asking the question: Is oral sex a powerful
carcinogen? (b) Examining the evidence for the vertical transmission of HPV infection. (c)
Examining the relationship between HPV and Epstein-Barr virus (EBV) infections and
nasopharyngeal cancer (NPC) in West European, East European, and East Asian countries. (d)
Examining the association between HPV-positive OPC and human leukocyte antigen (HLA). (3)
For non-smoking East Asian female lung adenocarcinoma-(a) Examining the incidence trends of
HPV-positive OPC and female lung adenocarcinoma according to birth cohorts. (b) Examining
the association between female lung adenocarcinoma and HPV. (c) Examining the associations
of lung adenocarcinoma with immune modulating factors. (4) For triple-negative breast
carcinoma (TNBC) in East Asians-(a) Examining the association between TNBC and HPV. (b)
Examining the unique epidemiological characteristics of patients with TNBC. A summary
"epidemiological" model tying some of these findings together.

Wenners, A., et al. (2017). "Reduced ovarian reserve in young early breast cancer patients: preliminary
data from a prospective cohort trial." BMC Cancer 17(1): 632.
BACKGROUND: The numerous side effects of chemotherapy in patients with breast cancer are
well known. However, the precise effects of chemotherapy on ovarian function in
premenopausal women are poorly investigated. The patients are at risk of developing sexual
hormone deficiency and impaired fertility. This prospective cohort study addresses predictive
parameters of ovarian reserve after chemotherapy. METHODS: Fifty-one premenopausal
women (28-46 years) with primary breast cancer were included in the trial. All of them received
anthracycline-based chemotherapy (n = 18), or combinations with taxanes (n = 30), or
anthracycline-free chemotherapy (n = 3). Changes in hormone levels (LH, FSH, E2 and Anti-
Mullerian hormone (AMH)), antral follicle count (AFC), and amenorrhea were determined
before (V1), and 6, 12 and 24 months after the initiation of chemotherapy (V2-V4). Quality of life
parameters were evaluated. The additional impact of parity, BMI, and smoking on ovarian
reserve was also assessed. RESULTS: AFC and AMH fell very markedly after chemotherapy and
did not return to pre-treatment levels until V4. A significant positive correlation was noted in
AFC before and 1 year after chemotherapy. AMH levels at V2-V4 were significantly correlated
with those registered at V1. AFC and AMH were negatively correlated with age. Continued
smoking had a significant detrimental effect on AFC after 24 months. LH and FSH levels
increased between V1 and V2 and fell at V3 and V4, but stayed above pre-chemotherapy values.
Two years after the start of chemotherapy 31/51 patients were amenorrhoic while 17 resumed
their menstrual cycle; this was not influenced by the type of chemotherapy or age. Non-smokers
were 13 times more likely to resume their menstruation than smokers. Quality of life (QL) was
significantly lower 6 months after the initiation of chemotherapy. QL at one and 2 years after
chemotherapy did not differ significantly from pre-chemotherapy scores. CONCLUSIONS: Our
study contributes to a better understanding and prediction of ovarian reserve in young early
breast cancer patients undergoing chemotherapy. The data suggest that personal counseling in
regard of the preservation of fertility should be offered especially to patients of a higher age,
with low AMH levels or low follicle counts. Patients should be advised to stop smoking in order
to enhance the likelihood of preserving their fertility.
White, A. J., et al. (2017). "Breast cancer and exposure to tobacco smoke during potential windows of
susceptibility." Cancer Causes Control 28(7): 667-675.
PURPOSE: An association between smoking and breast cancer is unresolved, although a higher
risk from exposure during windows of susceptibility has been proposed. The objective of this
prospective study was to evaluate the association between tobacco smoke and breast cancer
with a focus on timing of exposure, especially during early life. METHODS: Sister study
participants (n = 50,884) aged 35-74 were enrolled from 2003 to 2009. Women in the United
States and Puerto Rico were eligible if they were breast cancer-free but had a sister with breast
cancer. Participants completed questionnaires on smoking and environmental tobacco smoke
(ETS) exposure. Cox regression was used to estimate adjusted hazard ratios (HRs) and 95%
confidence intervals (95% CIs) for breast cancer risk. RESULTS: During follow-up (mean = 6.4
years), 1,843 invasive breast cancers were diagnosed. Neither active smoking nor adult ETS was
associated with breast cancer risk. However, never smoking women exposed to ETS throughout
their childhood had a 17% higher risk of breast cancer (95% CI 1.00-1.36) relative to those with
no exposure. In utero ETS exposure was also associated with breast cancer (HR = 1.16, 95% CI
1.01-1.32) and the HR was most elevated for women born in earlier birth cohorts (<1940, HR =
1.44, 95% CI 1.02-2.02; 1940-1949, HR = 1.28, 95% CI 1.01-1.62). CONCLUSION: In utero ETS and
ETS exposure during childhood and adolescence were associated with increased risk of breast
cancer and associations varied by birth cohort.

Yamamoto, H., et al. (2018). "Inherited lung cancer syndromes targeting never smokers." Transl Lung
Cancer Res 7(4): 498-504.
Lung cancer is the leading cause of cancer death worldwide. Most of lung cancers develop
sporadically and thus inherited lung cancers are rare. Several reports show that germline
mutations in the kinase domain of epidermal growth factor receptor (EGFR) such as R776G,
R776H, T790M, V843I and P848L, predispose to develop lung cancer. Most lung cancer cases
with germline EGFR T790M mutations had secondary EGFR somatic mutations. Never smokers
with germline EGFR T790M mutations develop lung cancer more frequently than ever smokers.
In addition, germline EGFR T790M mutations favored female gender. Therefore, germline EGFR
T790M mutations result in a unique inherited lung cancer syndrome targeting never smokers.
The authors previously reported a Japanese familial lung cancer pedigree with germline
mutations in the transmembrane domain of human epidermal growth factor receptor 2 (HER2).
The female proband and her mother in this pedigree, who were light or never smokers,
developed multiple lung adenocarcinomas, and had germline HER2 G660D mutations. They had
no EGFR somatic mutations or other genes known to cause lung cancers. Although we know
only one pedigree with germline HER2 mutations, these mutations may also cause inherited
lung cancers targeting female never smokers. Based on our in vitro analyses, we administered
HER2 inhibitor afatinib to the proband and achieved partial response. These lung cancers arising
from germline mutations of receptor tyrosine kinases such as EGFR and HER2 may have
different features from those with sporadic mutations.

Yuza, K., et al. (2017). "Hypermutation and microsatellite instability in gastrointestinal cancers."
Oncotarget 8(67): 112103-112115.
Recent progress in cancer genome analysis using next-generation sequencing has revealed a
high mutation burden in some tumors. The particularly high rate of somatic mutation in these
 tumors correlates with the generation of neo-antigens capable of eliciting an immune response.
Identification of hypermutated tumors is therefore clinically valuable for selecting patients
suitable for immunotherapy treatment. There are several known causes of hypermutation in
tumors, such as ultraviolet light in melanoma, tobacco smoke in lung cancer, and excessive
APOBEC (apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like) activity in breast
and gastric cancer. In gastrointestinal cancers, one of the leading causes of hypermutation is a
defect in DNA mismatch repair, which results in microsatellite instability (MSI). This review will
focus on the frequency, characteristics and genomic signature of hypermutated gastrointestinal
cancers with MSI. Detection of tumor hypermutation in cancer is expected to not only predict
the clinical benefit of immune checkpoint inhibitor treatment, but also to provide better surgical
strategies for the patients with hypermutated tumors. Thus, in an era of precision medicine,
identification of hypermutation and MSI will play an important role directing surgical and
chemotherapeutic treatment.

Zhang, Y., et al. (2018). "Clinical characteristics, classification and surgical treatment of periductal
mastitis." J Thorac Dis 10(4): 2420-2427.
Background: This study aimed to describe the clinical characteristics of periductal mastitis
(PDM), propose the practical clinical classification system and evaluate the results of different
surgical treatments in different type of PDM patients. Methods: A retrospective study was
carried out at department of breast surgery, Peking Union Medical College Hospital, Beijing,
China. A total of 152 patients with the diagnosis of PDM were reviewed from March 2012 to
December 2016. All of the patients underwent surgery. Data were collected regarding clinical
manifestation, treatment, and outcomes. Results: The median age was 36 years. A subareolar
breast mass was the most frequent symptom. The most common clinical manifestations were
mass (98.0%), rubefaction (41.1%), nipple retraction (36.8%), abscess (36.8%), skin ulceration
(25.7%), and mammary duct fistula (19.1%). Fourteen (9.2%) patients were recurrent PDM at
first hospitalization. Eight (5.3%) patients had prolactinoma. Five (3.3%) patients were taking
antipsychotic medications. Only four (2.6%) patients were smokers. Eight patients were highly
suspected to be breast cancer before surgery. A four-type classification system was first
proposed according to clinical manifestations. The different surgeries in each category were
evaluated. After 3 years median follow-up, 11 (7.2%) patients got recurrence including two
initial recurrent PDM. Conclusions: Periductal mastitis is a distinct benign breast condition of
unknown etiology. Mass, abscess and fistula are most common manifestations of the disease.
Wide surgical excision, fistulectomy and extended excision with transfer of a random breast
dermo-glandular flap (BDGF) are effective surgical modalities for different type of PDM.