Abstract
Expression of hormone receptor (HR) for estrogens (ER) and progesterone (PR) and HER2 remains the cornerstone to define the therapeutic strategy for breast cancer patients. We aimed to compare phenotypic profiles between matched primary and metastatic breast cancer (MBC) in the ESME database, a National real-life multicenter cohort of MBC patients. Patients with results available on both primary tumour and metastatic disease within 6 months of MBC diagnosis and before any tumour progression were eligible for the main analysis. Among the 16,703 patients included in the database, 1677 (10.0%) had available biopsy results at MBC diagnosis and on matched primary tumour. The change rate of either HR or HER2 was 27.0%. Global HR status changed (from positive = either ER or PR positive, to negative = both negative; and reverse) in 14.2% of the cases (expression loss in 72.5% and gain in 27.5%). HER2 status changed in 7.8% (amplification loss in 45.2%). The discordance rate appeared similar across different biopsy sites. Metastasis to bone, HER2+ and RH+/HER2- subtypes and previous adjuvant endocrine therapy, but not relapse interval were associated with an HR discordance in multivariable analysis. Loss of HR status was significantly associated with a risk of death (HR adjusted = 1.51, p = 0.002) while gain of HR and HER2 discordance was not. In conclusion, discordance of HR and HER2 expression between primary and metastatic breast cancer cannot be neglected. In addition, HR loss is associated with worse survival. Sampling metastatic sites is essential for treatment adjustment.
Highlights
Breast cancer (BC) is the most prevalent malignancy, and metastatic breast cancer (MBC) the leading cause of cancer mortality among women in Western countries[1]
Two thousands nine hundred thirty three patients (17.6%) had a metastatic biopsy performed at diagnosis or within the 6 months, among whom 1677 had hormone receptor (HR) and/or human epidermal growth factor receptor 2 (HER2) status available on both MBC biopsy and primary tumour samples
Factors associated with HR discordance are metastasis to bone, both HR+/HER2− and HER2 + MBC subtypes as well as endocrine therapy in adjuvant setting
Summary
Breast cancer (BC) is the most prevalent malignancy, and metastatic breast cancer (MBC) the leading cause of cancer mortality among women in Western countries[1]. Around 5% of women diagnosed with breast cancer have synchronous metastases, while ~20% of those with early breast cancers will relapse and develop an incurable metastatic disease[2] In both early and metastatic stages, therapeutic strategy and prognosis are highly dependent on the immunohistochemical evaluation of three major markers, estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2). In the past 20 years, several reports have highlighted the occurrence of ER, PR and HER2 expression changes between primary tumour and metastatic sites The frequency of such HR/HER2 status modifications varies widely in the literature with reported discordance rates ranging from 10 to 56% for ER, 25 to 49% for PR and 3 to 16% for HER24–10. The present study aimed at (i) comparing tumour immunophenotypic profiles between matched breast cancer primaries and metastatic sites in ESME-MBC, and (ii) assessing the impact of potential discordances on patient outcome
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