Symptoms related to estrogen deficiency are among the most common complaints that postmenopausal breast cancer patients bring to the attention of oncologists. Menopause develops in these patients either naturally or prematurely as a result of cancer chemotherapy and/or endocrine therapy.
The majority of newly diagnosed breast cancer patients present with early-stage disease will receive a recommendation for some form of adjuvant therapy that has the potential to cause premature menopause. Furthermore, most new breast cancer diagnoses occur in postmenopausal women who would otherwise be candidates for hormone replacement therapy (HRT). Thus, the issues outlined by Castiel are among the most important concerns facing breast cancer survivors.
Potential Benefits of HRT
Although recurrence is often foremost on the minds of breast cancer patients, other common medical conditions are more likely to cause morbidity and mortality in the postmenopausal population. Coronary artery disease and osteoporosis are the most prevalent and underappreciated medical problems facing women during and after menopause.
As outlined by Castiel, randomized trials have shown that hormone replacement prevents osteoporosis. Also, HRT can reduce the incidence of myocardial infarction by 30% to 70% in women undergoing natural menopause. The latter effect of HRT is attributed to favorable alterations in lipoproteins (ie, increased high-density lipoprotein cholesterol [HDL-C] and decreased lipoprotein[a] and plasminogen activator inhibitor-1 [PAI-1]) that retard the progression of atherogenesis.
Hot flashes and symptoms related to atrophic vaginitis (irritation, itching, and dyspareunia) are the symptoms that most directly affect the quality of life of menopausal women. Hormone replacement therapy can improve or eradicate these symptoms almost immediately. More recent data suggest that HRT may reduce the risk of dementia and, possibly, the incidence of colon cancer.
Is HRT Safe to Use in Breast Cancer Survivors?
If hormone replacement is so beneficial for so many conditions that commonly develop in postmenopausal women, how did the dogma that HRT should be avoided at all costs in breast cancer survivors evolve? Actually, the clinical data demonstrating that hormone replacement is detrimental in this patient population are sparse or nonexistent. Small studies have shown that the proliferative index of hormone-responsive breast tumors (gross tumor mass) can increase under the influence of estrogen, but whether that has an adverse impact on outcome has not been demonstrated.
Furthermore, the small pilot studies of HRT in breast cancer survivors (most with early-stage disease) do not suggest a rate of recurrence any greater than what would be expected in patients not receiving hormone replacement. The difficulty of assessing the safety of HRT in breast survivors is highlighted by a study conducted by Vassilopoulou-Sellin and colleagues. Two-thirds of patients were unwilling to participate in such a study either because of safety concerns or the requirements of the clinical trial.
Assessing the safety of HRT in breast cancer survivors remains an important and challenging issue to address in clinical trials. The clinical end points that will need to be evaluated include breast cancer recurrence rates and disease-specific survival. Of equal importance will be inclusion of quality-of-life measures that carefully assess the impact of hormone replacement on bone density, cardiovascular events, hot flashes, and vaginal symptoms.
A reality that all oncologists face is the widespread use of alternative therapies by our patients as treatment for common menopausal symptoms. The use of alternative therapies that have not been carefully evaluated may interfere with more conventional therapy (ie, tamoxifen(Drug information on tamoxifen) [Nolvadex]), and these therapies represent a large out-of-pocket expense to patients.
It has recently been suggested that the use of alternative therapies reflects greater anxiety on the part of some breast cancer survivors. It certainly also reflects an effort to attenuate or eliminate symptoms that physicians have failed to improve. Rather than simply endorsing the use of these compounds by silent acquiescence or, alternatively, suggesting that they have no value, clinicians should press for the initiation of clinical trials that objectively and quantitatively assess the efficacy of alternative therapies.
Conventional Medications That May Relieve Symptoms
Several conventional medications have been used in an effort to attenuate symptoms related to estrogen deficiency, particularly hot flashes. In patients receiving tamoxifen, progestins have been added to reduce the intensity and frequency of hot flashes. This combined endocrine therapy may not be deleterious, but it is possible that progestins may attenuate the activity of tamoxifen. In older trials evaluating combined endocrine therapy in patients with metastatic breast cancer, tamoxifen plus megestrol(Drug information on megestrol) acetate (Megace) had less antitumor activity than tamoxifen alone. 
Other compounds, such as the antidepressants, have also been reported to reduce hot flashes. Clinicians should be rigorous in trying to objectively assess the efficacy of these medications so as to avoid unneeded polypharmacy in their patients.
As therapy for breast cancer improves, patients can realistically expect to live longer. As the risk of breast cancer recurrence recedes, our ongoing challenge will be to improve patients quality of life by focusing on symptoms that have a major impact on day-to-day activities.