Role of Platinum in Early-Stage Triple-Negative Breast Cancer

Abstract Background The role of capecitabine in neoadjuvant and adjuvant chemotherapy for early-stage triple-negative breast cancer (TNBC) is highly controversial. Our meta-analysis was designed to further elucidate the effects of capecitabine on survival in early-stage TNBC patients and its safety. Methods PubMed, Embase, and papers presented at several main conferences were searched up to December 19, 2019, to investigate capecitabine-based versus capecitabine-free neoadjuvant and adjuvant chemotherapy in TNBC patients. Heterogeneity was assessed using I2 test, combined with hazard ratios (HRs) and odds ratios (ORs) with 95% confidence intervals (CI) computed for disease-free survival (DFS), overall survival (OS), and over grade 3 adverse events (AEs). Results A total of 9 randomized clinical trials and 3842 TNBC patients were included. Overall, the combined capecitabine regimens in neoadjuvant and adjuvant chemotherapy showed significantly improved DFS (HR = 0.75; 95% CI, 0.65–0.86; P < 0.001) and OS (HR = 0.63; 95% CI, 0.53–0.77; P < 0.001). In subgroup analysis, there were improvements in DFS in the groups with addition of capecitabine (HR = 0.64; 95% CI, 0.53–0.78; P < 0.001), adjuvant chemotherapy (HR = 0.73; 95% CI, 0.63–0.85; P < 0.001), and lymph node positivity (HR = 0.62; 95% CI, 0.44–0.86; P = 0.005). Capecitabine regimens were related to higher risks of diarrhea (OR = 2.88, 95% CI 2.23–3.74, P < 0.001), stomatitis (OR = 2.01, 95% CI 1.53–2.64, P < 0.001) and hand–foot syndrome (OR = 8.67, 95% CI 6.70–11.22, P < 0.001). Conclusion This meta-analysis showed that neoadjuvant and adjuvant chemotherapy combined with capecitabine significantly improved both DFS and OS in early-stage TNBC patients with tolerable AEs. There were benefits to DFS in the groups with the addition of capecitabine, adjuvant chemotherapy, and lymph node positivity.

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Treatment options in early triple-negative breast cancer

memo - Magazine of European Medical Oncology ◽

10.1007/s12254-020-00609-w ◽

2020 ◽

Vol 13 (3) ◽

pp. 346-348

Author(s):

Christoph Suppan ◽

Marija Balic

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Early Stage ◽

San Antonio ◽

Treatment Options ◽

Circulating Tumor Dna ◽

Predictive Tool ◽

New Treatment

Summary With a main focus on the early stage triple-negative breast cancer (TNBC), new data on immunotherapy in combination with chemotherapy, the role of capecitabine, the potential of circulating tumor DNA as a predictive tool in the postneoadjuvant setting and new treatment approaches were presented and discussed at the San Antonio Breast Cancer Symposium (SABCS) 2019.

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Dissecting the Heterogeneity of Triple-Negative Breast Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2011.38.2010 ◽

2012 ◽

Vol 30 (15) ◽

pp. 1879-1887 ◽

Cited By ~ 252

Author(s):

Otto Metzger-Filho ◽

Andrew Tutt ◽

Evandro de Azambuja ◽

Kamal S. Saini ◽

Giuseppe Viale ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Early Stage ◽

Parp Inhibitor ◽

High Sensitivity ◽

Phase Iii ◽

Breast Cancers ◽

Cancer Subtypes

Triple-negative breast cancer (TNBC) accounts for 15% to 20% of breast cancers. It is a heterogeneous disease, not only on the molecular level, but also on the pathologic and clinical levels. TNBC is associated with a significantly higher probability of relapse and poorer overall survival in the first few years after diagnosis when compared with other breast cancer subtypes. This is observed despite its usual high sensitivity to chemotherapy. In the advanced setting, responses observed with chemotherapy lack durability. Early-stage clinical studies suggested impressive potential when a poly (ADP-ribose) polymerase (PARP) inhibitor is given for the treatment of advanced TNBC with BRCA gene dysfunction. The molecular complexity of TNBC has led to proposed subclassifications, which will be of great value for the development of targeted therapies. In this review, we discuss the biology of TNBC at the pathologic and the molecular levels. We also elaborate on the role of systemic therapies and the results of the first phase III clinical trial evaluating the addition of iniparib, a novel investigational anticancer agent that does not possess characteristics typical of the PARP inhibitor class, in combination with chemotherapy in advanced TNBC.

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Unraveling the role of CDK8 in triple-negative breast cancer metastasis

Intrinsic Activity ◽

10.25006/ia.6.s1-a4.2 ◽

2018 ◽

Vol 6 (Suppl. 1) ◽

pp. A4.2

Author(s):

Vanessa M. Knab

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Cancer Metastasis ◽

Triple Negative ◽

Breast Cancer Metastasis

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Role of Carboplatin in the Treatment of Triple Negative Early- Stage Breast Cancer

Reviews on Recent Clinical Trials ◽

10.2174/1574887110666150624101343 ◽

2015 ◽

Vol 10 (2) ◽

pp. 101-110 ◽

Cited By ~ 5

Author(s):

Matias E. Valsecchi ◽

Gerrit Kimmey ◽

Arvinder Bir ◽

Damian Silbermins

Keyword(s):

Breast Cancer ◽

Triple Negative ◽

Early Stage ◽

Early Stage Breast Cancer

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19P A dichotomous oncogenic role of the splicing factor SF3A3 in MYC-driven triple-negative breast cancer

Annals of Oncology ◽

10.1016/j.annonc.2021.03.033 ◽

2021 ◽

Vol 32 ◽

pp. S28

Author(s):

A. Bosch ◽

M. Cieśla ◽

P. Cao Thi Ngoc ◽

S. Mutukumar ◽

G. Honeth ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Splicing Factor

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The Relevance of the SH2 Domain for c-Src Functionality in Triple-Negative Breast Cancer Cells

Cancers ◽

10.3390/cancers13030462 ◽

2021 ◽

Vol 13 (3) ◽

pp. 462

Author(s):

Víctor Mayoral-Varo ◽

María Pilar Sánchez-Bailón ◽

Annarica Calcabrini ◽

Marta García-Hernández ◽

Valerio Frezza ◽

...

Keyword(s):

Breast Cancer ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Sh2 Domain ◽

Model Systems ◽

System A ◽

Promising Therapeutic Target ◽

Relevant Role ◽

Inactivating Mutation

The role of Src family kinases (SFKs) in human tumors has been always associated with tyrosine kinase activity and much less attention has been given to the SH2 and SH3 adapter domains. Here, we studied the role of the c-Src-SH2 domain in triple-negative breast cancer (TNBC). To this end, SUM159PT and MDA-MB-231 human cell lines were employed as model systems. These cells conditionally expressed, under tetracycline control (Tet-On system), a c-Src variant with point-inactivating mutation of the SH2 adapter domain (R175L). The expression of this mutant reduced the self-renewal capability of the enriched population of breast cancer stem cells (BCSCs), demonstrating the importance of the SH2 adapter domain of c-Src in the mammary gland carcinogenesis. In addition, the analysis of anchorage-independent growth, proliferation, migration, and invasiveness, all processes associated with tumorigenesis, showed that the SH2 domain of c-Src plays a very relevant role in their regulation. Furthermore, the transfection of two different aptamers directed to SH2-c-Src in both SUM159PT and MDA-MB-231 cells induced inhibition of their proliferation, migration, and invasiveness, strengthening the hypothesis that this domain is highly involved in TNBC tumorigenesis. Therefore, the SH2 domain of c-Src could be a promising therapeutic target and combined treatments with inhibitors of c-Src kinase enzymatic activity may represent a new therapeutic strategy for patients with TNBC, whose prognosis is currently very negative.

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