Department of Population Sciences, Beckman Research Institute, City of Hope, 1500 East Duarte Rd., Duarte, CA, 91010, USA.
Cancer Registry of Norway, Oslo, Norway.
Breast Cancer Res. 2018 Jan 22;20(1):5. doi: 10.1186/s13058-017-0931-5.
Although it has been well-documented that obesity is associated with decreased risk of premenopausal breast cancer and increased risk of postmenopausal breast cancer, it is unclear whether these associations differ among breast cancer subtypes defined by the tumor protein expression status of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2).
We evaluated the associations of body mass index (BMI) at age 18 years and recent BMI in relation to risk of breast cancer overall and ER/PR/HER2-defined subtypes, in 6320 women (3934 case-patient participants, 2386 control participants) aged 35-64 years, who participated in one of three population-based case-control studies. We estimated multivariable-adjusted odd ratios (ORs) and corresponding 95% confidence intervals (CIs) using polychotomous unconditional logistic regression methods for case-control comparisons in premenopausal women and postmenopausal women.
BMI at age 18 years was inversely associated with risk of breast cancer, particularly among premenopausal women (≥ 25 vs. < 20 kg/m, OR = 0.72, 95% CI = 0.53-0.96; per 5 kg/m increase, OR = 0.83, 95% CI = 0.73-0.95). This inverse association did not differ across ER/PR/HER2-defined subtypes or by race (white women, African-American women). Recent BMI was not associated with risk of premenopausal breast cancer after adjustment for BMI at age 18 years; nevertheless, the analysis for the joint effects of BMI at age 18 years and recent BMI showed that premenopausal women in the highest categories of the two BMI measures (≥ 25 kg/m at age 18 years and ≥ 30 kg/m for recent BMI) had 46% lower risk of breast cancer than premenopausal women in the lowest categories of the two BMI measures (< 20 kg/m at age 18 years and < 25 kg/m for recent BMI; OR = 0.54, 95% CI = 0.38-0.78). Neither measure of BMI was statistically significantly associated with risk of postmenopausal breast cancer.
Our findings indicate that high BMI near the end of adolescence decreases risk of all ER/PR/HER2-defined subtypes of premenopausal breast cancer and also suggest that this benefit could be maximized among premenopausal women who consistently have high BMI during their premenopausal years.
虽然已有大量文献证明肥胖与绝经前乳腺癌风险降低和绝经后乳腺癌风险增加有关,但尚不清楚这些关联在根据肿瘤蛋白表达状态的雌激素受体(ER)、孕激素受体(PR)和人表皮生长因子受体 2(HER2)定义的乳腺癌亚型中是否存在差异。
我们评估了 6320 名年龄在 35-64 岁的女性(3934 名病例患者参与者和 2386 名对照参与者)中,18 岁时的体重指数(BMI)和近期 BMI 与乳腺癌总体及 ER/PR/HER2 定义的亚型风险之间的关联,这些女性参加了三项基于人群的病例对照研究之一。我们使用多变量调整的优势比(OR)和相应的 95%置信区间(CI),通过绝经前妇女和绝经后妇女的多分类非条件逻辑回归方法,对病例对照进行比较。
18 岁时的 BMI 与乳腺癌风险呈负相关,尤其是在绝经前妇女中(≥25 与<20 kg/m,OR=0.72,95%CI=0.53-0.96;每增加 5kg/m,OR=0.83,95%CI=0.73-0.95)。这种负相关在 ER/PR/HER2 定义的亚型或种族(白种妇女、非裔美国妇女)之间没有差异。在调整 18 岁时的 BMI 后,近期 BMI 与绝经前乳腺癌风险无关;然而,对 18 岁时的 BMI 和近期 BMI 的联合效应进行分析显示,处于这两个 BMI 指标最高类别(18 岁时 BMI≥25kg/m,近期 BMI≥30kg/m)的绝经前妇女患乳腺癌的风险比处于两个 BMI 指标最低类别的绝经前妇女低 46%(18 岁时 BMI<20kg/m,近期 BMI<25kg/m;OR=0.54,95%CI=0.38-0.78)。BMI 的两个指标均与绝经后乳腺癌风险无统计学显著关联。
我们的研究结果表明,青春期末期的高 BMI 降低了所有 ER/PR/HER2 定义的绝经前乳腺癌亚型的风险,并且还表明,在整个绝经前期间持续高 BMI 的绝经前妇女中,这种益处可能最大化。