Journal Article

Aromatase inhibitor-induced modulation of breast density: clinical and genetic effects

Zhou, C, Li, L, Dantzer, J, Philips, S, Robarge, J, Oesterreich, S, Storniolo, A M, Henry, N L, Flockhart, D A, Nguyen, A T, Helvie, M A, Goswami, C P, Chan, H-P, Skaar, T C, Desta, Z, Pinsky, R, Khouri, N, Stearns, V, Hadjiiski, L, Hayes, D F, Rae, J M

2013

Overview

Background: Change in breast density may predict outcome of women receiving adjuvant hormone therapy for breast cancer. We performed a prospective clinical trial to evaluate the impact of inherited variants in genes involved in oestrogen metabolism and signalling on change in mammographic percent density (MPD) with aromatase inhibitor (AI) therapy. Methods: Postmenopausal women with breast cancer who were initiating adjuvant AI therapy were enrolled onto a multicentre, randomised clinical trial of exemestane vs letrozole, designed to identify associations between AI-induced change in MPD and single-nucleotide polymorphisms in candidate genes. Subjects underwent unilateral craniocaudal mammography before and following 24 months of treatment. Results: Of the 503 enrolled subjects, 259 had both paired mammograms at baseline and following 24 months of treatment and evaluable DNA. We observed a statistically significant decrease in mean MPD from 17.1 to 15.1% ( P <0.001), more pronounced in women with baseline MPD ⩾20%. No AI-specific difference in change in MPD was identified. No significant associations between change in MPD and inherited genetic variants were observed. Conclusion: Subjects with higher baseline MPD had a greater average decrease in MPD with AI therapy. There does not appear to be a substantial effect of inherited variants in biologically selected candidate genes.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 692/699/67/1347 / 692/699/67/2321 / 692/700/565/238 / Adult / Aged / Aged, 80 and over / Androstadienes - therapeutic use / Aromatase - genetics / Aromatase Inhibitors - therapeutic use / Biological and medical sciences / Biomedical and Life Sciences / Biomedicine / Breast - drug effects / Breast - metabolism / Breast - pathology / Breast cancer / Breast Neoplasms - drug therapy / Breast Neoplasms - genetics / Breast Neoplasms - metabolism / Breast Neoplasms - pathology / Cancer Research / Chemotherapy, Adjuvant - methods / Clinical Study / Clinical trials / Drug Resistance / Epidemiology / Estrogens - metabolism / Female / Gynecology. Andrology. Obstetrics / Hormone replacement therapy / Humans / Letrozole / Mammary gland diseases / Mammography / Mammography - methods / Medical research / Medical sciences / Medicine / Middle Aged / Molecular Medicine / Multiple tumors. Solid tumors. Tumors in childhood (general aspects) / Nitriles - therapeutic use / Oncology / Polymorphism, Single Nucleotide / Postmenopause - drug effects / Postmenopause - genetics / Postmenopause - metabolism / Prospective Studies / Triazoles - therapeutic use / Tumors