Bendinelli Benedetta, Danza Giovanna, Assedi Melania, Villanelli Fabio, Vagnoni Giulia, Pastore Elisa, Saieva Calogero, Caini Saverio, Vignozzi Linda, Masala Giovanna
Clinical Epidemiology Unit, Institute for Cancer Research, Prevention and Clinical Network (ISPRO), Florence, Italy.
Department of Experimental Clinical and Biomedical Sciences "Mario Serio", University of Florence, Florence, Italy.
Int J Cancer. 2025 Jun 15;156(12):2294-2302. doi: 10.1002/ijc.35321. Epub 2024 Dec 29.
Mammographic breast density (MBD) is a known risk factor for breast cancer. This study aimed to evaluate prospectively how circulating levels of sex hormones and sex hormones binding globulin (SHBG) are associated with volumetric percent density (VPD, %) and absolute breast dense volume (DV, cm) measured after an average 13.5 years of follow up. We included 422 post- and 445 pre-menopausal women enrolled in the Florence section of the European Prospective Investigation into Cancer and Nutrition study. Blood levels of circulating sex hormones and SHBG were determined in serum samples collected at enrollment. The automated Volpara™ density software was used to obtain DV and VPD measures from the first available full-field digital mammography performed after enrollment. We carried out adjusted linear regression models for post-menopausal and pre-menopausal women, separately. Higher baseline blood levels of SHBG were associated with higher VPD both in post-menopausal (%Diff 17.2 III vs. I tertile, p-value 0.02, p-trend 0.02) and pre-menopausal women (%Diff 21.1 III vs. I tertile, p-value 0.004, p-trend 0.004). Among pre-menopausal women a modifying effect of parity emerged, with significant inverse associations of estradiol, free estradiol, estrone, and free testosterone with VPD in women with a lower number of births or higher age at every birth. DV was not associated with sex hormones or SHBG. A direct association between increasing serum level of SHBG and VPD was observed both in post- and pre-menopausal women. This association need to be further investigated in order to better understand the underlying mechanisms.
乳腺钼靶密度（MBD）是已知的乳腺癌风险因素。本研究旨在前瞻性评估性激素和性激素结合球蛋白（SHBG）的循环水平与平均随访13.5年后测得的体积百分比密度（VPD，%）和绝对乳腺致密体积（DV，cm³）之间的关联。我们纳入了欧洲癌症与营养前瞻性调查研究佛罗伦萨分部的422名绝经后女性和445名绝经前女性。在入组时采集的血清样本中测定循环性激素和SHBG的血液水平。使用自动化的Volpara™密度软件从入组后首次获得的全视野数字化乳腺钼靶检查中获取DV和VPD测量值。我们分别对绝经后和绝经前女性进行了校正线性回归模型分析。较高的SHBG基线血液水平与绝经后女性（第三三分位数与第一三分位数相比，%差异为17.2，p值为0.02，p趋势为0.02）和绝经前女性（第三三分位数与第一三分位数相比，%差异为21.1，p值为0.004，p趋势为0.004）的较高VPD相关。在绝经前女性中，产次出现了调节作用，在生育次数较少或每次生育年龄较大的女性中，雌二醇、游离雌二醇、雌酮和游离睾酮与VPD呈显著负相关。DV与性激素或SHBG无关。在绝经后和绝经前女性中均观察到SHBG血清水平升高与VPD之间存在直接关联。为了更好地理解潜在机制，这种关联需要进一步研究。
