Breast Cancer

General Data
A case of Mrs. C.H., 59 years old, married, housewife, Roman Catholic, and a resident of Brgy. Mabolo, Cebu City, was admitted for the second time at Cebu City Medical Center on January 6, 2014 at 3:00 PM.

Chief Complaint
Referred for surgery of a tumor on the inner lower quadrant of left breast

HISTORY OF PRESENT ILLNESS

Two years prior to admission, the patient palpated a nonmovable, nontender hard nodule, about 1 cm in size, on the inner lower quadrant of her left breast. She did not notice any nipple discharge or breast skin changes. There were no other symptoms. No consultation was done, and she did not take any medications. One year PTA, patient noticed a gradual increase in size of the breast tumor, but she still did not seek consultation. There was no pain on the area of the tumor, no nipple discharge, and no change in her weight or appetite. Three months PTA, patient began to feel intermittent, diffuse, dull pain on her left breast, which was more severe at night. She took Mefenamic acid as needed to control the pain. She also palpated another smaller nontender mass on the upper outer quadrant of her left breast. She decided to seek consultation at Chong Hua Hospital, and a biopsy was done on the breast tumor. There were no pertinent findings on chest xray and abdominal ultrasound She was referred to CCMC for continuing management and was subsequently admitted.

PAST MEDICAL HISTORY

Patient had surgery last 1992 for cystic masses on both her breasts. There were no follow-up checkups after her surgery. She also had an operation last July 2012 for an umbilical hernia. She did not report any complications following her surgery. She also has goiter since high school, but no consultation was done. She started taking Oldelangia, an herbal medicine, 1 year ago to reduce the enlargement of her thyroid gland. Patient has no recent vaccinations. Childhood vaccinations cannot be recalled. She has not undergone Pap smear, and she does not perform monthly breast self-examination.

MENSTRUAL HISTORY
Patient had menarche at 15 years old. Her monthly menstrual cycles were regular, with no other symptoms during menses. She had 1 year of irregular menstrual cycle prior to menopause at 51 years old. She did not report any perimenopausal symptoms, such as hot flushes or abnormal vaginal bleeding.

OBSTETRIC AND CONTRACEPTIVE HISTORY

Patient delivered through NSVD to her only child, female, when she was 33 years old. She did not have gestational hypertension, diabetes mellitus, or other diseases during pregnancy. She had two abortions last 1997 and 1998, wherein she underwent suction curettage at Chong Hua Hospital. She has never used oral contraceptive pills or other hormonal contraceptives throughout her life.

FAMILY HISTORY
There was no family history of breast cancer or other types of cancer in the patients family. Her mother has hypertension and arthritis. Her father and two of her siblings died from myocardial infarction.

PERSONAL HISTORY
The patient finished her high school education and worked as a checker at a store and then as cashier in Metro Gaisano before she got married at the age of 27. Her husband is a mechanic, and she stays at home as housewife. Patient does not smoke or drink alcoholic beverages. She has no history of illicit drug use.

SYSTEMS REVIEW
Skin: No rashes, redness, or yellowing of the skin noted. No ulcerations in the extremities. Itchiness of the skin was not noted. HEENT: No history of head injury. Seizures not noted. Eyes: No change in vision noted. No yellowing of sclera or conjunctiva. No cataracts noted. Ears: No tinnitus or infections. Abnormal ear discharges not noted. No history of vertigo. Nose: No mucosal irritation noted. No epistaxis noted. Mouth: Mild bleeding of the lips was noted. Mouth ulcers also noted. Throat: No pain or` difficulty in swallowing noted. No hoarseness of voice. Neck: No neck pain or limitation in neck movement. History of goiter noted since high school. No noted enlargement of lymph nodes. No noted sudden enlargement of thyroid gland.

Respiratory: No reported difficulty in breathing. No cough or history of respiratory illness in the past month.
Breast: No dimpling or thickening of the skin noted. Noted enlargement of breast mass on inner lower quadrant of left breast, recently associated with pain. Another nontender, nonmovable mass palpated on the upper outer quadrant of her left breast. No nipple discharge or redness of the overlying skin noted. Cardiovascular: No known heart disease. Blood pressure readings were normal. No chest pain or palpitations. Gastrointestinal: No vomiting or abdominal enlargement noted. No episodes of abdominal pain and diarrhea in the past month.

SYSTEMS REVIEW
Urinary: No dysuria, hematuria, or recent flank pain. Peripheral Vascular: No lower extremity ulcerations or changes in skin color noted. No edema of the lower extremities. Musculoskeletal: No joint pains or swelling. No limitation in body movement. No body malaise noted. Psychiatric: No diagnosed history of depression or treatment for psychiatric disorders. Neurologic: Occasional headache noted. No fainting, episodes of confusion, or seizures noted. Nutritional: No changes in appetite. No weight loss noted.

PHYSICAL EXAMINATION
General Survey: Patient is asthenic and well-groomed. She is alert, coherent, responsive, cooperative, and ambulatory. Vital Signs: BP: 120/70 mmHg HR: 98 bpm RR: 15 cpm Temp: 36.6 (axillary)

PHYSICAL EXAMINATION
Skin: Color is good. No rashes, jaundice, or ulcerations noted. Extremities are warm and well-perfused. Nails are pink and no clubbing noted. CRT<2 seconds. Skin turgor is good. HEENT: Head: Hair of average texture, scalp without lesions, normocephalic/atraumatic. Eyes: Conjunctiva pink, sclera white. Pupils are round, regular, and equally reactive to light. Blink reflex intact. No hemorrhages or exudates. Ears: Intact tympanic membrane. Acuity good to whispered voice. Nose: Mucosa pink, septum midline. No sinus tenderness. No mucosal bleeding. Mouth:Teeth are complete. Buccal mucosa moist with no ulcerations. Tongue is midline and nontender on palpation. No exudates noted. Throat: Both tonsils are not inflamed. Uvula is midline. No noted deformities.

PHYSICAL EXAMINATION
Neck: Trachea is midline. No jugular vein distention. Thyroid gland enlargement is noted but are nontender, soft in consistency and regular in contour on palpation. No palpable masses on the neck. Lymph nodes are nonpalpable. Thorax and Lungs: Thorax symmetric with good excursion. No tachypnea noted. No noted use of accessory muscles. Normal tactile fremitus. Lungs resonant. No adventitious breath sounds auscultated.

PHYSICAL EXAMINATION
Breast: Noted breast mass on lower inner quadrant of left breast, 8 cm x 11 cm in size, irregular contour, with overlying erythematous and dimpled skin. Tumor is non-tender and hard with irregular borders. No ulcerations noted. Another tumor palpated on upper outer quadrant of same breast, nontender, immovable, round with regular borders and hard in consistency. Overlying skin in nonerythematous and non-ulcerated. No nipple discharge noted. There is no nipple inversion of the left breast but it is displaced by the tumor to the lateral side. There are no palpable masses on the right breast. No nipple discharge or inversion. No skin dimpling or erythema noted.

PHYSICAL EXAMINATION
Cardiovascular: JVP 2 cm above sternal angle. Apical impulse is palpable in the 5th interspace left midclavicular line. No thrills. S1 and S2 sounds heard. No murmurs, bruits, or additional heart sounds noted. Abdomen: Noted midline surgical scar from the umbilicus to the suprapubic area. Bowel sounds are normoactive. No bruit on abdominal aorta. No tenderness or palpable lesions noted. No fluid wave noted. Liver size is 8 cm in right midclavicular line. Spleen and kidneys not palpable. No costovertebral angle tenderness. Peripheral Vascular: No peripheral edema, ulcerations, or skin color changes noted

PHYSICAL EXAMINATION
Musculoskeletal: No join swelling or deformities. Good ROM in hands, elbows, shoulders, ankles. Muscle strength 5/5 throughout. No joint tenderness noted. Neurologic: Cerebral: Alert, coherent, and cooperative. Oriented to person, place, and time. Cerebellar: Romberg test and gait not assessed. Rapid alternating movements intact. Sensory: Pinprick, light touch, position sense, vibration, and stereognosis intact. Lower extremity sensation is intact. Motor: Strength 5/5 throughout.

PHYSICAL EXAMINATION
Cranial Nerves: I: olfactory sense intact II: intact III, IV, VI: cardinal eye movements intact V: corneal blink reflex intact; facial sensory intact VII: face symmetric; no alterations in sense of taste VIII: good acuity to whispered voice IX, X, XII: Gag reflex intact XI: Symmetric shoulder movement

Differential Diagnoses
Fibroadenoma Usual Age (59 y.o) 15-25 years old and young adulthood Cysts 30-50, regress after menopause except with estrogen therapy Fibrocystic Changes 25-50 years old Fat necrosis Can affect any age Phyllodes tumor Occurs at any age (median age is the 5th decade of life) Breast Cancer 30-90, most common over age 50

Number (Multiple)

Usually single, may be multiple

Single or multiple

multiple

May be multiple

Usually single

Usually single, although may coexist with other nodules Irregular or stellate Firm or hard Not clearly delineated from surrounding tissues May be fixed to skin or underlying tissues

Shape (Irregular) Consistency (Firm) Delimitation (Irregular Borders)

Round, disclike or lobular May be soft, usually firm Well delineated

Round Soft to firm, usually elastic Well delineated

Ropelike/ nodular Soft to firm Well delineated

Round Firm Not well delineated

Round Firm Well delineated

Mobility (Immovable)

Very mobile

mobile

Freely movable

May be fixed

Freely movable

Tenderness Usually nontender (Present) Retraction signs absent (Present) Other remarks (No history of breast trauma or prior surgery)

Often tender absent

Usually tender Absent

Often nontender May be present History of Breast trauma or prior surgery

nontneder Absent

Usually nontender May be present

Clinical Impression
Breast Cancer

Case Discussion
Breast cancer is a malignant proliferation of epithelial cells lining the ducts or lobules of the breast. Epithelial malignancies of the breast are the most common cause of cancer in women (excluding skin cancer), accounting for about one-third of all cancer in women.

Epidemiology
Number one cancer in women Breast cancer is the most common site-specific cancer in women and is the leading cause of death from cancer for women age 40 to 44 years. It accounts for 33% of all female cancers and is responsible for 20% of the cancer-related deaths in women.

Risk Factors
HORMONE ASSOCIATED RISK FACTORS
Increased exposure to estrogen Factors that increase the number of menstrual cycles, such as early menarche, nulliparity, and late menopause, are associated with increased risk. Moderate levels of exercise and a longer lactation period, factors that decrease the total number of menstrual cycles, are protective.

Risk Factors
The terminal differentiation of breast epithelium associated with a full-term pregnancy is also protective, so older age at first live birth is associated with an increased risk of breast cancer. Finally, there is an association between obesity and increased breast cancer risk. Because the major source of estrogen in postmenopausal women is the conversion of androstenedione to estrone by adipose tissue, obesity is associated with a long-term increase in estrogen exposure

Risk Factors
Nonhormonal risk factors
radiation exposure.
Young women who receive mantle radiation therapy for Hodgkin's lymphoma have a breast cancer risk that is 75 times greater than that of age-matched control subjects. Survivors of the atomic bomb blasts in Japan during World War II have a very high incidence of breast cancer, likely because of somatic mutations induced by the radiation exposure. In both circumstances, radiation exposure during adolescence, a period of active breast development, magnifies the deleterious effect.

Risk Factors
Studies also suggest that the amount and duration of alcohol consumption are associated with an increased breast cancer risk.
Alcohol consumption is known to increase serum levels of estradiol.

Evidence suggests that chronic consumption of foods with a high fat content contributes to an increased risk of breast cancer by increasing serum estrogen levels

Dietary Influences
Committee on Diet, Nutrition, and Cancer of the National Academy of Sciences- concluded- a causal relationship exists between dietary mammalian fat and breast cancer. Fried, high fat foods- inc CA 2 fold Ethnic Hawaii- strong relationship between breast CA and total fat, animal fat, unsat fat NCI- beef or pork 2.7 times higher Japanese, Eskimo- low incidence despite large consumption of fat (omega 3 FA)

 Obesity- 1.5-2x higher than non obese Child bearing and fertility- nulliparity and infertility- higher probability (30-70%) Women- first pregnancy after 35-even greater risk than nullipara

70% 80% of breast cancer cases have no identifiable risk factors other than being a woman and growing older Majority are sporadic or index cases and have no family history of breast cancer.

Breast cancer risk assessment model

Breast cancer risk assessment model

BRCA Mutations
BRCA1
5% to 10% of breast Cancers are caused by inheritance of germline mutations such BRCA1 and 2, which are inherited in an autosomal dominant fashion Both BRCA1 and 2 function as TSGs, and for each gene, loss of both alleles is required for initiation of cancer BRCA1 predisposing genetic factor in as many as 45% of hereditary breast CA and in at least 80% of hereditary ovarian cancers.

 In general, associated breast cancers are invasive ductal carcinoma, are poorly differentiated, are hormone receptor negative. Distinguishing clinical features: early age of onset, higher prevalence of bilateral breast cancer, presence of associated cancers, esp. ovarian, possibly colon and prostate cancers

 BRCA2

Autosomal dominant trait and has a high penetrance Approximately 50% of children of carriers inherit the trait. Men w/ germline mutations in BRCA2 have an estimated breast cancer risk of 6%, represents 100 fold increase over the risk in the general male population. Associated breast cancers: invasive ductal carcinoma, well differentiated and express hormone receptors. Clinical features: early age of onset compared to sporadic cases, higher prevalence of bilateral breast cancer, associated cancers: ovarian, colon, prostate, pancreatic, gall bladder, bile duct, stomach cancers and melanomas

Cancer prevention for BRCA mutation Carriers

Prophylactic mastectomy and reconstruction Prophylactic oophorectomy and hormone replacement therapy Intensive surveillance for breast and ovarian cancer chemoprevention

Primary Breast Cancer

More than 80%- productive fibrosis that involves the epithelial and stromal tissues. With growth of the cancer and invasion of the surrounding breast tissues, the accompanying desmoplastic response entraps and shortens the suspensory ligaments of Cooper to produce a characteristic skin retraction. Localized edema (peau d'orange) develops when drainage of lymph fluid from the skin is disrupted.

 With continued growth, cancer cells invade the skin and eventually ulceration occurs. As new areas of skin are invaded, small satellite nodules appear near the primary ulceration.

 The size of the primary breast cancer correlates with diseasefree and overall survival, but there is a close association between cancer size and axillary lymph node involvement. In general, up to 20% of breast cancer recurrences are localregional, more than 60% are distant, and 20% are both localregional and distant.

Axillary Lymph Node Metastases

As the size of the primary breast cancer increases, some cancer cells are shed into cellular spaces and transported via the lymphatic network of the breast to the regional lymph nodes, especially the axillary lymph nodes. Lymph nodes that contain metastatic cancer are at first illdefined and soft, but become firm or hard with continued growth of the metastatic cancer.

Axillary Lymph Node Metastases

Eventually the lymph nodes adhere to each other and form a conglomerate mass. Cancer cells may grow through the lymph node capsule and fix to contiguous structures in the axilla including the chest wall. Typically, axillary lymph nodes are involved sequentially from the low (level I) to the central (level II) to the apical (level III) lymph node groups.

Distant Metastases
At approximately the twentieth cell doubling, breast cancers acquire their own blood supply (neovascularization). Thereafter, cancer cells may be shed directly into the systemic venous blood to seed the pulmonary circulation via the axillary and intercostal veins or the vertebral column via Batson's plexus of veins, which courses the length of the vertebral column. These cells are scavenged by natural killer lymphocytes and macrophages.

Common Sites of Involvement

1. 2. 3. 4. 5. Bone Lung Pleura Soft tissues Liver

Diagnostic Studies for Breast Cancer Patients

History & physical CBC, platelets Liver function tests Chest x-ray Bilateral mammogram Hormone-receptor status HER2/neu expression Bone scan Abdominal CT scan or ultrasound or MRI

Diagnosis
History 33% of breast cancer cases, woman discovers a lump in her breast Other less frequent presenting s/s: Breast enlargement or assymetry Nipple changes, retraction or discharge Ulceration or erythema of the skin of breast Axillary mass Musculoskeletal discomfort 50% of women w/ breast complaints have no physical signs of breast pathology Breast pain is usually associated with benign disease

Diagnosis
Physical Examination
Inspection: assymetry, dimpling, retraction, ulcers Palpation: mass, nipple discharge, lymph nodes
CBE every 3 years in women 20-40 years and annually after 40 yrs. BSE monthly, 5-7 days after the onset of menses

Diagnosis
Imaging Techniques
Mammography
Annually starting at age 40 Earlier for those with strong family history

 Ductography
Primary indication is nipple discharge

 Ultrasonography
Resolving equivocal mammographic findings, defining cystic masses, and demonstrating the echogenic qualities of specific solid abnormalities Used to guide FNAB, core needle biopsy, and needle localization of breast lesions

 MRI
In the process of evaluating MRI as a means of characterizing mammographic abnormalities, additional breast lesions have been detected.

Staging

Histopathology
Carcinoma in situ

LCIS
From the terminal duct lobular units Distention and distortion of the terminal duct lobular units by cancer cells, which are large but maintain a normal N:C ratio. Cytoplasmic mucoid globules- distinctive cellular feature Calcifications associated occur in adjacent tissues.

DCIS
Predominantly seen in female breast, 5% in male breast cancers Proliferation of the epithelium that lines the minor ducts, resulting in papillary growths within the duct lumina Papillary growths eventually coalesce and fill the duct lumina so that only scattered, rounded spaces remain between clumps of atypical cancer cells, which show hyperchromasia and loss of polarity (Cribriform pattern)

DCIS
Eventually, pleomorphic cancer cells w/ freq mitotic figures obliterate the lumina and distend the ducts (solid growth pattern). With continued growth, cells outstrip their blood supply and become necrotic (comedo growth pattern)

Classification of DCIS

Invasive Breast CA
Ductal/ Lobular 80% of invasive breast CAs are described as invasive Ductal carcinoma of no special type. Foot and Stewart originally proposed the following classification for invasive cancer:

Pagets disease
a chronic, eczematous eruption of the nipple, which may be subtle, but may progress to an ulcerated, weeping lesion. Paget's disease is usually associated with extensive DCIS and may be associated with an invasive cancer. A palpable mass may or may not be present.

Pagets Disease
Biopsy of the nipple will show a population of cells that are identical to the underlying DCIS cells (pagetoid features or pagetoid change). Pathognomonic of this cancer is the presence of large, pale, vacuolated cells (Paget's cells) in the rete pegs of the epithelium.

Invasive Ductal Carcinoma

80% of breast cancers and presents with macroscopic or microscopic axillary lymph node metastases in up to 60% of cases. Cancer cells are often arranged in small clusters, broad spectrum of histologic types with variable cellular and nuclear grades

Invasive DC

Mucinous CA
2% Presents in the elderly as bulky tumor Extracellular pools of mucin w/c surround aggregates of low grade cancer cells. The cut surface is glistening and gelatinous. 66% display hormone receptors

Medullary CA
4% Frequent phenotype of BRCA1 hereditary Breast CA Soft and Hemorrhagic 20% bilateral Microscopically:
Dense lymphoreticular infiltrate Large pleomorphic nuclei that are poorly differentiated and show active mitosis Sheet like growth pattern with minimal or absent ductal or alveolar differentiation.

Medullary CA
Approximately 50% are associated with DCIS, present at the periphery of the cancer, less than 10% demonstrate hormonal receptors

Medullary CA

Papillary CA
2% Small and rarely retain a size of 3cm in diameter Papillae with fibrovascular stalks and multilayered epithelium

Tubular CA
2% Under low power magnification: haphazard array of small, randomly arranged tubular elements

Invasive Lobular CA
10% Histopathological features:
Small cells with rounded nuclei, inconspicuous nuclei, scant cytoplasm

Lobular Ca

Inflammatory Breast CA
Rare and very aggressive with symptoms that include redness, swelling, tenderness and warmth Treatment is usually more aggressive People with this type of cancer are encouraged to enroll in clinical trials that are testing new treatments. 1-5% of all breast cancers

Inflammatory Breast Cancer

Progresses rapidly- weeks to months Stage III or IV at diagnosis Frequently hormone receptor negative More common in obese women