Germline mutation status and therapy response in high-risk early breast cancer: Results of the GeparOcto study (NCT02125344).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 573-573 ◽  
Author(s):  
Esther Pohl-Rescigno ◽  
Jan Hauke ◽  
Kerstin Rhiem ◽  
Volker Möbus ◽  
Jenny Furlanetto ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Early Breast Cancer ◽  
Germline Mutation ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Pegylated Liposomal Doxorubicin ◽  
Therapy Response ◽  
Mutation Status ◽  
Predisposition Genes

573 Background: GeparOcto compared the efficacy of two neoadjuvant treatment (NAT) regimens in high-risk early breast cancer (BC): Sequential intense dose-dense epirubicin, paclitaxel, and cyclophosphamide (iddEPC) and weekly paclitaxel plus non-pegylated liposomal doxorubicin (PM), plus carboplatin (PMCb) in triple-negative BC (TNBC). There was no difference in pathologic complete response (pCR) rates (Schneeweiss et al. Eur J Cancer 2019). Here, we stratified pCR rates according to germline mutation status. Methods: Germline (g) mutation analysis of BRCA1/2 and 16 further BC predisposition genes in 914 patients (pts) enrolled (393 pts with TNBC, iddEPC n = 194, PMCb n = 199; 156 pts with HER2-/HR+ BC, iddEPC n = 75, PM n = 81; and 365 pts with HER2+ BC, iddEPC n = 182, PM n = 183). Results: The gBRCA1/2 mutation prevalence was 17.6% in TNBC, 14.1% in HER2-/HR+ BC and 1.4% in HER2+ BC. Overall, pts with gBRCA1/2 mutations achieved higher pCR rates than gBRCA1/2 wildtype pts (60.4% vs 46.7%, OR 1.74, P = 0.012), with more pronounced effects in the PM(Cb) arm (68.1% vs 45.7%, OR 2.53, P = 0.005). Among gBRCA1/2 wildtype pts, 76 carried mutations in non- BRCA1/2 predisposition genes. pCR rates were similar to those observed in pts without any mutation. Conclusions: Pts with gBRCA1/2 mutations benefitted most from NAT with highest pCR rates achieved in the gBRCA1/2 TNBC / PMCb group. The role of Cb for NAT of gBRCA1/2 TNBC should be further explored. Clinical trial information: NCT02125344. [Table: see text]

Low-dose metronomic cyclophosphamide/methotrexate (LDCM) and aspirin for patients who fail to achieve pathologic complete response (pCR) after neoadjuvant treatment for stage II-III breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e12000-e12000
Author(s):  
Susan Burdette-Radoux ◽  
Chris E. Holmes ◽  
Farrah B. Khan ◽  
Kim Dittus ◽  
Karen M. Wilson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Neoadjuvant Chemotherapy ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Metastatic Breast ◽  
Poor Response ◽  
Stage Ii ◽  
Hematologic Toxicity ◽  
Angiogenic Activity

e12000 Background: Patients (pts) who fail to achieve pCR after neoadjuvant chemotherapy have a 20% risk of recurrence at two years. Data for effective postsurgical chemotherapy in this population is lacking. LDCM is an all-oral chemotherapy regimen with anti-angiogenic activity and acceptable toxicity in metastatic breast cancer. Aspirin is associated with a lower risk of breast cancer recurrence in retrospective studies and has anti-angiogenic activity. Here we combine LDCM and aspirin for high risk pts with poor response to neoadjuvant chemotherapy. Methods: Pts with stage II-III HER-2 negative breast cancer who had residual invasive cancer after neoadjuvant chemotherapy were eligible. Pts completed surgery and radiotherapy prior to enrolment and began study treatment within 180 days of surgery. Pts received four 28-day cycles of LDCM (cyclophosphamide 50 mg po daily, and methotrexate 2.5 mg po twice daily on days 1 and 2 each week ). Aspirin 325 mg daily was added on cycles 3 and 4. Pts were evaluated for the primary endpoint of toxicity and safety every 28 days. Secondary endpoint was 2 year relapse free survival. Results: 10 of 13 planned pts were evaluable for toxicity as of Jan 24, 2013. Pathologic stage ranged from T2N0 to T3N3. 70% of tumors were chemoresistant (stable or upstaged at time of surgery). 60% of pts had hormone receptor positive tumors and received concurrent hormonal therapy. Median age was 59 years (range 38-76). All pts completed 4 cycles of study treatment without dose reduction. There were no grade 3 or 4 related toxicities. Worst hematologic toxicity was grade 2 leukopenia. Worst nonhematologic toxicity was grade 2 fatigue; all other related toxicities were grade 1. 9 pts were evaluable for recurrence and none had recurred at a median followup of 13 months (range 7-23). Conclusions: This antiangiogenic regimen is well tolerated in patients at high risk for recurrence after neoadjuvant chemotherapy, resulting in no recurrences at 13 months followup, and suggesting it may be a candidate for future trials in this setting. Subsequent analyses will include longer term followup and biomarkers for angiogenesis. Clinical trial information: NCT01612247.

A randomised phase III trial comparing two dose-dense, dose-intensified approaches (EPC and PM(Cb)) for neoadjuvant treatment of patients with high-risk early breast cancer (GeparOcto).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 518-518 ◽  
Author(s):  
Andreas Schneeweiss ◽  
Volker Moebus ◽  
Hans Tesch ◽  
Claus Hanusch ◽  
Carsten Denkert ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Early Stage ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Complete Response ◽  
Primary Objective ◽  
Early Stage Breast Cancer ◽  
Phase Iii ◽  
Luminal B

518 Background: The sequential use of intense does-dense (idd) epirubicin, paclitaxel, cyclophosphamide (EPC) and weekly paclitaxel/liposomal doxorubicin (+/- carboplatin (Cb) in triple negative breast cancer (TNBC) (PM(Cb)) are considered highly efficient regimens for high-risk early stage breast cancer (BC). Methods: GeparOcto (NCT02125344) patients (pts) received 18 weeks (wks) either EPC (3x E 150mg/m² q2w followed by 3x P225 mg/m² q2w followed by 3x C 2000mg/m² q2) or PM(Cb) (12x P 80mg/m² plus M 20 mg/m² q1w, plus Cb AUC 1.5 q1w in TNBC). For HER2+ BC trastuzumab 6 (8) mg/kg q3w and pertuzumab 420 (840) mg q3w cycles were given concomitantly with P and C. Pts with histologically confirmed, cT1c - cT4a-d BC and central receptor assessment were included. Pts with HER2+ or TNBC were eligible irrespective of nodal status, luminal B-like tumours only if pN+. Primary objective compared pathologic complete response (pCR) rates (ypT0/is ypN0). Sample size calculations assumed a pCR rate of 50% for EPC and 60% for PM(Cb), requiring 950 pts to show superiority of PM(Cb). Secondary objectives compared pCR rates within the stratified subgroups (BC subtype, HER2+ vs HER2- HR+ vs HER2- HR-), amongst others. Results: 961 pts were recruited between 12/2014 and 05/2016, 945 started treatment. Median age was 48 years, 4% T3, 2% T4d, 46% N+, 82% ductal invasive, 66% G3 tumors; 40% were HER2+, 43% TNBC. 347 pts reported SAEs (176 EPC/171 PM(Cb)) and 2 pts died. 35 pneumonias (2 EPC vs 33 PM(Cb)) and 18 pneumonitis (3 EPC vs 15 PM(Cb)) were reported. 16.4% pts with EPC and 33.8% with PM(Cb) discontinued treatment (p<0.001), mainly due to AEs (47 EPC vs 113 PM(Cb)). Mean treatment duration was 17 wks with EPC and 16 wks with PM(Cb). pCR rate was 48.3% with EPC and 47.6% with PM(Cb)(OR 0.97 (95%CI 0.75-1.25), p=0.876). pCR rate in TNBC was 48.5% with EPC and 51.7% with PM(Cb); in HER2+ 62.0% vs 57.4% and in Luminal B 14.1% vs 14.6%. Conclusions: In high-risk early stage breast cancer pts pCR rates of idd EPC compared to weekly PM(Cb) were not significantly different. PM(Cb) appeared to be less feasible. Clinical trial information: NCT02125344.

Anlotinib plus chemotherapy as neoadjuvant treatment of high-risk, early-stage triple-negative breast cancer: A prospective, single-arm, single-center, phase II clinical study.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12585-e12585
Author(s):  
Xi Chen ◽  
Shuqun Zhang ◽  
Xuexin Li ◽  
Yinbin Zhang ◽  
Youhuai Li ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Neoadjuvant Chemotherapy ◽  
Phase Ii ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Early Stage ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Pathological Stage

e12585 Background: Anlotinib is an oral multi-targeted tyrosine kinase inhibitor (TKI) that strongly inhibits VEGFR, PDGFR, FGFR, and c-kit. Combining anti-angiogenesis with chemotherapy yielded increased response rates in patients with early-stage triple-negative breast cancer (TNBC). This phase II study aims to evaluate the efficacy and safety of adding anlotinib to standard neoadjuvant chemotherapy in primary TNBC. Methods: Patients aged 18 years or older with previously untreated stage ⅡB-IIIA histologically documented TNBC were assigned to receive chemotherapy plus oral Anlotinib (12 mg qd, d1-14; 21 days per cycle; total 8 cycles). Chemotherapy comprised of epirubicin at 90 mg/m2 and cyclophosphamide at 600 mg/m2 followed by docetaxel at 100 mg/m2, (21 days per cycle; both total 4 cycles), which was then followed by surgery. The primary endpoint was pathologic complete response (pCR) (no invasive carcinoma in breast or axilla). Stratification was based on the clinical breast cancer stage. This study is registered on Chinese Clinical Trials.gov (ChiCTR2000038174), and still ongoing. Results: Between July 2019 to June 2020, 18 patients (female) with pathological stage ⅡB (83.3%), and IIIA (16.7%) were enrolled with a median age of 46 years (range: 32-72). Overall pCR rate was 44.4% (8/18, CI 95%: 24.6%-66.3%). The pCR rate of pathological stage IIB patients was 46.7%(CI 95%: 26.7%-69.9%), which is tend to be better than the pCR rate of 33.3%(CI 95%: 6.2%-79.2%) for patients with pathological stage IIIA. There are 21 kind of AEs were observed, all including 56 times grade 1 AEs and 34 times grade 2 AEs, no grade 3 or higher AE was observed. The most common AEs included hand-foot syndrome(55.6% in total with 33.3% grade 2 and 22.2% grade 1), oral mucositis(50.00% in total with 33.3% grade 2 and 16.67% grade 1), fatigue(61.1%, all grade 1), hoarse voice(33.3%, all grade 1), nasal bleeding(27.8%, all grade 1), hypertension(22.2% with 5.6% grade 2) and diarrhea(22.2% with 5.6% grade 2). Neither unexpected safety signals nor treatment-related death occurred. Conclusions: The addition of anlotinib to neoadjuvant chemotherapy showed manageable toxicity and promising antitumor activity for patients with high-risk, early-stage TNBC. Clinical trial information: ChiCTR2000038174.

Low-dose metronomic cyclophosphamide/methotrexate (LDCM) and aspirin for patients without pathologic complete response (pCR) after neoadjuvant treatment for stage II-III breast cancer.

2013 ◽  
Vol 31 (26_suppl) ◽  
pp. 163-163 ◽  
Author(s):  
Susan Burdette-Radoux ◽  
Chris E. Holmes ◽  
Farrah B. Khan ◽  
Kim Dittus ◽  
Karen M. Wilson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Neoadjuvant Chemotherapy ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Metastatic Breast ◽  
Poor Response ◽  
Stage Ii ◽  
Hematologic Toxicity ◽  
Angiogenic Activity

163 Background: Patients (pts) who fail to achieve pCR after neoadjuvant chemotherapy have a 20% risk of recurrence at two years. Data for effective postsurgical chemotherapy in this population is lacking. LDCM is an all-oral chemotherapy regimen with anti-angiogenic activity and acceptable toxicity in metastatic breast cancer. Aspirin is associated with a lower risk of breast cancer recurrence in retrospective studies and has anti-angiogenic activity. Here we combine LDCM and aspirin for high risk pts with poor response to neoadjuvant chemotherapy. Methods: Pts with stage II-III HER-2 negative breast cancer who had residual invasive cancer after neoadjuvant chemotherapy were eligible. Pts completed surgery and radiotherapy prior to enrolment and began study treatment within 180 days of surgery. Pts received four 28-day cycles of LDCM (cyclophosphamide 50 mg po daily, and methotrexate 2.5 mg po twice daily on days 1 and 2 each week ). Aspirin 325 mg daily was added on cycles 3 and 4. Pts were evaluated for the primary endpoint of toxicity and safety every 28 days. Secondary endpoint was 2 year relapse free survival. Results: 10 of 13 planned pts were evaluable for toxicity as of May 4, 2013. Pathologic stage ranged from T2N0 to T3N3. 70% of tumors were chemoresistant (stable or upstaged at time of surgery). 60% of pts had hormone receptor positive tumors and received concurrent hormonal therapy. Median age was 59 years (range 38-76). All pts completed 4 cycles of study treatment without dose reduction. There were no grade 3 or 4 related toxicities. Worst hematologic toxicity was grade 2 leukopenia. Worst nonhematologic toxicity was grade 2 fatigue; all other related toxicities were grade 1. 9 pts were evaluable for recurrence and one had recurred at a median followup of 16 months (range 10-26). Conclusions: This antiangiogenic regimen is well tolerated in patients at high risk for recurrence after neoadjuvant chemotherapy, resulting in one recurrence at 16 months median followup, and it may be a candidate for future trials in this setting. Subsequent analyses will include longer term followup and biomarkers for angiogenesis. Clinical trial information: NCT01612247.

Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) for advanced breast cancer patients with high risk for Hereditary Breast and Ovarian Cancer Syndrome (HBOC).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13549-e13549
Author(s):  
Rosane Oliveira Sant'Ana ◽  
Isabelle Joyce de Lima Silva-Fernandes ◽  
Maria Claudia dos Santos Luciano ◽  
Paulo Goberlanio de Barros Silva ◽  
Marcos Venício Alves Lima
Keyword(s):  
Breast Cancer ◽  
High Risk ◽  
Advanced Breast Cancer ◽  
Germline Mutation ◽  
Advanced Breast ◽  
Breast Cancer Patients ◽  
Mutation Status ◽  
Risk Of Death ◽  
Mutational Status ◽  
The Impact

e13549 Background: Local Advanced Breast Cancer (LABC) is associated with high risk of death. NAC is a safe and effective approach for these populations. pCR is a proven prognostic factor in several studies of NAC. HBOC is associated to high risk of breast cancer usually in young age and especially for BRCA1 mutations with a basal phenotype. The aim of this study was to evaluate the influence of BRCA mutational status on frequence of pCR. Methods: this is part of a retrospective, observational study of prevalence of HBOC among patients admitted for cancer therapy in our institution. Since August, 2018 over 300 pte suspected for HBOC (by NCCN criteria) have been screened for NGS with a 31-gene painel. Statistical analysis performed Person X2/Fisher and logistic regression ( p< 0.05; SPSS 20.0). Results: Most pte were women (80%), with median age of 38y (22-72y), most tumors were (80%) stage III, Luminal B (23%) and TNBC (36%). Pathogenic mutations were identified in 34%(n = 28) of the sample ( BRCA1 50%, BRCA2 16.7%, PALB2 16.7%, follow by TP53, PMS2, XRCC2, MUTYH, BARD1 and ATM with 2.8% each).The majority of patients had more than 1 NCCN criteria: age < 45y (83%), family member with BC < 50y (24%) or TNBC (33%) the most common. TNBC tumors had stronger association with germline mutation ( p< 0.001). Regarding response rate there were 13 stable disease (SD), 5 progressive disease (PD), 43 pCR and 39 pathological partial response (pPR). There were no differences in pRC among mutated or no mutated pte, p= 0,170. However, among mutated TNBC there were strong correlation with more pCR, p< 0,006. There was no difference on pCR rate related to mutation status (BRCA vs Non-BRCA), p = 0,84. Conclusions: the present study corroborates other data about the impact of germline mutation status over pCR after NAC for LABC, except for mutated TNBC population, whose seems to be more NAC sensitive.

scholarly journals A Proposal to Redefine Pathologic Complete Remission as Endpoint following Neoadjuvant Chemotherapy in Early Breast Cancer

Breast Care ◽  
2019 ◽  
Vol 15 (1) ◽  
pp. 67-71
Author(s):  
Mircea Dediu ◽  
Christoph Zielinski
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Meta Analysis ◽  
Pathologic Complete Response ◽  
Neoadjuvant Treatment ◽  
Surrogate Endpoint ◽  
Complete Response ◽  
Lymph Node Status ◽  
Individual Level ◽  
Pathologic Complete Remission

Many analyses of the efficacy of neoadjuvant treatment (NAT) for early breast cancer including a meta-analysis derived from 10 randomized trials came to the conclusion that patients who would achieve pathologic complete response (pCR) following NAT would experience significant improvement in disease-free and overall survival (OS). Thus, pCR was proposed as a surrogate endpoint for OS, with pCR representing a robust prognostic marker for survival at an individual level. In the current analysis, we argue that OS following NAT-induced pCR might have reflected the initial prognosis of patients mainly defined – among other factors – by the initial pathological lymph node status while being largely independent on the type of administrated treatment, thus pleading against the pCR surrogacy hypothesis. We therefore propose to redefine pCR as a surrogate endpoint of NAT trials by the involvement of additional biologic parameters.

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