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

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

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

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

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

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

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. . and she stays at home as housewife. Patient does not smoke or drink alcoholic beverages. She has no history of illicit drug use. Her husband is a mechanic.

History of goiter noted since high school. No nipple discharge or redness of the overlying skin noted. No episodes of abdominal pain and diarrhea in the past month.SYSTEMS REVIEW • Skin: No rashes. No yellowing of sclera or conjunctiva. Itchiness of the skin was not noted. No noted sudden enlargement of thyroid gland. Seizures not noted. No cataracts noted. No history of vertigo. • Cardiovascular: No known heart disease. No chest pain or palpitations. No epistaxis noted. • Neck: No neck pain or limitation in neck movement. • Gastrointestinal: No vomiting or abdominal enlargement noted. • HEENT: No history of head injury. Eyes: No change in vision noted. Mouth: Mild bleeding of the lips was noted. Ears: No tinnitus or infections. No noted enlargement of lymph nodes. Throat: No pain or` difficulty in swallowing noted. Noted enlargement of breast mass on inner lower quadrant of left breast. redness. • Breast: No dimpling or thickening of the skin noted. or yellowing of the skin noted. No cough or history of respiratory illness in the past month. No ulcerations in the extremities. Mouth ulcers also noted. recently associated with pain. Nose: No mucosal irritation noted. No hoarseness of voice. Blood pressure readings were normal. Another nontender. • Respiratory: No reported difficulty in breathing. nonmovable mass palpated on the upper outer quadrant of her left breast. Abnormal ear discharges not noted. .

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

• • • • • Vital Signs: BP: 120/70 mmHg HR: 98 bpm RR: 15 cpm Temp: 36. and ambulatory.PHYSICAL EXAMINATION • General Survey: Patient is asthenic and well-groomed. responsive. coherent. cooperative. She is alert.6 (axillary) .

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

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

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

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

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

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

disclike or lobular May be soft. most common over age 50 Number (Multiple) Usually single. may be multiple Single or multiple multiple May be multiple Usually single Usually single.o) 15-25 years old and young adulthood Cysts 30-50. 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 . usually firm Well delineated Round Soft to firm. 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.Differential Diagnoses Fibroadenoma Usual Age (59 y. 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.

Clinical Impression • Breast Cancer .

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

. It accounts for 33% of all female cancers and is responsible for 20% of the cancer-related deaths 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.

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

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

. • 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. radiation exposure during adolescence. • In both circumstances. a period of active breast development. magnifies the deleterious effect.Risk Factors • Nonhormonal risk factors • radiation exposure. • 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.

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

Nutrition.beef or pork 2.low incidence despite large consumption of fat (omega 3 FA) .inc CA 2 fold • Ethnic Hawaii.Dietary Influences • Committee on Diet. high fat foods.a causal relationship exists between dietary mammalian fat and breast cancer. animal fat.7 times higher • Japanese.strong relationship between breast CA and total fat. • Fried. Eskimo.concluded. unsat fat • NCI. and Cancer of the National Academy of Sciences.

higher probability (30-70%) • Women.nulliparity and infertility.1.first pregnancy after 35-even greater risk than nullipara .5-2x higher than non obese • Child bearing and fertility.• Obesity.

.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 .

which are inherited in an autosomal dominant fashion • Both BRCA1 and 2 function as TSGs.BRCA Mutations • BRCA1 • 5% to 10% of breast Cancers are caused by inheritance of germline mutations such BRCA1 and 2. 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.

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

.

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

Cancer prevention for BRCA mutation Carriers • Prophylactic mastectomy and reconstruction • Prophylactic oophorectomy and hormone replacement therapy • Intensive surveillance for breast and ovarian cancer • chemoprevention .

productive fibrosis that involves the epithelial and stromal 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 growth of the cancer and invasion of the surrounding breast tissues.Primary Breast Cancer • More than 80%. .

.

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

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

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

. • 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.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.

• These cells are scavenged by natural killer lymphocytes and macrophages. breast cancers acquire their own blood supply (neovascularization). 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.Distant Metastases • At approximately the twentieth cell doubling. • Thereafter. .

5. 4.Common Sites of Involvement 1. 2. 3. Bone Lung Pleura Soft tissues Liver .

platelets Liver function tests Chest x-ray Bilateral mammogram Hormone-receptor status HER2/neu expression Bone scan Abdominal CT scan or ultrasound or MRI .Diagnostic Studies for Breast Cancer Patients History & physical CBC.

woman discovers a lump in her breast • Other less frequent presenting s/s: • Breast enlargement or assymetry • Nipple changes.Diagnosis • History • 33% of breast cancer cases. 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 .

dimpling. nipple discharge. retraction. • BSE monthly.Diagnosis • Physical Examination • Inspection: assymetry. lymph nodes • CBE every 3 years in women 20-40 years and annually after 40 yrs. ulcers • Palpation: mass. 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 .

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

• 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 .

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

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

DCIS • Eventually. • With continued growth. pleomorphic cancer cells w/ freq mitotic figures obliterate the lumina and distend the ducts (solid growth pattern). 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: .

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

Paget’s 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.

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

Invasive DC .

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

.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 .

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

Lobular Ca .

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.Inflammatory Breast CA • Rare and very aggressive with symptoms that include redness. • 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 .