Department of Community Medicine, Faculty of Health Sciences, UiT The Arctic University of Norway, 9037, Tromsø, Norway.
Cancer Registry of Norway, Norwegian Institute of Public Health, Oslo, Norway.
Breast Cancer Res. 2024 Nov 4;26(1):151. doi: 10.1186/s13058-024-01897-4.
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.
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.
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 (p = 0.02).
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.
绝经后激素治疗（MHT）与绝经后乳腺癌风险增加相关，主要与腔 A 样亚型相关。MHT 对乳腺癌亚型死亡的影响知之甚少。本研究旨在探讨 MHT 使用与内在样乳腺癌亚型的发病率、死亡率和生存率之间的关联。
对前瞻性挪威妇女与癌症研究中自我报告使用 MHT 的 160881 名参与者的数据进行分析。其中，发生了 7844 例乳腺癌病例和 721 例乳腺癌特异性死亡。使用 Cox 比例风险回归计算 MHT 使用与乳腺癌亚型发病率、死亡率和生存率之间的关联的风险比（HR）及其 95%置信区间（CI）。
MHT 使用与总体、腔 A 样和腔 B 样乳腺癌的风险增加相关，当前雌激素-孕激素治疗（EPT）使用者与从不使用者相比，相应的 HR 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）。EPT 使用的每年风险分别增加 4%、4%和 2%，用于总体、腔 A 样和腔 B 样乳腺癌。MHT 使用还与总体和腔 A 样乳腺癌死亡率的风险增加相关，当前 EPT 使用者与非使用者相比，相应的 HR 分别为 1.61%（95%CI 1.36-1.91）和 2.15%（95%CI 1.51-3.05）。在患有乳腺癌的患者中，MHT 的预先诊断性使用与整体乳腺癌的生存率降低无关，但与三阴性乳腺癌（TNBC）的生存率降低相关（死亡 HR 0.41；95%CI 0.24-0.73，当前使用者）。结果根据肿瘤亚型显著不同（p=0.02）。
我们的研究表明，MHT 使用增加了总体和腔 A 样、总体腔 B 样乳腺癌的发病率和死亡率风险，但并未降低乳腺癌患者的整体生存率。需要进一步研究以阐明 MHT 使用和乳腺癌致死性的机制，并探讨 TNBC 患者中 MHT 使用是否确实没有危害。
