Predictors of hot flashes with tamoxifen identified

NEW YORK (Reuters Health) - Genetic variants in estrogen receptors (ESR) and other clinical factors may help predict which women are likely to experience hot flashes during tamoxifen therapy, according to a report in the November 17th online issue of the Journal of Clinical Oncology.

Hot flashes are a common problem during tamoxifen therapy and are associated with treatment discontinuation, Dr. Vered Stearns from Johns Hopkins School of Medicine, Baltimore, and colleagues explain. When given as adjuvant therapy for breast cancer, completion of the full course of treatment is critical to optimally reduce the risk of disease recurrence and death.

Prior research has suggested that single nucleotide polymorphisms in ESR1 (alpha) and ESR2 (beta) may influence the occurrence certain tamoxifen side effects.

To examine this further, Dr. Stearns' team determined ESR1 and ESR2 genotypes in 297 women who were starting tamoxifen therapy. Symptom diaries completed before treatment and at 1, 4, 8, and 12 months were used to calculate a hot flash score.

Roughly 80% of subjects reported hot flashes either before treatment or at some point after starting tamoxifen.

In premenopausal women, not receiving prior chemotherapy was associated with a significant increase in the hot flash score at 4 months. By contrast, no significant change was seen in premenopausal women previously treated with chemotherapy.

In premenopausal women, an increase in ESR1 variants Pvull and XbaI CG alleles was associated with higher baseline hot flash scores. For postmenopausal women, ESR1 Pvull CC and ESR2-02 GG genotypes were tied to a 4.6-fold increase in hot flash scores at 4 months.

Conversely, the ESR2-02 AA genotype was associated with 74% reduced risk of hot flashes relative to carriage of at least one ESR2-02 G allele (p = 0.001).

In a related editorial, Dr. Carolyn J. Crandall from the University of California, Los Angeles, comments that "although it seems unlikely that routine genotype testing for the purpose of predicting hot flash symptoms will be pursued, if women are tested for ESR genotypes for other purposes, knowledge of ESR genotype may help identify women who should be carefully assessed for hot flash symptoms."

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