ERBB2-low tumours are not a distinct biologic or prognostic subgroup from ERBB2-0 tumour breast cancer.

1. No significant difference in pCR, DFS, or OS was found for subgroup analysis of ERBB2-0 vs. ERBB2-low tumours

2. Hormone receptor expression is positively associated with ERBB2-low tumours.

Evidence Rating Level: 2 (Good)

Study Rundown: Approximately 80% of breast cancers do not overexpress ERBB2 (formerly known as HER2), making them minimally responsive to targeted treatment options. However, about 50% of these “ERBB2-negative” tumours do have some ERBB2 immunohistochemical expression and therefore show a response to anti-ERBB2 antibody-drug conjugates. This study aimed to determine whether ERBB2-low breast cancer is a distinct subtype from ERBB2-0 by comparing pathologic complete response (pCR), disease-free survival (DFS), and overall survival (OS) after receiving standard treatment. Additionally, the association between ERBB2 and hormone receptor (HR) status was investigated. The pCR was higher for patients with ERBB2-0 tumours as compared to those with ERBB2-low tumours, though the HR-positive subgrouping of these same tumours showed no significant difference. After accounting for confounders, the multivariable analysis indicated that DFS and OS were not significantly different between ERBB2-low and ERBB2-0 tumours. Higher HR expression was found to be associated with higher ERBB2 expression. Limitations to this study included the retrospective nature of this study. Overall, ERBB2-low expression is positively associated with the level of hormone receptor expression after adjustment of confounders and appears to not be a distinct biological entity within breast cancer.

Click to read the study in JAMA Oncology

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In-Depth [prospective cohort]: This single-center cohort study based on a prospectively maintained database recruited 5,235 patients with ERBB2-negative breast cancer; 2,917 of which had ERBB2-low, and 2,318 of which had ERBB2-0 tumours. Exclusion criteria included patients with a tumour testing ERBB2-positive. Of the recruited patients, 675 were included in the outcome analysis, having received neoadjuvant chemotherapy (320 ERBB2-low and 355 ERBB2-0). The outcomes of interest included pathologic complete response (pCR), disease-free survival (DFS), and overall survival (OS). 95 patients with ERBB2-0 tumours had a pCR while 53 of those with ERBB2-low had a pCR (odds ratio (OR), 1.84; 95% confidence interval (CI), 1.27 to 2.70). Through subgroups of those respective categories, positive for HR, showed no significant difference in pCR (16 vs. 20 patients). While the DFS was found to be significantly different between ERBB2-low and ERBB2-0 groups, there was no significant difference when HR-positive tumours were analyzed separately (hazard ratio (HR), 1.13; 95% CI, 0.84-1.52). After adjustment for all confounders, similar outcomes were found for OS (HR, 1.14; 95% CI,0.77-1.67). HR was associated with the status of ERBB2 (adjusted odds ratio (OR), 2.1; 95% CI, 1.73-2.55) and HR expression was more common in ERBB2-low tumours than in ERBB2-0 tumours (2,643 patients vs. 1,895 patients, respectively).

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