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Pages: 1255-1266
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The Clinicopathological Features and Prognostic Impact of HER2-Low Breast Tumors Subtype in Morocco: New Opportunity for Untreated Patients

Author: Layla Tahiri Elousrouti, Sanaa Gamrani, Laila Akhouayri, Mehdi Karkouri, Hinde El Fatemi

Category: JMSR Pathology


Introduction: The emergence of a new tumor entity called HER2-low breast cancer leads us to reconsider therapeutic indications in patients whose tumors were considered as HER2-negative. HER2-Low subtype was defined as HER2 1+ and HER2 2+ FISH not amplified. The development of antibody-drug conjugates (ADCs) allows using HER2 as a vector of a cytotoxic drug with significant clinical efficacy and less side effects in breast cancer with HER2 low expression. Herein, we aimed to evaluate the differences in clinicopathological characteristics and prognostic factors between HER2-Low breast carcinoma and those with HER2-negative cancer, according to HR profile. Methods: We conducted a 10-years bicentric cohort study on 1955 invasive breast tumors of Moroccan patients, collected at two Moroccan centers between 2012 and 2022. Results: Out of 1955 BC patients, 49,3% were classified as HER2-Low; of which 80,7% were hormone receptors positive. The clinicopathological features indicate that HER2-Low subtype behave much more like HER2-positive than HER2-negative tumors. The survival analysis showed that the HER2-Low subtype-belonging patients present significantly the poorest prognosis in disease free survival (p=0,003). Hormonal dependent tumors show a significant difference according to HER2 subtypes in DFS (p<0,001). Moreover, patients with HR+/HER2-Low tumors subgroup present a significantly good prognosis in OS compared to the ones with hormonal negative tumors (p =0,008). Discussion: The introduction of the concept of HER2-low BC has extended the benefit observed with novel anti-HER2 agents to a much larger number of patients with BC from 15% to 70%. Several studies reported incidences of 31% to 59,7%, based on data from The Cancer Genome Atlas and clinical trial dataset. HER2-low tumors were frequently found within HR-positive BCs compared to HR-negative cancers. These findings are strongly similar to our results. Early and metastatic BCs characterized by a larger tumor size, more LN metastasis and slightly higher grade in her2-low BC compared to her2 negative, which is similar to our study. According to PAM50 intrinsic classifier, there was a significant difference between her2-low and her2 zero in HR negative group while there is no difference in HR positive group, in particular, HER2 enriched represented 13.7% in HR-/HER2 Low vs 1.6% IN HER2-ZERO. This intrinsic heterogeneity of HER2-Low group, reflected already on clinical outcome, highlights the importance of considering HR status in the HER2-low BCs. Conclusion: HER2-low breast cancer is now distinct subgroup of BCs of which is necessary to consider the HR status. To select HER2-low patients, pathologist must adhere to guidelines and maintain accurate performance and consistent interpretation of test results. Finally, Future prospective analysis and deeper understanding of HER2-low breast cancer requires to allow personalized treatment and avoid under or over treatment.

Keywords: HER2 low, breast cancer, hormone receptors, survival