Breast Flashcards
Epithelial breast lesions and risk of developing invasive carcnioma
Risk Factors for Developing Breast Cancer
Mutations in BRCA1 and BRCA2 are responsible for x% to x% of single gene familial breast cancers and about x% to x% of all breast cancers.
Approximately x of breast cancers are familial, being related to inheritance of genetic variants that increase breast cancer risk.
Mutations in BRCA1 and BRCA2 are responsible for 80% to 90% of single gene familial breast cancers and about 3% to 6% of all breast cancers.
Approximately a quarter to a third of breast cancers are familial, being related to inheritance of genetic variants that increase breast cancer risk.
High and low penetrance germline mutations in breast cancer
Luminal (ER-positive/HER2-negative) cancers arise via the dominant pathway of breast cancer development, constituting x% to x% of cases.
Luminal (ER-positive/HER2-negative) cancers arise via the dominant pathway of breast cancer development, constituting 50% to 65% of cases.
Breast cancers cluster into three major molecular groups
Luminal (ER-positive), HER2, and triple negative, each with distinctive biologic and clinical features.
- Luminal cancers are further divided into two groups, A and B, that differ mainly in terms of proliferation, which is low in group A and high in group B.
- HER2 cancers are defined by overexpression of the HER2 receptor, usually due to HER2 gene amplification, and respond well to HER2 inhibitors.
- TNBCs lack ER and HER2 expression, are often associated with defects in DNA repair or genomic stability (e.g., due to silencing of BRCA1 or TP53 mutation), and carry a relatively poor prognosis.
DCIS grows in several architectural patterns. Name them.
Some cases of DCIS have a single growth pattern, but most are comprised of a mixture of patterns.
Comedo DCIS may occasionally produce a vague nodularity, but more often is detected as clustered or linear and branching areas of calcification. It is defined by two features: (1) tumor cells with pleomorphic, high-grade nuclei and (2) areas of central necrosis
Non-comedo:
- Cribriform DCIS has rounded (cookie cutter–like) spaces, often filled with calcified secretory material.
- Micropapillary DCIS produces complex bulbous protrusions without fibrovascular cores.
- Papillary DCIS produces true papillae with fibrovascular cores that lack a myoepithelial cell layer.
Paget disease of the nipple
Rare manifestation of breast cancer (1% to 4% of cases) that presents as a unilateral erythematous eruption with a scale crust.
Pruritus is common, and the lesion may be mistaken for eczema.
Malignant cells (Paget cells) extend from DCIS within the ductal system via the lactiferous sinuses into nipple skin without crossing the basement membrane.
A palpable mass is present in 50% to 60% of women with Paget disease, and almost all of these masses prove to be invasive carcinoma.The carcinomas are usually ER-negative and overexpress HER2. In contrast, the majority of women without a palpable mass have only DCIS. Prognosis depends on the features of the underlying carcinoma and is not affected by the presence or absence of Paget disease.
TNBC (ER-negative, HER2-negative) often corresponds to one of several special histologic types. Chief among these is …
Carcinoma with medullary pattern.
These carcinomas are softer than other carcinomas (medulla is Latin for “marrow”) due to minimal desmoplasia and often form well-circumscribed masses. Histologic features include (1) solid sheets of large cells with pleomorphic nuclei and prominent nucleoli, (2) frequent mitotic figures, (3) a moderate to marked lymphoplasmacytic infiltrate surrounding and within the tumor, and (4) a pushing (noninfiltrative) border
DCIS is minimal or not seen.
Significance of inflammatory carcinoma?
Has a characteristic gross appearance caused by extensive plugging of the lymphovascular spaces of the dermis with carcinoma cells and carries a very poor prognosis, as most patients prove to have distant metastases.
It presents as breast erythema, swelling, and skin thickening. The edematous skin is tethered to the breast by Cooper ligaments and mimics the surface of an orange peel, an appearance referred to as peau d’orange.
The name “inflammatory” is a misnomer, as typically no inflammation is present. The underlying carcinoma is usually diffusely infiltrative and typically does not form a discrete palpable mass. The presentation can be confused with a breast infection, leading to delayed diagnosis. These tumors are usually of high grade but do not belong to any particular molecular subtype.
Most important prognostic factors in breast cancer
The most important familial factor conferring an increased risk for male breast cancer?
Germline mutation of the BRCA2 tumor suppressor gene
Some special histologic types of cancer almost always fall within the luminal (ER-positive/HER2-negative) group. These include:
lobular carcinoma, mucinous carcinoma, tubular carcinoma, and papillary carcinoma.
Two special histologic types frequently overexpress HER2.
Apocrine carcinoma
Micropapillary carcinoma
TNBC (ER-negative, HER2-negative) often corresponds to one of several special histologic types.
Carcinoma with medullary pattern.
Metaplastic carcinoma
Secretory carcinoma - more favorable prognosis