PMC

Potentially distinct susceptible windows (Including before childhood, childhood, adolescence, adult before first parity, between first parity and menopause, and after menopause, and senior) of breast cells and timing of exposure to environmental carcinogens, such as lifetime exposures to second-hand smoke Including before birth, and active smoking maybe starting during adolescence, over different breast Carcinogenesis stages (cancer initiation, promotion, and progression stages) and at different ages in a woman's life.

Detoxification: hepatic cytochrome P450 (CYP) enzymes and other non-P450 enzymes, such as uridine diphosphate glucuronosyltransferase (UGT) and N-acetyltransferase-2 (NAT2), detoxify X (representative of smoking carcinogens) in the liver and form X-OH (C-hydroxyl compound) and X-Gluc (N-glucuronide conjugated compound) or X-COCH3 (N-acetyl conjugated compound), which is eliminated by urine and feces,. Exogenous hormones inhibit or compete with the CYP enzymes because exogenous hormones need the hydroxyl enzymes to eliminate them in the liver and impede the detoxification of smoking carcinogens. These compounds remain in the blood for a long time and have a high chance to be transported to breast tissue, where they would be activated by heretofore unknown N-hydroxyl enzyme in breast epithelial cells to X-OH (N-hydroxyl compound) and then form X-OSO3⁻ (O-glucuronide conjugated compound). This resultant compound would then have the ability to combine with DNA and initiate mutations in breast epithelial cells. Exogenous hormones promote mutated cell proliferation, inhibit the apoptosis of cancer cells, and may synergistically cause breast cancer. Smoking could cause ovarian diseases and, as a consequence, ovarian function disorder. Some women could take hormone replacement therapy (HRT) and some could not. This increases the complexity of smoking carcinogens in the etiology of breast cancer. Finally, breast mutated cells progress towards immortality.