Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Charterhouse Square, Queen Mary University London, London, EC1M 6BQ, UK.
Division of Cancer Sciences, University of Manchester, Wilmslow Road, Manchester, M20 4BX, UK.
Breast. 2020 Dec;54:216-221. doi: 10.1016/j.breast.2020.10.015. Epub 2020 Oct 31.
Studies in the adjuvant setting have shown that endocrine therapy related side effects predict breast cancer recurrence risk. Here, we assess the relationship between early reported side effects and incidence of breast cancer in women randomised to tamoxifen for cancer prevention in the International Breast Intervention Study (IBIS)-I trial.
Women randomised to tamoxifen in the IBIS-I trial and for whom side effect status was known at the 6-month follow-up visit were included in this analysis. Side effects included in this analysis were hot flushes, vaginal discharge, and vaginal dryness. The primary endpoint was all breast cancer and secondary endpoint was oestrogen receptor (ER) positive breast cancer. Cox proportional hazard models were used to investigate breast cancer incidence in the tamoxifen group with and without side effects reported within 6 months of randomisation.
Women randomised to tamoxifen and reporting hot flushes at the 6-month follow-up visit had a non-statistically significant increase in breast cancer compared to those without hot flushes (HR = 1.26 (0.98-1.62), P = 0.08). A significant higher breast cancer risk was observed for postmenopausal women who reported hot flushes at the 6-month follow-up visit compared to those without hot flushes (HR = 1.59 (1.12-2.26), P = 0.01). A higher risk was observed for ER-positive breast cancer in postmenopausal women (HR = 1.81 (1.19-2.74), P = 0.01). No significant associations between gynaecological side effects and breast cancer occurrence was observed.
Overall, no association between side effects reported at 6 months and subsequent breast cancer occurrence was observed. Some side effects might be useful markers for breast cancer occurrence in postmenopausal women.
在辅助治疗环境下的研究表明，内分泌治疗相关的副作用可预测乳腺癌复发风险。在此，我们评估了国际乳腺干预研究（IBIS-I 试验）中随机接受他莫昔芬用于癌症预防的女性中早期报告的副作用与乳腺癌发生之间的关系。
本分析纳入了 IBIS-I 试验中随机接受他莫昔芬且在 6 个月随访时已知副作用状态的女性。本分析纳入的副作用包括热潮红、阴道分泌物和阴道干燥。主要终点是所有乳腺癌，次要终点是雌激素受体（ER）阳性乳腺癌。使用 Cox 比例风险模型研究了随机分组后 6 个月内报告副作用的他莫昔芬组和未报告副作用的他莫昔芬组的乳腺癌发病率。
在 6 个月随访时报告热潮红的随机接受他莫昔芬的女性与未报告热潮红的女性相比，乳腺癌的发生率虽略有增加，但无统计学意义（HR=1.26（0.98-1.62），P=0.08）。在报告 6 个月随访时出现热潮红的绝经后女性中，乳腺癌风险显著升高，与未报告热潮红的女性相比（HR=1.59（1.12-2.26），P=0.01）。在绝经后女性中，观察到 ER 阳性乳腺癌的风险更高（HR=1.81（1.19-2.74），P=0.01）。在报告 6 个月时出现妇科副作用的女性中，未观察到与乳腺癌发生之间存在显著关联。
总体而言，在报告 6 个月后的副作用与随后的乳腺癌发生之间未观察到关联。一些副作用可能是绝经后女性乳腺癌发生的有用标志物。
