Oncology in Clinical Practice · Published 2026-01-15 · DOI 10.5603/ocp.111460
INTRODUCTION: Receptor discordance between primary and recurrent breast cancer has major therapeutic implications. Dynamic changes in HER2 expression represent a clinically important but incompletely understood phenomenon in breast cancer biology, potentially arising from multiple mechanisms. We present a unique case of breast cancer demonstrating dynamic discordance in HER2 expression, including subsequent HER2-negative findings and later identification of HER2 amplification in the postoperative specimen after chemotherapy. CASE REPORT: A 42-year-old woman was diagnosed with left-sided invasive breast carcinoma (pT2N2, G2, HER2- -positive) and treated with breast-conserving surgery, radiotherapy, anthracycline–taxane chemotherapy with trastuzumab, and endocrine therapy. She remained disease-free for 16 years until imaging revealed suspicious lesions in the previously treated breast. Core biopsy demonstrated grade 3 ER-positive, PR-negative, HER2 1+ breast carcinoma in the region of the previously treated breast, with findings considered compatible with either recurrent disease or a second primary malignancy. Concurrent right axillary lymphadenopathy confirmed breast carcinoma with the same HER2-negative profile. Preoperative docetaxel–cyclophosphamide chemotherapy led to partial regression in both lesions. The patient underwent left mastectomy with excision of recurrent tumor and right modified radical mastectomy. Postoperative histopathology showed HER2 amplification with low proliferation (Ki-67 5%) in the residual left breast tumor, whereas right axillary metastases remained HER2-negative, indicating receptor heterogeneity after neoadjuvant therapy. Trastuzumab with letrozole was reintroduced as adjuvant therapy, along with radiotherapy to the right nodal regions. CONCLUSIONS: This case highlights the diagnostic challenges associated with dynamic receptor discordance and evolving breast cancer biology. Because molecular comparison between the original and subsequent tumors was unavailable, definitive distinction between late recurrence and a second primary malignancy could not be established. The observed heterogeneity in HER2 expression underscores the importance of repeat biomarker reassessment and cautious interpretation of single-site biopsy findings. The case may illustrate the potential impact of intratumoral heterogeneity and clonal selection on treatment decision-making.
Abstract from DOAJ. Public domain (CC0 1.0).
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