Breast Cancer Flashcards
Breast Cancer Risk Factors
- Hormonal factors
- Increasing age
- CA of contralateral breast/endometrium
- Radiation exposure
- Genetic susceptibility
- Diet
- Proliferative breast disease
- Males w/ Klinefelter’s
BRCA 1 and 2
- Breast cancer susceptibility genes
- Tumor suppressor genes
- Mutations of these genes predispose to breast, ovarian and even prostate cancer
- BRCA2- male breast cancer
- Ashkenazi (Eastern European) Jewish pop.
- Minority of breast cancer cases actually due to these mutationsd
HER2 Gene
- Breast Cancer susceptibility gene
- Oncogene, encodes transmembrane growth factor receptor
- Cytoplasmic tyrosine kinase is overexpressed and causes cell division
Majority of breast cancers are what type?
- ER positive
- HER2 neg.
- 50-65% of cancers
- “Luminal” type
Types of breats cancers
- ER pos., HER2 neg. (50-65%)
*“Luminal”
- HER2 pos. (20%)
*“HER2 enriched”
- ER neg. HER2 neg. (15%)
*“Basal-like”
Breast Quadrants Relationship w/ Cancer
- Symptoms:
*breast lumps
*nipple abnormalities
*discomfort
- Most breast cancer occurs in the upper outer quadrant
Symptoms of breast disease and presentations of breast cancer pie graph
Breast Cancer Mammography
Maligant lesions tend to be:
- Stellate and circular w/o calcifications (64%)
- Stellate and circular w/ calcifications (17%)
- Calcifications only (19%)
Myoepithelial Cells
- Surround glandular acini and help express secretory product into duct system
- Tend to be lost in invasive carcinoma
- Lesions that remain within the myoepithelial border are “in situ” and have not yet broke through
Most Breast Cancer Originate in the
- Terminal duct lobular unit
Ductal carcinoma in situ
- Age 50-60
- Neoplasia limited to epithelium
*neoplastic cells confined to ducts, expanding them, but not breaking into surrounding stroma
*may have central “comedo” necrosis
- Progression to invasive carcinoma is based on nuclear grade
*8-10x compared to general pop.
*evolution to invasive disease is unpredictable
- Accounts for 15-30% of all breast carcinoma
- Usually multifocal
- Excision recommended, sometimes radiation
Ductal carcinoma in situ vs. Ductal carcinoma histology
Ductal carcinoma
- Largest group of invasive breast cancers, accounting for 40-75%
- Grossly white-tan, firm, often stellate, causing puckering of surrounding tissue
- Type of adenocarcinoma in that its a glandular carcinoma presenting w/ irregularity of glands
Ductal carcinoma histological forms
- Cords, clusters, trabeculae, or solid
- Abundant cytoplasm
- Nuclei can be regular or pleomorphic
- Most cases have assoc. ductal carcinoma in situ
- Mitotic figures +/-
- Necrosis +/-
Metastatic ductal carcinoma histology
- “Cannonball” in pleural fluid typical of most metastatic adenocarcinomas
Lobular carcinoma in situ
- Avg age 53
- Present in 0.5 - 8% of benign breast biopsies
*usually not assoc. w/ microcalcifications
*risk of invasive lobular carcinoma after LCIS is 5x risk
- Watchful waiting
- If strong family history of carcinoma, can consider ipsilateral or B/L mstectomy
DCIS vs LCIS
- Distinguishing b/w DCIS and LCIS can be difficult
- E-cadherin stain:
*calcium-dependent transmebrane epithelial protein that promotes intercellular adhesion (makes cells stickier)
*abnormal function in carcinomas may facilitate detachment leading to metastasis
- Cells that express E-cadherin are less likely to metastasize b/c they’re stuck and are more cohesive
- Cells that dont have E-cadherin are more likely to metastasize
- DCIS stains strongly w/ E-cadherin, LCIS does not
Lobular Carcinoma
- 5-15% of all breast cancers
- 10-20% are B/L
- Often not well seen on mammograms
- Metastasizes to bone marrow, cerebrospinal fluid and leptomeninges GI tract, ovary, serosal surfaces, uterus more than other subtypesd
Lobular Carcinoma Histology
- Tends to form single file or targetoid streaming of the cells
- Cells may have intracytoplasmic mucin
- On E-cadherin staining, invasive lobular carcinoma will be evidenced by a lack of dye uptake
- Can have a signet ring variant where the nucleus looks like its being pushed up to the side
*tends to be more aggressive
Male Breast Cancer Characteristics
- BRCA2 mutation
- Usually ductal, as males often lack lobules or have atrophic lobules
- More likely to invade chest wall (less fat in breast)
Mucinous Carcinoma (aka colloid carcinoma)
- Well-circumscribed, crepitant to palpation
- Postmenopausal women
- Clusters of tumor cells floating in mucin
- Low incidence of metastasis
- Excellent short-term prognosis, but late recurrences
Apocrine Carcinoma
- Rare, 1-4% of all breast carcinomas
- Prognosis similar to ductal carcinoma
- Tumor cells have distinct cell margins, eosinophilic, granular cytoplasm, round nuclei, prominent nucleoli
- Glandular differentiation w/ apocrine snouts
Secretory Carcinoma
- Rare, primarily in children
- Well-circumscribed, small
- “Pushing margins”
- Vacuolated cytoplasm forming lumina containing eosinophilic secretions
- Excellent prognosis w/ 100% 5yr survival
Metaplastic Carcinoma
- Ductal carcinoma w/ sarcoma-like stroma
- Cartilagenous and/or osseous areas
- Very aggressive, hematogenous mets
Inflammatory Breast Cancer*
- Peau de orange (orange peel apperance)
- Redness, edema and induration from dermal lymphatic invasion
- Usually does not involve nipple (unlike Paget’s)
- Poor prognosis
*Take breat irritation in an older woman very seriously
Inflammatory Breast Cancer Histology
Paget’s Disease
- Crusted lesion of nipple caused by DCIS
- Often accompanied by invasive carcinoma, usually HER-2+
- Large, clear cells in epidermis
Malignant Phyllodes Tumor
- 10% of phyllodes tumors
- Rare under age 20
- Aggressive w/ local recurrence and metastasis
- Better prognosis than invasive ductal carcinoma
Malignant Phyllodes Tumor Histology
- Arborizing similar to fibradenoma, but w/ stromal overgrowth
- Sarcomatous elements
Angiosarcoma*
- Rare, <0.2% of primary breast tumors
- Women 5-10 yrs post-radiation therapy for breast carcinoma
- Chronically edematous arm after axillary lymph node dissection
- Median survival 3-6yrs
Angiosarcoma Histology
- Anastomsing vascular channels lined by atypical endothelial cells w/ pleomorphic, hyperchromatic nuclei
- Infiltrative margins
- Variable mitotic activity
- Typically high grade
Prognostic factors
- Sentinel lymph nodes
- Molecular profiles:
*estrogen and progesterone receptors
*ploidy
*HER2/neu
Sentinel lymph node staining
- Cytokeratin stain shows cluster of malignant epithelial cells in a lymph node
- Neg. sentel nodes = no axillary node dissection
Estrogen and progesterone receptors relationship to breast cancer
- Expressed by benign breast epithelial cells and over half of breast cancers
- Rectpros can bind estrogen and progesterone—> cell growth
- Expression- older women w/ lower grade tumors, better prognosis
- Better response to anti-estrogenic therapy or oophorectomy
Tamoxifen
- Drug w/ anti-estrogen effect useful for estrogen receptor expressing breast lesions
Male breast cancer is more commonly assoc. w/ what gene mutation?
- BRCA 2
What gene mutation is assoc. w/ breast cancers that are poorly differentiated and triple neg. (no estrogen, progesterone or HER-2 receptors)?
- BRCA1
Trastuzmab (Herceptin)
- Drug that can treat HER2-pos. breast cancers
- Reduces metastasis, recurrence and mortality
Poor prognostic factors
- High stage
*tumor size
*nodal and distant metastases
- High histologic grade
- Younger age
- Skin invasion
- Nipple invasion
- Angiolymphatic invasion
Luminal tumor expression
- Usually express Estrogen Receptors and/or Progesterone Receptors
- Mostly HER2 neg.
- Mostly low cell division (low Ki67)
Prognosis by histologic type
Favorable
- Tubular
- Cribiform
- Medullary
- Colloid
- Papillary
- Adenoid cystic and secretory/juvenile
Unfavorable
- Signet ring
- Basal-like
- Inflammatory
Mimics of breast cancer
- Present as a lump
- Examples:
*fibroadenoma
*Intraductal papilloma (may present w/ bloody nipple discharge)
*Lactating adenoma (beward of pregnancy related breast changes)
*Sclerosing adenosis
*Radial scar
*Traumatic fat necrosis
