Figueroa Jonine D, Pfeiffer Ruth M, Brinton Louise A, Palakal Maya M, Degnim Amy C, Radisky Derek, Hartmann Lynn C, Frost Marlene H, Stallings Mann Melody L, Papathomas Daphne, Gierach Gretchen L, Hewitt Stephen M, Duggan Maire A, Visscher Daniel, Sherman Mark E
Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
Medical School, The Usher Institute of Population Health Sciences and Informatics, The University of Edinburgh, Teviot Place, Edinburgh, EH8 9AG, UK.
Breast Cancer Res Treat. 2016 Aug;159(1):163-72. doi: 10.1007/s10549-016-3908-7. Epub 2016 Aug 3.
Lesser degrees of terminal duct-lobular unit (TDLU) involution predict higher breast cancer risk; however, standardized measures to quantitate levels of TDLU involution have only recently been developed. We assessed whether three standardized measures of TDLU involution, with high intra/inter pathologist reproducibility in normal breast tissue, predict subsequent breast cancer risk among women in the Mayo benign breast disease (BBD) cohort. We performed a masked evaluation of biopsies from 99 women with BBD who subsequently developed breast cancer (cases) after a median of 16.9 years and 145 age-matched controls. We assessed three metrics inversely related to TDLU involution: TDLU count/mm(2), median TDLU span (microns, which approximates acini content), and median category of acini counts/TDLU (0-10; 11-20; 21-30; 31-50; >50). Associations with subsequent breast cancer risk for quartiles (or categories of acini counts) of each of these measures were assessed with multivariable conditional logistic regression to estimate odds ratios (ORs) and 95 % confidence intervals (CI). In multivariable models, women in the highest quartile compared to the lowest quartiles of TDLU counts and TDLU span measures were significantly associated with subsequent breast cancer diagnoses; TDLU counts quartile4 versus quartile1, OR = 2.44, 95 %CI 0.96-6.19, p-trend = 0.02; and TDLU spans, quartile4 versus quartile1, OR = 2.83, 95 %CI = 1.13-7.06, p-trend = 0.03. Significant associations with categorical measures of acini counts/TDLU were also observed: compared to women with median category of <10 acini/TDLU, women with >25 acini counts/TDLU were at significantly higher risk, OR = 3.40, 95 %CI 1.03-11.17, p-trend = 0.032. Women with TDLU spans and TDLU count measures above the median were at further increased risk, OR = 3.75 (95 %CI 1.40-10.00, p-trend = 0.008), compared with women below the median for both of these metrics. Similar results were observed for combinatorial metrics of TDLU acini counts/TDLU, and TDLU count. Standardized quantitative measures of TDLU counts and acini counts approximated by TDLU span measures or visually assessed in categories are independently associated with breast cancer risk. Visual assessment of TDLU numbers and acini content, which are highly reproducible between pathologists, could help identify women at high risk for subsequent breast cancer among the million women diagnosed annually with BBD in the US.
终末导管小叶单位（TDLU）退化程度较低预示着乳腺癌风险较高；然而，用于量化TDLU退化水平的标准化方法直到最近才得以开发。我们评估了三种在正常乳腺组织中具有较高病理医生间/内重复性的TDLU退化标准化测量方法，能否预测梅奥良性乳腺疾病（BBD）队列中女性随后发生乳腺癌的风险。我们对99例BBD女性的活检样本进行了盲法评估，这些女性在中位时间16.9年后随后发生了乳腺癌（病例组），并与145例年龄匹配的对照进行比较。我们评估了与TDLU退化呈负相关的三个指标：TDLU计数/mm²、TDLU跨度中位数（微米，近似腺泡含量）以及腺泡计数/TDLU的中位数类别（0 - 10；11 - 20；21 - 30；31 - 50；>50）。使用多变量条件逻辑回归评估这些指标的四分位数（或腺泡计数类别）与随后乳腺癌风险的关联，以估计比值比（OR）和95%置信区间（CI）。在多变量模型中，与TDLU计数和TDLU跨度测量的最低四分位数相比，最高四分位数的女性与随后的乳腺癌诊断显著相关；TDLU计数四分位数4与四分位数1相比，OR = 2.44，95%CI 0.96 - 6.19，p趋势 = 0.02；TDLU跨度四分位数4与四分位数1相比，OR = 2.83，95%CI = 1.13 - 7.06，p趋势 = 0.03。在腺泡计数/TDLU的分类测量中也观察到显著关联：与腺泡/TDLU中位数类别<10的女性相比，腺泡计数>25/TDLU的女性风险显著更高，OR = 3.40，95%CI 1.03 - 11.17，p趋势 = 0.032。与这两个指标中位数以下的女性相比，TDLU跨度和TDLU计数测量高于中位数的女性风险进一步增加，OR = 3.75（95%CI 1.40 - 10.00，p趋势 = 0.008）。对于TDLU腺泡计数/TDLU和TDLU计数的组合指标也观察到类似结果。通过TDLU跨度测量近似或按类别视觉评估的TDLU计数和腺泡计数的标准化定量测量与乳腺癌风险独立相关。病理医生之间高度可重复的TDLU数量和腺泡含量的视觉评估，有助于在美国每年诊断为BBD的数百万女性中识别出随后患乳腺癌风险较高的女性。
