Breast pathology

breast patho

1. The Breast

2. Nipple Discharge If the history describes bilateral nipple discharge , think of prolactinoma . Order prolactin levels and TSH levels . • Nonbloody nipple discharge = most likely intraductal papilloma. May also be malignancy. • Bloody nipple discharge = most likely malignancy

3. Most Common Cause The most common cause of unilateral nonbloody nipple discharge is intraductal papilloma . It commonly presents with watery, serous or serosanguinous fluid discharge. The likelihood of cancer is greater if there is an associated palpable mass , involvement of more than one duct or bloody discharge.

4. Diagnostic Testing Mammogram : Look for underlying masses or calcifications. Surgical duct excision : Perform this for definitive diagnosis. Cytology is not helpful in the diagnosis and is never the answer for nipple discharge .

5. Breast Mass- Fibrocystic Disease This classically presents in a woman age 20–50 with cyclical, bilateral painful breast lump(s ). A clue to the diagnosis is that the pain will vary with the menstrual cycle . A simple cyst will have sharp margins and posterior acoustic enhancement on ultrasound. It will collapse on fine-needle aspiration FNA. Treatment is oral contraceptive pills/medications (OCP). In patients with severe pain, danazol may be used.

6. Mammogram

7. Answer : C

8. Fibroadenoma This classically presents as a discrete, firm, nontender , and highly mobile breast nodule. A clue to the diagnosis is a mass that’s highly mobile on clinical exam . Fibroadenomas are made up of stromal and epithelial cells.

9. Diagnostic Testing The steps in diagnosis of any patient (including pregnant women) with a breast mass are as follows: 1. Clinical breast examination (CBE) 2. Imaging: Ultrasound or diagnostic mammography (if patient > 40) 3. Fine-needle aspiration (FNA) biopsy

10. Treatment No treatment is necessary. Surgical removal can be done if the mass is growing Never diagnose a simple cyst on clinical exam alone. The diagnosis must be confirmed with either ultrasound or FNA.

11. A 30-year-old woman complains of bilateral breast enlargement and tenderness, which fluctuates with her menstrual cycle. On physical examination, the breast feels lumpy, and there is a painful, discrete 1.5-cm nodule. A fine-needle aspiration is performed, and clear liquid is withdrawn. The cyst collapses with aspiration. Which of the following is the next step in management? a. Clinical breast exam in 6 weeks b. Core needle biopsy c. Mammography d. Repeat FNA in 6 weeks e. Ultrasound in 6 weeks

12. Answer: A. Clinical breast exam in 6 weeks is appropriate follow-up for a cystic mass that disappears after FNA. If the mass recurs on the 6-week follow-up, FNA may be repeated , and a core biopsy can be performed.

13. When do you answer the following ? 1. Ultrasound : First step in workup of a palpable mass that feels cystic on exam. Imaging test for younger women with dense breast

14. Normal breast US

15. 2. Mammography Mammography (> 50 years old ) and biopsy (or biopsy alone if < 40 years old ): Cyst recurs > twice within 4 to 6 weeks. There is bloody fluid on aspiration. Mass does not disappear completely upon FNA. There is bloody nipple discharge (excisional biopsy). There are skin edema and erythema suggestive of inflammatory breast carcinoma (excisional biopsy ).

16. Mammography Mammogram should be done before biopsy. Biopsy distorts radiography.

17. 3. Fine-needle aspiration or core biopsy is needed for a palpable mass . May be done after ultrasound or instead of ultrasound . 4. Cytology : Any aspirate that is grossly bloody must be sent for cytology. Observation with repeat exam in 6–8 weeks : -- Cyst disappears on aspiration, and the fluid is clear. -- Needle biopsy and imaging studies are negative. Core biopsy is superior to FNA.

18. A 47-year-old woman completes her yearly mammogram and is told to return for evaluation. The mammogram reveals a “cluster” of microcalcifications in the left breast. What is the most appropriate next step in management? a. Excision biopsy b. Core needle biopsy c. Repeat screening mammogram in 6 months d. Repeat screening mammogram in 12 months e. Ultrasound

19. Answer: B. A cluster of microcalcifications are mostly benign; however, approximately 15–20 percent represent early cancer. The next step in workup is core needle biopsy under mammographic guidance.

20. Breast Cancer- Preinvasive Diseases Both ductal carcinoma in situ (DCIS) and lobular carcinoma in situ ( LCIS) increase the risk of invasive disease. If biopsy reveals DCIS , then schedule surgical resection with clear margins ( lumpectomy; i.e ., breast conserving surgical resection) and give radiation therapy ( RT) and tamoxifen for 5 years to prevent the development of invasive disease. LCIS , then tamoxifen alone given for 5 years to reduce risk of development of breast cancer. It is not necessary to perform surgery. Note that LCIS is classically seen in premenopausal women.

21. Tamoxifen is an estrogen receptor antagonist in the breast tissue. It acts as an endometrial agonist. Agonist drugs bind to and activate a receptor. Agonists cause an action. Antagonists are drugs with high affinity (bind to receptors well) but no efficacy (do not make the receptors work). Antagonists block an action.

22. schedule surgical resection with clear margins (lumpectomy; i.e., breast conserving surgical resection) and give radiation therapy (RT) and tamoxifen for 5 years to prevent the development of invasive disease

23. tamoxifen alone given for 5 years to reduce risk of development of breast cancer. It is not necessary to perform surgery

24. Risks associated with tamoxifen use: • Endometrial carcinoma • Thromboembolism Contraindications: • Patient is active smoker • Previous thromboembolism • High risk for thromboembolism

25. Invasive Breast Diseases Invasive ductal carcinoma is the most common form of breast cancer ( 85 percent of all cases). It is unilateral. It metastasizes to bone, liver, and brain . Invasive lobular carcinoma accounts for 10 percent of breast carcinomas. It tends to be multifocal (within the same breast) and is bilateral in 20 percent of cases .

26. 3. Inflammatory breast cancer is uncommon, grows rapidly, and metastasizes early. Look for a red, swollen, and warm breast and pitted, edematous skin (classic peau d’orange appearance). 4. Paget’s disease of the breast/nipple presents with a pruritic, erythematous, scaly nipple lesion. It’s often confused with dermatosis -like eczema or psoriasis. Look for an inverted nipple or discharge.

27. Established risk factors for breast cancer : Age ≥ 50 years old Familial BRCA1/BRCA2 mutation carrier Exposure to ionizing radiation First childbirth after age 30 or nulliparity History of breast cancer History of breast cancer in a first-degree relative Hormone therapy Obesity ( BMI ≥ 30 kg per m2)

28. When are BRCA1 and BRCA2 gene testing indicated? Family history of early-onse t (< 50 years of age) breast cancer or ovarian cancer Breast and/or ovarian cancer in the same patient Family history of male breast cancer Ashkenazi Jewish heritage

29. Treatment Primary treatment of invasive carcinoma when tumor size < 5 cm is lumpectomy + radiotherapy ± adjuvant therapy ± chemotherapy . Sentinel node biopsy is preferred over axillary node dissection. Always test for estrogen and progesterone receptors and HER2/ neu receptor protein . Primary treatment of inflammatory , tumor size > 5 cm, and metastatic disease is systemic therapy.

30. Breast cancer screening guidelines per the U.S.- Preventive Services Task Force (USPSTF ): • Mammogram every 1–2 years recommended for ages 50–74 . • Screening before age 50 is no longer routinely recommended . • Women < 50 should only consider mammographic screening based on high individual risk for early onset breast cancer . • Teaching breast-self exam is no l onger encouraged. • Clinical breast exams are no longer routinely advised .

31. A 68-year-old woman visits her primary care physician with a solid peanut-shaped hard mass in the upper outer quadrant of the left breast. A biopsy of the lesion reveals “infiltrating ductal breast cancer.” What is the next step in management ? a. Lumpectomy plus radiotherapy b. Modified radical mastectomy c. Modified radical mastectomy plus radiotherapy d. Neoadjuvant chemotherapy plus lumpectomy plus radiotherapy e. Tamoxifen and radiotherapy

32. Answer: A. Breast-conserving surgical therapy (lumpectomy) plus radiotherapy is the standard of care for invasive disease. There is no survival benefit with modified radical mastectomy .

33. When is breast-conserving ther apy not the answer? Pregnancy Prior irradiation to the breast Diffuse malignancy or ≥ 2 sites Is separate quadrants Positive tumor margins Tumor > 5 cm

34. When is adjuvant hormonal therapy included in management? In any hormone receptor-positive (HR+) tumors , regardless of age and regardless of menopausal status, stage, or type of tumor There is the greatest benefit when both ER+ and PR+ receptors are present. Therapy is nearly as good when there are only ER+ estrogen receptors. Adjuvant hormonal therapy has the least benefit when only PR+ receptors are present .

35. Tamoxifen competitively binds estrogen receptors. -- Five-year treatment → 50 percent decrease in the recurrence, 25 percent decrease in mortality. -- May be used in pre- or postmenopausal patients . Aromatase inhibitors ( anastrozole , exemestane , letrozole ) block peripheral production of estrogen . -- This is the standard of care in HR+ postmenopausal women (more effective than tamoxifen ). -- Does not cause menopausal symptoms but does increase the risk of osteoporosis .

36. LHRH analogs (e.g., goserelin ) or ovarian ablation ( surgical oophorectomy or external beam RT) is an alternative or an addition to tamoxifen in premenopausal women.

37. Benefits of Tamoxifen • ↓ incidence of contralateral breast cancer • ↑ bone density in postmenopausal women • ↓ fractures • ↓ serum cholesterol • ↓ cardiovascular mortality risk

38. Adverse Effects of Tamoxifen • Exacerbates menopausal symptoms • ↑↑ risk of endometrial cancer (1% in postmenopausal women after 5 yrs therapy) • ↑↑ risk of thromboembolism TIP: All women with a history of tamoxifen use and vaginal bleeding need evaluation & endometrial biopsy.

39. When is chemothera py included in management? Tumor size > 1 cm Lymph node-positive disease

40. When is trastuzumab included in management? It is indicated for metastatic breast cancer overexpressing HER2/ neu . Trastuzumab is a monoclonal antibody directed against the extracellular domain of the HER2/ neu receptor and is used to treat and control visceral metastatic sites .

41. If the case describes invasive breast cancer in an HR- negative , pre- or post menopausal woman  Give chemotherapy ± RT alone . HR- positive , pre menopausal woman Give chemotherapy ± RT + tamoxifen . HR- positive , post menopausal woman  Give chemotherapy ± RT + aromatase inhibitor