Metastatic Breast Cancer: Biomarker Differences Guide Treatment Decisions

A recent study published in the European Medical Journal (EMJ) on February 23, 2026, highlights crucial differences in biomarkers between primary and metastatic breast cancer, particularly focusing on invasive lobular carcinoma (ILC). The findings indicate substantial intra-patient heterogeneity across key prognostic and predictive markers, which raises significant concerns about relying solely on a single site biopsy to guide treatment decisions for metastatic disease. The research, which involved analyzing 306 metastases from 12 patients collected through postmortem tissue donation programs in Belgium (UPTIDER) and the United States (Hope for Others), revealed that metastatic ILC often presents with significantly lower estrogen receptor (ER) and progesterone receptor (PR) expression compared to primary tumors (p<0.01). Conversely, the expression of Ki67, a marker for cell proliferation, was found to be significantly higher in metastases (p=0.02). The study also noted the presence of HER2-low metastases in nearly all patients, though the proportion varied widely. These findings from the EMJ study are corroborated by broader scientific literature, which consistently demonstrates that biomarker status can change during metastatic progression. For example, a systematic review highlighted that biomarker discordance between primary and distant metastases is a recognized phenomenon in breast cancer, occurring more frequently with PR than ER or HER2, and influenced by the site of metastasis. Another study published in PMC indicated that ER and PR expression levels generally decrease during metastatic progression, with a significant rate of positive-to-negative conversion for ER, PR, and HER2 receptors. Such changes in biomarker status, particularly a negative conversion of ER, have been identified as independent poor prognostic factors, underscoring their impact on patient outcomes. The implications of these biomarker differences are profound for clinical practice. Traditionally, treatment decisions for recurrent breast cancer have often been based on the biomarker status of the primary tumor. However, the observed discordance means that treatments targeted at the primary tumor's characteristics may be ineffective or suboptimal against the metastatic lesions. The EMJ study explicitly suggests that reliance on a single metastatic biopsy may lead to inadequate treatment selection due to the significant biological diversity observed at the intra-patient level. This necessitates repeat biomarker testing at the metastatic sites to provide the most up-to-date and accurate information for treatment planning. Biomarker testing is crucial for optimizing patient care in metastatic breast cancer by providing actionable information about a tumor's genomic profile, thereby enabling a more personalized and precise approach to treatment. Various types of biomarkers, including ER, PR, HER2, AKT1, ESR1, NTRK gene fusion, PD-L1, PIK3CA, PTEN, and RET fusion, are routinely tested to guide therapy decisions. The concept of precision medicine, which tailors medical treatment based on an individual's genetic makeup, lifestyle, environment, and unique disease biology, is revolutionizing cancer care. For patients with metastatic breast cancer, precision medicine allows oncologists to select therapies most likely to be effective, improving outcomes and reducing side effects. In India, precision medicine is gaining traction as a transformative approach to breast cancer treatment, particularly given the country's diverse genetic landscape that can lead to significant variations in tumor molecular profiles. However, the implementation of precision oncology in India still faces challenges, including the need for robust biorepositories, state-of-the-art technologies, and timely, precise diagnostic methods to ensure effective therapeutic intervention. In summary, the EMJ article reinforces the critical understanding that metastatic breast cancer is not merely a spread of the primary disease but can evolve with distinct molecular characteristics. This emphasizes the necessity for ongoing and comprehensive biomarker testing of metastatic lesions to facilitate truly personalized and effective treatment strategies, thereby improving prognosis and quality of life for patients globally, including those in India. The study also highlighted moderate concordance between radiology and pathology in detecting metastatic ILC, indicating potential discrepancies that further complicate disease monitoring.

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