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Improved Prognosis for Patients With Estrogen Receptor–Positive Breast Cancer With Large Reductions in Mammographic Density After Tamoxifen Initiation

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Key Points

  • Women with estrogen receptor–positive breast cancer who experienced the highest percentage of decline in mammographic density following initiation of tamoxifen had a lower risk of breast cancer than did those with a lower percentage decline.
  • The odds ratio for the highest tertile of decline in mammographic density (> 8.7%) vs the lowest tertile (< 0.5%) was 0.44.
  • Results were similar among younger (≤ 50 years) and older (> 50 years) women.

Improved prognosis for women with estrogen receptor–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. While 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 anti-endocrine therapy,” Nyante et al wrote.

“Mammographic density reflects the fibroglandular composition of the breast, and women with the highest levels have approximately four-fold 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.”

Greatest Density Decline Linked to Lowest Risk

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 from 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% to 8.7%) did not have a lower risk of breast cancer death than did those in the lowest tertile.

Results Similar in Younger and Older Patients

“In this study, [estrogen receptor–]positive breast cancer patients who experienced greater than an 8.7% absolute reduction in mammographic percent density after approximately one year of tamoxifen treatment had a 56% lower risk of breast cancer death,” the investigators stated. “Accounting for other factors, including early tamoxifen non-adherence, 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 anti-endocrine 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.

Gretchen L. Gierach, PhD, MPH, of the National Institutes of Health, is the corresponding author for the Journal of the National Cancer Institute article.

The study was supported by the Intramural Research Program of the National Cancer Institute at the National Institutes of Health.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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