García-Sancha Natalia, Corchado-Cobos Roberto, Pérez-Losada Jesús
Institute of Molecular and Cellular Biology of Cancer (IBMCC-CIC), CSIC-University of Salamanca, 37007 Salamanca, Spain.
Institute of Biomedical Research of Salamanca (IBSAL), 37007 Salamanca, Spain.
Int J Mol Sci. 2025 Mar 25;26(7):2993. doi: 10.3390/ijms26072993.
Breast cancer is the most common malignancy among women globally, with incidence rates continuing to rise. A comprehensive understanding of its risk factors and the underlying biological mechanisms that drive tumor initiation is essential for developing effective prevention strategies. This review examines key non-modifiable risk factors, such as genetic predisposition, demographic characteristics, family history, mammographic density, and reproductive milestones, as well as modifiable risk factors like exogenous hormone exposure, obesity, diet, and physical inactivity. Importantly, reproductive history plays a dual role, providing long-term protection while temporarily increasing breast cancer risk shortly after pregnancy. Current chemoprevention strategies primarily depend on selective estrogen receptor modulators (SERMs), including tamoxifen and raloxifene, which have demonstrated efficacy in reducing the incidence of estrogen receptor-positive breast cancer but remain underutilized due to adverse effects. Emerging approaches such as aromatase inhibitors, RANKL inhibitors, progesterone antagonists, PI3K inhibitors, and immunoprevention strategies show promise for expanding preventive options. Understanding the interactions between risk factors, hormonal influences, and tumorigenesis is critical for optimizing breast cancer prevention and advancing safer, more targeted chemopreventive interventions.
乳腺癌是全球女性中最常见的恶性肿瘤,其发病率持续上升。全面了解其风险因素以及驱动肿瘤发生的潜在生物学机制对于制定有效的预防策略至关重要。本综述探讨了关键的不可改变风险因素,如遗传易感性、人口统计学特征、家族病史、乳腺X线密度和生殖里程碑,以及可改变的风险因素,如外源性激素暴露、肥胖、饮食和身体活动不足。重要的是,生殖史具有双重作用,在怀孕后短期内会暂时增加乳腺癌风险的同时,也提供长期保护。目前的化学预防策略主要依赖于选择性雌激素受体调节剂(SERM),包括他莫昔芬和雷洛昔芬,它们已被证明在降低雌激素受体阳性乳腺癌的发病率方面有效,但由于不良反应而未得到充分利用。芳香化酶抑制剂、RANKL抑制剂、孕酮拮抗剂、PI3K抑制剂和免疫预防策略等新兴方法有望扩大预防选择。了解风险因素、激素影响和肿瘤发生之间的相互作用对于优化乳腺癌预防以及推进更安全、更有针对性的化学预防干预措施至关重要。
Int J Mol Sci. 2025-3-25
Cancer Chemother Pharmacol. 2016-5
Pol Arch Med Wewn. 2014
J Mammary Gland Biol Neoplasia. 2003-1
Hematol Oncol Clin North Am. 2000-2
J Clin Oncol. 2005-1-10
Expert Opin Investig Drugs. 2006-12
Cochrane Database Syst Rev. 2019-4-29
Am J Health Syst Pharm. 2012-8-15
NPJ Breast Cancer. 2025-2-15
Clin Breast Cancer. 2025-4
J Cancer Prev. 2024-3-30