Abstract P2-13-20: Loss of HER2 expression in HER2-positive breast cancer patients after neoadjuvant therapy
Authors: Sang Yuting , Wu Jiong , Yang Benlong 
Published: March 2022

Background: Neoadjuvant therapy is an important part of treatments for patients with locally advanced operable breast cancer. Addition of HER2 targeted therapy to neoadjuvant therapy greatly improves the pathological complete response (pCR) and prognosis in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. As the essential markers for targeted therapy decision, HER2 status was reported that might be loss in patients undergo neoadjuvant therapy. Therefore, we evaluated the ratio of HER2 loss and its prognostic impact in HER2-positive breast cancer patients treated with neoadjuvant therapy in a large cohort.Methods: A total of 706 patients with HER2-positive breast cancer without distant metastasis who were diagnosed at the Department of Breast Surgery of Fudan University Cancer Hospital from September 2013 to January 2020 and received neoadjuvant treatment were enrolled in the study. After the neoadjuvant treatment, all patients underwent breast surgery. Patients who did not achieve complete pathological remission (non-PCR) would assess the discordance rate of HER2 status between pre- and post-treatment specimens. The expression of HER2 was assessed by immunohistochemistry or combined with fluorescence in situ hybridization (FISH).Results: 35.5.% (n=251) of HER2-positive breast cancer patients who received neoadjuvant therapy achieved pCR. They have prolonged overall survival than who did not achieve pCR (non-pCR) (hazard ratio [HR], 0.26; P = 0.0068). 83.5% (380/455) of the residual tumor lesions were re-tested by immunohistochemistry in non-PCR group. Among them, patients with loss of HER2 positivity accounted for 18.15% (n=69). The rate of HER2 loss was evaluated separately according to baseline status. In IHC 3+ group, 90.7% (258/289) patients remained as HER2 positive after treatment; In IHC 2+ group, 89.3% (47/78) were still HER2 positive while in IHC result 1+ group, 41.7% (5/12) were identified as HER2 positive. The loss of HER2 expression was significantly related to the baseline low HER2 expression (P &lt;0.001) and the application of targeted drugs (P = 0.004). In our study, all of the patients identified as HER2 negative after neoadjuvant therapy continued targeted therapy. In addition, there was no significant difference in overall survival between the HER2 expression loss and non-loss groups (P = 0.43).Conclusion: Our data confirmed a discordance HER2 status between pre- and post-neoadjuvant therapy. The frequency of HER2 loss was different according to the baseline status and the application of additional targeted therapy. No significant overall survival difference was observed.

Clinicopathological characteristics of HER2-positive breast cancer patients.Characteristics No. (%)No. of patients706Age at diagnosis, Median (range, years)59 (23-75)cT stageT04 (0.6)T193 (13.2)T2452 (64.0)T3109 (15.4)T448 (6.8)cN stageN081 (11.5)N1/N2506 (71.7)N3119 (16.8)ER statusPositive636 (90.1)Negative70 (9.9)PR statusPositive615 (87.1)Negative91 (12.9)HER2 statusIHC 3+, FISH-positive481 (68.12)IHC 3+, N/A98 (13.9)IHC 2+, FISH-positive113 (16.0)IHC 1+, FISH-positive14 (1.98)

HER2 status before and after neoadjuvant therapy in patients with HER2-positive breast cancer.Primary tumorn (%)Residual tumorn (%)HER2 statusHER2 statusPositive379 (100)Positive304 (80.2)Negative75 (19.8)HER2 status identified by IHCHER2 status identified by IHCHER2 3+289 (76.3)HER2 3+249 (86.2)HER2 2+31 (10.7)HER2 1+6 (2.1)HER2 03 (1.0)HER2 2+HER2 3+14 (17.9)HER2 2+53 (67.9)HER2 1+9 (11.5)HER2 02 (2.6)HER2 1+HER2 3+2 (16.7)HER2 2+3 (25.0)HER2 1+5 (41.7)HER2 02 (16.7)

Citation Format: Yuting Sang, Jiong Wu, Benlong Yang. Loss of HER2 expression in HER2-positive breast cancer patients after neoadjuvant therapy [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 P2-13-20.