Department of Epidemiology and Biostatistics, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Ann Oncol. 2013 Nov;24 Suppl 8(Suppl 8):viii37-viii41. doi: 10.1093/annonc/mdt310.
Mammographic density (MD), representing connective and epithelial tissue (fibroglandular tissue, FGT) is a major risk factor for breast cancer. In an analysis of an autopsy series (Bartow SA, Pathak DR, Mettler FA. Radiographic microcalcification and parenchymal patterns as indicators of histologic "high-risk" benign breast disease. Cancer 1990; 66: 1721-1725, Bartow SA, Pathak DR, Mettler FA et al. Breast mammographic pattern: a concatenation of confounding and breast cancer risk factors. Am J Epidemiol 1995; 142: 813-819), MD was found to be strongly correlated with the collagen and epithelial content of the breast (Li T, Sun L, Miller N et al. The association of measured breast tissue characteristics with MD and other risk factors for breast cancer. Cancer Epidemiol Biomarkers Prev 2005; 14: 343-349), and another report showed that breast epithelium was highly concentrated in the areas of collagen concentration (Hawes D, Downey S, Pearce CL et al. Dense breast stromal tissue shows greatly increased concentration of breast epithelium but no increase in its proliferative activity. Breast Cancer Res 2006; 8: R24). Collagen comprises the overwhelming majority of the FGT, occupying an area on the slides obtained from the autopsy series some 15 times the area of glandular tissue. The relationship of MD with breast cancer risk appears likely to be due to a major extent to increasing epithelial cell numbers with increasing MD. FGT is also seen in breast magnetic resonance imaging (breast MRI) and, as expected, it has been shown that this measure of FGT (MRI-FGT) is highly correlated with MD. A contrast-enhanced breast MRI shows that normal FGT 'enhances' (background parenchymal enhancement, BPE) after contrast agent is administered(Morris EA. Diagnostic breast MR imaging: current status and future directions. Radiol Clin North Am 2007; 45: 863-880, vii., Kuhl C. The current status of breast MR imaging. Part I. Choice of technique, image interpretation, diagnostic accuracy, and transfer to clinical practice. Radiology 2007; 244: 356-378), and a recent study suggests that BPE is also a major breast cancer risk factor, possibly as important as, and independent of MD (King V, Brooks JD, Bernstein JL et al. BPE at breast MR imaging and breast cancer risk. Radiology 2011; 260: 50-60). BPE is much more sensitive to the effects of menopause and tamoxifen than is FGT (King V, Gu Y, Kaplan JB et al. Impact of menopausal status on BPE and fibroglandular tissue on breast MRI. Eur Radiol 2012; 22: 2641-2647, King V, Kaplan J, Pike MC et al. Impact of tamoxifen on amount of fibroglandular tissue, BPE, and cysts on breast MRI. Breast J 2012; 18: 527-534). Changes in MD and BPE may be most useful in predicting response to chemopreventive agents aimed at blocking breast cell proliferation. More study of the biological basis of the effects of MD and BPE is needed if we are to fully exploit these factors in developing chemopreventive approaches to breast cancer.
乳腺密度（MD）代表着结缔组织和上皮组织（纤维腺体组织，FGT），是乳腺癌的主要危险因素。在对一系列尸检的分析中（Bartow SA、Pathak DR、Mettler FA。放射微钙化和实质模式作为组织学“高危”良性乳腺疾病的指标。癌症 1990；66:1721-1725，Bartow SA、Pathak DR、Mettler FA 等。乳腺 X 线摄影模式：混杂因素和乳腺癌危险因素的串联。美国流行病学杂志 1995；142:813-819），发现 MD 与乳腺的胶原蛋白和上皮含量密切相关（Li T、Sun L、Miller N 等。测量的乳腺组织特征与 MD 和乳腺癌其他危险因素的关系。癌症流行病学生物标志物预防 2005；14:343-349），另一项研究表明乳腺上皮组织高度集中在胶原蛋白浓度高的区域（Hawes D、Downey S、Pearce CL 等。致密乳腺基质组织显示乳腺上皮细胞高度浓缩，但增殖活性没有增加。乳腺癌研究 2006；8:R24）。胶原蛋白构成了 FGT 的绝大多数，在尸检系列中获得的幻灯片上占据了大约是腺体组织面积 15 倍的区域。MD 与乳腺癌风险的关系似乎主要归因于随着 MD 的增加，上皮细胞数量的增加。FGT 也可见于乳腺磁共振成像（乳腺 MRI）中，正如预期的那样，已经表明这种 FGT 测量方法（MRI-FGT）与 MD 高度相关。增强后的乳腺 MRI 显示正常的 FGT 在给予造影剂后会“增强”（背景实质增强，BPE）（Morris EA。诊断性乳腺磁共振成像：现状和未来方向。放射学临床北美 2007；45:863-880，vii.，Kuhl C. 乳腺 MRI 的现状。第一部分。技术选择、图像解释、诊断准确性以及向临床实践的转移。放射学 2007；44:356-378），最近的一项研究表明 BPE 也是乳腺癌的一个主要危险因素，可能与 MD 一样重要，并且独立于 MD（King V、Brooks JD、Bernstein JL 等。乳腺 MRI 上的 BPE 和乳腺癌风险。放射学 2011；260:50-60）。BPE 对绝经和他莫昔芬的影响比 FGT 敏感得多（King V、Gu Y、Kaplan JB 等。绝经状态对乳腺 MRI 上的 BPE 和纤维腺体组织的影响。欧洲放射学 2012；22:2641-2647，King V、Kaplan J、Pike MC 等。他莫昔芬对乳腺 MRI 上的纤维腺体组织、BPE 和囊肿的影响。乳房 J 2012；18:527-534）。MD 和 BPE 的变化可能最有助于预测针对阻止乳腺细胞增殖的化学预防剂的反应。如果我们要充分利用 MD 和 BPE 这些因素来开发乳腺癌的化学预防方法，就需要对其作用的生物学基础进行更多的研究。
