Lunenfeld-Tanenbaum Research Institute, Sinai Health System, 60 Murray Street Box 18, Toronto, ON, M6P 2G3, Canada.
Dalla Lana School of Public Health, University of Toronto, Toronto, ON, Canada.
Breast Cancer Res. 2018 Mar 22;20(1):23. doi: 10.1186/s13058-018-0948-4.
Mammographic density (MD) is an established predictor of risk of a first breast cancer, but the relationship of MD to contralateral breast cancer (CBC) risk is not clear, including the roles of age, mammogram timing, and change with treatment. Multivariable prediction models for CBC risk are needed and MD could contribute to these.
We conducted a case-control study of MD and CBC risk in phase II of the WECARE study where cases had a CBC diagnosed ≥ 2 years after first diagnosis at age <55 years and controls had unilateral breast cancer (UBC) with similar follow-up time. We retrieved film mammograms of the unaffected breast from two time points, prior to/at the time of the first diagnosis (253 CBC cases, 269 UBC controls) and ≥ 6 months up to 48 months following the first diagnosis (333 CBC cases, 377 UBC controls). Mammograms were digitized and percent MD (%MD) was measured using the thresholding program Cumulus. Odds ratios (OR) and 95% confidence intervals (CI) for association between %MD and CBC, adjusted for age, treatment, and other factors related to CBC, were estimated using logistic regression. Linear regression was used to estimate the association between treatment modality and change in %MD in 467 women with mammograms at both time points.
For %MD assessed following diagnosis, there was a statistically significant trend of increasing CBC with increasing %MD (p = 0.03). Lower density (<25%) was associated with reduced risk of CBC compared to 25 to < 50% density (OR 0.69, 95% CI 0.49, 0.98). Similar, but weaker, associations were noted for %MD measurements prior to/at diagnosis. The relationship appeared strongest in women aged < 45 years and non-existent in women aged 50 to 54 years. A decrease of ≥ 10% in %MD between first and second mammogram was associated marginally with reduced risk of CBC (OR 0.63, 95% CI 0.40, 1.01) compared to change of <10%. Both tamoxifen and chemotherapy were associated with statistically significant 3% decreases in %MD (p < 0.01).
Post-diagnosis measures of %MD may be useful to include in CBC risk prediction models with consideration of age at diagnosis. Chemotherapy is associated with reductions in %MD, similar to tamoxifen.
乳腺密度（MD）是预测首次乳腺癌风险的一个既定指标，但 MD 与对侧乳腺癌（CBC）风险的关系尚不清楚，包括年龄、乳房 X 光片检查时间以及与治疗相关的变化。需要建立用于预测 CBC 风险的多变量预测模型，而 MD 可以为此做出贡献。
我们对 WECARE 研究第二阶段的 MD 和 CBC 风险进行了病例对照研究，病例组为首次诊断年龄<55 岁后≥2 年诊断为 CBC，对照组为单侧乳腺癌（UBC）且随访时间相似。我们从两个时间点获取了未受影响乳房的胶片乳房 X 光片，第一次诊断前/时（253 例 CBC 病例，269 例 UBC 对照）和第一次诊断后≥6 个月至 48 个月（333 例 CBC 病例，377 例 UBC 对照）。乳房 X 光片被数字化，并使用 Cumulus 阈值程序测量了百分比 MD（%MD）。使用逻辑回归估计了 %MD 与 CBC 之间的关联的优势比（OR）和 95%置信区间（CI），并调整了年龄、治疗和与 CBC 相关的其他因素。线性回归用于估计在 467 名具有两个时间点乳房 X 光片的女性中，治疗方式与 %MD 变化之间的关联。
对于诊断后评估的 %MD，随着 %MD 的增加，CBC 的发生率呈统计学显著趋势（p = 0.03）。与 25%至<50%密度相比，较低密度（<25%）与 CBC 的风险降低相关（OR 0.69，95%CI 0.49，0.98）。在诊断前/时的 %MD 测量中也观察到了类似但较弱的关联。这种关系在年龄<45 岁的女性中最强，而在年龄 50 至 54 岁的女性中不存在。与第一次和第二次乳房 X 光片之间的 %MD 变化<10%相比，变化≥10%与 CBC 的风险降低呈边际相关（OR 0.63，95%CI 0.40，1.01）。与 tamoxifen 相比，他莫昔芬和化疗均与统计学上显著的 3%的 %MD 降低相关（p<0.01）。
在考虑诊断时年龄的情况下，诊断后测量的 %MD 可能有助于纳入 CBC 风险预测模型。化疗与 tamoxifen 相似，与 %MD 的降低相关。
