Kerlikowske Karla, Gard Charlotte C, Tice Jeffrey A, Ziv Elad, Cummings Steven R, Miglioretti Diana L
Affiliations of authors: Departments of Medicine and Epidemiology and Biostatistics (KK, JAT, EZ) and General Internal Medicine Section, Department of Veterans Affairs (KK), University of California, San Francisco, San Francisco, CA; Department of Economics, Applied Statistics, and International Business, New Mexico State University, Las Cruces, NM (CCG); San Francisco Coordinating Center, California Pacific Medical Center Research Institute, San Francisco, CA (SRC); Department of Public Health Sciences, University of California, Davis, Davis, CA (DLM); Group Health Research Institute, Group Health Cooperative, Seattle, WA (DLM).
J Natl Cancer Inst. 2016 Dec 31;109(5). doi: 10.1093/jnci/djw276. Print 2017 May.
Risk factors may differentially influence development of estrogen receptor (ER)-positive vs -negative breast cancer. We examined associations with strong, prevalent risk factors by ER subtype.
Of 1 279 443 women age 35 to 74 years participating in the Breast Cancer Surveillance Consortium, 14 969 developed ER-positive and 3617 developed ER-negative invasive breast cancer. We calculated hazard ratios (HRs) using Cox regression and compared ER subtype hazard ratios at representative ages or by menopausal status using Wald tests. All statistical tests were two-sided.
For women age 40 years, compared with no prior biopsy, ER-positive vs ER-negative HRs were 1.53 (95% CI = 1.30 to 1.81) vs 1.26 (95% CI = 0.90 to 1.76) for nonproliferative disease, 1.63 (95% CI = 1.23 to 2.17) vs 1.41 (95% CI = 0.78 to 2.57) for proliferative disease without atypia, and 4.47 (95% CI = 2.88 to 6.96) vs 0.20 (95% CI = 0.02 to 2.51) for proliferative disease with atypia. Benign disease proliferation risk was stronger for ER-positive than ER-negative cancer for women age 35 years (Wald P = .04), age 40 years (Wald P = .04), and age 50 years (Wald P = .06). Among pre/perimenopausal women, body mass index (BMI) had a stronger association with ER-negative than ER-positive cancer (obese II/III vs. normal weight: HR = 1.52, 95% CI = 1.19 to 1.94; vs 1.21, 95% CI = 1.08 to 1.36). Increasing BMI similarly increased ER-positive and ER-negative cancer risk among postmenopausal hormone users (Wald P = .15) and nonusers (Wald P = .08). Associations with ER subtype varied by race/ethnicity across all ages (P < .001) and by family history of breast cancer and breast density for specific ages.
Strength of risk factor associations differed by ER subtype. Separate risk models for ER subtypes may improve identification of women for targeted prevention strategies.
风险因素可能对雌激素受体（ER）阳性和阴性乳腺癌的发生发展产生不同影响。我们按ER亚型研究了与强大且常见的风险因素之间的关联。
在参与乳腺癌监测协会的1279443名35至74岁女性中，14969人患ER阳性浸润性乳腺癌，3617人患ER阴性浸润性乳腺癌。我们使用Cox回归计算风险比（HRs），并通过Wald检验比较代表性年龄或绝经状态下的ER亚型风险比。所有统计检验均为双侧检验。
对于40岁女性，与未进行过活检相比，非增殖性疾病的ER阳性与ER阴性HR分别为1.53（95%CI = 1.30至1.81）和1.26（95%CI = 0.90至1.76），无异型增生的增殖性疾病分别为1.63（95%CI = 1.23至2.17）和1.41（95%CI = 0.78至2.57），有异型增生的增殖性疾病分别为4.47（95%CI = 2.88至6.96）和0.20（95%CI = 0.02至2.51）。35岁（Wald P = 0.04）、40岁（Wald P = 0.04）和50岁（Wald P = 0.06）女性中，ER阳性癌的良性疾病增殖风险比ER阴性癌更强。在绝经前/围绝经期女性中，体重指数（BMI）与ER阴性癌的关联比与ER阳性癌更强（肥胖II/III级与正常体重：HR = 1.52，95%CI = 1.19至1.94；对比1.21，95%CI = 1.08至1.36）。在绝经后激素使用者（Wald P = 0.15）和非使用者（Wald P = 0.08）中，BMI升高同样增加了ER阳性和ER阴性癌的风险。所有年龄组中，与ER亚型的关联因种族/族裔而异（P < 0.001），特定年龄组中因乳腺癌家族史和乳腺密度而异。
风险因素关联的强度因ER亚型而异。针对ER亚型的单独风险模型可能会改善对女性的识别，以制定针对性的预防策略。
