Mockus Mary, Prebil LeeAnn, Ereman Rochelle, Dollbaum Charles, Powell Mark, Yau Christina, Benz Christopher C
Kaiser Permanente Department of Surgery, San Rafael, CA.
Marin County Department of Health and Human Services, San Rafael, CA.
BBA Clin. 2015 Jun;3:189-195. doi: 10.1016/j.bbacli.2015.02.003.
It remains unknown if later life breast cancer risk as determined by reproductive history is mediated by postmenopausal breast density and/or sex steroid levels.
Increased breast density is a strong surrogate for future breast cancer risk. A cross-sectional study with a longitudinal follow up for breast health outcomes evaluated women without breast cancer (n = 1,023; 682 = parous), drawn from a high risk postmenopausal population, with questionnaire reported reproductive histories. The questionnaire was linked to prospective screening mammogram breast density measurements, and saliva biospecimens that were used to assess sex steroid hormone levels.
Expected age and postmenopause related declines in salivary estradiol (E), progesterone (P), dehydroepiandrosterone (DHEA) and testosterone (T) levels were observed. This was most pronounced for DHEA and T, which were also the only postmenopausal hormone levels significantly associated with any reproductive characteristics: parity and breast feeding for DHEA, age-at-first birth for T. Postmenopausal breast density was borderline significantly lower with parity and higher body mass index (BMI). After multivariate analysis, T was the only hormone level to retain any association (negative, p<0.05) with breast density.
While reproductive characteristics, in particular parity, generally demonstrated independent associations with postmenopausal breast density and E, P and DHEA levels, T levels showed concordant inverse associations with age-at-first birth and breast density. These findings suggest that reproductive effects and later life salivary sex steroid hormone levels may have independent effects on later life breast density and cancer risk.
尚不清楚由生殖史所确定的晚年乳腺癌风险是否由绝经后乳房密度和/或性类固醇水平介导。
乳房密度增加是未来患乳腺癌风险的有力替代指标。一项针对乳房健康结局进行纵向随访的横断面研究，评估了来自绝经后高危人群、无乳腺癌的女性（n = 1023；682 名有生育史），这些女性通过问卷报告了生殖史。该问卷与前瞻性筛查乳房X光检查的乳房密度测量结果以及用于评估性类固醇激素水平的唾液生物标本相关联。
观察到唾液雌二醇（E）、孕酮（P）、脱氢表雄酮（DHEA）和睾酮（T）水平随预期年龄和绝经后相关下降。DHEA 和 T 的下降最为明显，它们也是仅有的与任何生殖特征显著相关的绝经后激素水平：DHEA 与生育次数和母乳喂养相关，T 与初产年龄相关。绝经后乳房密度在有生育史和较高体重指数（BMI）时略显著降低。多因素分析后，T 是唯一与乳房密度仍保持关联（负相关，p<0.05）的激素水平。
虽然生殖特征，特别是生育次数，通常显示出与绝经后乳房密度以及 E、P 和 DHEA 水平存在独立关联，但 T 水平与初产年龄和乳房密度呈一致的负相关。这些发现表明生殖影响和晚年唾液性类固醇激素水平可能对晚年乳房密度和癌症风险具有独立影响。
