Muñante Bruno, Paz-Manrique Roberto, Pinto Joseph A, Gomez Henry L
Oncosalud, AUNA, Lima, Peru.
Carrera de Medicina Humana, Facultad de Ciencias de la Salud, Universidad San Ignacio de Loyola, Lima, Peru.
Cancer Control. 2025 Jan-Dec;32:10732748251377864. doi: 10.1177/10732748251377864. Epub 2025 Sep 19.
BackgroundBreast cancer remains a leading cause of cancer-related morbidity and mortality globally, with BRCA1/2 mutation carriers facing distinct challenges due to aggressive tumor biology and heightened risks of contralateral and secondary cancers.PurposeThis review synthesizes evidence on managing early-stage breast cancer in BRCA mutation carriers, emphasizing Latin America's heterogeneous BRCA prevalence (ranging from 5% to 25.7% across countries), which underscores the need for region-specific genetic screening. BRCA-associated tumors exhibit homologous recombination deficiency, informing therapeutic strategies such as PARP inhibitors, which exploit synthetic lethality, as demonstrated by the OlympiA trial showing Olaparib's sustained survival benefits (28% reduction in mortality risk). Imaging strategies must adapt to BRCA-related tumor phenotypes: BRCA1 carriers often present mammography-elusive tumors, favoring MRI, while abbreviated MRI protocols offer cost-effective alternatives without compromising sensitivity. Surgical decision-making balances breast-conserving surgery (BCS) and mastectomy, with studies showing comparable survival outcomes but elevated contralateral cancer risk post-BCS (10-year risk: 14%), necessitating vigilant surveillance. Contralateral prophylactic mastectomy reduces contralateral cancer risk but requires personalized risk-benefit discussions. Neoadjuvant platinum-based chemotherapy shows higher pathologic complete response rates in BRCA carriers, particularly in triple-negative subtypes, though adjuvant platinum benefits remain under investigation. Emerging immunotherapies, such as pembrolizumab in KEYNOTE-522, show promise but lack BRCA-specific efficacy data. Special considerations for transgender BRCA carriers highlight evolving screening guidelines, including mammography for hormonally treated transgender women and multimodal imaging for non-mastectomized transgender men. ConclusionsOptimizing outcomes for BRCA mutation carriers demands multidisciplinary, personalized approaches integrating genetic, regional, and clinical factors. Advances in targeted therapies, refined imaging, and risk-adapted surgery emphasize the importance of shared decision-making and ongoing research to address knowledge gaps in survivorship and equitable care.
背景
乳腺癌仍然是全球癌症相关发病和死亡的主要原因,由于肿瘤生物学侵袭性强以及对侧和继发性癌症风险增加,BRCA1/2突变携带者面临着独特的挑战。
目的
本综述综合了关于BRCA突变携带者早期乳腺癌管理的证据,强调拉丁美洲BRCA患病率的异质性(各国范围从5%到25.7%),这突出了进行区域特异性基因筛查的必要性。与BRCA相关的肿瘤表现出同源重组缺陷,这为治疗策略提供了依据,如利用合成致死性的PARP抑制剂,OlympiA试验表明奥拉帕尼具有持续的生存益处(死亡风险降低28%)就证明了这一点。成像策略必须适应与BRCA相关的肿瘤表型:BRCA1携带者常出现乳腺X线摄影难以发现的肿瘤,更适合MRI检查,而简化的MRI方案在不影响敏感性的情况下提供了具有成本效益的替代方案。手术决策要在保乳手术(BCS)和乳房切除术之间权衡,研究表明两者生存结果相当,但BCS术后对侧癌症风险升高(10年风险:14%),因此需要进行密切监测。对侧预防性乳房切除术可降低对侧癌症风险,但需要进行个性化的风险效益讨论。新辅助铂类化疗在BRCA携带者中显示出更高的病理完全缓解率,尤其是在三阴性亚型中,不过辅助铂类化疗的益处仍在研究中。新兴的免疫疗法,如KEYNOTE-522中的帕博利珠单抗,显示出前景,但缺乏BRCA特异性疗效数据。对跨性别BRCA携带者的特殊考虑突出了不断演变的筛查指南,包括对接受激素治疗的跨性别女性进行乳腺X线摄影,以及对未接受乳房切除术的跨性别男性进行多模态成像。
结论
优化BRCA突变携带者的治疗结果需要综合基因、区域和临床因素的多学科、个性化方法。靶向治疗、精细成像和风险适应性手术的进展强调了共同决策和持续研究的重要性,以解决生存和公平护理方面的知识空白。