BRCA -1 Breast Cancer 1,Early onset ( Chr.17) BRCA-2, Breast Cancer 2,Early onset( Chr.13) p53( Chr.17) CHEK2( Chr. 22)
DNA Repair of double stranded breaks
Stability of the human genome
DNA double strand break repair.
Cell cycle control
Cell cycle checkpoint kinase, recognition and repair of DNA damage.
Activates BRCA1 and p53 by phosphorylation
Germline point mutations/Deletions of BRCA1 gene Hereditary breast & ovarian cancers. Mutations 20% Hereditary breast cancer, ovarian cancer, increased cancer risk in male carriers. Mutations Sporadic breast cancers. Li fraumeni syndrome Mutations - rare (<5%). Li fraumeni variant Increase breast cancer risk after radiation exposure
Most DCIS detected by calcifications on mammography /mammographic density - periductal fibrosis surrounding a DCIS/rarely palpable mass/ nipple discharge/incidental finding on a biopsy for another lesion.
Spreads through ducts & lobules extensive lesions entire sector of a breast.
DCIS – involves lobules – acini distorted, unfolded appear as small ducts.
Palpable mass/ mammographic density with irregular borders. Sometimes - tumor infiltrates the tissue diffusely – little desmoplasia, not palpable, no mammographic density. Metastases – difficult to detect.
Bilateral - 5 – 10 %.
Biallelic loss of expression of ( CDH1 , encodes E-cadherin ) d/t mutations.
Prognosis – determined by pathologic examination of primary carcinoma & axillary lymph nodes.
American Joint Committee on Cancer (AJCC) staging system divides patients into five stages (O to IV) correlated with survival.
Major prognostic factors strongest predictors of death.
Invasive vs insitu CA.
Lymph node metastasis
Locally advanced ds.
Stage T: Primary Cancer Lymph Nodes (LNs) M: Distant Metastasis 5-Year Survival (%) 0 DCIS or LCIS No metastases Absent 92 I Invasive carcinoma ≤2 cm No metastases Absent 87 II Invasive carcinoma >2 cm No metastases Absent 75 Invasive carcinoma <5 cm 1 to 3 positive LNs Absent III Invasive carcinoma >5 cm 1 to 3 positive LNs Absent 46 Any size invasive carcinoma ≥ 4 positive LNs Absent Invasive carcinoma with skin or chest wall involvement or inflammatory carcinoma 0 to >10 positive LNs. Absent IV Any size invasive carcinoma Negative or positive lymph nodes Present 13
In pericanalicular histologic pattern, the glands maintain their round or oval profiles. There is no prognostic or clinical significance attached to the pericanalicular and intracanalicular patterns. Both may be seen within the same lesion.
Majority palpable masses, few found by mammography.
Cystosarcoma phyllodes – Misnomer.
MORPHOLOGY : Few cms. to massive lesions involving the entire breast Larger lesions bulbous protrusions d/t the presence of nodules of proliferating stroma covered by epithelium . Some tumors - protrusions extend into a cystic space.
Cirrhosis of liver, Increased adrenal estrogens as androgenic functions of testis fail in very aged, Drugs – alcohol, marijuana, heroin, ART, anabolic steroids used by atheletes & body builders, Klinefelter syndrome.
D/t imbalance between estrogens, stimulate breast tissue and androgens which counteract these effects
Unilateral or bilateral
Button-like subareolar enlargement.
Morphology : Increase in dense collagenous connective tissue, marked micropapillary epithelial hyperplasia of the duct lining. Individual epithelial cells fairly regular, columnar to cuboidal cells with regular nuclei. Lobule formation is rare.