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Tamoxifen reduces density, improves survival in ER-positive breast cancer
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Women with ER-positive breast cancer who experience a decline in mammographic density after the initiation of tamoxifen may have improved prognosis regardless of age, according to study findings.
“Women with higher breast density before treatment experienced the greatest reductions in risk of death,” Gretchen L. Gierach, PhD, MPH, an investigator in the hormonal and reproductive epidemiology branch of the NCI, told HemOnc Today. “Our results, in conjunction with the literature, suggest that reductions in mammographic density may be an early indicator of the long-term effectiveness of tamoxifen and could inform decisions on continued tamoxifen therapy or a change clinical management.”
Gretchen L. Gierach
Previous studies had shown an association between reduced mammographic density after tamoxifen use and improved survival for postmenopausal women, but there were no data linking the two with premenopausal women.
Gierach and colleagues evaluated mammographic density change after tamoxifen and breast cancer death in a case-control study of 349 patients with ER-positive breast cancer. The women, who ranged in age from 32 to 87 years, underwent treatment at Kaiser Permanente Northwest in Portland, Oregon, from 1990 to 2008.
Researchers divided patients into a case group that consisted of 97 women who died of breast cancer and a control group of 252 women who did not experience breast cancer-related death. Patients were matched based on age at time of diagnosis and the stage of the disease.
The investigators measured mammographic density in the unaffected breast at baseline (mean, 6 months before tamoxifen initiation) and at follow-up (mean, 12 months after tamoxifen initiation).
Women in the tertile with the greatest percentage decline of mammographic density after tamoxifen had a lower risk for breast cancer-related death than women in the tertile with the lowest percentage decline (OR = 0.44; 95% CI, 0.22-0.88).
When adjusted for the baseline mammographic density, results were similar (OR = 0.49, 95% CI, 0.23-1.02).
Researchers observed reductions of death only among women in the middle and upper tertiles of baseline mammographic density.
Gierach and colleagues observed no differences in the association between mammographic density decline and survival based on age, duration of tamoxifen use, BMI, receipt of chemotherapy or radiation therapy, or estrogen and/or progestin use.
In total, patients who experienced more than an 8.7% reduction in mammographic density after a year of tamoxifen had a 56% lower risk for breast cancer-related death.
These data suggest that density reduction may be an early indicator of the efficacy of tamoxifen, and they could help decide whether tamoxifen should be continued or an alternate management approach should be undertaken.
Gierach and colleagues are conducting additional research to evaluate breast tumors using tissue microarrays and gene expression profile studies to determine whether certain molecular markers predict the relationship between change in density and risk for breast cancer death.
In a separate study, they are using ultrasound tomography to assess volumetric breast density repeatedly within the first year of tamoxifen use to try to determine how early in the treatment course tamoxifen-related declines may be detected.
“These studies may inform future investigations of mammographic density as a potentially modifiable ‘biosensor’ of breast cancer risk or treatment effectiveness, which may have utility in multiple populations,” Gierach said. – by Anthony SanFilippo
Disclosure: Gierach reports no relevant financial disclosures.
For more information:
Gretchen L. Gierach, PhD, MPH, can be reached at 9609 Medical Center Drive, Room 7-E108, Bethesda, MD 20892-9774; email: gierach@mail.nih.gov.
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