Manfrini Olivia, Cenko Edina, Bergami Maria, Yoon Jinsung, Kostadinovic Jelena, Zdravkovic Darko, Zdravkovic Marija, Bugiardini Raffaele
Laboratory of Epidemiological and Clinical Cardiology, Department of Medical and Surgical Sciences, University of Bologna, 40138 Bologna, Italy.
IRCCS Azienda Ospedaliero-Universitaria di Bologna, Sant'Orsola Hospital, 40138 Bologna, Italy.
J Clin Med. 2025 Jan 14;14(2):484. doi: 10.3390/jcm14020484.
Breast cancer is a prevalent malignancy with rising incidence globally. Advances in endocrine therapy have improved outcomes for premenopausal women with hormone receptor-positive breast cancer. However, these treatments may induce menopause-like states, potentially elevating cardiovascular risks, including left ventricular (LV) dysfunction. This study aims to evaluate the impact of one year of adjuvant endocrine therapy with goserelin and tamoxifen on LV function in premenopausal breast cancer patients. The ISACS cardiovascular toxicity (NCT01218776) is a pilot multicenter registry of breast cancer patients referred to hospitals for routine surveillance, suspected, or confirmed anticancer-drug-related cardiotoxicity (ADRC). Patients may be enrolled retrospectively (1 year) and prospectively. The pilot phase focused on the available data on combined goserelin and tamoxifen therapy for breast cancer and its impact on LV disfunction at 1-year follow-up. Inverse probability of treatment weighting (IPTW) analysis of the ISACS registry was performed assigning 70 patients to combined endocrine therapy (goserelin and tamoxifen). Controls consisted of 120 patients with no adjuvant combined goserelin and tamoxifen therapy. None of the patients developed distant metastasis. Primary outcome measures were as follows: low LV function in women as defined by a left ventricular ejection fraction (LVEF) < 65% and subclinical LV dysfunction as defined by a 10-percentage point decrease in LVEF. In the overall population, combined goserelin and tamoxifen therapy did not affect the mean LV function compared with controls at 3-, 6-, and 12-month follow-up (65.7 ± 2.7% versus 65.3 ± 2.1%, value = 0.27; 65.5 ± 2.9% versus 65.1 ± 2.5%, value = 0.34; 65.0 ± 3.2% versus 64.6 ± 3.1%, value = 0.29, respectively). The mean LVEF reduction in patients who did or did not receive combination therapy for 12 months was small and approximately similar (1.03 ± 2.5% versus 1.16 ± 2.9%, value = 0.73). Using IPTW analyses, there were no significant associations between combined therapy and low LV function (risk ratio [RR]: 1.75; 95% CI: 0.71-4.31) or subclinical LV dysfunction (RR: 1.50; 95% CI: 0.35-6.53) compared with controls. One year of endocrine therapy with goserelin and tamoxifen does not cause ADRC in patients with invasive breast cancer. Findings are independent of the severity of the disease. Results may not be definitive without replication in studies with larger sample size.
乳腺癌是一种全球发病率不断上升的常见恶性肿瘤。内分泌治疗的进展改善了激素受体阳性乳腺癌绝经前女性的治疗效果。然而，这些治疗可能会诱发类似更年期的状态，潜在地增加心血管风险，包括左心室（LV）功能障碍。本研究旨在评估戈舍瑞林和他莫昔芬辅助内分泌治疗一年对绝经前乳腺癌患者左心室功能的影响。ISACS心血管毒性研究（NCT01218776）是一项针对因常规监测、疑似或确诊的抗癌药物相关心脏毒性（ADRC）而转诊至医院的乳腺癌患者的多中心试点登记研究。患者可进行回顾性（1年）和前瞻性入组。试点阶段聚焦于戈舍瑞林和他莫昔芬联合治疗乳腺癌的现有数据及其在1年随访时对左心室功能障碍的影响。对ISACS登记研究进行了逆概率加权（IPTW）分析，将70例患者分配至联合内分泌治疗组（戈舍瑞林和他莫昔芬）。对照组由120例未接受戈舍瑞林和他莫昔芬联合辅助治疗的患者组成。所有患者均未发生远处转移。主要观察指标如下：左心室射血分数（LVEF）<65%定义的女性左心室功能低下，以及LVEF下降10个百分点定义的亚临床左心室功能障碍。在总体人群中，与对照组相比，戈舍瑞林和他莫昔芬联合治疗在3个月、6个月和12个月随访时对平均左心室功能无影响（65.7±2.7%对65.3±2.1%，P值=0.27；65.5±2.9%对65.1±2.5%，P值=0.34；65.0±3.2%对64.6±3.1%，P值=0.29）。接受或未接受联合治疗12个月的患者平均LVEF降低幅度较小且大致相似（1.03±2.5%对1.16±2.9%，P值=0.73）。使用IPTW分析，与对照组相比，联合治疗与左心室功能低下（风险比[RR]：1.75；95%置信区间：0.71 - 4.31）或亚临床左心室功能障碍（RR：1.50；95%置信区间：0.35 - 6.53）之间无显著关联。戈舍瑞林和他莫昔芬内分泌治疗一年不会导致浸润性乳腺癌患者发生ADRC。研究结果与疾病严重程度无关。在更大样本量的研究中未进行重复验证，结果可能不具有决定性。
