What question did this study set out to answer?

To investigate the role of a rare CASR mutation in a HER2-positive breast cancer patient and its implications for hereditary risk.

June 17, 2026Open Access

A Case Report: A Rare Casr Mutation Associated with HER2-Positive Breast Cancer

Key Points

To investigate the role of a rare CASR mutation in a HER2-positive breast cancer patient and its implications for hereditary risk.
Described clinical and genetic findings in a breast cancer patient with HER2-positive infiltrating ductal carcinoma.
Utilized next-generation sequencing to identify genetic variants, specifically the heterozygous CASR c.2265G>T mutation.
Conducted neoadjuvant chemotherapy followed by mastectomy and trastuzumab therapy.
The patient achieved complete pathological regression (pCR) following treatment with trastuzumab and no recurrence after ten months.
A rare CASR variant (p.Glu755Asp) was identified, classified as a variant of uncertain significance (VUS).
No pathogenic mutations were found in other known breast cancer susceptibility genes (BRCA1/2, CHEK2, PALB2).

Abstract

Although highly penetrant genes such as BRCA1, BRCA2, TP53, PALB2, CHEK2, and ATM are well known in hereditary breast cancer, genes with low penetrance may also contribute to the disease risk. The CASR (Calcium-Sensing Receptor) gene, located on chromosome 3q13.3-q21, encodes a G-protein-coupled receptor that regulates calcium homeostasis and parathyroid hormone secretion. here we describe the clinical course and genetic findings in a breast cancer patient diagnosed with hER2-positive (hER2/neu +++) and ER/PR-negative infiltrating ductal carcinoma with a rare CASR mutation and explore its potential role in the hereditary breast cancer predisposition. Next-generation sequencing re- vealed a heterozygous CASR variant, c.2265G>t (p.Glu755Asp), classified as a variant of uncertain significance (VUS). No pathogenic mutations were found in BRCA1/2, CHEK2, or PALB2. The patient underwent neoadjuvant chemothera- py, right-sided mastectomy, and trastuzumab therapy, achieving complete pathological regression (pCR) with no recur- rence after ten months of follow-up. Although the CASR p.Glu755Asp variant's pathogenic role is unproven, emerging evidence links CASR overexpression with hER2-positive breast cancers, promoting tumor progression via calcium- dependent signaling pathways (PI3K/AKt, MAPK). This case highlights the potential role of CASR as a low-penetrance susceptibility gene in breast cancer and supports further functional and genomic studies to clarify its clinical impact.

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