Williams Lindsay A, Nichols Hazel B, Hoadley Katherine A, Tse Chiu Kit, Geradts Joseph, Bell Mary Elizabeth, Perou Charles M, Love Michael I, Olshan Andrew F, Troester Melissa A
Department of Epidemiology, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
Cancer Causes Control. 2018 Jan;29(1):25-32. doi: 10.1007/s10552-017-0977-9. Epub 2017 Nov 9.
Invasive lobular breast tumors display unique reproductive risk factor profiles. Lobular tumors are predominantly Luminal A subtype, and it is unclear whether reported risk factor associations are independent of molecular subtype.
Polytomous logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (95% CIs) for the associations between risk factors and histologic subtype [ductal (n = 2,856), lobular (n = 326), and mixed ductal-lobular (n = 473)] in the Carolina Breast Cancer Study (1993-2013). Three-marker immunohistochemical clinical subtypes were defined as Luminal A (ER+ or PR+/HER2-), Luminal B (ER+ or PR+/HER2+), Triple Negative (ER-/PR-/HER2-), and HER2+ (ER-/PR-/HER2+).
In case-case analyses compared to ductal, lobular tumors were significantly associated with lactation duration > 12 months [OR 1.86, 95% CI (1.33-2.60)], age at first birth ≥ 26 years [OR: 1.35, 95% CI: (1.03-1.78)], and current oral contraceptive use [OR: 1.86, 95% CI: (1.08-3.20)]. Differences in risk factor associations between ductal and lobular tumors persisted after restricting to Luminal A subtype.
Lobular tumors were associated with older age at first birth, increased lactation duration, and current oral contraceptive use. Etiologic heterogeneity by histology persisted after restricting to Luminal A subtype, suggesting both tumor histology and intrinsic subtype play integral parts in breast cancer risk.
浸润性小叶乳腺癌肿瘤呈现出独特的生殖风险因素特征。小叶肿瘤主要为腔面A型亚型，目前尚不清楚所报道的风险因素关联是否独立于分子亚型。
在卡罗来纳乳腺癌研究（1993 - 2013年）中，采用多分类逻辑回归来估计风险因素与组织学亚型[导管癌（n = 2856）、小叶癌（n = 326）和导管 - 小叶混合癌（n = 473）]之间关联的比值比（OR）和95%置信区间（95% CI）。三种标志物免疫组化临床亚型定义为腔面A型（ER + 或PR + /HER2 - ）、腔面B型（ER + 或PR + /HER2 + ）、三阴性（ER - /PR - /HER2 - ）和HER2 + 型（ER - /PR - /HER2 + ）。
在病例 - 病例分析中，与导管癌相比，小叶癌与哺乳时间>12个月[OR 1.86，95% CI（1.33 - 2.60）]、初产年龄≥26岁[OR：1.35，95% CI：（1.03 - 1.78）]以及当前口服避孕药的使用[OR：1.86，95% CI：（1.08 - 3.20）]显著相关。在限定为腔面A型亚型后，导管癌和小叶癌之间风险因素关联的差异依然存在。
小叶癌与初产年龄较大、哺乳时间延长以及当前口服避孕药的使用有关。在限定为腔面A型亚型后，按组织学分类的病因异质性依然存在，这表明肿瘤组织学和内在亚型在乳腺癌风险中均起着不可或缺的作用。
