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- Title
Clinical, Epidemiologic, and Pathologic Significance of ERBB2-Low Expression in Breast Cancer.
- Authors
Khoury, Thaer; Mendicino, Lucas; Payne Ondracek, Rochelle; Yao, Song; Davis, Warren; Omilian, Angela R.; Kwan, Marilyn L.; Roh, Janise M.; D'Addario, Lia; Valice, Emily; Fernandez, Daniel; Ergas, Isaac J.; Chua Jr, Alfredo V.; Ambrosone, Christine B.; Kushi, Lawrence H.
- Abstract
Key Points: Question: Is ERBB2-low breast cancer a distinct biologic entity? Findings: In this cohort study of 2200 patients, there were differences in hormone-receptor status, family history, and self-identified race and ethnicity between ERBB2-low and ERBB2-negative status. Within hormone receptor–negative tumors, ERBB2-low status was associated with better survival compared with ERBB2-negative status. Meaning: These findings suggest that ERBB2-low breast cancer might be a distinct biologic entity. This cohort study evaluates the clinical, pathological, and epidemiologic features of breast cancer with ERBB2-low expression compared with BC classified as no ERBB2 expression (ERBB2-negative) in a large population study Importance: It is unclear whether breast cancer (BC) with low ERBB2 expression (ERBB2-low) is a distinct clinical, pathological, and epidemiological entity from BC classified as no ERBB2 expression (ERBB2-negative). Objective: To evaluate the clinical, pathological, and epidemiologic features of BC with ERBB2-low expression compared with ERBB2-negative BC in a large population study. Design, Setting, and Participants: This cohort study was conducted as part of the Pathways Study, a prospective, racially and ethnically diverse cohort study of women with BC enrolled between 2006 and 2013 in Kaiser Permanente Northern California (KPNC). The hematoxylin and eosin slides underwent centralized pathology review, including the percentage of tumor infiltrating lymphocytes (TILs). Breast biomarker results were extracted from pathology reports, and women were included if they had a documented ERBB2 value that was not classified ERBB2-positive. Data were analyzed from February 2023 through January 2024. Exposure: Clinical and tumor characteristics associated with BC and ERBB2-low or ERBB2-negative status. Main Outcome and Measures: ERBB2-low was defined as immunohistochemistry score of 1+ or 2+ (negative by in situ hybridization); ERBB2-negative was defined as immunohistochemistry score of 0+. Other data were collected by self-report or extraction from electronic health records, including BC risk factors, tumor characteristics, treatment modality, and survival outcomes, with recurrence-free survival (RFS) as the primary outcome and overall survival (OS) and BC-specific mortality (BCSM) as secondary outcomes. The clinical, pathological, and epidemiological variables were compared between ERBB2-low and ERBB2-negative BC. Results: Of 2200 eligible patients (all female; with mean [SD] age, 60.4 [11.9] years), 1295 (57.2%) had tumors that were ERBB2-low. Hormone receptors were positive in 1956 patients (88.9%). The sample included 291 Asian patients (13.2%), 166 Black patients (7.5%), 253 Hispanic patients (11.5%), 1439 White patients (65.4%), and 51 patients (2.3%) who identified as other race or ethnicity (eg, American Indian or Alaska Native and Pacific Islander). Within the hormone receptor–negative group, patients whose tumors had ERBB2-low staining, compared with those with ERBB2-negative tumors, had better OS (hazard ratio [HR], 0.54; 95% CI, 0.33-0.91; P =.02), RFS (HR, 0.53; 95% CI, 0.30-0.95; P =.03), and BCSM (HR, 0.43; 95% CI, 0.22-0.84; P =.01). In multivariable survival analysis stratified by hormone receptor status and adjusted for key covariates, patients with ERBB2-low and hormone receptor–negative tumors had lower overall mortality (HR, 0.48; 95% CI, 0.27-0.83; P =.009), RFS (HR, 0.45; 95% CI, 0.24-0.86; P =.02), and BCSM (subdistribution HR, 0.21; 95% CI, 0.10-0.46; P <.001) compared with patients with ERBB2-negative and hormone receptor–negative tumors. Within the hormone receptor–negative subtype, patients with ERBB2-low and high TILs tumors had better survival across all 3 outcomes compared with patients with ERBB2-negative and low TILs tumors. Additionally, patients with ERBB2-low and low TILs tumors had better BCSM (subdistribution HR, 0.36; 95% CI, 0.14-0.92; P =.03). Conclusions and Relevance: These findings suggest that there were clinical, pathological, and epidemiological differences between ERBB2-low and ERBB2-negative BC, raising the possibility that ERBB2-low might be a unique biologic entity.
- Subjects
CALIFORNIA; PEARSON correlation (Statistics); FLUORESCENT dyes; SELF-evaluation; T-test (Statistics); HORMONES; BODY mass index; RESEARCH funding; BREAST tumors; FISHER exact test; MANN Whitney U Test; CHI-squared test; LYMPHOCYTES; DESCRIPTIVE statistics; LONGITUDINAL method; IMMUNOHISTOCHEMISTRY; ELECTRONIC health records; COMPARATIVE studies; BENZOPYRANS; CONFIDENCE intervals; EPIDERMAL growth factor receptors; OVERALL survival
- Publication
JAMA Network Open, 2024, Vol 7, Issue 3, pe243345
- ISSN
2574-3805
- Publication type
Article
- DOI
10.1001/jamanetworkopen.2024.3345