Chae Heejung, Sim Sung Hoon, Kwon Youngmi, Lee Eun-Gyeong, Han Jai Hong, Jung So-Youn, Lee Seeyoun, Kang Han-Sung, Kim Yeon-Joo, Kim Tae Hyun, Lee Keun Seok
Department of Internal Medicine, Center for Breast Cancer, Hospital, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea.
Cancer Data Center, National Cancer Control Institute, National Cancer Center, 323 Ilsanro, Goyang 10408, Republic of Korea.
Cancers (Basel). 2024 Sep 10;16(18):3122. doi: 10.3390/cancers16183122.
The role of combining neoadjuvant endocrine therapy with conventional chemotherapy remains unclear; therefore, we conducted an open-label, single-center, nonrandomized phase II trial to assess the effect of this combination. Patients with previously untreated stage II or III HR-positive, HER2-negative breast cancer received concurrent letrozole 2.5 mg with standard neoadjuvant chemotherapy. The primary endpoint was pathologic complete response (pCR) at the time of surgery. We used Simon's minimax two-stage design; a pCR rate > 6% was necessary at the first stage to continue. Between November 2017 and November 2020, 53 women were enrolled in the first stage of the trial. Their median age was 49 years (range, 33-63), and 60% of them were premenopausal. Subsequently, 66% and 34% of patients with clinical stages II and III, respectively, were included; 93% had clinically node-positive disease. Two patients (4%) achieved pCR after neoadjuvant chemo-endocrine treatment, which did not satisfy the criteria for continuing to the second stage. The overall response rate was 83%. During the median follow-up of 53.7 months, the 3-year disease-free survival and overall survival rates were 87% and 98%, respectively. Neutropenia was the most common grade 3/4 adverse event (40%), but rarely led to febrile neutropenic episodes (4%). Myalgia (32%), nausea (19%), constipation (17%), heartburn (11%), oral mucositis (9%), and sensory neuropathy (9%) were frequently observed, but classified as grade 1 or 2. No deaths occurred during preoperative treatment. The addition of letrozole to standard neoadjuvant chemotherapy was safe and beneficial in terms of overall response rate, but did not provide a higher pCR rate in locally advanced HR-positive, HER2-negative breast cancer. Further research is needed to enhance neoadjuvant treatment strategies for this cancer subtype.
新辅助内分泌治疗与传统化疗联合应用的作用仍不明确；因此，我们开展了一项开放标签、单中心、非随机的II期试验，以评估这种联合治疗的效果。既往未经治疗的II期或III期激素受体（HR）阳性、人表皮生长因子受体2（HER2）阴性乳腺癌患者接受来曲唑2.5 mg与标准新辅助化疗联合治疗。主要终点为手术时的病理完全缓解（pCR）。我们采用西蒙最小最大二阶段设计；第一阶段pCR率>6%才有必要继续试验。2017年11月至2020年11月，53名女性纳入试验第一阶段。她们的中位年龄为49岁（范围33 - 63岁），其中60%为绝经前女性。随后，分别纳入66%的II期和34%的III期临床患者；93%有临床淋巴结阳性疾病。2例患者（4%）在新辅助化疗 - 内分泌治疗后达到pCR，未满足进入第二阶段的标准。总缓解率为83%。在中位随访53.7个月期间，3年无病生存率和总生存率分别为87%和98%。中性粒细胞减少是最常见的3/4级不良事件（40%），但很少导致发热性中性粒细胞减少发作（4%）。经常观察到肌痛（32%）、恶心（19%）、便秘（17%）、烧心（11%）、口腔黏膜炎（9%）和感觉神经病变（9%），但均分类为1级或2级。术前治疗期间无死亡发生。在标准新辅助化疗中加用来曲唑在总缓解率方面是安全且有益的，但在局部晚期HR阳性、HER2阴性乳腺癌中未提供更高的pCR率。需要进一步研究以加强针对这种癌症亚型的新辅助治疗策略。
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