Response to neo-adjuvant chemotherapy in women with BRCA1-positive breast cancers.
ABSTRACT There have been no studies to date which look at the relative effectiveness of different regimens of chemotherapy in women who have breast cancer and who carry a BRCA1 germ-line mutation. We wished to compare rates of response to neo-adjuvant chemotherapy in BRCA1 mutation carriers and non-carrier controls.
From a registry of 3,479 patients, we identified 44 Polish women who carried a BRCA1 founder mutation and who had been treated with neo-adjuvant chemotherapy for breast cancer, and 41 age- and hospital-matched controls.
35 of the 44 BRCA1 mutation carriers (80%) experienced a partial or complete response to neo-adjuvant chemotherapy, compared to 39 of the 41 (95%) non-carriers (P=0.05). In the hereditary subgroup, response rates differed depending on whether or not a taxane (docetaxel) was given. Six of the 15 BRCA1 carrier women given docetaxel with doxorubicin responded (complete or partial), compared to 29 of 29 given other (DNA-damaging) therapies (P=0.001). Among the non-carriers, the rates of response to the two categories of chemotherapy were similar.
Breast cancers among BRCA1 carriers frequently do not exhibit sensitivity to docetaxel in the neo-adjuvant setting. It is likely that normal BRCA1 is required for clinical response to mitotic spindle poisons.
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ABSTRACT: As anticipated by their structure and mechanism of action, platinum analogs exhibit clinically significant antitumor activity in the more aggressive forms of breast cancer, both alone and in combination with other cytotoxic agents and targeted therapies. In early-stage human epidermal growth factor receptor-2 (HER2)-positive breast cancer, the administration of carboplatin together with a taxane (usually docetaxel) and trastuzumab (and pertuzumab in the neoadjuvant setting) is a standard of care regimen. In BRCA1 mutation carriers, neoadjuvant treatment with single-agent cisplatin results in a high pathologic complete response (pCR) rate. In both BRCA-mutated and sporadic triple-negative breast cancer, the addition of carboplatin to neoadjuvant chemotherapy significantly increases pCR rates. Despite these encouraging results, many questions remain about the role of platinum analogs in these patient populations, including their optimal doses and schedules, and utility in patients with advanced stage disease. A number of these questions are addressed by ongoing trials.Current Oncology Reports 02/2015; 17(2):428. DOI:10.1007/s11912-014-0428-7 · 2.87 Impact Factor
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ABSTRACT: Breast cancers (BC) are treated with surgery, radiotherapy, and chemotherapy. Neoadjuvant chemotherapy (NACT) is an emerging treatment option in many cancers and is given before primary therapy to shrink tumor size. The efficacy of NACT in varied settings of BC, such as inoperable tumors, borderline resectable tumors, and breast-conserving surgery, has been debated extensively in literature, and the results remain unclear and depended on a wide variety of factors such as cancer type, disease extent, and the specific combination of chemotherapy drugs. This study was performed to examine the efficacy, toxicity, and tolerability of pirarubicin (THP) and epirubicin (EPI) in combination with docetaxel and cyclophosphamide in a NACT setting for BC. A total of 48 patients with stage II or III breast cancers were randomly divided into two groups: THP group and EPI group. The patients in THP group received 2-4 cycles of neoadjuvant chemotherapy with DTC regimen (docetaxel, THP, cyclophosphamide), while patients in the EPI group received 2-4 cycles of DEC regimen (docetaxel, EPI, cyclophosphamide) before surgery. The incidence of adverse reactions and the efficacy of the treatment regimen were compared between the two groups. Prognostic evaluation indexes were estimated by Kaplan-Meier survival analysis, including the 5-year disease-free survival (DFS) and overall survival (OS). The overall response rate in THP group was 83.3 %, and the EPI group showed a response rate of 79.2 %, with no statistically significant difference in response rate between the two groups. The incidence of cardiac toxicity, myelosuppression, nausea, and vomiting in the THP group was significantly lower than the EPI group (all P < 0.05). The incidence of hepatic toxicity, alopecia, and diarrhea in the THP group was also lower than the EPI group, but these differences were not statistically significant. The 5-year DFS and OS in THP versus EPI groups were 80 versus 76 % (DFS) and 86 versus 81 % (OS), respectively. Our study found that NACTwith DTC regimen and DEC regimen were both very effective in treatment of BC. However, THP-based combination therapy was associated with significantly lower incidence of cardiac toxicity, myelosuppression, nausea, and vomiting.Tumor Biology 02/2015; DOI:10.1007/s13277-015-3221-9 · 2.84 Impact Factor
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ABSTRACT: Objective. More and more evidences demonstrate that androgen receptor (AR), epidermal growth factor receptor (EGFR), and breast cancer susceptibility gene 1 (BRCA1) have unique clinical implications for targeted therapy or prognosis in triple-negative breast cancer (TNBC). Therefore, we conducted a meta-analysis to summarize the possible associations. Methods. We retrieved published articles about AR, EGFR, and BRCA1 in TNBC from PubMed and EMBASE. The analysis was performed with Rev-Man 5.2 software. Results. A total of 38 articles were eligible for the meta-analysis. Our study showed that the expression level of EGFR (OR = 6.88, P < 0.00001) and the prevalence of BRCA1 mutation (RR = 5.26, P < 0.00001) were higher in TNBC than non-TNBC. In contrast, the expression level of AR was lower in TNBC than non-TNBC (OR = 0.07, P < 0.00001). In the subgroup related to EGFR expression, the level of EGFR expression was significantly increased in Asians (OR = 9.60) compared with Caucasians (OR = 5.53) for TNBC patients. Additionally, the prevalence of BRCA1 mutation in Asians (RR = 5.43, P < 0.00001) was higher than that in Caucasians (RR = 5.16, P < 0.00001). Conclusions. The distinct expression of AR and EGFR and the prevalence of BRCA1 mutation indicated that AR, EGFR, and BRCA1 might be unique biomarkers for targeted therapy and prognosis in TNBC.BioMed Research International 2015:357485. DOI:10.1155/2015/357485 · 2.71 Impact Factor