The relationship between menopausal hormone therapy (HT) and breast cancer is complex and further complicated by misinformation, perception, and overgeneralization of data. These issues are addressed in this mini-review through the lens of the Women's Health Initiative (WHI) that has colored the view of HT and breast cancer. In the WHI, unopposed conjugated equine estrogen (CEE) reduced breast cancer risk and mortality. In the WHI CEE plus continuously combined medroxyprogesterone acetate (MPA) trial, although the hazard ratio (HR) was elevated it was statistically non-significant for an association between CEE + MPA and breast cancer. In fact, the increased HR was not due to an increased breast cancer incidence rate in women randomized to CEE + MPA therapy but rather due to a decreased and unexpectedly low breast cancer rate in the subgroup of women with prior HT use randomized to placebo. For women who were HT naïve when randomized to the WHI, the breast cancer incidence rate was not affected by CEE + MPA therapy relative to placebo for up to 11 years of follow-up. The current state of science indicates that HT may or may not cause breast cancer but the totality of data neither establish nor refute this possibility. Further, any association that may exist between HT and breast cancer appears to be rare and no greater than other medications commonly used in clinical medicine.

The interpretation of thyroid function tests should be cautiously made during the perimenopause and postmenopause period bearing in mind that physiologic changes do exist in this group of women in terms of secretion and metabolism of thyrotropin and thyroid hormones. Moreover the incidence of thyroid disorders increases in postmenopausal and elderly women. There is no consensus for screening postmenopausal women even though there is well-known evidence about the effect of thyroid status on cognitive function, cardiovascular risk, bone turnover, and longevity. The diagnosis of any thyroid disorder is challenging in these patients because the symptoms are more subtle and attributed to menopausal symptoms. Management requires more attention in this population than that of younger groups, because high doses of L-thyroxine can lead to cardiac complications and increased bone turnover. Furthermore radio-iodine is preferred in treatment of hyperthyroidism in older patients. The risk of nodular thyroid disease and thyroid cancers increases in this group. Although the diagnostic approach is the same as for young patients, the risk of surgery is high and disease prognosis is worse. Women with any form of thyroid disease should be treated according to the current guidelines. Decision for menopausal hormonal therapy should be individualized regardless of the concomitant presence of thyroid disorders.

Women carriers of mutations in the genes BRCA1 and BRCA2 coding for tumor suppressor proteins are at high risk of developing breast and ovarian cancers. Hereditary breast and ovarian cancers due to BRCA pathogenic mutations occur at earlier ages: mean age 43 years at diagnosis of breast cancer for BRCA1 mutations; onset of ovarian cancer up to 10-21% by age 50 years. Preventive strategies are then defined in the reproductive years. The National Comprehensive Cancer Network (NCCN) guidelines define that BRCA1/2 genetic testing should begin with the affected cancer individual (BRCA1/2 full sequencing); then, family members should be tested for the specific gene mutation found. A woman known to be a carrier needs a strict specific surveillance strategy to achieve early diagnosis. The NCCN proposes breast imageneological surveillance beginning at age 25 years; ovarian surveillance beginning at age 30-35 years. Concomitantly, risk-reducing strategies should be analyzed: surgical or pharmacological. When prophylactic bilateral salpingo-oophorectomy is performed before menopause, estrogen replacement therapy could be required. For BRCA, we review the risks of cancer in mutations carriers, criteria for genetic testing, surveillance and risk-reduction strategies, and the safety of prescribing hormone therapy when needed.