E23: Immunohistochemical Status Predicts Pathologic Complete Response to Neoadjuvant Therapy in HER2 Overexpressing Breast Cancers

ePoster Abstract Author(s)

Leah K. Winer, MD

Fellow
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States

Submitter(s)

Leah K. Winer, MD

Fellow
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States

Author(s)

Leah K. Winer, MD

Fellow
Fox Chase Cancer Center
Philadelphia, Pennsylvania, United States
KR

Karen Ruth, MS

Senior Research Biostatistician
Fox Chase Cancer Center, United States
RN

Rajeswari Nagarathinam, MD

Assistant Professor Pathology
Fox Chase Cancer Center, United States
MM

Melissa McShane, MD

Assistant Professor Medical Oncology
Fox Chase Cancer Center, United States
AP

Andrea S. Porpiglia, MD, Mac

Surgical Oncologist
Department of Surgical Oncology, Fox Chase Cancer Center, United States
MP

Mary Pronovost, MD

Associate Professor Division of Breast Surgical Oncology
Fox Chase Cancer Center, United States
AA

Allison Aggon, DO

Associate Professor Division of Breast Surgical Oncology
Fox Chase Cancer Center, United States
Richard J. Bleicher, MD

Breast Surgical Oncologist
Department of Surgical Oncology, Fox Chase Cancer Center, Philadelphia, PA
Philadelphia, Pennsylvania, United States
Austin D. Williams, MD, MSEd (he/him/his)

Breast Surgical Oncologist, Assistant Professor
Department of Surgical Oncology, Fox Chase Cancer Center; Philadelphia, PA, USA.
Philadelphia, Pennsylvania, United States

Introduction: HER2 overexpression is defined by immunohistochemistry (IHC) and in situ hybridization (ISH) as IHC3+ or IHC2+/ISH+. Many HER2+ breast cancer patients qualify for neoadjuvant anti-HER2 therapy (NT), but differences in response between IHC3+ and IHC2+/ISH+ are poorly understood. We sought to explore whether pathologic complete response (pCR) varies based on HER2 IHC status.

Methods: We identified patients with clinical stage I-III HER2+ breast cancer who underwent NT and surgery between 2013 and 2020 from the National Cancer Database. Patients were stratified by IHC status, and pathologic response in the breast and lymph nodes was analyzed. Multivariable logistic regression was performed to adjust for factors associated with pCR.

Results: Of 42,552 HER2+ patients, 83% were IHC3+ and 17% were IHC2+/ISH+. IHC3+ patients were more likely to be hormone receptor negative (HR-; 33 vs 21%), have high grade (61 vs 55%) and cT3/4 tumors (24 vs 21%), and be cN+ (52 vs 46%, all p< 0.001). Among all patients, the breast pCR rate was 48%, while the nodal pCR rate among the 21,538 cN+ patients was 63%. Compared with IHC2+/ISH+, IHC3+ patients had higher unadjusted breast (54 vs 22%, p< 0.001) and nodal pCR rates (67 vs 37%, p< 0.001). Breast conservation rates were similar (43 vs 44%, p=0.24), although IHC3+ patients had a lower ALND rate (41 vs 44%, p< 0.001). When stratified by HR status, pCR rates were lower among those with HR+ disease, but response rates remained higher among IHC3+ patients regardless of HR status (Table). Further subgroup analysis of patients with node-negative clinical T1c disease (in whom the benefit of NT is less clear) mirrored these trends. On multivariable analysis, adjusting for clinicopathologic features, IHC3+ remained a strong independent predictor of breast (OR 3.61 CI 3.36-3.89, p< 0.001) and nodal pCR (OR 3.07, CI 2.80-3.36, p< 0.001).

Conclusions: HER2 IHC status predicts pCR rates and may serve as a factor, along with HR status and tumor size, to select patients who will derive the greatest benefit from NT. These data offer more evidence that current HER2 classification may require revision to improve appropriate patient selection, counseling, and future trial design.

Learning Objectives:

Describe clinical and histologic differences between IHC2+ and IHC3+ HER2 overexpressing breast cancers.
Understand differences in pathologic response between IHC2+ and IHC3+ HER2+ breast cancers treated with neoadjuvant chemotherapy.
Predict a patient's breast and nodal pCR based on the combination of hormone status and HER IHC status.