Hormone replacement therapy for breast cancer survivors: Facts versus fears

Abstract

The 'standard of practice' has been to prohibit breast cancer survivors from using hormone replacement therapy (HRT). However, in the last two decades there has been ever increasing evidence that postmenopausal ERT (oestrogen replacement therapy) protects against osteoporosis and ischaemic heart disease. This author believes firmly that a reappraisal of the 'standard of practice' is essential and long overdue. The search for a prospective randomized study addressing this critical issue has been difficult and, to date, fruitless. The practitioner must at present utilize indirect evidence in helping patients to make a decision on this very important aspect of health and wellness for breast cancer survivors. In 1896, Beatson [1] reported a clinical response in a premenopausal patient with metastatic breast cancer following oophorectomy. Multiple subsequent reports of hormonal manipulation, including adrenalectomy and the use of adjunctive hormones, have played a role in the treatment of advanced breast cancer since that time. However, the response to hormonal manipulation has been variable and at times confusing. Administration of oestrogens and progestins, as well as ablative procedures, have yielded responses in about 30% of unselected cases and in nearly 50% of patients with positive ERs (oestrogen receptors). Large studies have shown that, while the overall response rate for drugs such as tamoxifen, remains at 30%, this figure climbs to 75% if the oestrogen receptor value is greater than 100 fm/ mg of cytosol protein. These responses have a mean duration of 12 months, yet other patients show a similar response to additive hormone therapy. Conjugated oestrogens at high doses of 10 mg t.i.d, will produce a 30% clinical response rate in unselected postmenopausal patients with metastatic breast cancer. These responses also last approximately 12 months. In ER-positive patients, the response rate is 50%, similar to that seen in antioestrogen therapy. Some ER-negative tumours respond to hormonal manipulation as well as to tamoxifen therapy, suggesting another mode of action is operational in addition to binding at receptive sites, at least in some patients. In 1989, Wile and DiSaia [2] suggested that, in the absence of a prospective study of ERT in breast cancer survivors, one could analyse situations in which these patients were inadvertently exposed to high levels of oestrogen at times when they may have been harbouring breast cancer cells. These situations were defined as pregnancy coincident with breast cancer, pregnancy subsequent to breast cancer, breast cancer in both previous and current users of oral contraceptives (OCs), and breast cancer in postmenopausal women receiving ERT. Currently, approximately 185 000 cases of breast cancer occur in the United States annually. As 67% of these patients will survive this devastating disease to experience old age, we must address the advisability of HRT in this setting.