Department of Pathology, The University of Melbourne, Parkville, VIC 3010, Australia.
Breast Cancer Res Treat. 2011 Jul;128(2):505-16. doi: 10.1007/s10549-011-1346-0. Epub 2011 Jan 22.
Mammographic density (MD) adjusted for age and body mass index (BMI) is a strong heritable breast cancer risk factor; however, its biological basis remains elusive. Previous studies assessed MD-associated histology using random sampling approaches, despite evidence that high and low MD areas exist within a breast and are negatively correlated with respect to one another. We have used an image-guided approach to sample high and low MD tissues from within individual breasts to examine the relationship between histology and degree of MD. Image-guided sampling was performed using two different methodologies on mastectomy tissues (n = 12): (1) sampling of high and low MD regions within a slice guided by bright (high MD) and dark (low MD) areas in a slice X-ray film; (2) sampling of high and low MD regions within a whole breast using a stereotactically guided vacuum-assisted core biopsy technique. Pairwise analysis accounting for potential confounders (i.e. age, BMI, menopausal status, etc.) provides appropriate power for analysis despite the small sample size. High MD tissues had higher stromal (P = 0.002) and lower fat (P = 0.002) compositions, but no evidence of difference in glandular areas (P = 0.084) compared to low MD tissues from the same breast. High MD regions had higher relative gland counts (P = 0.023), and a preponderance of Type I lobules in high MD compared to low MD regions was observed in 58% of subjects (n = 7), but did not achieve significance. These findings clarify the histologic nature of high MD tissue and support hypotheses regarding the biophysical impact of dense connective tissue on mammary malignancy. They also provide important terms of reference for ongoing analyses of the underlying genetics of MD.
乳腺密度（MD）经年龄和体重指数（BMI）校正后是一种较强的遗传性乳腺癌风险因素；然而，其生物学基础仍难以捉摸。尽管有证据表明乳腺内存在高 MD 区和低 MD 区，且彼此之间呈负相关，但之前的研究使用随机抽样方法评估了与 MD 相关的组织学。我们使用图像引导方法从个体乳房内取样高 MD 和低 MD 组织，以研究组织学和 MD 程度之间的关系。在乳房切除术组织中使用两种不同的方法进行图像引导取样（n = 12）：（1）在 X 射线胶片上的亮（高 MD）和暗（低 MD）区域引导下对切片内的高 MD 和低 MD 区域进行取样；（2）使用立体定向引导的真空辅助核心活检技术对整个乳房内的高 MD 和低 MD 区域进行取样。尽管样本量较小，但考虑到潜在混杂因素（即年龄、BMI、绝经状态等）的成对分析为分析提供了适当的能力。与同乳房的低 MD 组织相比，高 MD 组织具有更高的基质（P = 0.002）和更低的脂肪（P = 0.002）组成，但在腺泡区域没有差异（P = 0.084）。与低 MD 区域相比，高 MD 区域具有更高的相对腺泡计数（P = 0.023），并且在 58%的受试者（n = 7）中观察到高 MD 区域中 I 型小叶占优势，但未达到显著性。这些发现阐明了高 MD 组织的组织学性质，并支持关于致密结缔组织对乳腺恶性肿瘤的生物物理影响的假说。它们还为正在进行的 MD 潜在遗传学分析提供了重要的参考标准。
