SAN ANTONIO — Hormone therapy is not effective for hot flashes in women on tamoxifen, Ivana Sestak, Ph.D., reported at a breast cancer symposium sponsored by the Cancer Therapy and Research Center.
This was the clear-cut conclusion of a new secondary analysis of the International Breast Cancer Intervention Study I (IBIS-I), in which 7,152 postmenopausal women at increased breast cancer risk were randomized to 20 mg/day of tamoxifen or placebo.
The new finding is unwelcome news for women on tamoxifen for breast cancer chemoprevention who find their vasomotor symptoms intolerable. Those who don't solve their problems by discontinuing tamoxifen have often turned to hormone therapy (HT) in an effort to find relief, despite the fact that HT is believed to confer a modest increase in breast cancer risk.
The primary results of IBIS-I, in which tamoxifen reduced the risk of breast cancer by one-third over 4 years, have been published (Lancet 2002;360:817–24). The new secondary analysis focused on quality of life issues, chief of which for many women on tamoxifen are vasomotor symptoms.
Indeed, 71% of women in the tamoxifen group of IBIS-I reported hot flashes during 84 months of follow-up, compared with 57% on placebo. Most were rated mild to moderate. But 12% of affected women in the tamoxifen group had severe hot flashes, a rate twice that in the placebo group, said Dr. Sestak of Cancer Research UK, London.
Menstrual irregularities and night sweats were also 33%–54% more common among tamoxifen-treated women than placebo-treated women. These vasomotor symptoms were much less of an issue than the hot flashes, as they affected only 11% and 4%, respectively, of women on tamoxifen.
HT was effective in curbing hot flashes in the placebo group. For example, among placebo-treated women who were current HT users at study entry, the prevalence of hot flashes at the 6-month follow-up visit was 23%, compared with 34% among HT-nonusers. Similarly, women in the placebo group using HT at study entry and still using it during months 6–12 had a 20% rate of hot flashes at the 12-month follow-up visit, compared with a 39% rate among women who entered IBIS-I on HT but discontinued it during the first 6 months.
In contrast, women in the tamoxifen arm who entered the trial on HT and continued using it during months 6–12 had a 48% prevalence of hot flashes at 12 months, which wasn't significantly different than the 51% rate among tamoxifen users who were on HT at entry but who quit using it during the first 6 months.
Among 2,658 women in the tamoxifen group who had never used HT or stopped prior to study entry, 43% were experiencing hot flashes 6 months into the study. Among those who went on HT at that point, the rate of hot flashes at 12 months was 74%, which wasn't significantly different than the 67% rate among non-HT users.
It was quite a different story in the placebo group. One-quarter of the 2,613 women not on HT at entry had hot flashes at 6 months. Among those who went on HT at that point, the rate of hot flashes at 12 months was 43%, compared with 65% in those who didn't.
Physicians will need to come up with an effective therapy for tamoxifen-induced vasomotor symptoms to improve adherence. Agents worthy of further study by dint of having mechanisms of action not mediated solely by estrogen levels include progestins, clonidine, tibolone, some of the selective serotonin reuptake inhibitors, and black cohosh, she added.