Oh Hannah, Eliassen A Heather, Beck Andrew H, Rosner Bernard, Schnitt Stuart J, Collins Laura C, Connolly James L, Montaser-Kouhsari Laleh, Willett Walter C, Tamimi Rulla M
Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA USA.
Channing Division of Network Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, MA USA.
NPJ Breast Cancer. 2017 Oct 2;3:39. doi: 10.1038/s41523-017-0041-7. eCollection 2017.
Studies have suggested that hormone receptor and Ki67 expression in normal breast tissue are associated with subsequent breast cancer risk. We examined the associations of breast cancer risk factors with estrogen receptor (ER), progesterone receptor (PR), insulin-like growth factor-1 receptor (IGF-1R), and Ki67 expression in normal breast tissue. This analysis included 388 women with benign breast disease (ages 17-67 years) in the Nurses' Health Studies. Immunohistochemical staining was performed on tissue microarrays constructed from benign biopsies containing normal breast epithelium and scored as the percentage of epithelial cells that were positively stained. Ordinal logistic regression (outcomes in tertiles), adjusting for age and potential confounders, was performed to estimate odds ratios (OR) and 95% confidence intervals (CI) for the associations with risk factors. Alcohol consumption was positively associated (≥2.5 vs.<0.4 drink/wk: OR = 2.69, 95% CI = 1.26-5.75, -trend = 0.008) and breastfeeding was inversely associated (≥6 months vs. never: OR = 0.11, 95% CI = 0.04-0.35, -trend = 0.0003) with ER expression. Height (≥66 vs.<64 inches: OR = 2.50, 95% CI = 1.34-4.67, -trend = 0.005) and BMI at age 18 (≥22 vs.<20 kg/m: OR = 2.33, 95% CI = 1.18-4.62, -trend = 0.01) were positively associated with PR expression. Body size at age 5-10 years was inversely associated with Ki67 (Level ≥ 2.5 vs. 1: OR = 0.55, 95% CI = 0.30-1.01, -trend = 0.03). Premenopausal BMI (≥25 vs.<20 kg/m) was positively associated with cytoplasmic IGF-1R (OR = 5.06, 95% CI = 1.17-21.8, -trend = 0.04). Our data suggest that anthropometrics, breastfeeding, and alcohol intake may influence the molecular characteristics of normal breast tissue, elucidating the mechanisms by which these risk factors operate. However, larger studies are required to confirm these results.
研究表明，正常乳腺组织中的激素受体和Ki67表达与随后患乳腺癌的风险相关。我们研究了乳腺癌风险因素与正常乳腺组织中雌激素受体（ER）、孕激素受体（PR）、胰岛素样生长因子-1受体（IGF-1R）及Ki67表达之间的关联。该分析纳入了护士健康研究中的388例患有良性乳腺疾病的女性（年龄17 - 67岁）。对由包含正常乳腺上皮的良性活检样本构建的组织微阵列进行免疫组织化学染色，并将其评分作为阳性染色上皮细胞的百分比。进行有序逻辑回归分析（结果分为三分位数），并对年龄和潜在混杂因素进行校正，以估计与风险因素关联的比值比（OR）和95%置信区间（CI）。饮酒与ER表达呈正相关（每周≥2.5杯 vs. <0.4杯：OR = 2.69，95% CI = 1.26 - 5.75，-趋势 = 0.008），而母乳喂养与ER表达呈负相关（≥6个月 vs. 从未：OR = 0.11，95% CI = 0.04 - 0.35，-趋势 = 0.0003）。身高（≥66英寸 vs. <64英寸：OR = 2.50，95% CI = 1.34 - 4.67，-趋势 = 0.005）和18岁时的体重指数（BMI）（≥22 vs. <20 kg/m²：OR = 2.33，95% CI = 1.18 - 4.62，-趋势 = 0.01）与PR表达呈正相关。5至10岁时的体型与Ki67呈负相关（水平≥2.5 vs. 1：OR = 0.55，95% CI = 0.30 - 1.01，-趋势 = 0.03）。绝经前BMI（≥25 vs. <20 kg/m²）与细胞质IGF-1R呈正相关（OR = 5.06，95% CI = 1.17 - 21.8，-趋势 = 0.04）。我们的数据表明，人体测量学指标、母乳喂养和饮酒可能会影响正常乳腺组织的分子特征，从而阐明这些风险因素起作用的机制。然而，需要更大规模的研究来证实这些结果。
