Prognostic value of HER2-low status in breast cancer: A systematic review and meta-analysis

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Published: 6 Jun 2023
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Dr Chiara Molinelli - Università degli Studi di Genova, Genoa, Italy

Dr Chiara Molinelli speaks to ecancer about a systematic review and meta-analysis that investigated the prognostic value of HER2-low status in breast cancer.

In this study, a systematic literature research of PubMed, Cochrane and conference proceedings up to December 8, 2022, was performed to identify studies comparing survival outcomes of patients affected by HER2-Low BC versus. HER2-zero breast cancer.

The analysis of this data found that regardless of hormone-receptor expression, HER2-low status appears to be associated with an increased overall survival both in the advanced and early settings.


My name is Chiara Molinelli, I am a medical oncology Fellow of Ospedale Policlinico San Martino in Genova, currently a visiting Fellow at the Institut Jules Bordet in Brussels. Today we have presented at the poster session our systematic review and meta-analysis about the prognostic value of HER2 low status. This work was coordinated by Professor de Azambuja from the Institut Jules Bordet and Professor Matteo Lambertini from Policlinico San Martino.

HER2 low breast cancer was previously categorised as HER2 negative but now after the impressive results obtained with trastuzumab deruxtecan they can be considered a target for therapy. Despite these impressive results it was unclear if HER2 low status has a prognostic value or not. That’s why we decided to perform this systematic review and meta-analysis.

We included 42 studies in this meta-analysis with more than 1.7 million patients. What we found is that HER2 low status is associated with better overall survival, both in metastatic and in the early setting. Moreover, we found no significant difference in terms of progression free survival between HER2 zero and HER2 low breast cancer but we found that HER2 low breast cancer reached less frequently pathologic complete response after neoadjuvant therapy as compared to HER2 zero cancers, both in the overall population and in the hormone receptor positive population.

This could be justified by the fact that most of the HER2 low breast cancers are hormone receptor positive and usually luminal cancers are characterised by a less frequent response to neoadjuvant chemotherapy but better overall survival. However, the difference that we found in favour of HER2 low breast cancer in terms of overall survival as light and therefore we cannot consider HER2 low breast cancer a biological entity as of now.

Our work has been accepted in a peer-reviewed journal and it will be published soon so we are very proud of that.