Tbl Flashcards
Breast cancer
Breast cancer is the most common non-skin malignancy in women and the second most common cause of cancer deaths in the United States.
Risk Factors
The most important risk factors for sporadic cancers in women are estrogenic stimulation and age.
Familial Breast Cancer
Approximately a quarter to a third of breast cancers are familial, being related to inheritance of genetic variants that increase breast cancer risk.
High-risk Genes
High-risk genes associated with familial breast cancer include several involved with DNA repair and genomic stability, most notably BRCA1, BRCA2, and TP53.
Breast Cancer Groups
Breast cancers cluster into three major molecular groups, luminal (ER-positive), HER2, and triple negative, each with distinctive biologic and clinical features.
Luminal Cancer
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 Cancer
HER2 cancers are defined by overexpression of the HER2 receptor, usually due to HER2 gene amplification, and respond well to HER2 inhibitors.
Triple Negative Breast Cancer
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.
Comedo DCIS
May occasionally produce a vague nodularity, but more often is detected as clustered or linear and branching areas of calcification. Defined by two features: (1) tumor cells with pleomorphic, high-grade nuclei and (2) areas of central necrosis.
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
A 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.
Paget Cells
Malignant cells extend from DCIS within the ductal system via the lactiferous sinuses into nipple skin without crossing the basement membrane.
Tumor Cells
The tumor cells disrupt the normal epithelial barrier, allowing extracellular fluid to seep out onto the nipple surface.
Detection
Paget cells are readily detected by nipple biopsy or cytologic preparations of the exudate.
Palpable Mass
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.
Invasive Carcinoma in paget disease
The carcinomas are usually ER-negative and overexpress HER2.
Without Palpable Mass
The majority of women without a palpable mass have only DCIS.
Prognosis
Prognosis depends on the features of the underlying carcinoma and is not affected by the presence or absence of Paget disease.
Lobular Carcinoma and cell cohesion
Loss of cellular adhesion is due to dysfunction of E-cadherin, a transmembrane protein that contributes to the cohesion of normal epithelial cells in the breast and other glandular tissues.
E-cadherin Function
E-cadherin functions as a cellular adhesive and as a tumor suppressor protein and may be lost due to neoplasticism actions.
Gene mutation for E-cadherin Loss
Loss of E-cadherin can occur through various mechanisms, including mutation of the E-cadherin gene (CDH1).
LCIS Cell Characteristics
LCIS consists of a uniform population of cells with oval or round nuclei and small nucleoli involving ducts and lobules. Mucin-positive signet ring cells are commonly present.
