ROLE OF REPLACEMENT OF METASTATIC BREAST CANCER REBIOPSIES BY CIRCULATING TUMOR CELLS (CTCS) -COMPARISON OF ESTROGEN RECEPTOR (ER), PROGESTERONE RECEPTOR (PR) AND HER2 EXPRESSION IN CTCS, PRIMARY TUMORS AND BREAST CANCER (BC) METASTASES

Background: Biopsy of breast cancer (BC) metastases is recommended, confirming the diagnosis, determining ER, PR and HER2 expression and potentially directing treatment according to its findings. Discordances in ER, PR and HER2 status between primary BC and metastases occur in up to 40% of cases. Due to limitations and risks of performing biopsies, more agile and less invasive tools, such as CTCs should be explored. Objective: Correlate ER, PR and HER2 status of CTCs, metastases and primary BC, exploring whether CTCs can be used as surrogates for biopsies of metastases. Study design and statistics: prospective study conducted between Sep/17- Jul/19. Blood sample were collected from BC patients immediately before biopsy of suspected lesion, in any line of treatment (CEP 2345/17). CTCs were isolated by ISET® and ER, PR and HER2 immunocytochemistry assays were performed and compared with those of the primary tumor and metastasis. Concordance between tumor compartments was assessed by the kappa test. Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy values were also determined. Results: 39 patients were enrolled in the study, 12 patients excluded due to negative biopsies, second malignancy or biopsies not performed. Age ranged from 26 to 78y (median 39y), 55% were ER+/HER2-, 29.6% triple negative (TN). Median CTCs count was 3.25 cells/ml (0 to 23). There was a high rate of concordance of ER (92.5%), PR (81.5%) and HER2 (96.2%) status in primary tumor and metastasis. According to subtypes of BC, HER2 expression and triple negative (TN) pattern remained the same in primary tumors and metastases (kappa= 0.938, p <0.0001). Comparison between protein expression of CTCs and metastases showed great variability and the concordance of CTCs and metastases subtypes were not significant (kappa = 0.156; p = 0.31). However, CTCs were able to predict non-TN metastasis subtype with high specificity(93%) and accuracy(84,2%). Conclusions: – In this cohort, we did not observe a significant change in ER, PR and HER2 status between primary BC and metastases. – The expression of ER, PR and HER2 of the CTCs identified by ISET® did not present a consistent correlation with those expressed by metastases. However, CTCs had a high specificity differentiating TN and non-TN tumors, and could favor CTCs as surrogates of biopsy of the metastatic site. Expanding the sample is essential.