Breast Cancer: Classification & Pathogenesis

Question 1

breast cancer - defined

Answer 1

*a malignant neoplasm (usually an adenocarcinoma) of the breast
*uncontrolled growth of breast cells
*not a single disease; several types of tissue malignancy can affect the breast

Question 2

breast cancers - subclassifications

Answer 2

*2 basic categories:
1. carcinomas (originating from the epithelium of breast tissue)
-infiltrating ductal carcinoma
-infiltrating lobular carcinoma
-medullary carcinoma
-less common types (mucinous, inflammatory, metaplastic)
2. sarcomas (rare; originate from connective tissue)

Question 3

breast cancers - risk factors of inherited genetic mutations

Answer 3

*family history of breast cancer in a first-degree relative (before age 50)
*breast and ovarian cancer on same side of family or in same patient
*relative with “triple-negative breast cancer” (does not express estrogen receptor, progesterone receptor, or HER2)
*family history of bilateral breast cancer
*known breast cancer gene in family

Question 4

breast cancer genes: BRCA1 and BRCA2

Answer 4

*normal function: repair cell damage to maintain normal breast, ovarian, and other tissue cell division
*mutated genes → lose ability to repair cell damage → uncontrolled cell division → breast cancer, other cancers (ovary, colon, pancreas, skin)
*women with BRCA1 or BRCA2 mutations tend to develop breast cancer at a much younger age than average

Question 5

other heritable breast cancer mutations

Answer 5

*PALB2
*ATM
*MSH6
*PTEN
*TP53

Question 6

breast cancer - risk factors of acquired (somatic) mutations

Answer 6

*increased age
*HER2 mutations
*prolonged exposure to elevated levels of sex hormones (eg. estrogen)
*ionizing radiation exposure

Question 7

hormone receptor positive breast cancers

Answer 7

*estrogen receptor (ER) positive: breast cancer cells with estrogen receptors
*progesterone receptor (PR) positive: breast cancer cells with progesterone receptors
*can have one, both, or neither positive

Question 8

invasive ductal carcinoma of the breast

Answer 8

*most common type of breast cancer (about 75%)
*malignant epithelial cells begin forming their own neoplastic ducts among the normal ductal tissue
*characteristics: firm, fibrous, rock-hard mass with sharp margins and small, glandular, ductlike cells in desmosplastic stroma

Question 9

invasive lobular carcinoma of the breast

Answer 9

*tumors cells are not very cohesive; usually form single-file lines
*characteristics: decreased E-cadherin expression → orderly row of cells (“single file”) and no duct formation; often lacks desmoplastic response
*often bilateral with multiple lesions in the same location

Question 10

inflammatory breast cancer

Answer 10

*characteristics: dermal lymphatic space invasion → breast pain with warm, swollen, erythematous skin around exaggerated hair follicles (peau d’orange)
*poor prognosis
*often mistaken for mastitis or Paget’s disease
*usually lacks a palpable mass

Question 11

ductal carcinoma in situ (DCIS)

Answer 11

*a form of noninvasive carcinoma of the breast
*early malignancy without basement membrane penetration; usually does not produce a mass
*fills ductal lumen
*arises from ductal atypia
*often seen early as microcalcifications on mammography

Question 12

Paget disease of the breast

Answer 12

*a form of noninvasive carcinoma of the breast
*extension of underlying DCIS / invasive breast cancer up the lactiferous ducts and into the contiguous skin of nipple → eczematous patches over nipple & areolar skin
*Paget cells = intraepithelial adenocarcinoma cells

Question 13

lobular carcinoma in situ (LCIS)

Answer 13

*a form of non-invasive carcinoma of the breast
*decreased E-cadherin expression
*no mass or calcifications → incidental biopsy finding
*increased risk of cancer in EITHER breast