A high-risk 70-gene signature is not associated with the detection of tumor cell dissemination to the bone marrow.

PURPOSE: The 70-gene signature (70-GS) is a prognostic tool, grouping patients in risk groups to assess their need for adjuvant chemotherapy. Tumor cell dissemination to the bone marrow is a marker of minimal residual disease and associated with impaired survival. In this study, we aimed to evaluate whether 70-GS is associated with the presence of disseminated tumor cells (DTCs) in the bone marrow of patients with early breast cancer. METHODS: In patients with hormone receptor-positive HER2-negative early breast cancer, the 70-GS was obtained and the presence of DTCs was immunohistochemically evaluated using cytokeratin staining with the A45-B/B3 antibody. RESULTS: 149 patients were included into the analysis. 40 (27%) had a high-risk 70-GS and 35 (23%) had detectable DTCs in their bone marrow. 9 (22%) of the 40 patients with high-risk 70-GS and 26 (24%) of the 109 patients with a low-risk 70-GS were positive for DTCs (p = 0.863). CONCLUSIONS: As both 70-GS and DTC detection are known prognostic factors but do not seem to correlate, a follow-up on a larger cohort is warranted to evaluate if a combination of the two is able to better stratify the relapse risk in early breast cancer patients.

Simultaneous detection of circulating and disseminated tumor cells in primary breast cancer patients following neoadjuvant chemotherapy.

PURPOSE: Pathological complete response (pCR) is a common endpoint in neoadjuvant chemotherapy (NACT) of primary breast cancer patients (PBC), but does not address the systemic prevalence of minimal residual disease. In this study, we compared pCR with the detection of circulating (CTC) and disseminated tumor cells (DTC) following NACT, as well as their impact on survival. METHODS: Patients with PBC receiving NACT and consecutive surgery were eligible for this study. CTCs were detected using the CellSearch® system and DTCs were determined using immunocytochemistry (cytokeratin staining with the A45-B/B3 antibody). pCR was defined as ypT0/ypTis and ypN0. RESULTS: 58 patients were included in the analysis with a median follow-up of 30 months. Of these, 5 (9%) presented with CTCs and 36 (62%) with DTCs. 16 patients (28%) achieved a pCR. No significant correlation between CTCs, DTCs and pCR and no statistically significant impact on disease free (DFS) or overall survival (OS) was apparent. CONCLUSIONS: Both CTCs and DTCs are detectable after NACT. As we could not show a significant relationship between CTC detection, DTC detection and pCR, all three methods may provide independent information regarding treatment response. Since we were unable to show a significant impact on survival, larger prospective studies that include CTCs and DTCs are needed. These trials should include the molecular characterization of primary tumor tissue, CTCs and DTCs to determine whether these cells are independent subpopulations of malignant cell clones.

Distribution of the 21-Gene Breast Recurrence Score in Patients with Primary Breast Cancer in Germany.

Background Multigene assays are being used increasingly to aid in decision-making about chemotherapy in breast cancer. Here, we present the 21-gene recurrence score (RS) of patients tested in routine clinical practice in Germany. Patients and Methods In a retrospective analysis, 4695 patients with hormone receptor-positive and HER2-negative early breast cancer (pT1 - 3, pN0 - 1, M0) were included in whom RS testing was conducted in Germany between November 2015 and July 2018. RS groups as defined in the TAILORx trial (RS result 0 - 10; 11 - 25; 26 - 100) were used. Results Of these patients, 21% were assigned to the low RS group, 63% to the midrange RS group, and 15% to the high RS group. 1772 (81%) of 2175 node-negative patients over 50 years of age were grouped either into the low RS group or the midrange RS group. The portion of patients with a low or midrange RS was 90% among node-positive patients (1284 of 1432 patients), 79% among patients with Ki-67-high (≥ 20%) tumors (1829 of 2310 patients), 86% vs. 70% among patients with G2 and G3 tumors (3244 of 3762 patients and 368 of 522 patients), respectively, 88% among patients with a tumor size of > 5 cm (140 of 159 patients), and 82% among node-negative patients at high clinical risk (1110 of 1352). Conclusions The distribution of the 21-gene RS in German patients that were tested in routine clinical practice indicates that, according to the results of the TAILORx trial, chemotherapy may not be beneficial in most of these.