后绝经期肥胖女性患乳腺ER阳性（ER+）肿瘤的风险明显增加，这种肿瘤对治疗具有抗药性，与更高的复发和死亡率相关。全球超重/肥胖女性的患病率已经达到令人担忧的水平，并且在女性中（即乳腺、子宫内膜和卵巢）中，绝经后ER+乳腺癌（BC）的发病率最高，这是一个重要问题。阐明肥胖在ER+BC中促癌作用的精确分子机制对于疾病预防和新治疗措施至关重要。有趣的是，累积数据显示肥胖与癌症在绝经前或绝经后的女性中之间存在相反的关系。超重体重与绝经后乳腺癌的风险增加以及绝经前女性乳腺癌的风险减少有关。此外，早期过度脂肪堆积似乎对绝经后乳腺癌具有保护作用，包括ER阳性和ER阴性BC亚型。总体而言，与雌激素依赖机制有关的机制被认为是肥胖相关乳腺肿瘤发生的主要推动力。在本综述中，我们主要讨论了绝经后肥胖与乳腺肿瘤之间的流行病学和机制方面的关联，特别是激素依赖性的背景下。这种关联下的分子和细胞事件作为治疗干预以及防止与过度脂肪堆积相关的促进BC过程的潜在途径，对于日益肥胖的全球人口至关重要。版权所有©2023 Elsevier Ltd。保留所有权利。

Postmenopausal, obese women have a significantly higher risk of developing estrogen receptor-positive (ER+) breast tumors, that are resistant to therapies and are associated with higher recurrence and death rates. The global prevalence of overweight/obese women has reached alarming proportions and with postmenopausal ER+ breast carcinoma (BC) having the highest incidence among the three obesity-related cancers in females (i.e., breast, endometrial and ovarian), this is of significant concern. Elucidation of the precise molecular mechanisms underlying the pro-cancerous action of obesity in ER+BC is therefore critical for disease prevention and novel treatment initiatives. Interestingly, accumulating data has shown opposing relationships between obesity and cancer in either pre- or post-menopausal women. Excess body weight is associated with an increased risk of breast cancer in postmenopausal women and a decreased risk in pre-menopausal women. Moreover, excess adiposity during early life appears to be protective against postmenopausal breast cancer, including both ER+ and ER negative BC subtypes. Overall, estrogen-dependent mechanisms have been implicated as the main driving force in obesity-related breast tumorigenesis. In the present review we discuss the epidemiologic and mechanistic aspects of association between obesity and breast tumors after menopause, mainly in the context of hormone dependency. Molecular and cellular events underlying this association present as potential avenues for both therapeutic intervention as well as the prevention of BC-promoting processes linked to excess adiposity, which is proving to be vital in an increasingly obese global population.Copyright © 2023 Elsevier Ltd. All rights reserved.