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
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 [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 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
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postmenopausal women: Effects on cognitive function and dementia.
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