scholarly journals Optimal Systemic Treatment for Early Triple-Negative Breast Cancer

Breast Care ◽  
2020 ◽  
Vol 15 (3) ◽  
pp. 217-226
Author(s):  
Jenny Furlanetto ◽  
Sibylle Loibl
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Checkpoint Inhibitors ◽  
Distant Metastases ◽  
Complete Response ◽  
Outcome Data ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Dose Dense

Background: Approximately 10–15% of all breast tumors are triple-negative breast cancer (TNBC). TNBC have a higher risk of relapse and distant metastases compared to other subtypes. The optimal systemic management of TNBC according to national and international guidelines is discussed herein. Summary: Anthracycline/taxane-based chemotherapy for patients with TNBC either in the neoadjuvant (NACT) or the adjuvant setting is considered standard of care. Exceptions are small tumors and a low-risk histology, in which chemotherapy can be spared. Dose-dense therapy is more effective in preventing recurrence and increasing survival. The use of nab-paclitaxel instead of a solvent-based taxane can lead to higher pathological complete response (pCR) rates and better outcomes. Platinum agents are effective in increasing pCR when added to anthracycline/taxane-based chemotherapy at the cost of increased toxicity. Long-term outcome data are lacking. In patients without a pCR, capecitabine leads to improved outcomes. Key Messages: The standard treatment approach of TNBC is anthracycline/taxane-based chemotherapy, preferably within the NACT setting. Dose-dense schedules as well as platinum should be considered in the NACT setting. For patients without a pCR, capecitabine is an option to improve the outcome. The role of nab-paclitaxel is under debate. In case of immunogenic tumors, checkpoint inhibitors are promising new agents that merit further investigation.

scholarly journals Impact of the Addition of Carboplatin and/or Bevacizumab to Neoadjuvant Once-per-Week Paclitaxel Followed by Dose-Dense Doxorubicin and Cyclophosphamide on Pathologic Complete Response Rates in Stage II to III Triple-Negative Breast Cancer: CALGB 40603 (Alliance)

2015 ◽  
Vol 33 (1) ◽  
pp. 13-21 ◽  
Author(s):  
William M. Sikov ◽  
Donald A. Berry ◽  
Charles M. Perou ◽  
Baljit Singh ◽  
Constance T. Cirrincione ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Stage Ii ◽  
Open Label ◽  
Grade 3 ◽  
Dose Dense ◽  
The Impact

Purpose One third of patients with triple-negative breast cancer (TNBC) achieve pathologic complete response (pCR) with standard neoadjuvant chemotherapy (NACT). CALGB 40603 (Alliance), a 2 × 2 factorial, open-label, randomized phase II trial, evaluated the impact of adding carboplatin and/or bevacizumab. Patients and Methods Patients (N = 443) with stage II to III TNBC received paclitaxel 80 mg/m2 once per week (wP) for 12 weeks, followed by doxorubicin plus cyclophosphamide once every 2 weeks (ddAC) for four cycles, and were randomly assigned to concurrent carboplatin (area under curve 6) once every 3 weeks for four cycles and/or bevacizumab 10 mg/kg once every 2 weeks for nine cycles. Effects of adding these agents on pCR breast (ypT0/is), pCR breast/axilla (ypT0/isN0), treatment delivery, and toxicities were analyzed. Results Patients assigned to either carboplatin or bevacizumab were less likely to complete wP and ddAC without skipped doses, dose modification, or early discontinuation resulting from toxicity. Grade ≥ 3 neutropenia and thrombocytopenia were more common with carboplatin, as were hypertension, infection, thromboembolic events, bleeding, and postoperative complications with bevacizumab. Employing one-sided P values, addition of either carboplatin (60% v 44%; P = .0018) or bevacizumab (59% v 48%; P = .0089) significantly increased pCR breast, whereas only carboplatin (54% v 41%; P = .0029) significantly raised pCR breast/axilla. More-than-additive interactions between the two agents could not be demonstrated. Conclusion In stage II to III TNBC, addition of either carboplatin or bevacizumab to NACT increased pCR rates, but whether this will improve relapse-free or overall survival is unknown. Given results from recently reported adjuvant trials, further investigation of bevacizumab in this setting is unlikely, but the role of carboplatin could be evaluated in definitive studies, ideally limited to biologically defined patient subsets most likely to benefit from this agent.

Immunological predictive and prognostic factors in patients with stage II-III triple negative breast cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e12581-e12581
Author(s):  
Olga Gordeeva ◽  
Irina Vladimirovna Kolyadina ◽  
Antonina Chertkova ◽  
Esma Shoua ◽  
Zaira Kadagidze ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Prognostic Factors ◽  
Triple Negative Breast Cancer ◽  
Peripheral Blood ◽  
Triple Negative ◽  
Reference Group ◽  
Pathologic Complete Response ◽  
Stage Ii ◽  
Term Outcome ◽  
Long Term Outcome

e12581 Background: Triple negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Pathologic complete response (pCR) achievement during neoadjuvant chemotherapy (NACT) is very important for these pts as it correlates with long-term outcome. Predictive and prognostic factors for this group of pts are needed. Methods: Since 2014 we treated 98 pts with histologically confirmed stage II-III TNBC with following regimen of NACT: 6 cycles of Cisplatin 75mg/m2 day 1 and Paclitaxel 80mg/m2 days 1, 8, 15, every 4 weeks according to local protocol. After NACT pts proceeded to radical breast surgery with assessing of pathological response. Before the treatment we assessed TILs in biopsy samples of all patients. We also conducted subpopulation analysis of lymphocytes in peripheral blood before treatment. We analyzed CD8+, CD25+, NK and NKT cells as they were reported to be significant earlier. We compared results with median value in reference group (mRG) of healthy women. Results: Among all 98 pts 86 (87%) were operated, pCR was achieved in 60,5% of operated pts. pCR strongly correlated with TILs level: 38,5% for pts with TILs < 5% and 69,8% for pts with TILs > 5% (p = 0,05). We also found that NKT population was associated with pCR: 77,8% vs 45,8% among patients with NKT above mRG and up to mRG, respectively (p = 0,01). It correlated also with tpCR: 22,2% vs 70,6% (p = 0,01). When both CD25+ and NKT population were above mRG pCR rate achieved in 85,7% pts vs 50,0% pts if it was up to mRG (p = 0,049). NK, CD8+ and CD25+ did not show any correlation with pCR. Survival results are presented in table below. NK, NKT and TILs did not show any correlation with survival. Interestingly, CD8+ were also associated with lower incidence of visceral metastases: 42,1% in pts with normal CD8+ and 15,7% in pts with CD8+ above normal (p = 0,19). Conclusions: Not only TILs, but also NKT and CD25+/NKT population in the peripheral blood could be possible predictive factors for patients with stage II-III TNBC receiving NACT. CD8+, CD25+ and NKT populations could be further studied as prognostic markers for this group of patients. [Table: see text]

scholarly journals Novel therapeutic strategies for patients with metastatic triple-negative breast cancer

2021 ◽  
Vol 22 (4) ◽  
pp. 60-65
Author(s):  
Inna P. Ganshina ◽  
Olga O. Gordeeva ◽  
Mariam Sh. Manukian
Keyword(s):  
Breast Cancer ◽  
Clinical Practice ◽  
Russian Federation ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Checkpoint Inhibitors ◽  
Clinical Trial Data ◽  
Distant Metastases ◽  
Resistance Mechanisms ◽  
The Russian Federation

Triple-negative breast cancer (TNBC) remains the most aggressive subtype of breast cancer. In the presence of distant metastases, the median overall survival does not exceed 14 months. TNBC is an extremely heterogeneous group of tumors, it includes both tumors extremely sensitive to chemotherapy and tumors that require targeted or immunotherapy for the best treatment outcomes. Such subtype features make it difficult to develop a single treatment strategy for all patients. Current perceptions of resistance mechanisms and molecular drivers progression have increased therapeutic opportunities for metastatic TNBC (mTNBC). For example, in the last few years, checkpoint inhibitors and PARP inhibitors have entered into clinical practice in the Russian Federation. This review presents clinical trial data, as well as an algorithm for choosing therapy for patients with TNBC, based on the results of recent clinical studies. The review focuses mainly on drugs registered at the territory of the Russian Federation, that allows to apply these options in everyday clinical practice. Promising directions therapy of mTNBC not registered at the territory of the Russian Federation yet will be showed in a separate review in the next issue in the Journal of Modern Oncology.

scholarly journals Clinical and genomic assessment of PD-L1 SP142 expression in triple-negative breast cancer

2021 ◽  
Author(s):  
Sung Gwe Ahn ◽  
Seon-Kyu Kim ◽  
Jonathan H. Shepherd ◽  
Yoon Jin Cha ◽  
Soong June Bae ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Checkpoint Inhibitors ◽  
Pathologic Complete Response ◽  
Gene Expression Signature ◽  
Complete Response ◽  
Gene Signature ◽  
Expression Signature

Abstract Purpose The SP142 PD-L1 assay is a companion diagnostic for atezolizumab in metastatic triple-negative breast cancer (TNBC). We strove to understand the biological, genomic, and clinical characteristics associated with SP142 PD-L1 positivity in TNBC patients. Methods Using 149 TNBC formalin-fixed paraffin-embedded tumor samples, tissue microarray (TMA) and gene expression microarrays were performed in parallel. The VENTANA SP142 assay was used to identify PD-L1 expression from TMA slides. We next generated a gene signature reflective of SP142 status and evaluated signature distribution according to TNBCtype and PAM50 subtypes. A SP142 gene expression signature was identified and was biologically and clinically evaluated on the TNBCs of TCGA, other cohorts, and on other malignancies treated with immune checkpoint inhibitors (ICI). Results Using SP142, 28.9% of samples were PD-L1 protein positive. The SP142 PD-L1-positive TNBC had higher CD8+ T cell percentage, stromal tumor-infiltrating lymphocyte levels, and higher rate of the immunomodulatory TNBCtype compared to PD-L1-negative samples. The recurrence-free survival was prolonged in PD-L1-positive TNBC. The SP142-guided gene expression signature consisted of 94 immune-related genes. The SP142 signature was associated with a higher pathologic complete response rate and better survival in multiple TNBC cohorts. In the TNBC of TCGA, this signature was correlated with lymphocyte-infiltrating signature scores, but not with tumor mutational burden or total neoantigen count. In other malignancies treated with ICIs, the SP142 genomic signature was associated with improved response and survival. Conclusions We provide multi-faceted evidence that SP142 PDL1-positive TNBC have immuno-genomic features characterized as highly lymphocyte-infiltrated and a relatively favorable survival.

scholarly journals Multi-Gene Testing Overview with a Clinical Perspective in Metastatic Triple-Negative Breast Cancer

2021 ◽  
Vol 22 (13) ◽  
pp. 7154
Author(s):  
Martina Dameri ◽  
Lorenzo Ferrando ◽  
Gabriella Cirmena ◽  
Claudio Vernieri ◽  
Giancarlo Pruneri ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Triple Negative Breast Cancer ◽  
Triple Negative ◽  
Checkpoint Inhibitors ◽  
Gene Testing ◽  
Repair Deficiency ◽  
Targeted Treatments ◽  
Recombination Repair ◽  
Tumor Mutational Burden ◽  
Next Generation Sequencing Ngs

Next-generation sequencing (NGS) is the technology of choice for the routine screening of tumor samples in clinical practice. In this setting, the targeted sequencing of a restricted number of clinically relevant genes represents the most practical option when looking for genetic variants associated with cancer, as well as for the choice of targeted treatments. In this review, we analyze available NGS platforms and clinical applications of multi-gene testing in breast cancer, with a focus on metastatic triple-negative breast cancer (mTNBC). We make an overview of the clinical utility of multi-gene testing in mTNBC, and then, as immunotherapy is emerging as a possible targeted therapy for mTNBC, we also briefly report on the results of the latest clinical trials involving immune checkpoint inhibitors (ICIs) and TNBC, where NGS could play a role for the potential predictive utility of homologous recombination repair deficiency (HRD) and tumor mutational burden (TMB).

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