Razzaghi Hilda, Troester Melissa A, Gierach Gretchen L, Olshan Andrew F, Yankaskas Bonnie C, Millikan Robert C
Breast Cancer Res. 2013;15(5):R76. doi: 10.1186/bcr3470.
Mammographic density is a strong risk factor for breast cancer overall, but few studies have examined the association between mammographic density and specific subtypes of breast cancer, especially aggressive basal-like breast cancers. Because basal-like breast cancers are less frequently screen-detected, it is important to understand how mammographic density relates to risk of basal-like breast cancer.
We estimated associations between mammographic density and breast cancer risk according to breast cancer subtype. Cases and controls were participants in the Carolina Breast Cancer Study (CBCS) who also had mammograms recorded in the Carolina Mammography Registry (CMR). A total of 491 cases had mammograms within five years prior to and one year after diagnosis and 528 controls had screening or diagnostic mammograms close to the dates of selection into CBCS. Mammographic density was reported to the CMR using Breast Imaging Reporting and Data System categories. The expression of estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 1 and 2 (HER1 and HER2), and cytokeratin 5/6 (CK5/6) were assessed by immunohistochemistry and dichotomized as positive or negative, with ER+ and/or PR+, and HER2- tumors classified as luminal A and ER-, PR-, HER2-, HER1+ and/or CK5/6+ tumors classified as basal-like breast cancer. Triple negative tumors were defined as negative for ER, PR and HER2. Of the 491 cases 175 were missing information on subtypes; the remaining cases included 181 luminal A, 17 luminal B, 48 basal-like, 29 ER-/PR-/HER2+, and 41 unclassified subtypes. Odds ratios comparing each subtype to all controls and case-case odds ratios comparing mammographic density distributions in basal-like to luminal A breast cancers were estimated using logistic regression.
Mammographic density was associated with increased risk of both luminal A and basal-like breast cancers, although estimates were imprecise. The magnitude of the odds ratio associated with mammographic density was not substantially different between basal-like and luminal A cancers in case–control analyses and case-case analyses (case-case OR = 1.08 (95% confidence interval: 0.30, 3.84)).
These results suggest that risk estimates associated with mammographic density are not distinct for separate breast cancer subtypes (basal-like/triple negative vs. luminal A breast cancers). Studies with a larger number of basal-like breast cancers are needed to confirm our findings.
乳腺X线密度是乳腺癌总体的一个强风险因素,但很少有研究探讨乳腺X线密度与乳腺癌特定亚型之间的关联,尤其是侵袭性基底样乳腺癌。由于基底样乳腺癌较少通过筛查发现,了解乳腺X线密度与基底样乳腺癌风险之间的关系很重要。
我们根据乳腺癌亚型估计乳腺X线密度与乳腺癌风险之间的关联。病例和对照是卡罗来纳乳腺癌研究(CBCS)的参与者,他们在卡罗来纳乳腺X线摄影登记处(CMR)也有乳腺X线摄影记录。共有491例病例在诊断前五年内及诊断后一年内进行了乳腺X线摄影,528例对照在接近入选CBCS的日期进行了筛查或诊断性乳腺X线摄影。乳腺X线密度通过乳腺影像报告和数据系统分类报告给CMR。通过免疫组织化学评估雌激素受体(ER)、孕激素受体(PR)、人表皮生长因子受体1和2(HER1和HER2)以及细胞角蛋白5/6(CK5/6)的表达,并将其分为阳性或阴性,ER+和/或PR+以及HER2-的肿瘤分类为腔面A型,ER-、PR-、HER2-、HER1+和/或CK5/6+的肿瘤分类为基底样乳腺癌。三阴性肿瘤定义为ER、PR和HER2均为阴性。在491例病例中,175例缺少亚型信息;其余病例包括181例腔面A型、17例腔面B型、48例基底样型、29例ER-/PR-/HER2+以及41例未分类亚型。使用逻辑回归估计将每种亚型与所有对照进行比较的比值比以及将基底样乳腺癌与腔面A型乳腺癌的乳腺X线密度分布进行比较的病例-病例比值比。
乳腺X线密度与腔面A型和基底样乳腺癌风险增加均相关,尽管估计值不精确。在病例对照分析和病例-病例分析中,与乳腺X线密度相关的比值比大小在基底样癌和腔面A型癌之间没有实质性差异(病例-病例比值比=1.08(95%置信区间:0.30,3.84))。
这些结果表明,与乳腺X线密度相关的风险估计对于不同的乳腺癌亚型(基底样/三阴性与腔面A型乳腺癌)并无差异。需要更多基底样乳腺癌病例的研究来证实我们的发现。