Breast Oncology Program, University of Michigan Comprehensive Cancer Center, 1500 East Medical Center Drive, Med Inn Building C450, Ann Arbor, MI 48109-5843, USA.
Br J Cancer. 2013 Oct 29;109(9):2331-9. doi: 10.1038/bjc.2013.587. Epub 2013 Oct 1.
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.
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.
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.
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.
乳腺密度的变化可能预测接受乳腺癌辅助激素治疗的女性的结局。我们进行了一项前瞻性临床试验，以评估参与雌激素代谢和信号转导的基因中的遗传变异对芳香酶抑制剂（AI）治疗期间乳腺 X 线摄影百分比密度（MPD）变化的影响。
入组了正在接受辅助 AI 治疗的绝经后乳腺癌女性，她们参加了一项多中心、随机临床试验，比较依西美坦与来曲唑，旨在鉴定 AI 诱导的 MPD 变化与候选基因中单核苷酸多态性之间的相关性。在治疗 24 个月前后对受试者进行单侧头尾位乳腺 X 线摄影。
在入组的 503 名受试者中，有 259 名受试者在基线和 24 个月治疗后都有双侧乳腺 X 线摄影且可评估 DNA。我们观察到 MPD 的平均从 17.1%下降到 15.1%（P<0.001），基线 MPD≥20%的女性更明显。在 MPD 变化方面，未发现 AI 特异性差异。未观察到 MPD 变化与遗传变异之间存在显著关联。
基线 MPD 较高的受试者接受 AI 治疗后 MPD 平均下降幅度更大。在生物学选择的候选基因中，遗传变异似乎没有明显的影响。
