Docetaxel carboplatin breast cancer triple negative

Background : Cancer initiation typically occurs when a proto-oncogene's coding region undergoes mutation, resulting in uncontrollable cell growth and division, or when a tumour suppressor gene's coding region is affected by a mutation that inhibits activity of the resulting gene product. The pathophysiologic result is, respectively, exaggerated cell-cycle growth or deficient programmed cell death. Osteopontin (opn) is an integrin-binding phosphoprotein that is expressed on the surface of normal cells. Osteopontin has a major role in diverse tumour components, especially those implicated in invasion and metastasis...

PURPOSE: Addition of carboplatin (Cb) to anthracycline chemotherapy improves pathologic complete response (pCR), and carboplatin plus taxane regimens also yield encouraging pCR rates in triple-negative breast cancer (TNBC). Aim of the NeoSTOP multisite randomized phase II trial was to assess efficacy of anthracycline-free and anthracycline-containing neoadjuvant carboplatin regimens. PATIENTS AND METHODS: Patients aged ≥18 years with stage I-III TNBC were randomized (1:1) to receive either paclitaxel (P) weekly × 12 plus carboplatin AUC6 every 21 days × 4 followed by doxorubicin/cyclophosphamide (AC) every 14 days × 4 (CbP → AC, arm A), or carboplatin AUC6 + docetaxel (D) every 21 days × 6 (CbD, arm B)...

Background: Cancer initiation typically occurs when a proto-oncogene's coding region undergoes mutation, resulting in uncontrollable cell growth and division, or when a tumour suppressor gene's coding region is affected by a mutation that inhibits activity of the resulting gene product. The pathophysiologic result is, respectively, exaggerated cell-cycle growth or deficient programmed cell death. Osteopontin (opn) is an integrin-binding phosphoprotein that is expressed on the surface of normal cells...

BACKGROUND: In the TNT trial of triple negative breast cancer (NCT00532727), germline BRCA1/2 mutations were present in 28% of carboplatin responders. We assessed quantitative measures of structural chromosomal instability (CIN) to identify a wider patient subgroup within TNT with preferential benefit from carboplatin over docetaxel. PATIENTS AND METHODS: Copy number aberrations (CNAs) were established from 135 formalin-fixed paraffin-embedded primary carcinomas using Illumina OmniExpress SNP-arrays...

Orbital metastases are rare. Breast cancer represents the first etiology to be evoked in carcinomas. We report a rare case of a young 43-year-old patient who developed significant orbital metastasis 2 months after the end of adjuvant treatment for triple-negative breast cancer. Good partial response was shown with an improvement of symptoms under chemotherapy (docetaxel combined with carboplatin), zoledronic acid and palliative radiotherapy. The patient quickly progressed in the pulmonary, hepatic and lymph nodes with mucocutaneous jaundice related to hepatic dysfunction after which she died within 20 days...

Importance: The value of platinum-based adjuvant chemotherapy in patients with triple-negative breast cancer (TNBC) remains controversial, as does whether BRCA1 and BRCA2 (BRCA1/2) germline variants are associated with platinum treatment sensitivity. Objective: To compare 6 cycles of paclitaxel plus carboplatin (PCb) with a standard-dose regimen of 3 cycles of cyclophosphamide, epirubicin, and fluorouracil followed by 3 cycles of docetaxel (CEF-T). Design, Setting, and Participants: This phase 3 randomized clinical trial was conducted at 9 cancer centers and hospitals in China...

This study aimed to compare the efficacy and safety of the EC-T (4 cycles of epirubicin 90 mg/m2 + cyclophosphamide 600 mg/m2, followed by 4 cycles of docetaxel 75 mg/m2) and TCb (6 cycles of docetaxel 75 mg/m2, intravenous drip (ID), day 1+carboplatin AUC 6, ID, day 1) neoadjuvant regimens in patients with TOP2A-normal stage II-III breast cancer. This study analyzed 280 patients enrolled from three studies registered with ClinicalTrials.gov (NCT03140553, NCT03154749, NCT03507465) with early TOP2A-normal stage II-III breast cancer who received neoadjuvant chemotherapy, including 100 patients who received the EC-T regimen and 180 patients who received the TCb regimen...

Numerous recent works highlight the limited utility of established tumor cell lines in recapitulating the heterogeneity of tumors in patients. More realistic preclinical cancer models are thought to be provided by transplantable, patient-derived xenografts (PDXs). The inter- and intratumor heterogeneity of PDXs, however, presents several challenges in developing optimal quantitative pipelines to assess response to therapy. The objective of this work was to develop and optimize image metrics for 18 F-FDG PET to assess response to combination docetaxel and carboplatin therapy in a co-clinical trial involving triple-negative breast cancer PDXs...

Triple-negative breast cancer (TNBC) is associated with a high risk of recurrence and generally a bad prognosis. More than one-third of patients with TNBC will present distant metastases during the course of their disease. Although chemotherapy has been the main treatment option for metastatic TNBC for a long time, this scenario has changed recently with the advent of the polyadenosine diphosphate-ribose polymerase inhibitors (PARPis) for patients harbouring a mutation in the BRCA genes (BRCAmut) and also with the results of immunotherapy in patients with PD-L1-positive tumours...

Taxanes are the mainstay of treatment in triple-negative breast cancer (TNBC), with de novo and acquired resistance limiting patient's survival. To investigate the genetic basis of docetaxel resistance in TNBC, exome sequencing was performed on matched TNBC patient-derived xenografts (PDX) sensitive to docetaxel and their counterparts that developed resistance in vivo upon continuous drug exposure. Most mutations, small insertions/deletions, and copy number alterations detected in the initial TNBC human metastatic samples were maintained after serial passages in mice and emergence of resistance...

Germline pathogenic mutations in breast cancer (BC) susceptibility genes (gBRCA1/2) are the most frequent inherited alterations in BC and are involved in the homologous recombination pathway, the principal mechanism of DNA double strand break repair. Platinum salts which act as DNA cross-linking agents are therefore more likely to be active in BRCA-deficient tumors. Women with gBRCA-associated tumors, particularly with triple negative BC, receiving neoadjuvant platinum containing regimens achieved higher pCR rates as compared to wild-type BC...

Purpose: Prognostic 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. Experimental Design: One-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...

Anthracycline-based regimens have been an important treatment component for patients with breast cancer. As demonstrated in the last Early Breast Cancer Trialists' Collaborative Group (EBCTCG) meta-analysis, anthracycline-based regimens decrease breast cancer mortality by 20-30%. Anthracycline toxicities include the rare-but potential morbid-cardiotoxicity or leukemogenic effect, and the almost universal-but very distressing-alopecia. Due to potential toxicities, and large number of patients being exposed, several worldwide trials have re-examined the role of anthracycline-based regimens in the management of breast cancer...

Germline mutations in BRCA1/2 predispose individuals to breast cancer (termed germline-mutated BRCA1/2 breast cancer, gBRCA-BC) by impairing homologous recombination (HR) and causing genomic instability. HR also repairs DNA lesions caused by platinum agents and PARP inhibitors. Triple-negative breast cancers (TNBCs) harbor subpopulations with BRCA1/2 mutations, hypothesized to be especially platinum-sensitive. Cancers in putative 'BRCAness' subgroups-tumors with BRCA1 methylation; low levels of BRCA1 mRNA (BRCA1 mRNA-low); or mutational signatures for HR deficiency and those with basal phenotypes-may also be sensitive to platinum...

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...

We report a case of TNBC treated effectively with a platinum-based regimen after developing resistance to anthracycline and taxane-based neoadjuvant chemotherapy(NAC). A 59-year-old woman with a right breast mass and high fever visited our clinic and was diagnosed as having inflammatory triple negative breast cancer(iTNBC). She was treated with NAC of docetaxel, doxorubicin, and cyclophosphamide(TAC)using pegfilgrastim. After 5 courses of TAC, the therapy failed and the disease progressed. Thus, a combination regimen of gemcitabine and carboplatin(GC)was administered...

Today, neoadjuvant therapy can be considered a therapy standard in triple negative (TNBC) and in HER2-positive (HER2+) (particularly in HER2+ HR-) early breast cancer (EBC). Patients with a pathological complete response (pCR) will have a very favorable outcome. In TNBC, chemotherapy with anthracyclines and taxanes is standard. Data regarding addition of bevacizumab are rather heterogeneous. Addition of carboplatin improves pCR rates independent of BRCA status; whether this will translate into a survival benefit is still unclear...

BACKGROUND: Taxanes are a mainstay in the treatment of metastatic breast cancer (mBC). Combination chemotherapy, including platinum-taxens doublets, can improve tumor responses and progression-free survival (PFS), but is associated with more toxicities and an uncertain benefit in terms of overall survival (OS). METHODS: We performed a retrospective study on 274 consecutive patients with mBC treated at the Division of Medical Oncology of Fondazione IRCCS Istituto Nazionale Tumori, Milan, Italy, during the decade 2007-2016 with the combination of carboplatin AUC 2 plus paclitaxel 80 mg/m2 , both given on days 1 and 8 in every 21-day cycle...

AIM OF THE STUDY: The aim of this trial was to compare overall survival (OS), disease-free survival (DFS), and toxicity of two adjuvant regimens in triple negative patients with Iranian ethnicity. MATERIAL AND METHODS: In a phase II trial, patients with previously untreated triple negative breaststroke cancer were randomly assigned by using docetaxel 70 mg/m2 and carboplatin AUC = 7 every three weeks with granulocyte colony-stimulating factor for sin courses (arm A) or doxorubicin hydrochloride 60 mg/m2 and cyclophosphamide 600 mg/m2 every three weeks with G-CSF for four courses followed by docetaxel 70 mg/m2 and carboplatin AUC = 7 every three weeks with G-CSF for four courses (arm B)...

The authors present the history of two patients. The first patient, a 69-year-old woman was diagnosed with locally invasive triple negative breast cancer with pulmonary and cerebral metastases. Complete radiological remission of the clinically asymptomatic cerebral metastases was detected under systemic chemotherapy with carboplatin-docetaxel (75 mg/m2 ). Later, the patient received whole brain radiotherapy and a second line of chemotherapy. The overall survival was 20 months from the diagnosis of cerebral metastases with conservation of partial autonomy...