Phytoestrogens and Antioxidants -- Bits of Experimental Evidence

Highlights of the Society for Integrative Oncology 1st International Conference; November 17-19, 2004; New York, NY

Sara M. Mariani, MD, PhD

Disclosures
In This Article

Phytoestrogens and Menopausal Symptoms

The use of phytoestrogens has been proposed also for the management of menopausal symptoms in breast cancer survivors, to bypass the unwanted toxicities associated with conventional hormone replacement therapies. Estrogens, in fact, can induce proliferation of ER-positive breast cancer cells. A number of studies, however, have so far not found a significant benefit from the administration of phytoestrogens in this group of patients.[11]

Melanie Palomares,[12] of City of Hope Cancer Center, Duarte, California, presented the results of one more study addressing this potential treatment. The issue is important because breast cancer survivors represent a fairly young and numerous population: The mean age of breast cancer survivors is 51, and 1 of 8 US women has been or is affected by breast cancer. The overall prognosis for all patients (independently of tumor type and/or staging) is quite high compared with most other tumors, with a chance of survival of 85% at 5 years and of 70% at 10 years. Of note, approximately 60% to 65% of breast cancers express ERs.

Tamoxifen, a partial agonist, has antiestrogenic effects on breast and vasomotor tissues, but it had a proestrogenic effect on uterine, bone, and liver tissues. Thus, it has an inhibitory effect on breast cancer growth, but it can stimulate proliferation of cervical cancer cells. In addition, administration of tamoxifen may protect from excessive osteoporosis, but it is associated with the occurrence of hot flashes. The precise mechanisms of action of phytoestrogens on a variety of tissues are still not well characterized.

A survey done recently showed that approximately 49% of women reported the inclusion of soy in their diets for the relief of menopausal symptoms. Some of them also believed that soy might help in preventing tumor recurrence. "What can physicians say when confronted with this belief of the 'healing power of soy?'" wondered Palomares.

Studies with 90 or 150 mg/die of isoflavone[13] or 500 mL/die of soy[14] showed no toxicity but also no efficacy as compared with placebo. There was no specific effect from the administration of soy: The occurrence of hot flashes was decreased in both intervention groups (soy and placebo) during the studies.

The study reported by Dr. Palomares[12] was performed with administration of 50 mg/day isoflavone in tablets for 1 year. Biopsies, taken at baseline and at months 6 and 12, were evaluated for expression of the proliferation-associated marker Ki67 and expression of the estrogen and progesterone receptor. Mammographic density was recorded for all patients.

A total of 23 breast cancer survivors with a mean age of 57 years and a mean of 5.9 years after diagnosis of breast cancer were included in the study. Hormonal treatments and hormonally active treatments were not allowed for 3 months before the trial. Seventeen patients completed the study with an average follow-up of 9.8 months.

No statistical difference was found in the occurrence of hot flashes in isoflavone- or placebo-treated women at months 3, 9, and 12. There was, however, a short-term, statistically nonsignificant trend (at month 3 but not 12) toward a reduction in hot flashes in women receiving soy. There were no significant differences in genitourinary symptoms. Measurement of urine isoflavones showed an increase in women receiving soy vs placebo at months 6 and 12 (9.8 nM/day and 9.0 nM/day with isoflavone vs 6.3 nM/day and 6.5 nM/day, respectively with placebo).[12]

Limitations intrinsic to the study were, as noted by the presenter, the small sample size with single-institution recruitment. Nonetheless, the results of this small study appear in line with previous data, and do not support a specific benefit of soy for hot flushes in postmenopausal breast cancer survivors.[11,13,14,15]

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