Abstract P2-13-11: Response to anti-HER2 neoadjuvant chemotherapy in invasive breast cancers with different HER2 FISH-positive patterns

Abstract Backgrounds: Since human epidermal growth factor receptor 2 (HER2)-positive breast cancers may have different HER2/CEP17 ratios and HER2 copy numbers, outcomes of HER2-positive breast cancer patients treated with anti-HER2 neoadjuvant chemotherapy (NACT) may be different. The aim of this study is to explore the relationship between different groups of HER2 fluorescence in situ hybridization (FISH) positive patterns and response to anti-HER2 NACT. Methods: 513 HER2-positive invasive breast cancers who received anti-HER2 NACT in Fudan University Shanghai Cancer Center, during January 2015 to September 2020, were collected. According to FISH results, 513 patients were divided into three groups. Group A: HER2/CEP17 < 2.0 and HER2 average copy number ≥6.0; Group B: HER2/CEP17≥2.0 and HER2 average copy number ≥4.0 and < 6.0; Group C: HER2/CEP17≥2.0 and HER2 average copy number ≥6.0. Clinicopathological characteristics and pathological complete response(pCR) rates of three groups were analyzed. Results: All 513 patients were treated with anti-HER2 NACT. The anti-HER2 treatment included trastuzumab in 463 (90.3%) patients, trastuzumab plus pertuzumab in 21 (4.1%) patients, trastuzumab plus lapatinib in 3 (0.6%) patients, and trastuzumab plus pyrotinib in 1 (0.2%) patient. 25 (4.9%) cases were unblinded in clinical trials, who were treated either with trastuzumab plus pertuzumab or with trastuzumab plus pyrotinib. Among 513 patients, 237 cases (46.2%)were luminal B (hormone receptor positive and HER2 positive) and 276 cases (53.8%) were hormone receptor negative and HER2 overexpressed (HER2 overexpression type). According to IHC results, cases with HER2 1+,2+ and 3+ were 8 (1.6%), 123 (24.0%) and 382(74.5%), respectively. Among them, 0.0%, 25.2%, and 48.7% achieved pCR (p<0.001). The pCR rate of HER2 overexpression type was higher than that of luminal B type (54.0% vs 28.7%, P<0.001). Lymph nodes with metastasis after NACT in luminal B type was higher than that of HER2 overexpression type (43.0% vs 21.4%, P<0.001). According to HER2-FISH results, 11 cases (2.1%) were group A, 28 cases (5.5%) were group B and 474 cases (92.4%) were group C. Compared with the pCR rate of group A (36.4%) and group C (44.5%), the pCR rate in group B (7.1%) was significantly lower (p<0.001). Conclusions: Among HER2-positive breast cancers, HER2 protein expression level was positively correlated with pCR rate. Luminal B(HER2+)patients benefited less from anti-HER2 NACT than HER2 overexpression patients. Although all were invasive breast cancers with positive HER2-FISH results, patients with HER2/CEP17≥2.0 and HER2 copy number ≥4.0 and <6.0 seemed to respond less favorably to anti-HER2 NACT compared with other groups. The biological characteristics of this group of patients are worthy of further study. Citation Format: Hong Lv, Qian-Ming Bai, Yin Liu, Zhong-Hua Wang, Ruo-Hong Shui, Hong-Fen Lu, Xiao-Li Xu, Bao-Hua Yu, Xiao-Yu Tu, Rui Bi, Yu-Fan Cheng, Xiao-Yan Zhou, Zhi-Min Shao, Wen-Tao Yang. Response to anti-HER2 neoadjuvant chemotherapy in invasive breast cancers with different HER2 FISH-positive patterns [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-13-11.