scholarly journals A review of current progress in triple-negative breast cancer therapy

Open Medicine ◽  
2020 ◽  
Vol 15 (1) ◽  
pp. 1143-1149
Author(s):  
Meiying Shen ◽  
Huawen Pan ◽  
Yuxia Chen ◽  
Yu Hang Xu ◽  
Weixiong Yang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Brca Mutation ◽  
Complete Response ◽  
Parp Inhibitors ◽  
The Past ◽  
Germline Brca Mutation ◽  
Aggressive Subtype

AbstractTriple-negative breast cancer (TNBC) is a particularly aggressive subtype known for its extremely high drug resistance, progression, poor prognosis, and lack of clear therapeutic targets. Researchers are aiming to advance TNBC treatment worldwide. In the past 2–3 years, more positive results have emerged in the clinical research on TNBC treatment. Based on the results, several impressive drugs have been approved to benefit patients with TNBC, including the PARP inhibitors olaparib and talazoparib for germline BRCA mutation-associated breast cancer (gBRCAm-BC) and immunotherapy using the checkpoint inhibitor atezolizumab in combination with nab-paclitaxel for programmed cell death-ligand 1-positive (PD-L1+) advanced TNBC. Although neoadjuvant therapy has focused on combinations of systemic agents to optimize pathologically complete response, metastatic TNBC still has a poor prognosis. Innovative multidrug combination systemic therapies based on neoadjuvants and adjuvants have led to significant improvements in outcomes, particularly over the past decade.

scholarly journals Triple-negative breast cancer: recent treatment advances

F1000Research ◽  
2019 ◽  
Vol 8 ◽  
pp. 1342 ◽  
Author(s):  
Alice R T Bergin ◽  
Sherene Loi
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Poor Prognosis ◽  
Triple Negative ◽  
Residual Disease ◽  
Breast Cancer Subtype ◽  
Complete Response ◽  
Parp Inhibitors ◽  
Younger Women ◽  
History Of

Triple-negative breast cancer (TNBC) is a breast cancer subtype renowned for its capacity to affect younger women, metastasise early despite optimal adjuvant treatment and carry a poor prognosis. Neoadjuvant therapy has focused on combinations of systemic agents to optimise pathological complete response. Treatment algorithms now guide the management of patients with or without residual disease, but metastatic TNBC continues to harbour a poor prognosis. Innovative, multi-drug combination systemic therapies in the neoadjuvant and adjuvant settings have led to significant improvements in outcomes, particularly over the past decade. Recently published advances in the treatment of metastatic TNBC have shown impressive results with poly (ADP-ribose) polymerase (PARP) inhibitors and immunotherapy agents. Immunotherapy agents in combination with traditional systemic chemotherapy have been shown to alter the natural history of this devastating condition, particularly in patients whose tumours are positive for programmed cell death ligand 1 (PD-L1).

scholarly journals The overview of modern approaches in treatment of triple negative breast cancer

2020 ◽  
Vol 7 (1) ◽  
pp. 55-65
Author(s):  
A. A. Kharitonova ◽  
I. A. Smirnova ◽  
M. V. Kiseleva
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Parp Inhibitors ◽  
Morphological Response ◽  
Chemotherapy Drugs ◽  
Treatment Regimens ◽  
Dose Dense ◽  
Platinum Preparations ◽  
Aggressive Subtype

By far the most aggressive subtype of breast cancer is triple negative cancer. The purpose of this review is to analyze current ideas about the pathogenesis, clinical characteristics of different subtypes of triple negative breast cancer, the nature of its metastasis, mechanisms of chemoresistance. The review presents the results of modern regimens of drug therapy of triple negative breast cancer according to the publications of domestic and foreign oncologists. On the basis of various clinical studies, the effectiveness of the use of anthracyclines, taxanes in the dose-dense regime, platinum preparations and other chemotherapy drugs for the treatment of triple-negative cancer has been shown. The presented treatment regimens allow to achieve a complete morphological response in 85% of patients, to increase the rates of relapse-free and overall survival, comparable with other subtypes of breast cancer. The review highlights the possibilities of modern targeted drugs-PARP inhibitors, chk1 inhibitors UCN‑01, immunotherapy possibilities for the treatment of this aggressive subtype of breast cancer.

scholarly journals PARP Inhibitor Olaparib Use in a BRCA1-Positive Patient With Metastatic Triple-Negative Breast Cancer, Without the Initial Use of Platinum-Based Chemotherapy, Showing Significant Rapid Near Resolution of Large Liver Metastasis While Patient Experienced Gout-Like Symptoms

2019 ◽  
Vol 7 ◽  
pp. 232470961986498 ◽  
Author(s):  
Trevanne Matthews Hew ◽  
Lara Zuberi
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Brca Mutation ◽  
Parp Inhibitor ◽  
Parp Inhibitors ◽  
Management Options ◽  
Federal Drug Administration ◽  
Platinum Based Chemotherapy ◽  
Metastatic Setting

Triple-negative breast cancer (TNBC) accounts for 20% of breast cancers diagnosed worldwide. This subtype of breast cancer tends to behave more aggressively, and unlike other breast cancer subtypes, there are no standard targeted treatments for most patients. However, up to 20% of patients with TNBC harbor a breast cancer gene (BRCA) mutation, particularly in BRCA1. For patients who carry this gene mutation, this opens the door for new management options by the use of newer agents such as polyadenosine diphosphate-ribose polymerase (PARP) inhibitors in the metastatic setting. Given that this is uncommon and that PARP inhibitors have only recently received Federal Drug Administration approval, the experience with these drugs is relatively new. In this article, we present a case of a patient treated in this setting with olaparib who developed an unanticipated side effect as a result of the high efficacy of the drug.

An adaptive randomized phase II trial to determine pathologic complete response with the addition of carboplatin with and without ABT-888 to standard chemotherapy in the neoadjuvant treatment of triple-negative breast cancer.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS1135-TPS1135
Author(s):  
Tiffany P. Avery ◽  
Adam C. Berger ◽  
Albert J. Kovatich ◽  
Hallgeir Rui ◽  
Terry Hyslop ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Trials ◽  
Phase Ii ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Parp Inhibitors ◽  
Weekly Cycles ◽  
Carboplatin Auc

TPS1135 Background: Inhibition of poly (ADP-ribose) polymerase (Parp) is a potential targeted therapy for triple-negative breast cancer (TNBC). Clinical trials of Parp inhibitors in metastatic TNBC have shown conflicting results. Issues regarding the use of Parp inhibitors in TNBC include choosing a selective Parp inhibitor and selecting an appropriate chemotherapy backbone. The current trial addresses these questions by combining a validated Parp inhbitor, ABT-888, with carboplatin and paclitaxel. Platinum agents have shown synergy with Parp inhibitors in preclinical models and efficacy in clinical trials. The combination of paclitaxel and carboplatin with Parp inhibitors has shown efficacy in phase I trials. Methods: This is a phase II, two-arm neoadjuvant trial of women with TNBC. Eighty patients will be enrolled. Randomization will follow a 1:1 allocation initially, then will follow a Bayesian adaptive allocation in which each prior response will be evaluated and patients assigned preferentially to the better responding arm. The primary endpoint is pathologic complete response (pCR). Secondary endpoints include correlation of pCR with biomarkers, imaging, and circulating tumor cells (CTCs). Treatment: Arm 1: Paclitaxel 80 mg/m2 + carboplatin AUC=2 (12 weekly cycles) + filgrastim followed by doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 (4 cycles every 3 weeks) + pegfilgrastim. Arm 2: ABT-888 (150mg PO bid) + paclitaxel 80 mg/ m2 + carboplatin AUC=2 (12 weekly cycles) + (filgrastim) followed by doxorubicin 60 mg/m2 + cyclophosphamide 600 mg/m2 (4 cycles every 3 weeks) + (pegfilgrastim). Eligibility: Women ≥ 18 years old with clinical stage IIB or stage IIIA, IIIB, or IIIC untreated TNBC (ER <1% , PR <1% , Her-2/neu 0, 1+ on IHC or 2+ and FISH ratio < 1.8) are eligible. Correlative Studies: Correlation of pCR with tissue expression of CK5, EGFR, ERCC1, Ki-67, Parp1, and longitudinal enumeration of CTCs will be done. Exploratory tissue biomarkers with prognostic and predictive value will be correlated with pCR. Enrollment: The trial will begin accrual in February 2013.

Pathological complete response rate and survival in patients with BRCA-associated triple-negative breast cancer after 12 weeks of de-escalated neoadjuvant chemotherapy: Translational results of the WSG-ADAPT TN randomized phase II trial (NCT01815242).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. 579-579
Author(s):  
Lisa Katharina Katharina Richters ◽  
Oleg Gluz ◽  
Nana Weber-Lassalle ◽  
Matthias Christgen ◽  
Heinz Haverkamp ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Ii ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Pathological Complete Response ◽  
Phase Ii Trial ◽  
Brca Mutation ◽  
Complete Response ◽  
Mutation Status

579 Background: The phase II trial WSG-ADAPT TN randomized triple-negative breast cancer (TNBC) patients to receive 12 weeks of neoadjuvant nab-paclitaxel (nab-pac) combined with carboplatin (carbo) vs gemcitabine (gem) and showed a substantial improvement of pathological complete response (pCR: ypT0/is, ypN0) with carbo (45.9% vs 28.7%). pCR had a strong favorable impact on iDFS after 3-year follow-up. Distribution of tumor mutations in BC-associated genes and impact of BRCA mutation status on pCR and outcome are analyzed here. Methods: NGS-based mutational analysis of BRCA1/2 and 18 further (potentially) BC-associated genes was performed on DNA derived from pretreatment FFPE samples (gem: n = 158, carbo: n = 108) using a customized gene panel. Variants with a variant fraction of ≥5% were included and classified according to IARC and ENIGMA guidelines. Results: In 42 of the 266 analyzed samples, at least one deleterious BRCA1/2-variant was found (15.8%; BRCA1 n = 37, BRCA2 n = 3, BRCA1+ BRCA2 n = 2) one of which displayed an additional STK11-mutation. In the BRCA1/2-negative cohort, a mutation in one of 14 further analyzed (potential) BC-risk genes was found in 19 samples (7.1%; BARD1 n = 3, CHEK2 n = 2, CDH1 n = 2, FANCM n = 3, PALB2 n = 5, RAD50 n = 1, RAD51C n = 1, RAD51D n = 1, XRCC2 n = 1; no deleterious mutations were found in ATM, BRIP1, MRE11A, NBN). At least one deleterious variant in TP53, PIK3CA, PTEN or MAP3K1 was seen in 89.1% (n = 237; TP53 n = 233, PIK3CA n = 22 PTEN n = 15, MAP3K1 n = 1). In 22 samples (8.3%) no deleterious mutation was identified in the analyzed genes. Overall, patients with tumor BRCA mutation (carbo n = 14, gem n = 28) had 45.2% vs 34.4% pCR (OR = 1.58, 95%-CI: 0.81-3.07, p =.18) without a mutation. pCR in the small group with mutation receiving carbo (n = 14) was 64.3% vs. 34.5% in all others (OR = 3.41, 95%-CI: 1.11-10.50; p =.03); direct comparison to BRCA-positive patients receiving gem (n = 28, 35.7%, OR = 3.2, 95%-CI: 0.85-12.36, p = 0.079) did not reach statistical significance. The results suggest that the strong favorable impact of pCR on iDFS is preserved even among BRCA-positive patients (n = 42, p =.07), as well as in the BRCA-negative subgroup (p <.001). No evidence for a predictive impact of BRCA mutation on efficacy of 4xEC additional chemotherapy was seen overall or within pCR subgroups. Conclusions: Twelve weeks of neoadjuvant nab-pac/carbo is a highly effective anthracycline-free regimen that leads to an excellent pCR-rate of 64% in tumor BRCA1/2-mutated cases. BRC A1/2 mutation status could support this de-escalation strategy in early TNBC, but further prospective validation of survival impacts in larger cohorts and with longer follow up is needed. More detailed survival analyses will be presented at the meeting. Clinical trial information: NCT01815242.

scholarly journals Expanding the Use of PARP Inhibitors as Monotherapy and in Combination in Triple-Negative Breast Cancer

2021 ◽  
Vol 14 (12) ◽  
pp. 1270
Author(s):  
Mariya Yordanova ◽  
Audrey Hubert ◽  
Saima Hassan
Keyword(s):  
Breast Cancer ◽  
Homologous Recombination ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Brca Mutation ◽  
Single Agent ◽  
Parp Inhibitors ◽  
Breast Cancer Patients ◽  
Homologous Recombination Deficiency ◽  
Dosing Strategies

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and is known to be associated with a poor prognosis and limited therapeutic options. Poly (ADP-ribose) polymerase inhibitors (PARPi) are targeted therapeutics that have demonstrated efficacy as monotherapy in metastatic BRCA-mutant (BRCAMUT) TNBC patients. Improved efficacy of PARPi has been demonstrated in BRCAMUT breast cancer patients who have either received fewer lines of chemotherapy or in chemotherapy-naïve patients in the metastatic, adjuvant, and neoadjuvant settings. Moreover, recent trials in smaller cohorts have identified anti-tumor activity of PARPi in TNBC patients, regardless of BRCA-mutation status. While there have been concerns regarding the efficacy and toxicity of the use of PARPi in combination with chemotherapy, these challenges can be mitigated with careful attention to PARPi dosing strategies. To better identify a patient subpopulation that will best respond to PARPi, several genomic biomarkers of homologous recombination deficiency have been tested. However, gene expression signatures associated with PARPi response can integrate different pathways in addition to homologous recombination deficiency and can be implemented in the clinic more readily. Taken together, PARPi have great potential for use in TNBC patients beyond BRCAMUT status, both as a single-agent and in combination.

scholarly journals Emerging Role of PARP Inhibitors in Metastatic Triple Negative Breast Cancer. Current Scenario and Future Perspectives

2021 ◽  
Vol 11 ◽  
Author(s):  
Giacomo Barchiesi ◽  
Michela Roberto ◽  
Monica Verrico ◽  
Patrizia Vici ◽  
Silverio Tomao ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Brca Mutation ◽  
Brca2 Mutation ◽  
Metastatic Breast ◽  
Parp Inhibitors ◽  
Phase Iii ◽  
Targeted Agents

Triple negative tumors represent 15% of breast cancer and are characterized by the lack of estrogen receptors, progesterone receptor, and HER2 amplification or overexpression. Approximately 25% of patients diagnosed with triple negative breast cancer carry a germline BRCA1 or BRCA2 mutation. They have an aggressive biology, and chemotherapy has been the mainstay of treatment for a long time. Despite intensive therapies, prognosis is still poor, and many patients will eventually relapse or die due to cancer. Therefore, novel targeted agents that can increase the treatment options for this disease are urgently needed. Recently, a new class of molecules has emerged as a standard of care for patients with triple negative breast cancer and germline BRCA1 or BRCA2 mutation: poly (ADP-ribose) (PARP) inhibitors. In the first part of the review, we summarize and discuss evidence supporting the use of PARP inhibitors. Currently, two PARP inhibitors have been approved for triple negative metastatic breast cancer—olaparib and talazoparib—based on two phase III trials, which showed a progression-free survival benefit when compared to chemotherapy. Safety profile was manageable with supportive therapies and dose reductions/interruptions. In addition, other PARP inhibitors are currently under investigation, such as talazoparib, rucaparib, and veliparib. Subsequently, we will discuss the potential role of PARP inhibitors in the future. Clinical research areas are investigating PARP inhibitors in combination with other agents and are including patients without germline BRCA mutations: ongoing phase II/III studies are combining PARP inhibitors with immunotherapy, while phases I and II trials are combining PARP inhibitors with other targeted agents such as ATM and PIK3CA inhibitors. Moreover, several clinical trials are enrolling patients with somatic BRCA mutation or patients carrying mutations in genes, other than BRCA1/2, involved in the homologous recombination repair pathway (e.g., CHECK2, PALB2, RAD51, etc.).

Does pathologic complete response predict for outcome in BRCA mutation carriers with triple-negative breast cancer?

2014 ◽  
Vol 32 (15_suppl) ◽  
pp. 1023-1023 ◽  
Author(s):  
Shani Paluch-Shimon ◽  
Eitan Friedman ◽  
Raanan Berger ◽  
Moshe Zvi Papa ◽  
Maya Dadiani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Brca Mutation ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Mutation Carriers ◽  
Brca Mutation Carriers

Breast conservation after neoadjuvant chemotherapy for triple-negative breast cancer: Surgical results from an international randomized trial (BrighTNess).

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 514-514
Author(s):  
Mehra Golshan ◽  
Sibylle Loibl ◽  
Jens Bodo Huober ◽  
Joyce O'Shaughnessy ◽  
Hope S. Rugo ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Randomized Trial ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Brca Mutation ◽  
Pathologic Complete Response ◽  
Breast Conservation ◽  
Complete Response ◽  
Neoadjuvant Systemic Therapy ◽  
The Impact

514 Background: Neoadjuvant systemic therapy (NST) increases the frequency of breast-conserving therapy (BCT) in stage II-III breast cancer, but there is little data on how often it converts patients (pts) from BCT-ineligible (BCT-I) to BCT-eligible (BCT-E) and on the impact of other factors on surgical choices. We collected surgical assessment and management data from an international randomized trial of NST in triple-negative breast cancer (TNBC). Methods: Women with operable TNBC were randomized to veliparib (V) with carboplatin (C) and paclitaxel (P), placebo with C and P or placebo with P followed by doxorubicin and cyclophosphamide. The surgeons assessed BCT candidacy by clinico-radiographic criteria before and after NST; surgical management was at surgeon and patient discretion. We assessed interactions between BCT eligibility pre- and post-NST, germline BRCA mutation ( gBRCA) status, continent of treatment and achievement of pathologic complete response(pCR) and percentage of pts who underwent BCT versus mastectomy. Results: Pre- and post-NST surgical assessments were available for 604 pts who underwent surgery. BCT rates are listed in the Table. The BCT rate was 68% among pts deemed BCT-E after NST. pCR rates were identical between BCT-E pts who chose BCT (55%) vs. mastectomy (53%). Of 141 pts deemed BCT-I at baseline, 75 (53%) converted to BCT-E but only 42 (56%) of these opted for BCT. pCR rates were 49% in BCT-E converts vs. 36% in those remained BCT-I. gBRCA pts (n = 84) were less likely to choose BCT even if they were BCT-E. Pts treated in North America (NA) were less likely to choose BCT (55% vs. 80% for Europe and Asia P<0.0001) even among non- gBRCA considered BCT-E post-NST (61% vs. 85% P<0.0001). Conclusions: This largest prospective analysis of the impact of NST in TNBC demonstrates a conversion rate from BCT-I to BCT-E of 53%. BCT rates were lower in pts with gBRCA; the much higher mastectomy rate among BCT-E pts in NA merits investigation. Clinical trial information: NCT02032277. [Table: see text]

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