Early stage breast cancers (BC) are treated the same whether they are HER2 Negative (Neg), which stain 0 for HER2 by immunohistochemistry (IHC), or HER2 Low, which stain 1+ by IHC or 2+ with a negative result for HER2 amplification by fluorescence in-situ hybridization (FISH). Recent studies show metastatic HER2 Low patients can benefit from HER2 targeted therapy. Our study aims to describe the prevalence, pathological, and clinical aspects of HER2 Low compared to HER2 Neg in high risk early stage BC patients within a community practice setting in the United States. High risk early stage BC was defined as BC of stages I-III treated with neoadjuvant or adjuvant chemotherapy.
This retrospective study analyzed 1,106 patients, excluding patients with HER2-positive or metastatic disease. 136 of the 440 HER2 Low patients and 128 of the 365 HER2 Neg patients received chemotherapy and were included. Patients had diagnosis dates between January 1st, 2015 and December 31st, 2021. Categorical and continuous analyses (two-proportion Z test) were performed to study differences between HER2 Low and HER2 Neg patients at time of diagnosis in age, BMI, menopausal status, smoking status, histology, grade, and surgery.
51% of the 264 included patients were HER2 Low and 49% HER2 Neg. 85% of HER2 Low and 83% of HER2 Neg (p=.69) were ductal in histology. Most HER2 Low patients were grade 2 (65%), whereas most HER2 Neg patients were grade 3 (46%). HR+ status was found in 99% of HER2 Low and 71% of HER2 Neg. Mean BMI was 30.6 for HER2 Low and 29.5 for HER2 Neg. HER2 Low (98%) and HER2 Neg (88%) were mainly postmenopausal (p=.58). The majority of HER2 Low (51%) and HER2 Neg (47%) had never smoked (p=.98). Lumpectomies were most common in HER2 Low (51%) and HER2 Neg (49%) (p=.81).
Our study demonstrates that there are both distinguishable and similar aspects between HER2 Low and HER2 Neg patients. A predominant ductal histology and post-menopausal status between both groups was revealed. Differences included a higher prevalence of grade 2 histology and black women affected with HER2 Low tumors. These groups should be studied further in a more diverse patient population with long-term follow up data looking at overall and progression free survival.
1. Hannah Barger, Comprehensive Hematology Oncology: Park Street 2. Rebecca Nashed, Comprehensive Hematology Oncology: Park Street 3. Dylan Schlyer, Comprehensive Hematology Oncology: Park Street 4. Ankur Verma, Comprehensive Hematology Oncology: Park Street 5. Dr. Neeharika Srivastava Makani MD, Comprehensive Hematology Oncology: Park Street.
Dr. Neeharika Srivastava Makani MD.
Has not received any funding.
All authors have declared no conflicts of interest.