Breast cancer

Question 1

What is lobular carcinoma in situ?

Answer 1

incidental ddx
- incr risk breast cancer
- tx: surgical excision if diagnosed by needle biopsy. Can use tamoxifen to decrease risk breast cancer

Question 2

What is ductal carcinoma in situ?

Answer 2

cancer cells fill portions of mammary ductal system WITHOUT invading beyond duct’s basement membrane
- Stage 0 breast cancer
- imaging: pleomorphic, linear, branching calcifications
- Morphologic types: cribriform, solid, micropapillary, comedo.
- classified by morphologic type, presence of comedonecrosis and nuclear grade. Grade=most predictive of cancer/dz/recurrence
- Tx: wide excision or mastectomy. if breast conservation, radiation.

Question 3

What is Paget Disease?

Answer 3

type of DCIS - focal rash of nipple.
- ductal carcinoma cells migrate to nipple and induce skin breakdown.
- high risk underlying DCIS (2/3) and invasive cancer (1/3).
- Tx: wide excision.

Question 4

Strategies for managing breast cancer risk?

Answer 4

1. Lifestyle modification/weight loss
2. screening w/ MRI
3. Chemoprevention w/ SERM or aromatase inhibitor (tamoxifen if >35, raloxifene if post-menopausal)
4. Prophylactic surgery

Question 5

What are genetic syndromes associated with increased breast cancer risk?

Answer 5

BRCA1/2
Li-Fraumeni (p53)
Cowden (PTEN)
Peutz-Jegher (STK11)
Hereditary diffuse gastric cancer (CHD1), ATM

Question 6

What are most common forms of invasive breast cancer?

Answer 6

1st: Infiltrating ductal carcinoma (80%)
2nd: Infiltrating lobular carcinoma (15%)
Others: phyllodes tumor, sarcoma, lymphoma

Question 7

What is workup of invasive breast cancer?

Answer 7

mets sites: bone then lung/liver/brain. Need CBC, LFTs, CT, bone scan, PET.

Question 8

What is treatment of invasive breast cancer?

Answer 8

Surgery
Radiation, adjuvant chemo (doxorubicin, cyclophosphamide, cis/carboplatin to replace doxorubicin if use cardiotoxic trastuzumab)

Question 9

What are hormonal therapies for breast cancer?

Answer 9

ER-positive tumors:
Tamixofen: pre/post menopausal. SE: menopausal sx, inca risk VTE/endometrial cancer.
Anastrazole/Letrozole: incr risk bone loss (need bone mineral density testing) + bisphosphonates (Zoledronic acid).

Question 10

What are non-proliferative breast lesions?

Answer 10

• Simple cysts=most common
• cysts w/ apocrine metaplasia
  -mild hyperplasia (usual type)
• papillary apocrine change
  Cysts seen in ⅓ of women ages 35-50. Simple cysts (no septations or mural thickening) always benign and no aspiration unless bothersome

Question 11

What are proliferative breast lesions without atypia?

Answer 11

• fibroadenoma
• intraductal papilloma
• moderate/florid hyperplasia
• epithelial hyperplasia
• sclerosing adenosis
• complex sclerosing scar

Question 12

What is a fibroadenoma?

Answer 12

most common cause breast masses in adolescents/young women.
- Firm, well-circumscribed mobile mass. Look like cysts on exam
Giant fibroadenoma (>10cm) unusual variant of fibroadenomas, account for 4%. Enlarging masses that distort breasts.

Question 13

What is sclerosing adenosis?

Answer 13

type of proliferative breast lesion.
- increased #/size of glandular components within lobular units. small/mod incr risk of breast cancer

Question 14

What is an intraductal papilloma?

Answer 14

Type of proliferative breast lesion.
- tumors in lactiferous duct, centrally located near duct opening/solitary or multiple/peripherally located. Solitary ones can present as nipple discharge (bloody, serous, clear). In ages 30-50, typically small

Question 15

What are proliferative lesions WITH atypia?

Answer 15

• atypical ductal hyperplasia
• atypical lobular hyperplasia
  Management: surgical excision. DCIS or invasive cancer detected at tiem of excision in 15% of cases. Then get an annual mammogram and breast exam q6-12 months. Risk reduction w/ tamoxifen (pre/post menopausal), raloxifene, aromatase inhibitors (post menopausal).

Question 16

What is atypical lobular hyperplasia?

Answer 16

incidental finding on mammography histologic evaluation. substuntially incr risk of invasive cancer in affected and contralateral breast

Question 17

What is a tubular adenoma?

Answer 17

benign proliferators breast lesion
- glandular cells w/ minimal stromal elements. Can present as breast mass and solid on US.

Question 18

What is a phyllodes tumor?

Answer 18

uncommon fibroepithelial tumors (only 0.4%) can be benign to propensity for recurrence to sarcoma. Median age is 40, single enlarging breast mass.
- Ddx: imaging, need excisional biopsy bc look like fibroadenoma or benign tumor but can invade locally and cause distant mets.

Question 19

What is lobular carcinoma in situ?

Answer 19

incidental at time of breast biopsy. NOT precursor lesion for breast cancer like DCIS. incr risk for future cancer 10-20% chance of developing DCIS or invasive cancer in 15 years.
Risk reduction w/ tamoxifen (pre/post menopausal), raloxifene, aroatase inhibitors (post menopausal).

Question 20

What is management of nipple discharge?

Answer 20

Benign: bilateral, milky/green, multidouctal
If unilateral, uniductal, spontaneous, higher risk of malignancy
If <30, get US. If birads 1-3, duct excision
If >30, get mammogram + US. If birads 4-5, tissue biopsy

Question 21

What is tamoxifen?

Answer 21

SERM: anti-estrogen effect on breast, pro-estrogen effect on bone and endometrium. Prevents osteoporosis in post-menopausal.
- incr risk endometrial hyperplasia and VTE (decreases antithrombin 3). most common side effect=hot flushes.
Teratogenic, no pregnancy!
post-menopausal sx increases: hot flushes, vaginal dryness, decreased libido, thin vaginal discharge
pre-menopausal: menorrhagia and ovarian cysts 2/2 ovarian stimulator.
if 5 year risk breast cancer >1.7%, use tamoxifen
reduces breast cancer in BRCA2 by 60% (higher prevalence of ER-positive breast cancer with brca2 than brca1).

Question 22

What are aromatase inhibitors?

Answer 22

indicated ONLY in postmenopausal (unlike tamoxifen). side effects=joint and muscle pain, hair thinning. Incr risk fractures. incr in disease free survival!! (Better than tamoxifen).

Question 23

How is Tamoxifen used?

Answer 23

in BRCA2 carriers, can reduce risk of breast cancer by 62%
- BRCA2 more likely to be ER positive

• reduces risk by 50%! use for 5 years only.

Question 24

BRCA1 carriers are at risk for which other cancers?

Answer 24

pancreatic
ovarian
- NOT brain or melanoma (melanoma only in BRCA2!!)
- assoc w/ triple neg (ER/PR/Her 2 neu) vs. BRCA2 assoc w/ ER/PR pos.

-BRCA1/2 are tumor suppressor genes, do homologous recombination that repairs double stranded DNA breaks

Question 25

What is the lifetime risk of breast cancer?

Answer 25

12%

Question 26

facts about breast cancer

Answer 26

Ashkenazi Jews: 1 in 40 will have BRCA

Protective factors: LESS estrogen so late menarche, early menopause, breastfeeding, young age at 1st pregnancy

• RRSO reduces risk of developing breast cancer by 50%. roughly 4% of RRSO specimens will have occult malignancies.

management: age 25, annual breast MRI. age 30: annual breast MRI + mammogram