Vaginal Health During Aromatase Inhibitor Therapy for Breast Cancer

To the Editor The article by Melisko and coworkers and the accompanying Editorial by Reeder-Hays and Muss highlight an important issue for patients who take long-term adjuvant aromatase inhibitor (AI) therapy to avoid death from breast cancer. Vaginal atrophy and dryness are addressed using a 12-week safety period for an estradiol-releasing vaginal ring or an intravaginal testosterone cream. Results were improved clinically, but Reeder-Hays and Muss appropriately ask, "How safe is safe enough?" This question may be answered soon by the results of the Study of Letrozole Extension (SOLE). The trial is a 5-year AI extension of adjuvant antiestrogen therapy that compares a 12-week drug holiday annually for 4 years with continuous adjuvant AI treatment to determine whether intermittent AI adjuvant therapy (or, looked at differently—intentional annual noncompliance) will reduce recurrences and contralateral breast cancer. The hypothesis that is addressed is whether the woman's own circulating estrogen will return during the 12-week drug holiday to kill vulnerable micrometastases by means of estrogen-induced apoptosis. If there are no difference between continuous and intermittent arms with AI therapy, this will indicate that a woman's own estrogen, in the short term, is not adequate to kill vulnerable breast cancer cells; either longer drug holidays are necessary or the administration of estrogen may be required to kill cancer cells. This latter scenario is supported by numerous facts. We know from the laboratory that low-dose estrogen causes apoptosis in estrogen-deprived breast cancer cells. In the clinic, estrogen alone reduces breast cancer incidence in the Woman's Health Initiative. In addition, low-dose estrogen, when used as a salvage therapy in metastatic breast cancer, causes a 30% clinical benefit rate after AI failure.

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