Mammographic Density After Tamoxifen Initiation Linked to Improved Prognosis for Pre- and Postmenopausal Women With ER-Positive Breast Cancer

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An improved prognosis for women with estrogen receptor (ER)-positive breast cancer who experience a large reduction in mammographic density following the initiation of tamoxifen treatment extends to premenopausal as well as postmenopausal women, researchers reported in the Journal of the National Cancer Institute. Although a previous analysis linked decline in mammographic density following initiation of tamoxifen with improved survival in postmenopausal women, this more recent evaluation of change also showed improved survival in premenopausal women, “for whom tamoxifen is the primary antiendocrine therapy,” Sarah J. Nyante, MD, and colleagues wrote. Dr. Nyante is currently affiliated with the University of North Carolina but was previously associated with the National Cancer Institute, which supported the study.

“Mammographic density reflects the fibroglandular composition of the breast, and women with the highest levels have approximately fourfold higher breast cancer risk compared with women with the lowest density,” the investigators noted. “Emerging evidence,” they added, “indicates that density reductions specifically among tamoxifen users may predict treatment effectiveness in adjuvant and chemopreventative settings, which could have value for planning long-term treatment.”

The case-control study included 349 estrogen receptor–positive breast cancer patients, aged 32 to 87 years, who were treated with tamoxifen at Kaiser Permanente Northwest in Portland, Oregon, between 1990 and 2008: 97 who died of breast cancer (case patients) and 252 who did not (control patients), matched on age and year at diagnosis and disease stage. The mean age at diagnosis was 59 years. Mammographic density in the unaffected breast was measured at baseline (with a mean of 6 months before tamoxifen initiation) and again at a mean of 12 months after tamoxifen was started.

“Absolute change in percent density ranged from a 41.7% reduction to a 17.2% increase, with smaller changes among case patients (mean, 3.1% reduction) than control patients (mean, 5.2% reduction),” the researchers reported. Patients with the highest percentage of decline in mammographic density had a lower risk of breast cancer than did those with a lower percentage decline. The odds ratio (OR) for the highest tertile of decline in mammographic density (> 8.7%) vs the lowest tertile (< 0.5%) was 0.44 (95% confidence interval [CI] = 0.22–0.88). Results were similar after adjustment for baseline mammographic density (OR = 0.49, 95% CI = 0.23–1.02). Patients in the middle tertile of density change (0.5%–8.7%) did not have a lower risk of breast cancer death than did those in the
lowest tertile.

Study Implications

“In this study, estrogen receptor–positive breast cancer patients who experienced greater than an 8.7% absolute reduction in mammographic percent density after approximately 1 year of tamoxifen treatment had a 56% lower risk of breast cancer death,” the investigators stated. “Accounting for other factors, including early tamoxifen nonadherence, tamoxifen use duration, other adjuvant treatments, and antidepressant use, did not alter the results.

Furthermore, results were similar among younger (≤ 50 years) and older (> 50 years) women.” This similarity among younger and older women “reinforces the clinical relevance of these findings, as tamoxifen is the primary antiendocrine treatment available to the former group, whereas use has diminished among the latter,” the authors noted.

Confirming these findings with studies involving large numbers of estrogen receptor–positive premenopausal women “could support monitoring of mammographic density as an approach for assessing tamoxifen effectiveness,” the investigators wrote. ■

Nyante SJ, et al: J Natl Cancer Inst 107:dju425, 2015.