Clinical and histopathological characterization of metastatic lobular breast cancer: lessons learned from post-mortem tissue donation programs

TL;DR

This study examines metastatic lobular breast cancer using post-mortem tissue donations to better understand tumor characteristics and improve detection methods.

Contribution

The study provides new insights into intra-patient heterogeneity and detection accuracy in metastatic lobular breast cancer using post-mortem data.

Findings

Metastases showed lower ER and PR expression and higher KI67 compared to primary tumors.

HER2-low metastases were common across patients but varied in proportion.

Imaging and pathology had moderate agreement in detecting metastases, highlighting limitations in current methods.

Abstract

While primary invasive lobular carcinoma (ILC) is well characterized, metastatic ILC remains understudied. Within the post-mortem tissue donation programs, UPTIDER (Belgium) and Hope for Others (USA), we first aimed to explore intra-patient heterogeneity of key prognostic and predictive markers (stromal tumor-infiltrating lymphocytes (sTIL), estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and KI67). Secondly, we compared detection of the metastases by pathology on autopsy samples versus pre-mortem imaging. In total, 306 metastases from 12 patients were collected at autopsy (median: 27 per patient). Both primary tumors (n = 15) and metastases (n = 232) had low sTIL levels, with a median of 2% (range: 0.67–6.67%) and 0.67% (range: 0–13.33%), respectively. Regression models showed lower ER- and PR-expression in metastases (respectively, n = 265 and n = 64) compared to primary tumors (both p < 0.01). KI67 was significantly higher in metastases (n = 262, p = 0.02). HER2-low metastases were found in all but one patient although in varying proportion of metastases (range: 7.5–100%). Central radiology and pathology review had a median concordance of 78% at organ level (range: 33.33–100%) and 71% at patient level (range: 55.88-85.29%). Our findings suggest that a single metastatic biopsy has great limitations to guide treatment and that more adequate methods are needed to detect and monitor ILC metastases.

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