Increased mammographic density (MD) has been shown beyond doubt to be a marker for increased breast cancer risk, though the underpinning pathobiology is yet to be fully elucidated. Estrogenic activity exerts a strong influence over MD, which consequently has been observed to change predictably in response to tamoxifen anti-estrogen therapy, although results for other selective estrogen receptor modulators and aromatase inhibitors are less consistent. In both primary and secondary prevention settings, tamoxifen-associated MD changes correlate with successful modulation of risk or outcome, particularly among pre-menopausal women; an observation that supports the potential use of MD change as a surrogate marker where short-term MD changes reflect longer-term anti-estrogen efficacy. Here we summarize endocrine therapy-induced MD changes and attendant outcomes and discuss both the need for outcome surrogates in such therapy, as well as make a case for MD as such a monitoring marker. We then discuss the process and steps required to validate and introduce MD into practice as a predictor or surrogate for endocrine therapy efficacy in preventive and adjuvant breast cancer treatment settings.
Keywords: breast cancer; endocrine therapy; mammographic density; predictive biomarker; surrogate.