3.  49 y.o.  Female  Bataan  “bukol sa suso”

4. 1 year PTA – Noted a firm bandlike mass ~1cm at left breast. Consulted but no treatment done 5 mos PTA – Noted increase in size to ~2cm and change in shape, to round. Felt upper back pain and numbness of Left arm

5. Consulted at a private clinic. FNAB was done showing malignant cells. Advised surgery. 1 mo PTA – Sought second opinion at PGH. Slide review done. Mammogram requested. Diagnosed with breast cancer hence admission for surgery

6. (-) headache(-) constipation (-) blurring of vision(-) urinary problems (-) cough, cold(-) joint pain (-) dysphagia(-) dizziness (-) dyspnea (-) fever (-) chest pain(-) malaise (-) abdominal pain(-) weight loss (-) diarrhea(+) anorexia

7. (+) ovarian cyst, Left, 2010, no treatment (-) Diabetes mellitus, Hypertension, Bronchial asthma, Pulmonary tuberculosis, allergies (-) previous surgeries and hospitalizations

8. No similar illnesses in the family (-) Diabetes mellitus, Hypertension, Bronchial asthma, Pulmonary tuberculosis

9. Menarche – 14 y.o. Menopause – 47 y.o. Previouslyregular menses G4P4 (4004)

10.  2 nd year high school  Employed as receiving clerks  No vices

12. General Survey: awake, coherent, not in cardiorespiratory distress Vital Signs: BP: 110/70 HR: 84 RR: 20 Temperature: 37.5 HEENT:pink conjunctivae, anicteric sclerae, (-)cervical lymphadenopathy, (-) anterior neck mass

13. Chest/ Lungs: Equal chest expansion, clear breath sounds, (-) retractions/rales/wheezes Breast exam: Right: no masses, no axillary nodes, no skin and nipple changes, no nipple discharge Left: 3.5x4.5cm firm slightly tender slightly moveable mass at the 11 o clock direction 10 cm from the nipple, no axillary nodes, no skin and nipple changes, no nipple discharge

14. Cardio vascular: Adynamic precordium, distinct heart sounds, normal rate, regular rhythm, (-) murmurs Abdomen:Flabby, NABS, soft, nontender, (-) masses/tenderness

15. Skin/ Extremities: Full, strong equal pulses, pink nailbeds, (-) edema (-) jaundice Genitalia:Deferred Neurologic:Essentially normal

18. Benign no skin change smooth soft to firm mobile well-defined margins diffuse, symmetric thickening, which is common in the upper outer quadrants, may indicate fibro-cystic changes.

19. Malignant hard immobile fixed to surrounding skin and soft tissue, poorly defined or irregular margins.

20. LikelyLess likely Infection Abscess Hidradenitis suppurativa Mondor’s disease mass/lump tenderness mass/lump chronic condition tenderness cord-like structure no signs of erythema, hyperthermia no signs of inflammation cannot explain other symptoms acute/self-limited condition

21. \ANDI Fibroadenoma Duct ectasia Periductal mastitis mass/lump grow 1-2 cm,  stable  enlarge palpable more common in 35-55 y/o tenderness behind the nipple-areola complex cannot explain other symptoms more common in 15-25 y/o often associated with thick nipple discharge often nipple discharge, retraction

22. ANDI Cyst Incapacitating mastalgia more common in 35-55 y/o Tenderness often subclinical more common in 25-40 y/o associated with severely painful nodularity persisting > 1 wk of menstrual cycle Malignancymass anorexia can explain upper back pain and numbness; no history of cancer

24.  Positive for malignant cell, suggestive of ductal carcinoma

25.  Liver is normal in size measuring 12.2 cm in its midsagittal axis. Echo pattern is heterogenous with moderate increase in parenchymal reflectivity. Intrahepatic veins and ducts are not dilated. Negative for solid nor fluid filled masses.  Impression: Normal size liver with moderate diffuse parenchymal fatty liver changes.

26.  Lungs are clear. Heart is mildly enlarged with left ventricular form. Aorta is tortuous. Diaphragm and sinuses are intact.  Impression: Clear lungs. Left ventricular cardiomegaly. Tortuous aorta.

27.  AB+

28. NormalResult WBC4-11x10 9 /L10.0 RBC4-6x10 12 /L4.8 Hgb120-180g/L141 Hct0.370-0.540%0.414 MCV80-100fL86.3 MCH27-31pg39.3 MCHC320-360g/L340 RDW-CV11-16%13.4 Platelets150-450x10 9 /L215 Neut%0.5-0.70.700 Lymph%0.2-0.50.241 Mono%0.02-0.090.041 Eo%0.0-0.060.015 Baso%0.0-0.020.002

29. NormalResult BUN3.2-8.0 mmol/L3.50 Creatinine53-133umol/L63 Sodium135-145mmol/L141 Potassium4.0-4.5mmol/L3.9 Chloride99-110mmol/L107

31. Breast cancer St IIA (T2N0Mx)

32.  Genetic + environmental factors  Genetic › p53 tumor suppressor gene › BRCA 1 (17q21) › BRCA2 (13q12.3) *hormone-dependent  Spontaneous mutations  Other factors › Diet, smoking

33. Two Types:  Invasive Ductal Carcinoma › an infiltrating, malignant and abnormal proliferation of neoplastic cells in the breast tissue  Ductal Carcinoma In Situ › Proliferation of cytologically malignant breast epithelial cells within the ducts

35.  Carcinoma confined to the ducts or lobules C arcinoma in situ: Lobular carcinoma in situ Ductal carcinoma in situ

36.  Cancer that has spread from the ducts and lobules into the breast tissue. Invasive ductal carcinoma Medullary carcinoma Tubular carcinoma Metaplastic tumors Colloid carcinoma

37. Invasive lobular carcinoma Mixed tumors Inflammatary breast cancer

38. TNM Staging Tumor size Tisused for carcinoma in situ T1</= 2cm T2>2cm but <5cm T3>/= 5cm T4any size that has spread to chest wall or the skin

39. TNM Staging Lymphy nodes Nxcannot be assessed N0no regional lymph node metastasis N1metastasis in movable ipsilateral axillary lymph node(s) N2Metastasis in ipsilateral axillary lymph node(s) fixed or matted, or in clinically apparent ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node metastasis

40. N2aMetastasis in ipsilateral axillary lymph nodes fixed to one another or to other structures N2b Metastasis only in clinically apparent ipsilateral internal mammary nodes and in the absence of clinically evident axillary lymph nodes

41. N3Metastasis in ipsilateral infraclavicular or supraclavicular lymph node(s) with or without axillary lymph node involvement, or clinically apparent ipsilateral internal mammary lymph node(s) and in the presence of axillary lymph node N3aMetastasis in ipsilateral infraclavicular lymph node(s) N3bMetastasis in ipsilateral internal mammary lymph node(s) and axillary lymph node(s) N3cMetastasis in ipsilateral supraclavicular lymph node(s)

42. TNM Staging Distant metastasis MxDistant metastasis cannot be assessed M0No distant metastasis M1Distant metastasis

47.  Given after the primary treatment (surgery); additional treatment  Designed to treat micrometastases (breast cancer cells that have escaped the breast and regional lymph nodes but which have not yet had an established identifiable metastasis) › TYPES:  Adjuvant Radiotherapy --High risk of local recurrence  Adjuvant Chemotherapy --“Micrometastases”  Adjuvant Hormonal Treatment --“Micrometastases”  Evaluation of response may be categorized according to the following parameters: › No visible tumor, rates of recurrence, disease-free survival and overall survival

48.  Adjuvant Radiotherapy › Breast-conserving radiation therapy  To eradicate local subclinical residual disease while reducing local recurrence rates by approximately 75%  2 general approaches:  Conventional external beam radiotherapy (EBRT)  Partial breast irradiation (PBI) › Post-mastectomy radiation therapy

49.  Adjuvant Chemotherapy › Taxanes  Among most active and commonly used chemotherapeutic agents for the treatment of early-stage beast cancer › Anthracyclines  Anthracycline-containing adjuvant chemotherapy regimens have been used in the treatment of early-stage breast cancers

50.  Adjuvant Hormonal Treatment › Tamoxifen  Only hormonal therapy currently approved for adjuvant therapy in patients treated with breast-conserving surgery and radiation for DCIS › Aromatase inhibitors  anastrozole, letrozole, exemestane

51.  Systemic treatment given before any planned local treatment (surgery or radiotherapy)  Initial treatment for localized cancer in which there is an alternative but less than completely effective local treatment › Objectives:  Permits in vivo chemosensitivity testing  Can downstage locally advanced disease and render it respectable  May allow breast-conservation surgery to be performed

52.  Best candidates for neoadjuvant chemotherapy: › ER-negative or HER-2 positive expressing tumors

53.  Anthracycline-based › FAC (doxorubicin in combination with fluorouracil and cyclophosphamde)  Docetaxel, paclitaxel  Trastuzumab  for patients with HER-2 positive phenotype  Pertuzumab  Approved in combination with trastuzumab and docetaxel

54.  Supportive Treatment › pain control for bone metastases › drainage of pleural fluid  Systemic Chemotherapy › visceral metastases  Hormonal and Radiotherapy › bone and brain metastases

56.  Question of conservative vs. radical › A number of RCTs have documented that for stage I and stage II BRCA, mastectomy with axillary lymph node dissection is equivalent to breast-conserving therapy with lumpectomy, axillary dissection and whole breast irradiation

57. Contraindications for breast conserving therapy: Absolute:  Prior radiation therapy to the breast or chest wall  Radiation therapy during pregnancy  Diffuse suspicious or malignant appearing microcalcifications  Widespread disease that cannot be incorporated by local excision through a single incision  Positive pathologic margin

58. Contraindications for breast conserving therapy: Relative: Active connective tissue disease involving the skin (especially scleroderma and lupus) Tumors > 5 cm (category 2B) Focally positive margin Women greater than 35 y or premenopausal women with a known BRCA 1/2 mutation: May have an increased risk of ipsilateral breast recurrence or contralateral breast cancer with breast conserving therapy Prophylactic bilateral mastectomy for risk reduction may be considered.

59. Considered for women with large IIA, IIB or T3N1M0 tumors who meet the criteria for breast-conserving therapy except for tumor size Want to undergo breast-conserving therapy For stage II: no benefit over post-operative adjuvant chemotherapy

60. Whole breast irradiation Inadequate data to support partial breast irradiation Dose/fraction schedules of either 50 Gy in 25 fractions over 35 days or 42.5 Gy in 16 fractions over 22 days

61.  Resection of primary breast cancer with a margin of normal-appearing breast tissue  Excision: Segmental mastectomy, lumpectomy, partial mastectomy, wide local excision, tylectomy  Currently the standard of treatment for women with stage O, I or II cancer  Curvilinear incision concentric to the nipple-areola complex

62.  If on the upper aspect of the breast: Curvilinear incision concentric to the nipple- areola complex  If on the lower aspect: radial incisions preferred  Breast cancer is removed with an envelope of normal-appearing breast tissue for a 2mm cancer-free margin  * Additional samples from surgical bed to prove negative margins  * From the samples: hormone receptor status determination

63.  Skin-sparing › Removes all breast tissue, nipple-areola complex (NAC), scars  Total (simple) › Removes all breast tissue, NAC, skin  Extended › Removes all breast tissue, NAC, skin and level I and level II axillary lymph nodes  Halsted radical mastectomy › Removes all breast tissue and skin, NAC, pectoralis major and pectoralis minor + level I, II, III axillary lymph nodes

64.  Preserves both pectoralis major and pectoralis minor  Removes level I and II axillary lymph nodes but not III › Patey modification: removes pectoralis minor muscle and allows complete dissection of level III axillary lymph nodes › Modified radical mastectomy permits preservation of medial (ant. Thoracic) pectoral nerve Anatomic boundaries: latissimus dorsi, midline of sternum, subclavius, caudal extension of breast 2 to 3 cm below inframammary fold

66.  NCCN Breast Cancer Treatment Guidelines: a typical woman with clinical stage I or stage II breast cancer requires pathologic assessment of axillary lymph node status  Sentinel lymph node mapping and resection › Decreased arm and shoulder morbidity in patients with breast cancer who undergo lymph node biopsy compared vs. axillary lymph node dissection › Not for all women: potential candidates have access to sentinel lymph node team & clinically negative axillary lymph node or negative core or FNA biopsy

68.  Prognostic factor › any measurement available at the time of surgery that correlates with disease-free or overall survival in the absence of systemic adjuvant therapy and, as a result, is able to correlate with the natural history of the disease.  Predictive factor › any measurement associated with response to a given therapy.

69. Significance of prognostic and predictive factors a. to identify patients with good prognoses for whom adjuvant systemic therapy would not provide a large enough benefit to warrant the risks b. to identify patients whose prognosis is poor enough to justify a more aggressive adjuvant approach c. to select patients whose tumors are more or less likely to benefit from different forms of therapy.

70. Prognostic Factors  Axillary nodal status  Tumor size  Tumor type and grade  Lymphatic and vascular invasion  Proliferation markers  Ethnicity and patient age at diagnosis ER/PR status HER2/neu Predictive factors ER/PR status HER2/neu

71.  most significant prognostic indicator for patients with early-stage breast cancer  direct relationship between the number of involved axillary nodes and the risk for distant recurrence  most consistent prognostic factor used in adjuvant therapy decision making › it is standard practice to administer adjuvant therapy to patients with lymph nodes that are positive

72.  most powerful prognostic factor and is routinely used to make adjuvant treatment decisions  In general, patients with a tumor size of >1–2 cm warrant consideration of adjuvant therapy since they may have a distant recurrence risk of ≥20%.

73.  subtypes such as tubular, mucinous, and medullary have a more favorable prognosis than unspecified breast cancer  Scarff-Bloom-Richardson (SBR) classification › Mitotic index, differentiation, and pleomorphism are scored from 1 to 3 and the scores from each category are totaled. › Tumors with scores from 3 to 5 are well differentiated (grade 1), from 6 to 7 are moderately differentiated (grade 2), and 8 to 9 are poorly differentiated (grade 3).  It is primarily used to make decisions for lymph node-negative patients with borderline tumor sizes.

74.  recurrence rate for women with was higher with LVI-positive disease  used to make decisions for lymph node- negative patients with borderline tumor sizes

75.  Includes S-phase fraction (SPF), thymidine labeling index, mitotic index  patients with high SPF tumors had a higher risk of both recurrence and death compared with those with low SPF tumors  elevated SPF is primarily used as justification to administer adjuvant therapy to lymph node-negative patients with borderline tumor sizes

76.  African American and Hispanic women have a decreased survival from breast cancer compared with white women › This source of this disparity is likely multifactorial, including issues such as lack of access to care resulting in a higher stage at diagnosis  some trials showed worse prognosis for patients younger than 35 years of age

77.  Presence of ER/PR in an invasive breast CA is both prognostic and predictive  Women with ER-positive tumors have better prognosis than women with ER-negative tumors  Its optimal use is as predictive factor for the benefit of adjuvant tamoxifen therapy › all hormone-positive women who warrant adjuvant systemic therapy should receive hormonal therapy unless otherwise contraindicated

78. › The c-erbB-2 (HER2/neu) proto-oncogene is located on 17q21 and encodes an Mr 185,000 transmembrane glycoprotein, p185HER2, with intrinsic tyrosine kinase activity homologous to the epidermal growth factor receptor  It is amplified and/or overexpressed in approximately 30% of human breast tumors  HER2/neu overexpression is a prognostic factor that is associated with a more aggressive tumor. › Overexpression is associated with increased tumor aggressiveness, increased rates of recurrence, and increased mortality in node-positive patients, while the influence in node-negative patients is more variable.  The optimal use of HER2/neu status may be as a predictive factor, especially in predicting response to trastuzumab in the metastatic setting.

80. Interval history and physical exam every 4-6 months for 5 years, then every 12 months Annual mammography Women on tamoxifen: annual gynecologic assessment every 12 months if uterus present Women on an aromatase inhibitor or who experience ovarian failure secondary to treatment should have monitoring of bone health with a bone mineral density determination at baseline and periodically thereafter Assess and encourage adherence to adjuvant endocrine therapy Active lifestyle, achieving and maintaining an ideal body weight (20-25 BMI) may lead to optimal breast cancer outcomes

81.  History and PE performed every 3-6 months for the first 3 years, every 6-2 months for years 4 and 5, and annually thereafter.  For those who have undergone breast-conserving surgery: › post-treatment mammogram 1 year after the initial mammogram and at least 6 months after completion of radiation therapy › Thereafter, unless otherwise indicated, a yearly mammographic evaluation should be performed.  Patients at high risk for familial breast cancer syndromes should be referred for genetic counseling.  CBCs, chemistry panels, bone scans, chest radiographs, liver UTZ, CT scans, PET scanning, MRI, or tumor markers (CEA, CA 15-3, and CA 27.29) is not recommended for routine breast cancer follow-up in an asymptomatic patient with no specific findings on clinical examination.