Marit Busund, Giske Ursin, Eiliv Lund, Sairah Lai Fa Chen, Charlotta Rylander
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引用次数: 0
Abstract
Background: Menopausal hormone therapy (MHT) is associated with an increased risk of postmenopausal breast cancer, predominantly the luminal A-like subtype. The impact of MHT on deaths from breast cancer subtypes is less understood. This study aimed to explore associations between MHT use and the incidence, mortality, and survival of intrinsic-like breast cancer subtypes.
Methods: Data from 160,881 participants with self-reported MHT use from the prospective Norwegian Women and Cancer Study were analyzed. Among them, 7,844 incident breast cancer cases, and 721 breast cancer-specific deaths occurred. Cox proportional hazard regression was performed to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) for the association between MHT use and the incidence, mortality, and survival of breast cancer subtypes.
Results: MHT use was associated with increased risk of overall, luminal A-like, and luminal B-like breast cancer, with respective HRs of 1.44 (95% CI 1.36-1.52), 1.41 (95% CI 1.31-1.52), and 1.23 (95% CI 1.09-1.40) among current estrogen-progestin therapy (EPT) users compared with never users. The risk increased by 4%, 4%, and 2% per year of EPT use for overall, luminal A-like, and luminal B-like breast cancers, respectively. MHT use was also associated with increased risk of overall and luminal A-like breast cancer mortality, with HRs 1.61% (95% CI 1.36-1.91) and 2.15% (95% CI 1.51-3.05) increased risk among current EPT users compared with non-users. Among patients with breast cancer, pre-diagnostic MHT use was not associated with worse survival from overall breast cancer but was inversely associated with survival from triple-negative breast cancer (TNBC; HR death 0.41; 95% CI 0.24-0.73 among current users). Results varied significantly according to tumor subtype (pheterogeneity = 0.02).
Conclusions: Our study suggests that MHT use increases the risk of incident and fatal overall and luminal A-like, and incident luminal B-like breast cancer but does not decrease overall survival among patients with breast cancer. Further research is needed to elucidate the mechanisms underlying MHT use and breast cancer lethality, and to explore whether MHT use among patients with TNBC is indeed free from harm.
背景:绝经期激素治疗(MHT)与绝经后乳腺癌(主要是管腔A样亚型)风险增加有关。人们对更年期激素疗法对乳腺癌亚型死亡的影响了解较少。本研究旨在探讨MHT的使用与内在样乳腺癌亚型的发病率、死亡率和存活率之间的关系:分析了前瞻性挪威妇女与癌症研究中160881名自述使用过MHT的参与者的数据。其中有7844例乳腺癌病例和721例乳腺癌死亡病例。结果显示,使用MHT与乳腺癌亚型的发病率、死亡率和存活率之间的相关性,采用考克斯比例危险回归法计算出危险比(HRs)和95%置信区间(CIs):与从未使用过雌激素-孕激素疗法(EPT)者相比,目前使用雌激素-孕激素疗法(EPT)者罹患总体乳腺癌、管腔A样乳腺癌和管腔B样乳腺癌的风险分别为1.44(95% CI 1.36-1.52)、1.41(95% CI 1.31-1.52)和1.23(95% CI 1.09-1.40)。在总体乳腺癌、管腔 A 型乳腺癌和管腔 B 型乳腺癌中,使用 EPT 的风险每年分别增加 4%、4% 和 2%。MHT的使用也与总体乳腺癌和管腔A样乳腺癌死亡风险的增加有关,与未使用EPT者相比,目前使用EPT者的风险分别增加了1.61%(95% CI 1.36-1.91)和2.15%(95% CI 1.51-3.05)。在乳腺癌患者中,诊断前使用 MHT 与总体乳腺癌生存率下降无关,但与三阴性乳腺癌(TNBC;当前使用者的死亡 HR 为 0.41;95% CI 为 0.24-0.73)的生存率成反比。不同肿瘤亚型的结果差异很大(同质性 = 0.02):我们的研究表明,使用 MHT 会增加乳腺癌患者罹患乳腺管 A 型乳腺癌和乳腺管 B 型乳腺癌的风险,但不会降低乳腺癌患者的总生存率。需要进一步研究阐明使用MHT与乳腺癌致死的内在机制,并探讨在TNBC患者中使用MHT是否真的无害。
期刊介绍:
Breast Cancer Research, an international, peer-reviewed online journal, publishes original research, reviews, editorials, and reports. It features open-access research articles of exceptional interest across all areas of biology and medicine relevant to breast cancer. This includes normal mammary gland biology, with a special emphasis on the genetic, biochemical, and cellular basis of breast cancer. In addition to basic research, the journal covers preclinical, translational, and clinical studies with a biological basis, including Phase I and Phase II trials.