School of Public Health, University of Haifa, Haifa, Israel.
Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA.
Breast Cancer Res Treat. 2021 May;187(1):215-224. doi: 10.1007/s10549-020-06049-8. Epub 2021 Jan 4.
We evaluated the association of percent mammographic density (PMD), absolute dense area (DA), and non-dense area (NDA) with risk of "intrinsic" molecular breast cancer (BC) subtypes.
We pooled 3492 invasive BC and 10,148 controls across six studies with density measures from prediagnostic, digitized film-screen mammograms. We classified BC tumors into subtypes [63% Luminal A, 21% Luminal B, 5% HER2 expressing, and 11% as triple negative (TN)] using information on estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and tumor grade. We used polytomous logistic regression to calculate odds ratio (OR) and 95% confidence intervals (CI) for density measures (per SD) across the subtypes compared to controls, adjusting for age, body mass index and study, and examined differences by age group.
All density measures were similarly associated with BC risk across subtypes. Significant interaction of PMD by age (P = 0.001) was observed for Luminal A tumors, with stronger effect sizes seen for younger women < 45 years (OR = 1.69 per SD PMD) relative to women of older ages (OR = 1.53, ages 65-74, OR = 1.44 ages 75 +). Similar but opposite trends were seen for NDA by age for risk of Luminal A: risk for women: < 45 years (OR = 0.71 per SD NDA) was lower than older women (OR = 0.83 and OR = 0.84 for ages 65-74 and 75 + , respectively) (P < 0.001). Although not significant, similar patterns of associations were seen by age for TN cancers.
Mammographic density measures were associated with risk of all "intrinsic" molecular subtypes. However, findings of significant interactions between age and density measures may have implications for subtype-specific risk models.
我们评估了百分比乳腺密度（PMD）、绝对致密区（DA）和非致密区（NDA）与“内在”分子乳腺癌（BC）亚型风险的关联。
我们汇集了六项研究中 3492 例浸润性 BC 和 10148 例对照，这些研究均使用数字化胶片筛查乳房 X 光片的密度测量值。我们使用雌激素受体（ER）、孕激素受体（PR）、人表皮生长因子受体 2（HER2）和肿瘤分级的信息，将 BC 肿瘤分为亚型[63%为 Luminal A、21%为 Luminal B、5%为 HER2 表达、11%为三阴性（TN）]。我们使用多变量逻辑回归计算了与对照相比，各密度指标（每标准差）在各亚型中的比值比（OR）和 95%置信区间（CI），并调整了年龄、体重指数和研究因素，同时还检查了不同年龄组之间的差异。
所有密度指标与各亚型的 BC 风险均具有相似的相关性。PMD 与年龄的交互作用具有显著性（P=0.001），在 Luminal A 肿瘤中更为明显，对于年龄较小的女性（<45 岁），PMD 每标准差的效应大小较大（OR=1.69），而年龄较大的女性（OR=1.53，年龄为 65-74 岁；OR=1.44，年龄为 75 岁及以上）则较小。对于 Luminal A 肿瘤，NDA 与年龄的交互作用具有相似但相反的趋势：对于年龄较小的女性（<45 岁），NDA 每标准差的风险（OR=0.71）低于年龄较大的女性（OR=0.83 和 OR=0.84，年龄为 65-74 岁和 75 岁及以上）（P<0.001）。尽管不具有显著性，但对于 TN 癌症，年龄与各密度指标之间也存在类似的关联模式。
乳腺密度测量值与所有“内在”分子亚型的风险相关。然而，年龄与密度指标之间存在显著交互作用的发现可能对特定亚型的风险模型具有影响。
