对于三阴性乳腺癌和HER2阳性乳腺癌，如果淋巴细胞比例较高，那么术前新辅助治疗后病理完全缓解率可能较高、生存结局可能较好。不过，新辅助治疗后间质肿瘤浸润淋巴细胞比例对于病理完全缓解预测和生存结局预后的影响，以及新辅助治疗前后肿瘤浸润淋巴细胞比例的变化尚未得到充分研究。
2019年7月11日，欧洲癌症治疗研究组织、欧洲癌症组织、欧洲乳腺癌专科医师学会《欧洲癌症杂志》在线发表日本圣路加国际大学医院、冈山大学医院、东海大学医学院、日本医科大学医院、意大利圣拉斐尔大学科学研究院、米兰大学欧洲肿瘤学研究院的研究报告，探讨了三阴性乳腺癌和HER2阳性乳腺癌术前新辅助治疗前后，间质肿瘤浸润淋巴细胞比例及其变化和药物效应动力学调节作用，对病理完全缓解预测和无复发生存结局预后的价值。
该研究对2001～2009年日本圣路加国际大学医院连续209例早期乳腺癌（三阴性80例，HER2阳性129例）患者新辅助治疗前肿瘤浸润淋巴细胞比例与新辅助治疗后病理完全缓解的相关性、新辅助治疗前与新辅助治疗后肿瘤浸润淋巴细胞比例的相关性、残余病变患者免疫动态变化与无复发生存的相关性。
结果，新辅助治疗前肿瘤浸润淋巴细胞比例<10%与≥10%相比，病理完全缓解率较低：
三阴性乳腺癌：4.0%比43.6%
HER2阳性乳腺癌：26.0%比51.9%
中位随访98个月，根据多因素分析，对于残余病变的三阴性乳腺癌，肿瘤浸润淋巴细胞比例：
新辅助治疗前<10%与≥10%相比：复发或死亡风险高3.844倍（95%置信区间：1.190～12.421，P=0.024）
新辅助治疗后<10%与≥10%相比：复发或死亡风险高2.836倍（95%置信区间：0.951～ 8.457，P=0.061）
肿瘤浸润淋巴细胞比例变化与无复发生存无显著相关性。
对于HER2阳性乳腺癌，新辅助治疗前肿瘤浸润淋巴细胞比例<10%与≥10%相比，无复发生存相似。
因此，该研究结果表明，对于三阴性乳腺癌和HER2阳性乳腺癌，如果新辅助治疗前肿瘤浸润性淋巴细胞比例较低，那么病理完全缓解可能性较低。对于残余病变的三阴性乳腺癌，如果新辅助治疗前后肿瘤浸润淋巴细胞比例较低，那么无复发生存时间可能较短。对于新辅助治疗后可能需要进一步治疗的患者，应该将肿瘤浸润淋巴细胞一起考虑进去。
Eur J Cancer. 2019 Jul 11;118:41-48.
Predictive and prognostic value of stromal tumour-infiltrating lymphocytes before and after neoadjuvant therapy in triple negative and HER2-positive breast cancer.
Tomohiro Ochi, Giampaolo Bianchini, Michiko Ando, Fumi Nozaki, Daiki Kobayashi, Carmen Criscitiello, Giuseppe Curigliano, Takayuki Iwamoto, Naoki Niikura, Hiroyuki Takei, Atsushi Yoshida, Junko Takei, Koyu Suzuki, Hideko Yamauchi, Naoki Hayashi.
St. Luke's International Hospital, Tokyo, Japan; San Raffaele Scientific Institute, Milan, Italy; European Institute of Oncology IRCCS, Milan, Italy; University of Milan, Milan, Italy; Okayama University Hospital, st Okayama, Japan; Tokai University School of Medicine, Kanagawa, Japan; Nippon Medical School Hospital, Tokyo, Japan.
HIGHLIGHTS
In TNBC and HER2+ BC, low pre-NAT TILs were associated with low pCR rate.
Low pre-NAT TILs had strong association with poor prognosis in TNBC.
Low post-NAT TILs were associated with shorter RFS in TNBC with RD.
The change of TILs level during NAT did not associate with RFS.
AIM: Lymphocyte predominant breast cancer (BC) is associated with higher pathological complete response (pCR) rate after neoadjuvant therapy (NAT) and favorable outcome in triple negative breast cancer (TNBC) and HER2+ BC. The predictive and prognostic impact of stromal tumour-infiltrating lymphocytes (TILs) after NAT and the change of TILs before (pre-) and after (post-) NAT are not well studied. We aimed to assess the predictive and prognostic value of pre- and post-NAT TILs, as well as their pharmacodynamics modulation and their change for TNBC and HER2+ BC.
MATERIALS AND METHODS: Two-hundred and nine consecutive patients (n = 80 TNBC, n = 129 HER2+ BC) who received NAT between 2001 and 2009 in a single institution were included. We evaluated the association between pre-NAT TILs and pCR, and the association between pre- and post-NAT TILs, as well as their immunodynamics change with relapse-free survival (RFS) for patients with residual disease (RD).
RESULTS: Low pre-NAT TILs compared to int/high were significantly associated with lower pCR rate (TNBC: 4.0% vs 43.6%; HER2+ BC: 26.0% vs 51.9%). The median follow-up period was 98 months. In TNBC with RD, low pre-NAT TILs showed significant association with shorter RFS (HR = 3.844 [1.190-12.421], p = 0.024) in multivariate analysis. Low post-NAT TILs showed borderline significant association with shorter RFS (HR = 2.836 [0.951-8.457], p = 0.061). The change in TILs was not associated with RFS. In HER2+ BC, low pre-NAT TILs were not associated with RFS.
CONCLUSION: In TN and HER2+ BCs, low pre-NAT TILs tumours had a low likelihood of achieving pCR. In TNBC with RD, both low pre- and post-NAT TILs were associated with shorter RFS. These results suggest that TILs information should be taken into account when additional therapies may be given in the post-neoadjuvant setting.
KEYWORDS: Breast cancer, Triple negative breast cancer, Human epithelial growth factor receptor 2, Tumour-infiltrating lymphocytes
DOI: 10.1016/j.ejca.2019.05.014
联系客服
