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BREAST CANCER / CARCINOMA Is a heterogeneous disease with a wide array of histology appearances.

s. Risk factors:: Gender ::: only 1% of breast cancer occurs in men Age ::: breast cancer is very rare before the age of 25 Age at menarche ::: women who reach menarche when younger than 11 years old have a 20% increased risk compared with women who are more than 14 years old at menarche. Late menopause also increased risk. Age at first live birth ::: women who experience a first full term pregnancy at ages younger than 20 years have half the risk of the nulliparous women (women that never having given birth to a child) or women over the age of 35 at their first birth. It is because that pregnancy results in terminal differentiation of milk producing luminal cells, removing them from the potential pool of cancer precursors. First degree relatives with breast cancer ::: the risk of breast cancer is increased with the number of affected first degree relatives (mother, sister, or daughter), especially if the cancer is occurred in young aged. Obesity ::: there is decreased risk in obese woman younger than 40 years as a result of the association with the anovulatory cyclesand lower progesterone levels late in the cycle. In contrast, the risk will increased for postmenopausal obese woman, which is attributed to the synthesis of estrogens in fat depots. Breastfeeding ::: the longer woman breastfeed, the greater the reduction in risk. Environmental toxins ::: such as organochlorine pesticides have estrogenic effects on humans. Breast carcinomas can be divided into hereditary breast cancer and sporadic breast cancer. Most common single gene mutations associated with heredity susceptibility to breast cancer ::: BRCA1 (17q21) Familial breast and ovarian cancer (1 in 860) Function ::: tumor suppressor, transcriptional regulation, repair of dsDNA breaks. Other associated cancer ::: ovarian, male breast cancer (but lower than BRCA2), prostate, pancreas, and fallopian tube. BRCA2 (13q12-13) Familial breast and ovarian cancer (1 in 740) Function ::: same with BRCA1

Other associated cancer ::: ovarian, male breast cancer, prostate, pancreas, stomach, melanoma, gallbladder, bile duct, and pharynx P53 (17p13.1) Li-fraumeni (1 in 5000) Functions ::: tumor suppressors with critical roles in cell cycle control, DNA replication, DNA repair, and apoptosis. Is the most commonly mutated in sporadic breast cancer Other associated cancer ::: sarcoma, leukemia, brain tumor, adrenocortical carcinoma. CHEK2 (22q12.1) Li-fraumeni variant (1 in 100) Function ::: cell cycle checkpoint kinase, recognition and repair of DNA damaged, activates BRCA1 and p53 by phosphorylation. May increased risk for breast cancer after radiation exposure. Other associated cancer ::: prostate, thyroid, kidney, and colon. PTEN (cowden syndrome), LKBI/STK11 (peutz-jeghers syndrome), and ATM (ataxia telangiectasia) ::: mutated tumor suppressor gene ( <1% of all breast cancer) Sporadic breast cancer is most commonly caused by hormone exposure. And mostly occur in post menopausal women.