Miyazato Keiko, Ohtsu Hiroshi, Shimomura Akihiko, Yonemoto Naohiro, Shimizu Chikako, Sase Kazuhiro, Ueda Shinichiro
Department of Clinical Research and Management, Graduate School of Medicine, University of Ryukyus, Japan; Department of Breast Surgery, Urasoe General Hospital, Japan.
Faculty of Health Data Science, Juntendo University, Japan; Clinical Pharmacology and Regulatory Science, Graduate School of Medicine, Juntendo University, Japan; Institute for Medical Regulatory Science, Organization for University Research Initiatives, Waseda University, Japan.
Breast. 2025 Feb;79:103871. doi: 10.1016/j.breast.2024.103871. Epub 2024 Dec 31.
Standard trastuzumab therapy can reduce the risk of early recurrence of HER2-positive breast cancer. However, trastuzumab-induced cardiac dysfunction may force the discontinuation of adjuvant trastuzumab therapy. Incidentally, there are still unclear whether or not trastuzumab treatment should be continued in the setting of reduced cardiac function. We aimed to investigate the association between trastuzumab discontinuation, the development of cardiac dysfunction during trastuzumab treatment, and all-cause mortality using the JMDC as the Japanese claims database. Between 2010 and 2019, 1779 women with early-stage breast cancer underwent surgery with adjuvant trastuzumab therapy (TZ). A 1:1 propensity score (PS) matching was conducted for patients who completed or discontinued TZ. The rates of cancer therapy-related-cardiovascular toxicity (CTR-CVT) and mortality in the TZ completion and discontinuation groups were compared. After PS matching, the TZ completion group (CMP_PSM: n = 83) and discontinuation group (INT_PSM: n = 83) were included in the study. TZ was administered for 12 and 5 months in CMP_PSM and INT_PSM, respectively. The cumulative incidence of CTR-CVT was significantly higher in CMP_PSM than INT_PSM (log-rank test, P = .0096). The mortality rate was significantly higher in INT_PSM than in CMP_PSM. The all-cause mortality in INT_PSM tended to increase at a constant rate after treatment, even after discontinuation. Our findings suggest that discontinuation of trastuzumab treatment worsens patient prognosis due to insufficient treatment of breast cancer rather than due to the cardiovascular toxicity of the drug.
标准曲妥珠单抗治疗可降低HER2阳性乳腺癌的早期复发风险。然而，曲妥珠单抗引起的心脏功能障碍可能会迫使辅助性曲妥珠单抗治疗中断。顺便提一下，在心脏功能下降的情况下是否应继续曲妥珠单抗治疗仍不明确。我们旨在利用日本医疗数据中心（JMDC）这一日本索赔数据库，研究曲妥珠单抗停药、曲妥珠单抗治疗期间心脏功能障碍的发生与全因死亡率之间的关联。2010年至2019年期间，1779例早期乳腺癌女性接受了辅助性曲妥珠单抗治疗（TZ）的手术。对完成或停用TZ的患者进行1:1倾向评分（PS）匹配。比较了TZ完成组和停用组中癌症治疗相关心血管毒性（CTR-CVT）和死亡率。PS匹配后，研究纳入了TZ完成组（CMP_PSM：n = 83）和停用组（INT_PSM：n = 83）。CMP_PSM组和INT_PSM组分别接受了12个月和5个月的TZ治疗。CMP_PSM组的CTR-CVT累积发生率显著高于INT_PSM组（对数秩检验，P = 0.0096）。INT_PSM组的死亡率显著高于CMP_PSM组。即使在停药后，INT_PSM组的全因死亡率在治疗后仍呈恒定速率上升。我们的研究结果表明，曲妥珠单抗治疗的中断会使患者预后恶化，原因是乳腺癌治疗不足，而非药物的心血管毒性。
