Breaking News:Biomarker Diversity In Metastatic ILC– What Just Happened

METASTATIC invasive lobular carcinoma (ILC) demonstrates substantial intra patient heterogeneity across key prognostic and predictive markers, raising concerns about the reliability of single site biopsy to guide treatment decisions.

Metastatic invasive lobular carcinoma was examined through two postmortem tissue donation programmes, UPTIDER in Belgium and Hope for Others in the United States, to characterise variability in stromal tumour infiltrating lymphocytes (sTIL), oestrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), and KI67. Researchers also compared detection of metastases by pathology at autopsy with premortem imaging findings.

Biomarker Heterogeneity in Metastatic ILC

A total of 306 metastases from 12 patients were collected at autopsy, with a median of 27 per patient. Both primary tumours n=15 and metastases n=232 showed low sTIL levels. Median values were: 2% range: 0.67–6.67% in primary tumours; 0.67% range: 0–13.33% in metastases.

Regression modelling demonstrated significantly lower ER and PR expression in metastases compared with primary tumours both p<0.01. KI67 expression was significantly higher in metastases n=262; p=0.02. HER2 low metastases were identified in all but one patient, although the proportion of affected metastases varied widely range: 7.5–100%. These data highlight marked biological diversity within metastatic invasive lobular carcinoma at the intra patient level.

Radiology And Pathology Concordance

Central radiology and pathology review showed moderate concordance in detecting metastatic invasive lobular carcinoma. Median concordance at organ level was: 78% range: 33.33–100%; at patient level: 71% range: 55.88–85.29%. These findings indicate discrepancies between imaging and pathological assessment, with potential implications for disease monitoring.

Clinical Implications for Treatment Selection

The data suggest that reliance on a single metastatic biopsy may inadequately reflect the biological landscape of metastatic invasive lobular carcinoma. Given the observed heterogeneity in hormone receptor expression, proliferation index, and HER2 status, more comprehensive strategies may be required to detect and monitor metastases effectively. For clinicians managing patients with metastatic invasive lobular carcinoma, these findings underscore the need to consider tumour variability about therapeutic planning.

Reference

Zels G et al. Clinical and histopathological characterization of metastatic lobular breast cancer: lessons learned from post-mortem tissue donation programs. Npj Breast Cancer. 2026;