Minimal impact of adjuvant exemestane or tamoxifen treatment on mammographic breast density in postmenopausal breast cancer patients: A Dutch TEAM trial analysis

Abstract

AbstrActbackground. Mammographic breast density is one of the strongest independent risk factors for developing breast cancer. We examined the effect of exemestane and tamoxifen on breast density in Dutch postmenopausal early breast cancer patients participating in the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial. Material and methods. Analogue mammograms of selected TEAM participants before start, and after one and two (and if available after three) years of adjuvant endocrine therapy were collected centrally and reviewed. Study endpoints were change in breast density over time, and correlations between breast density and locoregional recurrence (LRR), distance recurrence (DR), and contralateral breast cancer (CBC). results. Mammograms of 378 patients (181 tamoxifen, 197 exemestane) were included in the current per protocol analyses. Baseline breast density was low (breast density score  50% in 75% of patients) and not different between patients randomised to exemestane or tamoxifen (coefficient 0.16, standard error 0.17). Breast density did not change during treatment in exemestane (p  0.25) or tamoxifen users (p  0.59). No relation was observed between breast density and the occurrence of a LRR [hazards ratio (HR) 0.87, 95% CI 0.45-1.68, p  0.67], a DR (HR 1.02, 95% CI 0.77-1.35, p  0.90), or CBC (HR 1.31, 95% CI 0.63-2.72, p  0.48). conclusion. The in general low breast density score in early postmenopausal breast cancer patients did not substantially change over time, and this pattern was not different between tamoxifen and exemestane users. Breast density was not a predictive marker for efficacy of adjuvant endocrine therapy.

Mammographic density: a potential monitoring biomarker for adjuvant and preventative breast cancer endocrine therapies

“…Risk reductions were uniformly significant and robust for disease free survival (DFS) (0.36-0.52) and overall or BC specific survival (0.44-0.50), although these trials involved mostly tamoxifen and were mostly in younger women. One study failed to demonstrate an association between MD reduction and lowering of recurrence events in response to exemestane or tamoxifen in post-menopausal women, although the MD changes were small [59]. Contrary to this, the studies of Kim et al [57] and interim analysis of a study by members of our group [58], found MD reduction to be a predictor of outcome in mixed tamoxifen and AIs treated cohorts.…”

“…The detailed results however are yet to be reported in the final analysis [58]. In contrast, in the study of Van Nes et al of patients from the prospective TEAM study, infrequent MDRs and a lack of correlation with outcome were observed [59]. The reason for this heterogeneity is unclear.…”

“…The most common AIs in general use, and used in the study of Kim et al, are the non-steroidal AIs (NSAIs) letrozole and anastrozole. In contrast, the negative study [59] employed exclusively exemestane. Inter-agent differences in effect on MD are thus a possibility although efficacy differences have not been seen in head-to-head trials between AIs.…”

Dense breast tissue in postmenopausal women is associated with a pro-inflammatory microenvironment in vivo

“…26 AIs exhibit a greater reduction in breast cancer risk and recurrence rates compared with tamoxifen; however, tamoxifen exerts a greater reduction of mammographic density compared to AIs. [25][26][27][28] This suggests that a quantitative imaging technique with a direct measurement of the breast composition, as described in the present study, may be necessary as a surrogate in the development of breast cancer preventive therapeutics.…”

“…24 The effects on mammographic density between these therapies are, however, somewhat different; tamoxifen seems to reduce mammographic density, whereas AI have lesser effect. [25][26][27][28] Anti-estrogen therapies are associated with severe side-effects and decreased quality of life and the adherence of these therapeutics is very low. 29,30 Hence, other less toxic prevention therapies, that may include anti-inflammatory treatments, need to be developed.…”