Immunological and clinicopathological features predict HER2-positive breast cancer prognosis in the neoadjuvant NeoALTTO and CALGB 40601 randomized trials
Journal Title
Nature Communications
Publication Type
Research article
Abstract
The identification of prognostic markers in patients receiving neoadjuvant therapy is crucial for treatment optimization in HER2-positive breast cancer, with the immune microenvironment being a key factor. Here, we investigate the complexity of B and T cell receptor (BCR and TCR) repertoires in the context of two phase III trials, NeoALTTO and CALGB 40601, evaluating neoadjuvant paclitaxel with trastuzumab and/or lapatinib in women with HER2-positive breast cancer. BCR features, particularly the number of reads and clones, evenness and Gini index, are heterogeneous according to hormone receptor status and PAM50 subtypes. Moreover, BCR measures describing clonal expansion, namely evenness and Gini index, are independent prognostic factors. We present a model developed in NeoALTTO and validated in CALGB 40601 that can predict event-free survival (EFS) by integrating hormone receptor and clinical nodal status, breast pathological complete response (pCR), stromal tumor-infiltrating lymphocyte levels (%) and BCR repertoire evenness. A prognostic score derived from the model and including those variables, HER2-EveNT, allows the identification of patients with 5-year EFS > 90%, and, in those not achieving pCR, of a subgroup of immune-enriched tumors with an excellent outcome despite residual disease.
Keywords
Female; Humans; Antineoplastic Combined Chemotherapy Protocols/therapeutic use; *Breast Neoplasms/drug therapy/genetics; Hormones; Neoadjuvant Therapy; Randomized Controlled Trials as Topic; Receptor, ErbB-2/genetics/therapeutic use; Trastuzumab/therapeutic use; Treatment Outcome; Tumor Microenvironment
Department(s)
Laboratory Research; Medical Oncology
PubMed ID
37923752
Open Access at Publisher's Site
https://doi.org/10.1038/s41467-023-42635-2
Terms of Use/Rights Notice
Refer to copyright notice on published article.


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