Low versus null HER2 tumour expression in "HER2-negative" breast cancer: long-term outcomes based on phenotypes.

Abstract

Background: Two new categories of breast cancer (BC) have been proposed among HER2-negative patients: HER2 0 + and HER2-low breast cancer. We combined these two categories with Perou's classification. We aimed to identify potential differences in clinicopathological features and prognosis using a new, unofficial classification: Luminal A HER2 0 + , Luminal A HER2-Low, Luminal B HER2 0 + , Luminal B HER2- Low, Triple Negative HER2 0 + , and Triple Negative HER2-Low.

Patients and methods: We conducted a retrospective analysis of our database from January 1, 2005, to December 31, 2018. Cox Regression served as the basis for our study.

Results: We identified 1704 BC tumor cases from 1,639 HER2-negative patients (65 had bilateral BC). Among these, 608 cases were HER2 0 + , and 1096 were HER2-Low (aggregate). The median follow-up period was 120 months after surgery. None of the patients received anti-HER2 therapy. Case distribution was as follows: Luminal A HER2 0 + : 259. Luminal A HER2-low: 501. Luminal B HER2 0 + : 219. Luminal B HER2-low: 499. Triple-Negative HER2 0 + : 130. Triple-Negative HER2-low: 96. There was a 12.2% excess in the Triple Negative rate in the HER2 0 + group, compared with the HER2 Low group (aggregate), which was highly significant (Chisquare, p < 0.01). Although the HER2 0 + versus HER2 Low Hazard Ratio (HR) for Specific Mortality was of borderline significance:1.39 (IC 1.00-1.92, p = 0.049), the TN imbalance complicated a direct comparison between the two groups. After stratification using the noncanonical classification, the HR was highly significant, but only for the Luminal A subtype: 2.28 (IC 1.09-4.36, p = 0.028).

Comments: In the noncanonical classification, the effect of the unbalanced Triple-Negative proportions disappeared, and a significant finding emerged: HER2 0 + status had a negative prognostic influence exclusively in Luminal A patients.