Reducing primary tumor volume is the main role of neoadjuvant chemotherapy for breast cancer. We evaluated the benefit of adding docetaxel to anthracyclin as neoadjuvant therapy. This study is a retrospective cohort analysis comparing the efficacy of neoadjuvant chemotherapy in patients subjected to docetaxel and epirubicin or 5-fluoruracil, epirubicin and cyclophosphamide combinations (DE and FEC group, respectively). The mean number of chemotherapy delivered was similar in both groups (P = 0.8). A total of 316 patients were treated (151 in FEC group and 165 in DE group). Primary endpoint was the clinical and pathological response to therapy. Breast conserving surgery rate was compared. In T1/2 staged patients, the complete clinical response rate was 7.5% in FEC group and 32% in DE group (P = 0.002), and the breast conserving surgery rate was 72 and 73% in FEC and DE groups, respectively (P = 0.9). In the subset of patients staged as T3 and T4a-c, objective response was higher in DE group (P < 0.0001 and P = 0.008, respectively). Breast conserving surgery rate was 38 and 63% in FEC and DE groups, respectively, in T3 staged patients and, 20.5 and 37% in T4a-c staged patients (P = 0.003 and 0.08). Despite the similar number of chemotherapy cycles delivered in both groups, the presence of microscopic axillary lymph node involvement after chemotherapy was less frequent in DE group. Neoadjuvant chemotherapy with DE combination is more effective in terms of clinical and pathological response propitiating higher breast conserving surgery rate than FEC combination in stage II and III breast cancer.
e12007 Background: The identification of cancer stem cell (CSC) markers gives opportunity to develop new target therapies. ABCG2 protein is reported as a predictive marker for breast cancer resistance to chemotherapy and as a potential marker for CSC in solid tumors. Methods: We included prospectively 41 patients with locally advanced or metastatic (LAMBC) invasive ductal carcinomas treated with NACT. The expression of CD44/CD24 and ABCG2 was analyzed by flow cytometry after fresh tumor sample digestion. The mammosphere assay (Mammocult) was carried out in 23 samples. We analyzed the correlation between the percentage of ESA+/ABCG2+ and ESA+/CD44+/CD24- cells within the primary tumor with the number of spheres in culture and their relationship with clinical and pathological parameters. ABCG2+ and ABCG2- cells from four primary tumors and from MDA-MB231 cell line were sorted and cultured in triplicate in Mammocult medium for 7 days. The ability to form sphere was analyzed. Patients’ mean age was 52.8 ± 10.3 yo. The ER, PgR and HER2 positive expression rates were 65%, 58% and 45%, respectively. Patients were treated with docetaxel/anthracycline combination (n = 33) of FEC75 combination (n = 8). Results: Complete pathological response was observed in 10 patients (24%). ER negative patients and patients with lower percentage of ABCG2+ cells within the tumor were more likely to achieve near pCR (44% versus 11%, p = 0.04; and 50% versus 14%, p = 0.04, respectively). We did not observe a significant association between pCR and PgR and HER2 expression or the percentage of CD44+/CD24- cells within the tumor. There was a strong correlation between the percentage of ESA+/ABCG2+ cells and the number of mammospheres in culture (r = 0.63; p= 0.0007). This correlation was not significant comparing to CD44+/CD24- cells. Additionally, ABCG2+ cells from primary tumors and MB-231 cell line form a higher number of spheres in culture than ABCG2- (mean difference = 1.15±0.45 /1000 cells, p = 0.04; mean difference = 0.48±0.04 /1000cells, p = 0.008, respectively). Conclusions: ABCG2 is a potential marker for CSC in breast cancer, and the percentage of ABCG2+ cancer cells within the tumor is a predictive factor for pCR in LAMBC patients subjected to NACT.
1075 Background: the expressions of CD44/CD24, CXCR4 and ABCG2 have been reported as potential breast cancer stem-like cell (CSLC) markers. The association between the quantity of CSLCs and the response to neoadjuvant chemotherapy (NACT) remains unclear. Methods: we prospectively analyzed the expression of CD44/CD24, CXCR4 and ABCG2 in 20 patients with locally advanced or metastatic (LAMBC) invasive ductal carcinomas of the breast subjected to NACT. The mammosphere assay (Mammocult) was studied in 10 samples. Patients’ mean age was 55.6 ± 8.2 yo. According to clinical stage (CS), 5 patients were IIb, 4 - IIIa, 8 - IIIb and 3 - IV. The mean clinical tumor diameter was 6.3 ± 2.8cm. The ER, PgR and HER2 positive expression rates were 50%, 45% and 50%, respectively. Ten patients were treated with EC-T, eight were treated with EC-TH (HER2+) and two were treated with FEC75 combination as NACT. The median percentage CD44+/CD24-, CXCR4+, ABCG2+ and ESA+ cells within Lin- cells were determined by flow cytometry in fresh sampled tumors after tissue digestion. The relationship between flow cytometry analyses and clinical and pathological response to therapy was analyzed. Results: complete clinical response (cCR) and complete pathological response (pCR) was observed in 9 (45%) and 5 (25%) patients. We did not observe a significant association between pCR and ER, PgR or HER2 expression. We observed and association between the pCR with percentage of ABCG2+ cells within the tumor and with the number of mammospheres. No correlation between pCR and CD44+/CD24- cell population within the tumor was observed. The median percentage of ESA+/Lin-/ABCG2+ cells within the tumor in pCR patients was 0.6% and 3.5% in patients with no pCR (p= 0.02). The median number of sphere formation was 5/100 cells and 0.9/1000 cells in pCR and non-pCR patients, respectively (p= 0.02). Interestingly, there was a positive correlation between ABCG2 expression and the number of mammosfere formation (r= 0.66; p= 0.03). This correlation was not significant comparing to CD44+/CD24- cells or CXCR4. Conclusions: the percentage of ABCG2+ cancer cells within the tumor and the number of mammosphere formation are predictive factors for pCR in LAMBC patients subjected to NACT. ABCG2 is a potential marker for CSLCs.
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