original article

Annals of Oncology 21: 961967, 2010

doi:10.1093/annonc/mdq041
Published online 8 March 2010

Weekly paclitaxel plus carboplatin is an effective

nonanthracycline-containing regimen as neoadjuvant
chemotherapy for breast cancer
X. S. Chen1,2,3, X. Q. Nie1,3, C. M. Chen1,3, J. Y. Wu1,2,3, J. Wu1,3, J. S. Lu1,3, Z. M. Shao1,3,
Z. Z. Shen1,3 & K. W. Shen1,2,3*
1

Department of Breast Surgery, Cancer Hospital, Fudan University; 2Comprehensive Breast Health Center, Ruijin Hospital, Shanghai Jiaotong University School of
Medicine and 3Department of Oncology, Shanghai Medical College, Fudan University, Shanghai, China

Received 9 August 2009; accepted 27 January 2010

m2 and carboplatin at an area under the curve of 2 mg min/ml, given day 1, day 8 and day 15 of every 4 weeks.
Pathological complete remission (pCR) was defined as no invasive cancer in breast and axillary samples.
Results: Overall, 107 consecutive patients received weekly PCb treatment from December 2007 to December 2008,
and one was diagnosed with bilateral breast cancer. A total of 85.2% of patients were initially diagnosed with stage III
diseases. Clinical response rate was 86.1% with complete remission rate 32.4%. Twenty-one patients achieved pCR
after neoadjuvant treatment, with pCR rate 19.4%. The incidence of grade 34 neutropenia was 40.2% and only one
patient was reported with febrile neutropenia. Severe anemia and thrombocytopenia occurred in 4.7% and 0.9%,
respectively, of patients. Peripheral neuropathy was frequent but never severe. Patients with estrogen receptornegative, progesterone receptor-negative, triple-negative or human epidermal growth factor receptor 2 (Her2)-positive
subtype disease had higher pCR.
Conclusions: Weekly PCb regimen was very active and tolerable as neoadjuvant treatment of breast cancer. This
weekly PCb regimen should consider as a reasonable nonanthracycline-containing option in the neoadjuvant
treatment of breast cancer.
Key words: breast cancer, carboplatin, neoadjuvant chemotherapy, paclitaxel, weekly administration

introduction
Breast cancer is the most common malignancy affecting women
and the second leading cause of cancer death in the United
States; however, the overall mortality due to breast cancer has
decreased, attributed in part to early diagnosis and application
of various treatments [1]. Neoadjuvant chemotherapy has been
widely accepted as the standard treatment of patients with
locally advanced disease and now has become a frequently used
option for systemic therapy in primary operable breast cancer
[2]. Several randomized trials conducted in 1990s and a metaanalysis have demonstrated that neoadjuvant chemotherapy
was apparently equivalent to adjuvant chemotherapy in terms
of overall survival and distance metastasis and allowed
a significantly more patients to receive breast-sparing treatment
*Correspondence to: Professor K. W. Shen, Comprehensive Breast Health Center, Ruijin
Hospital, Shanghai Jiaotong University School of Medicine, 197 Ruijin Second Road,
Shanghai 200025, China. Tel: +86-21-64370045-602208; Fax: +86-21-64156886;
E-mail: kwshen@medmail.com.cn

These authors have contributed equally to this work.

[3]. Furthermore, these randomized studies have shown that

patients achieving a pathological complete remission (pCR)
after neoadjuvant chemotherapy have superior outcome than
those who are not [46]. So, another advantage of neoadjuvant
chemotherapy is the possibility of quickly determining the
response to treatment [2].
There are lots of chemotherapy regimens tested in the
neoadjuvant setting in phase II and III trials. The introduction
of the taxanes, including docetaxel and paclitaxel, realizing
their cytotoxicity via tubulin stabilization and cell cycle arrest,
has revolutionized breast cancer therapy [7]. The Early Breast
Cancer Trialists Collaborative Group has revealed that taxanebased adjuvant chemotherapy can significantly improve the
outcome of patients than those treated with anthracyclinebased therapy [8]. In neoadjuvant treatment, National Surgical
Adjuvant Breast and Bowel Project (NSABP) B27 and Aberdeen
studies showed that addition of docetaxel to anthracyclines
resulted in a doubling of the pCR rate than those treated with
the standard arm [5, 9]. Nowadays, anthracycline- and taxanebased therapies are recommended in neoadjuvant treatment of
breast cancer [2].

The Author 2010. Published by Oxford University Press on behalf of the European Society for Medical Oncology.
All rights reserved. For permissions, please email: journals.permissions@oxfordjournals.org

original
article

carboplatin] regimen in neoadjuvant treatment of breast cancer.

Patients and methods: Eligible patients were assigned to receive four cycles of PCb with dose of paclitaxel 80 mg/

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Background: To evaluate the activity and safety of nonanthracycline-containing weekly PCb [paclitaxel (Taxol) plus

original article

patients and methods

patient population
Patients with histological confirmation (core needle biopsy) of large operable
(T 3 cm and N01) or locally advanced breast cancer without prior
chemotherapy, radiotherapy or hormone treatment were considered eligible.
Other inclusion criteria of eligible patients had to meet females at least 18
years and 70 years considered to be fit to receive chemotherapy; absence of
systemic disease measured by bilateral mammogram, bilateral magnetic
resonance imaging, chest computed tomography scan, abdominal ultrasound
and bone scintigraphy; ECOG performance status of one or less; adequate
bone marrow [absolute neutrophil count (ANC) 1.5 109/l, platelet count

962 | Chen et al.

100 109/l and hemoglobin level 100 g/l], liver [bilirubin level and
aspartate aminotransferase and/or alanine aminotransferase <1.5 the upper
limit of normal], renal (creatinine clearance 60 ml/min) and absence of
severe cardiac arrhythmia or heart failure; no previous chemotherapy
treatment for any previous malignancy and previous or concurrent
malignancy were also considered as exclusion criteria, except for inactive
nonmelanoma skin cancer and in situ carcinoma of the cervix. Patients with
sensorial neurotoxicity more than grade 1 on the basis of the National Cancer
InstituteCommon Toxicity Criteria version 3.0 (NCI-CTC v3.0) score
system were excluded. The protocol was reviewed and approved by the
independent ethical committee/institutional review board, and all patients
gave their written informed consent before inclusion in this study.

immunohistochemical evaluation and subtype

classification
Immunohistochemical (IHC) assessment of the main biomarkers, like
estrogen receptor (ER), progesterone receptor (PgR) and Her2 was
conducted in paraffin-embedded tumor samples before treatment. The cutoff for ER positivity (ER+) and PgR positivity (PgR+) was 1% positive
tumor cells with nuclear staining. Her2 positive (Her2+) was considered as
Her2 3+ by IHC or positive on FISH, whereas cases with 0 to 1+ or 2+
without FISH detecting were regarded as negative (Her22).
Hormonal receptor (HR) positive was defined as either ER+ or PgR+,
and HR2 was defined as both ER2 and PgR2. Patients were categorized
on the basis of IHC HR and Her2 status of their primary tumors. Therefore,
four breast cancer subtypes were approximately classified as follows:
luminal A (HR+/Her22), luminal B (HR+/Her2+), triple negative (HR2/
Her22) and Her2 positive (HR2/Her2+) [22].

treatment
All eligible patients received four cycles of paclitaxel (Taxol; Bristol-Myers
Sqiubb Company, NJ) 80 mg/m2 in a 1-h infusion immediately followed by
carboplatin at an area under the curve (AUC) of 2 mg min/ml in a
30-min infusion given on days 1, 8 and 15 of a 28-day cycle. Creatinine
clearance was calculated using the Jelliffe formula [23] and AUC, the
Calvert formula [24]. Patients received dexamethasone 10 mg, cimetidine
300 mg i.v. and promethazine 12.5 mg i.m. 30 min before chemotherapy.
Furthermore, antiemetic prophylaxis (hydroxytryptamine-3 receptor
antagonists) was also carried out before chemotherapy and prophylaxis
granulocyte colony-stimulating factor was also allowed to use between
cycles by investigators discretion. Chemotherapy was delivered at full doses
if ANC >1.0 109/l and platelets >75 109/l. The treatment was postponed
a week in case of ANC <1.0 109/l and/or platelet count <75 109/l.
Chemotherapy was administered at doses reduced to 25% <0.5 109/l, and/
or platelet count <50 109/l, febrile neutropenia (temperature >38
C and
ANC <1.0 109/l), any more than grade 2 non-hematological toxicity,
except nausea and vomiting or alopecia.
Patients with operable disease after chemotherapy should receive surgery
within 4 weeks from the last scheduled chemotherapy cycle. An additional
two cycles of weekly PCb were delivered after surgery in patients who
achieved pCR. Four cycles of cyclophosphamide, epirubicin or two cycles of
weekly PCb could be administrated after surgery in patients showing
response at pathologic assessment. In case of confirmed progression disease
at any time during the neoadjuvant treatment, chemotherapy was to be
discontinued and the patient was asked to undergo salvage surgery and
receive four cycles of cyclophosphamide, epirubicin chemotherapy. The
decision about further radiotherapy and endocrine therapy was at the
discretion of the treating physician.

response and toxicity evaluation

A pCR was defined as the absence of invasive tumor in the final surgical
breast and axillary lymph nodes (ALNs) sample. Residual ductal carcinoma

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Dose density and intensity play an important role in breast

cancer chemotherapy since Cancer and Leukemia Group B
(CALGB) 9741 trial confirmed that dose dense was better
compared with standard schedule in the adjuvant setting [10].
And then, Eastern Cooperative Oncology Group (ECOG) 1199
trial demonstrated that weekly administration of paclitaxel was
superior to the every 3-week schedule [11]. In addition, in
neodajuvant setting, M.D. Anderson Cancer Center study
showed that weekly paclitaxel improved pCR in operable breast
cancer when compared with paclitaxel once every 3 weeks [12].
Platinum complexes are active in a wide range of solid tumors
[13]. Compared with cisplatin, carboplatin has shown same
activity in breast cancer and may be the more appropriate choice
for treatment because it might have lower toxicity without
affecting antitumor efficacy [14]. Paclitaxel combined with
carboplatin (PCb) has shown great activity in ovarian and nonsmall-cell lung cancer treatment. In addition, the overall response
rate of PCb was between 53% and 62% in the first-line
treatment of metastatic breast cancer [15]. Furthermore, Hellenic
Cooperative Oncology Group group has reported that every
3-week PCb regimen had equal response rate and median survival
compared with paclitaxel plus epirubicin group which indicated
that PCb regimen can be considered as an effective therapeutic
alternative to the anthracycline-containing regimen [16].
Three recent meta-analyses have indicated that
anthracycline-containing regimens provide more benefit than
nonanthracycline-containing regimens in patients with human
epidermal growth factor receptor 2 (Her2)-overexpressed
or -amplified breast cancer [1719]. Furthermore, Breast
Cancer International Research Group (BCIRG) 006 trial has
demonstrated that nonanthracycline-containing regimen TCH
(docetaxel + carboplatin + trastuzumab) had superior outcome
than doxorubicin + cyclophosphamide followed docetaxel
(AC/T) regimen in treatment of Her2-positive patients [20].
In addition, Jones et al. [21] reported that docetaxel and
cyclophosphamide (TC) regimen was associated with a better
outcome compared with conventional AC regimen. With the
development of these new drugs, we now recognize that
anthracylines may be not necessary for every patient in
adjuvant chemotherapy of breast cancer and there are several
clinical trials to directly evaluate the role of anthracyclines in
breast cancer treatment.
On the basis of these data, we initiated this phase II study to
evaluate the activity and safety of nonanthracycline-containing
weekly PCb regimen as neoadjuvant treatment in women with
locally advanced breast cancer or large operable disease.

Annals of Oncology

original article

Annals of Oncology

in situ was included in the pCR category. Standard RECIST guidelines were
used to evaluate clinical and pathological response. No clinical evidence of
palpable tumor in the breast and ALNs was defined as a clinical complete
remission (cCR). Reduction in greatest tumor diameter of 30% was
graded as a partial response (PR). An increase in greatest tumor diameter of
>20% or appearance of new disease was considered as progressive disease
(PD). Tumors that did not meet the criteria for objective PR or PD were
considered as stable disease (SD). Toxicity was evaluated at every period of
chemotherapy treatment and recorded according to the NCI-CTC v3.0.

statistics
The primary end point for this analysis was pCR rate. Logistic regression
analysis was used to determine factors predictive of pCR. All statistical tests
were two-sided and carried out at significance level of 0.05 using the SPSS
statistical software package (version 13.0; SPSS Company, Chicago, IL).

results

treatment compliance and surgery

One hundred and two (94.4%) patients have completed all four
cycles of weekly PCb treatment. Two patients only received
three cycles and one patient received six cycles of treatment due
to patients willing. Two patients who suffered from PD were
asked to undergo salvage surgery at the end of first cycle and
second cycle of treatment and another one experienced brain
metastasis after three cycles of treatment.
Among these 108 cases, 106 patients received modified
radical mastectomy, only one patient received breastconservation surgery and one patient treated with immediate
breast reconstruction with latissimus dorsi muscular flap,
respectively.
response rates
The overall clinical response rate was 86.1% with cCR rate 32.4%
(Figure 1). A total of 100 patients (92.6%) experienced
pathological response [PR + Complete Remission (CR)] and 21
patients achieved pCR after four cycles of treatment, with pCR
rate 19.4%. Table 2 shows the clinical and pathological response
rate. Furthermore, there were 27 cases (25.0%) without invasive
residual disease in breast after treatment. In addition, 30 cases
who were positive for ALN before chemotherapy showed
negative result in the surgery specimen after treatment; the ALN
downstage rate was 36.6%.
molecular subtypes and response
Table 3 shows that pCR rate associates with the main biological
features at diagnosis including HR, molecular subtypes and

Volume 21 | No. 5 | May 2010

Characteristics
Age 51 (3270) years
35
3555
>55
BMI index
<24
24
Menopausal status
Pre-/perimenopausal
Postmenopausal
Histology
Infiltrating ductal carcinoma
Infiltrating (mixed) carcinoma
Others
Tumor status
02
3
4
Lymph node status
0
1
2
3
Lymph node metastasis
Negativea
Positive (confirmed by FNA)
Tumor stage
II
IIIA
IIIB
IIIC
Estrogen receptor status
Negative
Positive
Progesterone receptor status
Negative
Positive
Her2 status
Negative
Positive

Number of patients

7
69
32

6.5
63.9
29.6

63
45

58.3
41.7

54
54

50.0
50.0

68
37
3

63.0
34.3
2.8

38
38
32

35.2
35.2
29.6

15
24
60
9

13.9
22.2
55.6
8.3

25
83

23.1
76.9

16
57
26
9

14.8
52.8
24.1
8.3

46
62

42.6
57.4

49
59

45.4
54.6

84
24

77.8
22.2

Clinical negative lymph node or clinical positive lymph node with negative
result by FNA.
BMI, body mass index; FNA, fine needle aspiration; Her2, human
epidermal growth factor receptor 2.

Her2 status. Patients with absence of ER expression were

associated with a higher probability of achieving pCR (ER2
versus ER +, 32.6% versus 9.7%; P = 0.005). A significantly
higher pCR probability was also observed in PgR2 patients
(30.6% versus 10.2%; P = 0.010). Overall, Her2+ tumors apt
to have a higher pCR rate than Her22 tumors. Furthermore,
we approximately classified breast cancer into different
subtypes using IHC ER, PgR and Her2 status, which could
predict the response of weekly PCb neoadjuvant treatment.
Patients classified with luminal A subtype had the lowest pCR
rate, which was 8.3% less than 22.2% in luminal B, 33.3% in

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patient characteristics
Overall, 107 consecutive patients with breast cancer were
enrolled from December 2007 to December 2008 to receive
weekly PCb neoadjuvant chemotherapy, and there was one case
with bilateral breast cancer. A total of 108 cases were eligible for
response evaluation. Table 1 summarizes the main clinical and
pathological characteristics. The median age was 51 years (range
3270 years). A total of 85.2% of patients were initially diagnosed
with stage III diseases, whereas 83 patients had positive ALN
confirmed by fine needle aspiration before chemotherapy.
Twenty-four patients were Her2+ detected by IHC or FISH.

Table 1. Pretreatment patient and tumor characteristics (N = 108)

original article

Annals of Oncology

Table 2. Clinical and pathological response

Response

Number of patients

Clinical tumor response

CR
35
PR
58
SD
11
PD
4
Pathological response (breast)
CR
27
PR
73
SD
4
PD
4
Pathological response (breast + ALN)
CR
21
PR
79
SD
4
PD
4
Post-treatment ALN status (n = 82)a
Negative
30
Positive
52

%
32.4
53.7
10.2
3.7
25.0
67.6
3.7
3.7
19.4
73.1
3.7
3.7
36.6
63.4

A total of 83 patients had metastasis lymph node confirmed by fine needle

aspiration before treatment, one patient did not receive surgery due to
brain metastasis.
CR: complete remission; PR, partial response; SD, stable disease; PD,
progression disease; ALN, axillary lymph node.

triple-negative and 40.0% in Her2-positive subtype patients,

P = 0.017. However, three patients with PD were also classified
into triple-negative subtype, which needed further
investigation.

toxicity
Table 4 summarizes the main treatment-related toxicity
observed in 107 patients. There was one patient with long
history of diabetes experienced monocular deprivation after

964 | Chen et al.

four cycles of treatment. No episode of death, symptomatic

cardiac adverse event or life-threatening event was recorded.
The incidence of grade 34 neutropenia was 40.2% and only
one patient was reported with febrile neutropenia. Severe
anemia and thrombocytopenia only occurred in 4.7% and 0.9%
of patients, respectively. Alopecia was almost universal.
Peripheral neuropathy was frequent, but never severity, only
five (4.7%) patients recorded had more than grade 1 toxicity.
The incidence and severity of gastrointestinal toxic effects were
frequent, but none of them suffered from severe toxicity.

discussion
In our present study, we aimed at evaluating the efficacy and
safety of nonanthracycline-containing weekly PCb regimen as
neodajuvant treatment of breast cancer. Four cycles of weekly PCb
yield a pCR rate of 19.4% in large operable or locally advanced
breast cancer. Furthermore, this nonanthracycline-containing
regimen achieved a high pCR rate in Her2+ disease (33.3%).
In view of the later stage of tumors, the high pCR rate obtained
is particularly interesting which deserves further investigation.
Neoadjuvant chemotherapy has become the standard
treatment of locally advanced breast cancer, which can
downstage the disease and improve the surgery option [2, 3].
Our anthracycline-sparing weekly PCb regimen achieved a pCR
rate as high as 19.4% with the definition of no invasive disease
in breast and ALN, which was much higher than our previous
study conducted in locally advanced disease with vinorelbine
+ epirubicin regimen [25]. Furthermore, the pCR rate was
improved a lot compared with previous study, like paclitaxel +
epirubicin regimen with pCR rate 10% [26] and adriamycin
+ docetaxel with pCR rate from 7.7% to 15% [2729]. If we
applied the NSABP pCR definition [4, 5], then the pCR rate in
our study would increase to as high as 25%, which was similar
with the AC/T regimen in NSABP B27 trial (26.3%) [5].
There are two main features that make our regimen
substantially different from other regimens, including the

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Figure 1. Clinical and pathological response. cRR, clinical response rate; pRR (T), pathological response rate in breast; ALN, axillary lymph node; pRR (T +
ALN), pathological response rate in breast and ALN; CR, complete remission; PR, partial remission; SD, stable disease; PD, progression disease.

original article

Annals of Oncology

Table 3. Pathological response according to ER, PR and Her2 status

ER status
Negative
Positive
PgR status
Negative
Positive
Her2 status
Negative
Positive
Molecular classification
Luminal A
Luminal B
Triple negative
Her2 positive

pCR
(n = 21)

Non-pCR
(n = 87)

pCR rate

15
6

31
56

32.6
9.7

15
6

34
53

30.6
10.2

13
8

71
16

15.5
33.3

5
2
8
6

55
7
16
9

8.3
22.2
33.3
40.0

P valuea
0.005

0.010

0.057

0.017

P value was calculated by Logistic regression.

pCR, pathological complete remission; ER, estrogen receptor; PgR,
progesterone receptor; Her2, human epidermal growth factor receptor 2.

Table 4. Toxicity
Toxicity

Grade 12,
number of
patients (%)

Grade 34,
number of
patients (%)

Neutropenia
Thrombocytopenia
Anemia
Nausea and vomiting
Diarrhea
Liver
Neurotoxicity
Alopecia
Skin toxicity

53
35
77
92
38
21
51
107
25

43
1
5
0
0
0
0
0
1

(49.5)
(32.7)
(71.9)
(86.0)
(35.5)
(19.6)
(47.7)
(100.0)
(23.4)

(40.2)
(0.9)
(4.6)
(0.0)
(0.0)
(0.0)
(0.0)
(0.0)
(0.9)

application of a weekly schedule for these two drugs and the

usage of carboplatin instead of anthracyclines. Meta-analysis
and several large randomized trials have demonstrated that
taxanes can improve the outcome compared with
anthracyclines in the adjuvant treatment of breast cancer [8].
Weekly administration of paclitaxel was also associated with
a better treatment efficacy compared with the every 3-week
schedule [11, 12]. In recent years, there are increasing trials
about the platinum compounds in the management of breast
cancer [14]. The replacement of anthracyclines with platinum
compounds combination with trastuzumab has been widely
used in Her2-overexpressing patients in order to reduce the risk
of cardiac toxicity [29]. Furthermore, there are several
cisplatin-containing regimens, including or not taxanes, which
have been tested in the neoadjuvant setting, showing a high
antitumor activity [3032].
Overall, in our study, a total of 82 patients with proven ALN
metastasis received surgery indicated that our study population
was not at all a favorable one and showed that 30 patients were
free of metastasis after neoadjuvant chemotherapy with axillary

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downstage rate 36.6%, which was similar with previous study

conducted in early operable disease [4, 33].
Several trials like NSABP B27 [5] and German Preoperative
Adriamycin and Docetaxel Study II [34] have demonstrated
that patients with HR-negative disease had a higher pCR rate
compared with HR-positive cases. One favorable feature of our
study population which can explain the high pCR rate achieved
by non-anthracycline-containing PCb regimen was the relative
high proportion of ER2 patients. In our study, we also found
that ER2 or PgR2 diseases, which accounted for 45%
patients, were associated with higher pCR rate.
With the development of gene chip technology, we now can
classify breast cancer into different molecular subtypes which at
least contain five subtypes, including luminal A, luminal B,
basal-like (triple-negative), Her2-positive and normal-like
subtype [35]. Rouzier et al. [36] has demonstrated that patients
with basal-like and Her2-positive diseases were associated with
the highest rate of pCR, 45% and 45%, respectively, whereas the
luminal tumors had a pCR rate of only 6% . Furthermore,
Carey et al. used IHC profiles (ER, PgR and Her2) to subtype
patients with breast cancer and found that triple-negative and
Her2-positive subtypes were more sensitive to anthracyclinebased neoadjuvant chemotherapy than luminal diseases, which
indicated that using IHC profiles to subtype breast cancers can
also predict the response of chemotherapy. However, patients
with triple-negative or Her2-positive subtype diseases had the
worse outcome and higher relapse, which may be due to those
with residual disease after treatment [22]. In our present study,
we also found that patients with triple-negative or Her2positive subtype disease had higher pCR rate compared with
luminal A patients. However, there were three patients with PD
and all of them were classified with triple-negative disease,
which was paradox in triple-negative subtype disease treatment.
Different biological activities can be invoked for these subtypes,
which can result in different probability of achieving a pCR.
Several studies have showed that Her2 status may be
a predictor of anthracycline or taxane response and Her2+
diseases may get more benefit for anthracycline- or taxanecontaining chemotherapy [37]. Patients with Her22 disease
may get little benefit from anthracycline-containing regimen
compared with nonanthracycline-containing regimen, like
CMF (combination chemotherapy with cyclophosphamide,
methotrexate and 5-fluorouracil). Furthermore, US Oncology
9735 [21] and BCIRG 006 [20] trials showed that
anthracyclines may be not an essential drug for breast cancer
adjuvant treatment. pCR rate of nonanthracycline-containing
weekly PCb regimen was 19.4% in all patients and increased to
33.3% in Her2+ diseases, which was also of interest because the
anthracycline drugs were not used. Frasci et al. [38] has
reported that a 2-month cisplatinepirubicinpaclitaxel weekly
combination as neoadjuvant therapy for large operable breast
cancer achieved pCR rate as high as 32% and even higher in
triple-negative disease (62%) [39]. However, the differences in
trial design, eligibility criteria and treatment duration make it
very hard to compare our study regimen with others. Finally,
we should take these data into account when designing a new
clinical trial, like nonanthracycline-containing weekly PCb
regimen versus weekly PCb + anthracycline or cisplatin
epirubicinpaclitaxel regimen, as well as to detect some

original article

funding
Multidiscipline Comprehensive Treatment Cooperation Group
Foundation of Fudan University Cancer Hospital, Shanghai,
China (DXK200801).

acknowledgements
The authors thank the patients and family members for their
willingness to cooperate with our study.

disclosure
We declare that we have no conflict of interest.

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with or without tamoxifen as preoperative therapy in patients with operable

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biological predictive markers, which can directly evaluate the

role anthracycline in breast cancer treatment.
The incidence of severe adverse events was low in our study
besides the alopecia. At the beginning of this trial, we really
concerned about the risk of severe anemia and
thrombocytopenia toxicity, but with the 1-week rest between
every cycle, the incidence was relatively low. Besides these,
severe gastrointestinal toxicity was rare which was very
attractive for patients to receive this neoadjuvant regimen.
Furthermore, we found that no episode of symptomatic cardiac
adverse event was recorded for this anthracycline-sparing
regimen, which can be used for some patients with high risk of
cardiotoxicity and as an attractive option for trastuzumab
combination treatment of Her2-positive breast cancer. At last,
there were only five patients recorded had more than grade 1 of
peripheral neuropathy toxicity, which was much lower than the
previous study [11, 12] and the major reason we believe is the
administration schedule allowing 1-week rest after 3-week
treatment, which has been reported can reduce the incidence of
toxicity [40, 41].
In conclusion, four cycles of nonanthracycline-containing
weekly PCb regimen achieved a pCR rate of 19.4% in large
operable or locally advanced breast cancer with acceptable
safety profiles. Patients with ER2, PgR2, triple-negative or
Her2-positive subtype disease had a higher probability to
achieve pCR. This weekly PCb regimen should consider as
a reasonable nonanthracycline-containing option in
neoadjuvant treatment of breast cancer.

Annals of Oncology

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