Abstract 3222: Assessment of change in HER2 status and its outcomes after neoadjuvant chemotherapy with trastuzumab and/or pertuzumab in early-stage breast cancer patients
Authors: Godbole Manasi M. , Shango Kathren , Meranda Matthew , Wilson Carl P. , Dabak Vrushali 
Published: April 2023

The use of neoadjuvant chemotherapy (NAC) has contributed to increased rates of disease-free survival (DFS) as well as overall survival in breast cancer patients, specifically those with HER2-positive disease. Pathological complete remission (pCR) in HER2-positive breast cancer patients has been associated with better overall prognosis. A discordance in HER2 status between biopsy at diagnosis and that of residual tumor after NAC has been noted in 10-30%; however, the clinical significance remains unclear. We extracted data on patients with stages I-IIIB breast cancer who had HER2-positive status on initial biopsy and received NAC plus anti-HER2 therapy in the Henry Ford Health System between January 2016 to June 2022. Patients with stage 4 breast cancer at diagnosis were excluded. HER2 status detected using IHC and/or FISH testing on initial biopsy samples as well as surgical pathology samples were compared and outcomes for those patients were determined. Of the 200 total patients evaluated, 85 received NAC. The majority of these were females (98%). 51 (60%) were Caucasian and the rest were African American. The median age at diagnosis was 56 years. 45 (53%) had stage 2 disease at diagnosis, 26 (31%) were stage 1 including T1CN0. Lymph node positive disease (N1-N3B) was seen in 52 (62%) patients. Estrogen receptor positivity was noted in 61 (72%) patients. Eight of the 85 patients did not have HER2 status evaluation post NAC due to minimal sample available and therefore, were not included in further analysis. 58 of the 77 patients (76%) had HER2 IHC 3+ and 19 (34%) had HER2 IHC 2+ status on initial biopsy. 35 (45%) of the 77 patients achieved pCR. Of the remaining 42 patients (55%), 10 (24%) did not undergo change in management despite positive HER-2 status on residual tumor due to social issues or side effects from NAC. 26 patients (62%) received treatment with trastuzumab-deruxtecan (t-dxd), 3 (7%) underwent repeat surgery and 3 (7%) had radiation therapy. As per the latest follow up visit, 30 of the 32 (95%) patients have remained in remission after receiving additional treatment and only 2 (5%) had disease progression. In our study, discordance in HER2 status on residual tumor was noted in 10 of 42 patients (24%) after NAC; of these, 7 received treatment with t-dxd and 3 did not undergo change in treatment. All these patients remain disease free at this time. At our institution, the use of NAC as well as t-dxd for HER2 positive patients has shown excellent DFS. The discordance in HER2 status after NAC appears to be similar to available literature. Despite discordant HER2 status after NAC, most patients in our study still switched treatment to t-dxd as per recent guidelines. At this time, a more tailored approach in the post-neoadjuvant setting based on the biological profile of residual disease remains to be an area for further investigation.

Citation Format: Manasi M. Godbole, Kathren Shango, Matthew Meranda, Carl P. Wilson, Vrushali Dabak. Assessment of change in HER2 status and its outcomes after neoadjuvant chemotherapy with trastuzumab and/or pertuzumab in early-stage breast cancer patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3222.