Jacob Saya, Christofferson Anika, Fisch Samantha, Norwood Peter, Castillo Paolo, Yu Hongmei, Hirst Gillian, Soliman Hatem, Nanda Rita, Mukhtar Rita A, Ewing Cheryl, Majure Melanie, Melisko Michelle, Rugo Hope S, Esserman Laura, Price Elissa, Chien A Jo
University of California San Francisco Comprehensive Cancer Center, 1825 4 Street, San Francisco, CA, 94158, USA.
University of California San Diego, 9500 Gilman Dr, La Jolla, CA, 92093, USA.
Breast Cancer Res Treat. 2025 Jan;209(1):147-159. doi: 10.1007/s10549-024-07481-w. Epub 2024 Sep 21.
Establishing breast MRI imaging patterns associated with neoadjuvant immunotherapy is needed to monitor response. We analyzed serial breast MRIs in patients receiving neoadjuvant chemo-immunotherapy on the I-SPY2 clinical trial.
Patients with stage 2-3 HER2-negative breast cancer were randomized to weekly paclitaxel (control), weekly paclitaxel and pembrolizumab, or weekly paclitaxel, pembrolizumab and intra-tumoral injection of SD-101, a TLR9 agonist. All patients received AC. Regional lymph nodes were retrospectively evaluated on breast MRI at baseline, 3, 12 and 20 weeks by a single blinded radiologist. MRIs were assessed for development of new regional lymphadenopathy, or increase in the longest diameter or cortical thickness of the largest abnormal regional lymph node.
Between 12/2015 and 4/2021, a total of 43 patients enrolled in the control (n = 16) and paclitaxel + pembrolizumab ± SD-101 (n = 27) arms. 12 of 27 patients (44.4%) receiving chemo-immunotherapy experienced increased lymphadenopathy within the first 12 weeks compared to 1 of 16 patients (6.3%) in the control group (p = 0.014). Most patients with increased lymphadenopathy were in the SD101/pembro arm (n = 10, p = 0.002). Increased lymphadenopathy was observed despite concomitant decrease in breast tumor size at all time points. 11 of 12 patients with increased lymphadenopathy had pathologically negative nodes at surgery. There was no association between lymphadenopathy and lower residual cancer burden or immune-related toxicity.
The combination of neoadjuvant paclitaxel and pembrolizumab ± SD101 intratumoral injection was associated with early increases in regional lymphadenopathy on MRI despite decreased breast tumor size. Increased lymphadenopathy was not associated with node positive disease at surgery.
需要建立与新辅助免疫治疗相关的乳腺MRI成像模式以监测疗效。我们在I-SPY2临床试验中分析了接受新辅助化疗免疫治疗患者的系列乳腺MRI。
将2-3期HER2阴性乳腺癌患者随机分为每周接受紫杉醇（对照组）、每周接受紫杉醇和帕博利珠单抗，或每周接受紫杉醇、帕博利珠单抗及瘤内注射TLR9激动剂SD-101。所有患者均接受AC治疗。由一名单盲放射科医生在基线、第3、12和20周时对乳腺MRI上的区域淋巴结进行回顾性评估。评估MRI上新区域淋巴结病的发生情况，或最大异常区域淋巴结最长径或皮质厚度的增加情况。
在2015年12月至2021年4月期间，共有43例患者入组对照组（n = 16）和紫杉醇+帕博利珠单抗±SD-101组（n = 27）。与对照组16例患者中的1例（6.3%）相比，27例接受化疗免疫治疗的患者中有12例（44.4%）在最初12周内出现淋巴结病增加（p = 0.014）。大多数淋巴结病增加的患者在SD101/帕博利珠单抗组（n = 10，p = 0.002）。尽管在所有时间点乳腺肿瘤大小均有下降，但仍观察到淋巴结病增加。12例淋巴结病增加的患者中有11例在手术时病理检查淋巴结为阴性。淋巴结病与较低的残余癌负担或免疫相关毒性之间无关联。
新辅助紫杉醇与帕博利珠单抗±瘤内注射SD101联合使用，尽管乳腺肿瘤大小减小，但与MRI上区域淋巴结病早期增加相关。淋巴结病增加与手术时淋巴结阳性疾病无关。
