scholarly journals Better pathologic complete response and relapse-free survival after carboplatin plus paclitaxel compared with epirubicin plus paclitaxel as neoadjuvant chemotherapy for locally advanced triple-negative breast cancer: a randomized phase 2 trial

Oncotarget ◽  
2016 ◽  
Vol 7 (37) ◽  
pp. 60647-60656 ◽  
Author(s):  
Pin Zhang ◽  
Yi Yin ◽  
Hongnan Mo ◽  
Bailin Zhang ◽  
Xiang Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Phase 2 ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Phase 2 Trial ◽  
Randomized Phase 2

scholarly journals Neoadjuvant Therapy in Operable Breast Cancer: Application to Triple Negative Breast Cancer

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Foluso O. Ademuyiwa ◽  
Matthew J. Ellis ◽  
Cynthia X. Ma
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Chemotherapy Resistance ◽  
Treatment Strategies ◽  
Surrogate Endpoint ◽  
Complete Response

Systemic treatment for triple negative breast cancer (TNBC: negative for the expression of estrogen receptor and progesterone receptor and HER2 amplification) has been limited to chemotherapy options. Neoadjuvant chemotherapy induces tumor shrinkage and improves the surgical outcomes of patients with locally advanced disease and also identifies those at high risk of disease relapse despite today’s standard of care. By using pathologic complete response as a surrogate endpoint, novel treatment strategies can be efficiently assessed. Tissue analysis in the neoadjuvant setting is also an important research tool for the identification of chemotherapy resistance mechanisms and new therapeutic targets. In this paper, we review data on completed and ongoing neoadjuvant clinical trials in patients with TNBC and discuss treatment controversies that face clinicians and researchers when neoadjuvant chemotherapy is employed.

Results of the East Carolina Breast Center phase II trial of neoadjuvant metronomic chemotherapy in triple-negative breast cancer (NCT00542191).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e11550-e11550
Author(s):  
Stephen Tiley ◽  
Rachel Elizabeth Raab ◽  
Lisa Sheri Bellin ◽  
Jan H. Wong ◽  
Jackie Unger ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Inflammatory Breast Cancer ◽  
Triple Negative ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Metronomic Chemotherapy ◽  
Complete Response ◽  
Weekly Paclitaxel ◽  
Breast Cancers ◽  
Grade 3

e11550 Background: Triple negative (ER negative, PR negative and HER 2 negative) breast cancers (TNBC) lack effective targeted therapy. We sought to determine the benefit of metronomic neoadjuvant chemotherapy utilizing doxorubicin with cyclophosphamide followed by paclitaxel with carboplatin in women with TNBC. Methods: Patients (pts) with TNBC>2cm were eligible (including locally advanced or inflammatory breast cancer). Pretreatment sentinel node biopsy (SLNB) was performed in patients with clinically N0 disease. Treatment consisted of weekly doxorubicin 24 mg/m2 + daily oral cyclophosphamide 60 mg/m2 x 12 weeks followed by weekly paclitaxel 80 mg/m2 + weekly carboplatin AUC 2 x 12 weeks. Granulocyte colony stimulating factor was added for ANC<= 1000. Pts received standard surgery and radiation therapy as indicated. The primary endpoint was pathologic response. Results: Between 2006 and 2011, 17 pts with infiltrating ductal TNBC were enrolled and 15 were analyzed. Age ranged from 25 to 83 (mean age 45yrs), primary tumor size ranged from 2cm to 7cm (mean 3.5cm). Three pts presented with inflammatory breast cancer, 4 had clinical N1 disease and 2 had clinical N0 disease that did not receive SLNB. Six pts underwent SLNB; 3 were pN0 and 3 were pN positive. Two pts came off study due to prolonged neutopenia. Three pts died during therapy-one of MI, one of PE and one had progressive pulmonary disease. No deaths were therapy related. Ten pts completed therapy. One experienced grade 3 (G3) thrombocytopenia, five patients had G4 neutropenia and one developed G3 neuropathy. Ten pts had a clinical complete response (cCR), four had a clinical partial response (cPR) and one progressed on therapy. The rate of pathologic complete response (pCR) was 46.6% (40% pCR, 6.6% CR with foci of DCIS). One patient had a 0.7cm focus of residual invasive carcinoma. Positive nodes were identified in 13.3%-one patient who progressed on therapy and one who experienced a cPR. Conclusions: Neoadjuvant metronomic chemotherapy with weekly doxorubicin plus daily oral cyclophosamide followed by weekly paclitaxel plus carboplatin revealed high rates of pCR with toxicities limited to marrow suppression.

Pathologic complete response rates observed in women with locally advanced and inflammatory breast cancer receiving neoadjuvant carboplatin and paclitaxel.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 1035-1035 ◽  
Author(s):  
Arvind Manohar Shinde ◽  
John H Yim ◽  
Laura Kruper ◽  
Courtney Vito ◽  
Steven L. Chen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Inflammatory Breast Cancer ◽  
Triple Negative ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Hematologic Malignancies ◽  
Cancer Center ◽  
Dose Reductions

1035 Background: Pathologic complete response (pCR) following neoadjuvant chemotherapy (NCT) is predictive of outcome in patients with locally advanced breast cancer (LABC). A non-anthracycline containing NCT regimen (Sikov et al. JCO 10/09) may reduce the risk of associated secondary hematologic malignancies and cardiac toxicity while yielding comparable pCR rates. Methods: A retrospective review of all LABC and inflammatory breast cancer (IBC) cases treated from 4/09 to 12/11 with a NCT regimen of carboplatin (AUC of 6, administered on day 1) and paclitaxel 80 mg/m2 (given weekly on a 21-28 day cycle) was conducted at the City of Hope Cancer Center (COHCC). Pts with HER2+ (HER+) tumors received trastuzumab during the NCT treatment. All pCRs (pCR of primary only – "pCR1°"; pCR of primary and lymph nodes – "pCR-All") were determined by a COHCC pathologist based on final surgical specimens. Results: 38 pts were identified, with 39 breast primaries; 18% had IBC, 62% of LABCs/IBCs were hormone receptor positive (HR+), 46% of tumors were HER2+, and 26% were triple negative. Median age was 51 [27-63]. All pts completed the planned number of cycles. Four pts required carboplatin dose reductions, 4 pts required dose reductions in paclitaxel, 3 pts had paclitaxel changed to nab-paclitaxel, and 17 pts required G-CSF to complete their planned treatment. One pt receiving trastuzumab experienced asymptomatic LVEF decline below normal limits. Conclusions: A non-anthracycline-containing NCT regimen of carboplatin/paclitaxel was well tolerated and resulted in high pCRs when given to triple negative (HER2-/HR-) pts, and HER2+ pts, especially with HER2+HR- subtypes. The findings warrant further studies of this regimen in a prospective randomized setting. [Table: see text]

Capecitabine in operable triple receptor–negative breast cancer: A subgroup analysis of a randomized phase III trial.

2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 292-292
Author(s):  
C. M. Kelly ◽  
M. C. Green ◽  
K. Broglio ◽  
L. Pusztai ◽  
E. Thomas ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Subgroup Analysis ◽  
Triple Negative ◽  
Pathological Complete Response ◽  
Complete Response ◽  
Phase Iii ◽  
Relapse Free Survival ◽  
Phase Iii Trial ◽  
Free Survival

292 Background: Recent data suggest that patients with operable triple negative breast cancer (TNBC) may derive greater benefit from the addition of capecitabine to anthracycline-taxane regimens. Methods: We examined pathological complete response (pCR), relapse-free survival (RFS) and overall survival (OS) in patients with TNBC randomized to paclitaxel 80mg/m2 weekly (WP) x 12 followed by fluorouracil (500mg/m2), epirubicin (100mg/m2), cyclophosphamide (500mg/m2) every 3 weeks x 4 cycles (FEC) vs. docetaxel (75mg/m2) 3 weekly and capecitabine D1-14 (1500mg/m2 daily; DX) followed by FEC. Patients were stratified by timing of chemotherapy (preoperative vs. adjuvant). Results: 149 patients with TNBC comprising 25% of all patients randomized (N=601). Median age; 49 years (IQR; 41 to 55). The number and proportion of patients by stage were; I (n=32: 21.5%), IIA (n=72: 48.3%), IIB (n=34: 22.8%), IIIA (n=9: 6.0%) and IIIC (n=2; 1.3%). Preoperative therapy was administered to 58 patients (39%) and adjuvant to 91 (61%). There were 17 events (21%) in the DX arm and 10 events (15%) in the WP arm (P=0.36) including 11 distant recurrences in the DX arm and 9 in the WP arm (P=0.99). We observed a pCR in 11 patients (37%) and 10 (36%) in the DX and WP arms respectively (P=0.94). The odds ratio for pCR for patients with TNBC given DX vs. WP was 0.98 (95% CI; 0.33 to 2.80: P=0.94). At 50-months median follow-up the RFS and OS in patients with TNBC randomized to DX or WP was 77% (66 to 86%) and 83% (73 to 92%) (P=0.41) and 78% (67 to 87%) and 87% (77 to 95%) (P=0.16) respectively. RFS and OS for WP vs. DX for non-TNBC was 93% (87 to 95%) and 92% (88 to 96%) (p=0.91) and 96% (92 to 98%) and 97% (94 to 99%) for WP and DX respectively (P=0.39). Conclusions: In this unplanned subgroup analysis there was no difference in pCR, RFS or OS in patients with operable TNBC randomized to WP or DX however, power is limited and should be considered when interpreting these data.

Results of a novel neoadjuvant chemotherapy (NAC) regimen for breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e11610-e11610
Author(s):  
Noridza Rivera-Rodriguez ◽  
Fernando Cabanillas ◽  
Lesley Lawrenson ◽  
Viviana Negron ◽  
Orestes Antonio Pavia ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Triple Negative ◽  
Pathologic Complete Response ◽  
Disease Free Survival ◽  
Complete Response ◽  
Her2 Positive ◽  
Free Survival ◽  
Residual Cancer Burden ◽  
Significant Difference

e11610 Background: Achieving a pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) has been associated with improved disease free survival (DFS) and overall survival (OS). The Residual Cancer Burden Score (RCB) method is a useful tool that predicts DFS and OS after NAC. We present the results of pts with either triple negative or HER2 positive breast cancer treated with a novel NAC. Methods: 34 pts with localized breast cancer >1 cm with HER2+ (N=19) or triple negative breast cancer (TNBC) (N=15) were treated with this novel regimen consisting first of TEC (docetaxel 75 mg/m2, epirubicin 80 mg/m2, and cyclophosphamide 500 mg/m2) + PEG Filgrastim x 4 cycles. Following the 4th course, TNBC patients received 4 additional TEC cycles if they achieved CR by MRI, or were switched to a non cross-resistant regimen (vinorelbine, bevacizumab, capecitabine) if they had < CR. HER2+ pts received TEC x4 followed by docetaxel + trastuzumab x 4. RCB score was used to measure pathologic response. Pretreament PET scan was done and repeated after course 1 in order to correlate with RCB. Results: Median age was 56 (58 for Her2+ and 49 for TNBC). RCB= 0 (pCR) was achieved in 76%, while only 1 responded poorly (RCB=3). There was no significant difference in the pCR rate between Her2+ and TNBC patients (74% vs 80% respectively), but there was a difference in the rate of pCR without DCIS and invasive cancer between these two (see table, p=0.034). Pts with SUV drop > 5% after 1st TEC had 84% pCR while none with < 5% achieved pCR (p=0.001). Comparison of our results with other NAC regimens reported in the literature is summarized in the table below. Conclusions: This novel chemotherapy approach results in a high pCR rate and RCB 0-1, which have been associated with improved clinical outcomes. Early PET can predict pCR. Although sample size is modest, results are encouraging and deserve further evaluation. Clinical trial information: NCT 00830544. [Table: see text]

Neoadjuvant platinum-based chemotherapy (CT) for triple-negative locally advanced breast cancer (LABC): Retrospective analysis of 125 patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 625-625 ◽  
Author(s):  
J. P. Leone ◽  
V. Guardiola ◽  
A. Venkatraman ◽  
M. D. Pegram ◽  
C. Welsh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative ◽  
Locally Advanced Breast Cancer ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Growth Factor Receptor ◽  
Complete Response ◽  
Invasive Disease ◽  
Breast Cancers ◽  
Platinum Based Chemotherapy

625 Background: Triple-negative breast cancer (TNBC), defined by lack of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2, accounts for 15–20% of all breast cancers and is associated with poor prognosis. There is no consensus regarding optimal CT for treatment of such patients. Preclinical data suggests TNBC may be sensitive to platinums because of deficiencies in BRCA-associated DNA repair. The aim of this study was to evaluate pathologic complete response (pCR) and overall survival (OS) in patients with TNBC treated with neoadjuvant platinum-based CT. Methods: We identified 674 patients with LABC who received neoadjuvant CT between January 1999 and June 2008 at University of Miami. Of these, 125 (18.5%) had histopathologic confirmation of TNBC. All patients received neoadjuvant platinum salts + docetaxel. 76 (61%) also received neoadjuvant AC, while 42 (34%) received adjuvant AC. pCR was defined as no residual invasive disease in breast and axilla. OS was calculated according to Kaplan-Meier. Results: Demographics: median age 50 (28–86 years). 60% premenopausal. TNM stage distribution: T1 0.9%, T2 5.2%, T3 53.4%, T4 40.5%, N0 25.0%, N1 36.2%, N2 35.4%, N3 3.4%, M0 100%, inflammatory 11%, median tumor size = 9.5 cm. Follow up duration ranged from 0.3 to 8.9 years. pCR was observed in 42 of 125 patients (34%; 95% CI 26–43%). Among patients receiving neoadjuvant AC, 30 of 76 (40%; 95% CI 28–51%) had pCR, while amongst those receiving adjuvant AC, 12 of 42 (29%, 95% CI 16–45%) had pCR at the time of definitive surgery. Patients achieving pCR had significantly higher OS (5-yr rate = 73% in pCR, vs. 49% in non-pCR; p < 0.001). OS in TNBC patients receiving cisplatin/docetaxel was significantly superior to those receiving carboplatin/docetaxel (11 mortality events out of 78 patients receiving cisplatin based CT vs 24 out of 47 receiving carboplatin based CT logrank p = 0.001). Conclusions: To date, this is the largest single institution cohort of locally advanced TNBC uniformly treated with platinum+docetaxel-based CT regimens. Platinum/docetaxel-based neoadjuvant CT provided high rates of pCR and excellent OS for women with locally advanced TNBC. No significant financial relationships to disclose.

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