Incidence of Outcomes Per 1,000 Women continued...
Studies of the harms of prophylactic mastectomy have been retrospective. Most women reported relief of anxiety about breast cancer, and few were dissatisfied with their choice to undergo the procedure. A higher dissatisfaction rate occurred among women who chose reconstruction over those who did not.
Women at high risk due to BRCA1 or BRCA2 gene mutations who had prophylactic oophorectomies to prevent ovarian cancer were found to have a lower incidence of breast cancer than age-matched mutation carriers who did not undergo prophylactic oophorectomy.[112,113,114] The reported reductions in RR were approximately 50%. These observational studies, however, are confounded by selection bias, family relationships between patients and controls, indications for oophorectomy, and inadequate information about hormone use. A prospective cohort study has confirmed a reduction in breast cancer risk by about 50% with prophylactic oophorectomy, and a greater reduction in BRCA2 mutation carriers than in BRCA1 carriers.
These findings are similar to those for women who undergo castration for nononcologic diagnoses. Women treated with thoracic radiation who undergo radiation therapy or chemotherapy, which often results in ovarian ablation, also have similar findings.
A multicenter phase III RCT of fenretinide versus no treatment was performed in 2,867 women who received local therapy for stage 0 (DCIS) or stage I (T1–T2, N0, M0; T = tumor, N = node, M = metastasis) breast cancer. An analysis at 8 years showed no difference in contralateral or ipsilateral breast cancer, but a post hoc analysis revealed differential effects for premenopausal and postmenopausal women. A subsequent analysis at 15 years of the 1,739 women enrolled at the organizing center confirmed the beneficial effect in premenopausal women, reducing both contralateral and ipsilateral cancers, HR = 0.62 (95% CI, 0.46–0.83). This beneficial effect was age dependent, with the youngest women achieving the most benefit. Although the daily fenretinide 200 mg was withheld for 3 days each month, there was a cumulative incidence of low-grade dark adaptation (i.e., night blindness) and dermatologic disorders. As with any vitamin A analog, women taking this drug should avoid pregnancy because of potential teratogenic effects.