We utilized data from the comparison group of the Women's Healthy Eating and Living randomized trial to investigate an "a priori" hypothesis suggested by
CYP2D6 studies that
hot flashes may be an independent predictor of
tamoxifen efficacy. A total of 1551 women with early stage
breast cancer were enrolled and randomized to the comparison group of the WHEL multi-institutional trial between 1995 and 2000. Their primary
breast cancer diagnoses were between 1991 and 2000. At study entry, 864 (56%) of these women were taking
tamoxifen, and
hot flashes were reported by 674 (78%). After 7.3 years of follow-up, 127 of those who took
tamoxifen at baseline had a confirmed
breast cancer recurrence. Women who reported
hot flashes at baseline were less likely to develop recurrent
breast cancer than those who did not report
hot flashes (12.9% vs 21%, P = 0.01).
Hot flashes were a stronger predictor of
breast cancer specific outcome than age,
hormone receptor status, or even the difference in the stage of the
cancer at diagnosis (Stage I versus Stage II). These findings suggest an association between side effects, efficacy, and
tamoxifen metabolism. The strength of this finding suggests that further study of the relationship between
hot flashes and
breast cancer progression is warranted. Additional work is warranted to clarify the mechanism of
hot flashes in this setting.