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RNAseq of a Triple-Negative Breast Cancer Cohort Treated with Neoadjuvant Carboplatin and Docetaxel According to Lehmann's Refined Classification

ABSTRACT: Our aims is correlate the data and classification of the subtype breast cancer obtained with the Pam50 assay with the data obtained from the analysis of the same patients RNAseq

ORGANISM(S): Homo sapiens

PROVIDER: GSE181466 | GEO | 2021/08/07

REPOSITORIES: GEO

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Pam50 of a Triple-Negative Breast Cancer Cohort Treated with Neoadjuvant Carboplatin and Docetaxel According to Lehmann's Refined Classification

Project description:Our aims is correlate the data and classification of the subtype breast cancer obtained with the Pam50 assay with the data obtained from the analysis of the same patients RNAseq

2021-08-07 | GSE181548 | GEO

Pathological Response in a Triple-Negative Breast Cancer Cohort Treated with Neoadjuvant Carboplatin and Docetaxel According to Lehmann's Refined Classification.

Project description:Purpose: Triple-negative breast cancer (TNBC) requires the iden- tification of reliable predictors of response to neoadjuvant chemotherapy (NACT). For this purpose, we aimed to evaluate the performance of the TNBCtype-4 classifier in a cohort of patients with TNBC treated with neoadjuvant carboplatin and docetaxel (TCb).Methods: Patients with TNBC were accrued in a nonrandomized trial of neoadjuvant carboplatin AUC 6 and docetaxel 75 mg/m2 for six cycles. Response was evaluated in terms of pathologic complete response (pCR, ypT0/is ypN0) and residual cancer burden by Symmans and colleagues. Lehmann's subtyping was performed using the TNBCtype online tool from RNAseq data, and germline sequencing of a panel of seven DNA damage repair genes was conducted.Results: Ninety-four out of the 121 patients enrolled in the trial had RNAseq available. The overall pCR rate was 44.7%. Lehmann subtype distribution was 34.0% BL1, 20.2% BL2, 23.4% M, 14.9% LAR, and 7.4% were classified as ER+. Response to NACT with TCb was significantly associated with Lehmann subtype (P = 0.027), even in multivariate analysis including tumor size and nodal involvement, with BL1 patients achieving the highest pCR rate (65.6%), followed by BL2 (47.4%), M (36.4%), and LAR (21.4%). BL1 was associated with a significant younger age at diagnosis and higher ki67 values. Among our 10 germline mutation carriers, 30% were BL1, 40% were BL2, and 30% were M.Conclusions: TNBCtype-4 is associated with significantly different pCR rates for the different subtypes, with BL1 and LAR displaying the best and worse responses to NACT, respectively. Clin Cancer Res; 24(8); 1845-52. ©2018 AACR.

| S-EPMC5899625 | biostudies-literature

Pam50 of a Triple-Negative Breast Cancer Cohort Treated with Neoadjuvant Carboplatin and Docetaxel According to Lehmann's Refined Classification

Project description:Pam50 of a Triple-Negative Breast Cancer Cohort Treated with Neoadjuvant Carboplatin and Docetaxel According to Lehmann's Refined Classification

| PRJNA752528 | ENA

RNAseq of a Triple-Negative Breast Cancer Cohort Treated with Neoadjuvant Carboplatin and Docetaxel According to Lehmann's Refined Classification

Project description:RNAseq of a Triple-Negative Breast Cancer Cohort Treated with Neoadjuvant Carboplatin and Docetaxel According to Lehmann's Refined Classification

| PRJNA752116 | ENA

Pathological Response and Survival in Triple-Negative Breast Cancer Following Neoadjuvant Carboplatin plus Docetaxel.

Project description:PurposePrognostic value of pathologic complete response (pCR) and extent of pathologic response attained with anthracycline-free platinum plus taxane neoadjuvant chemotherapy (NAC) in triple-negative breast cancer (TNBC) is unknown. We report recurrence-free survival (RFS) and overall survival (OS) according to degree of pathologic response in patients treated with carboplatin plus docetaxel NAC.Patients and methodsOne-hundred and ninety patients with stage I-III TNBC were treated with neoadjuvant carboplatin (AUC6) plus docetaxel (75 mg/m2) every 21 days × 6 cycles. pCR (no evidence of invasive tumor in breast and axilla) and Residual cancer burden (RCB) were evaluated. Patients were followed for recurrence and survival. Extent of pathologic response was associated with RFS and OS using the Kaplan-Meier method.ResultsMedian age was 51 years, and 52% were node-positive. pCR and RCB I rates were 55% and 13%, respectively. Five percent of pCR patients, 0% of RCB I patients, and 58% of RCB II/III patients received adjuvant anthracyclines. Three-year RFS and OS were 79% and 87%, respectively. Three-year RFS was 90% in patients with pCR and 66% in those without pCR [HR = 0.30; 95% confidence interval (CI), 0.14-0.62; P = 0.0001]. Three-year OS was 94% in patients with pCR and 79% in those without pCR (HR = 0.25; 95% CI, 0.10-0.63; P = 0.001). Patients with RCB I demonstrated 3-year RFS (93%) and OS (100%) similar to those with pCR. On multivariable analysis, higher tumor stage, node positivity, and RCB II/III were associated with worse RFS.ConclusionsNeoadjuvant carboplatin plus docetaxel yields encouraging efficacy in TNBC. Patients achieving pCR or RCB I with this regimen demonstrate excellent 3-year RFS and OS without adjuvant anthracycline.

| S-EPMC6279513 | biostudies-literature

Efficacy of Neoadjuvant Carboplatin plus Docetaxel in Triple-Negative Breast Cancer: Combined Analysis of Two Cohorts.

Project description:PurposeRecent studies demonstrate that addition of neoadjuvant (NA) carboplatin to anthracycline/taxane chemotherapy improves pathologic complete response (pCR) in triple-negative breast cancer (TNBC). Effectiveness of anthracycline-free platinum combinations in TNBC is not well known. Here, we report efficacy of NA carboplatin + docetaxel (CbD) in TNBC.Experimental designThe study population includes 190 patients with stage I-III TNBC treated uniformly on two independent prospective cohorts. All patients were prescribed NA chemotherapy regimen of carboplatin (AUC 6) + docetaxel (75 mg/m2) given every 21 days × 6 cycles. pCR (no evidence of invasive tumor in the breast and axilla) and residual cancer burden (RCB) were evaluated.ResultsAmong 190 patients, median tumor size was 35 mm, 52% were lymph node positive, and 16% had germline BRCA1/2 mutation. The overall pCR and RCB 0 + 1 rates were 55% and 68%, respectively. pCRs in patients with BRCA-associated and wild-type TNBC were 59% and 56%, respectively (P = 0.83). On multivariable analysis, stage III disease was the only factor associated with a lower likelihood of achieving a pCR. Twenty-one percent and 7% of patients, respectively, experienced at least one grade 3 or 4 adverse event.ConclusionsThe CbD regimen was well tolerated and yielded high pCR rates in both BRCA-associated and wild-type TNBC. These results are comparable with pCR achieved with the addition of carboplatin to anthracycline-taxane chemotherapy. Our study adds to the existing data on the efficacy of platinum agents in TNBC and supports further exploration of the CbD regimen in randomized studies. Clin Cancer Res; 23(3); 649-57. ©2016 AACR.

| S-EPMC5156592 | biostudies-literature

Activity of docetaxel, carboplatin, and doxorubicin in patient-derived triple-negative breast cancer xenografts.

Project description:Triple-negative breast cancer (TNBC) is highly responsive to neoadjuvant polychemotherapy regimens including anthracyclines, taxanes, and, more recently, carboplatin. However, there is inadequate information on the individual contribution of each of these agents to the global activity of the combinations, and the use of combinations of up to four of these drugs is associated with relevant toxicity. Identifying single-drug activity in the clinical neoadjuvant setting is challenging. We developed patient-derived xenografts (PDXs) from several chemotherapy-naïve TNBC samples to assess the antitumor activity of single drugs and combinations of drugs. PDXs were established from chemotherapy-naïve TNBC samples. Nine TNBC PDX models (all of which corresponded to a basal-like phenotype according to the PAM50 classifier) were treated with carboplatin, docetaxel, and doxorubicin and the combination of docetaxel and carboplatin. Only one of nine PDX models showed sensitivity to doxorubicin, while eight of nine PDX models showed sensitivity to docetaxel and carboplatin as single agents. The 3 PDX models derived from patients with gBRCA-1 or gPALB2 mutations were very sensitive to carboplatin single agent. All 6 PDX models from patients without hereditary germ-line mutations showed increased sensitivity to the combination of docetaxel and carboplatin. In the present study, docetaxel and carboplatin single agents were active drugs against basal-like TNBC, while doxorubicin monotherapy showed low activity. The combination of docetaxel and carboplatin was more effective than the drugs used as single agents, except in the PDX from patients with gBRCA1/PALB2 mutations.

| S-EPMC8007714 | biostudies-literature

Clinical and Pathologic Response of the Primary Tumor in Women Receiving Neoadjuvant Docetaxel-Capecitabine (+/- Trastuzumab) Chemotherapy

Project description:Results: In subjects who completed treatment and surgery, the pCR and near-complete response rates were 15.8% in HER2-negative and 50% in HER2-positive subjects. When stratified by genomic subtype, subjects of the HER2-enriched subtype had the best response (66.7%), the luminal A (11%) and B (4.8%) subtypes the poorest. Of 147 patients tested for p53 mutations using the AmpliChip test, 78 variants were detected; 55 were missense. The response rate among TP53 mutated patients was 30%, significantly higher than the rate in TP53 wild-type patients (10%, P = .0032). Concordance between AmpliChip mutation status versus IHC staining was 65%, with AmpliChip status being predictive of response and IHC status being not being predictive. Conclusion: Capecitabine plus docetaxel in HER2-negative subjects, and with trastuzumab in HER2-positive subjects, provided a good response rate with fewer cycles. p53 mutational analysis using the AmpliChip p53 assay, and genomic subtyping using the PAM50 assay, were promising predictive tests of response. reference x sample

2011-03-18 | E-GEOD-22358 | biostudies-arrayexpress

The Role of Carboplatin in the Neoadjuvant Chemotherapy Treatment of Triple Negative Breast Cancer.

Project description:Triple negative breast (TNBC) cancer constitutes a heterogeneous group of disease with histologic and molecular differences. Complete pathologic response to neoadjuvant chemotherapy (NACT) in TNBC is associated with improved outcomes. Efforts have been made in identifying drug combinations that will increase the response rate to preoperative chemotherapy. In this review we present recent studies that have incorporated carboplatin (Cb) in the NACT of TNBC. We discuss the homologous recombination deficiency score and the somatic or germline mutation for BRCA as potential biomarkers for future selection of patients that could benefit from the addition of Cb to NACT.

| S-EPMC5365000 | biostudies-literature

Clinical and Pathologic Response of the Primary Tumor in Women Receiving Neoadjuvant Docetaxel-Capecitabine (+/- Trastuzumab) Chemotherapy

2011-03-18 | GSE22358 | GEO