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      Chemotherapy Options beyond the First Line in HER-Negative Metastatic Breast Cancer

      review-article
      , ,
      Journal of Oncology
      Hindawi

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          Abstract

          Despite the recent advances in the biological understanding of breast cancer (BC), chemotherapy still represents a key component in the armamentarium for this disease. Different agents are available as mono-chemotherapy options in patients with locally advanced or metastatic BC (MBC) who progress after a first- and second-line treatment with anthracyclines and taxanes. However, no clear indication exists on what the best option is in some populations, such as heavily pretreated, elderly patients, triple-negative BC (TNBC), and those who do not respond to the first-line therapy. In this article, we summarize available literature evidence on different chemotherapy agents used beyond the first-line, in locally advanced or MBC patients, including rechallenge with anthracyclines and taxanes, antimetabolite and antimicrotubule agents, such as vinorelbine, capecitabine, eribulin, ixabepilone, and the newest developed agents, such as vinflunine, irinotecan, and etirinotecan.

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          Most cited references115

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          Global Cancer Statistics 2018: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries

          This article provides a status report on the global burden of cancer worldwide using the GLOBOCAN 2018 estimates of cancer incidence and mortality produced by the International Agency for Research on Cancer, with a focus on geographic variability across 20 world regions. There will be an estimated 18.1 million new cancer cases (17.0 million excluding nonmelanoma skin cancer) and 9.6 million cancer deaths (9.5 million excluding nonmelanoma skin cancer) in 2018. In both sexes combined, lung cancer is the most commonly diagnosed cancer (11.6% of the total cases) and the leading cause of cancer death (18.4% of the total cancer deaths), closely followed by female breast cancer (11.6%), prostate cancer (7.1%), and colorectal cancer (6.1%) for incidence and colorectal cancer (9.2%), stomach cancer (8.2%), and liver cancer (8.2%) for mortality. Lung cancer is the most frequent cancer and the leading cause of cancer death among males, followed by prostate and colorectal cancer (for incidence) and liver and stomach cancer (for mortality). Among females, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death, followed by colorectal and lung cancer (for incidence), and vice versa (for mortality); cervical cancer ranks fourth for both incidence and mortality. The most frequently diagnosed cancer and the leading cause of cancer death, however, substantially vary across countries and within each country depending on the degree of economic development and associated social and life style factors. It is noteworthy that high-quality cancer registry data, the basis for planning and implementing evidence-based cancer control programs, are not available in most low- and middle-income countries. The Global Initiative for Cancer Registry Development is an international partnership that supports better estimation, as well as the collection and use of local data, to prioritize and evaluate national cancer control efforts. CA: A Cancer Journal for Clinicians 2018;0:1-31. © 2018 American Cancer Society.
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            4th ESO–ESMO International Consensus Guidelines for Advanced Breast Cancer (ABC 4)†

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              Carboplatin in BRCA1/2-mutated and triple-negative breast cancer BRCAness subgroups: the TNT Trial

              BRCA1/2 germline mutations predispose to breast cancer (gBRCA-BC) by impairing homologous recombination (HR) causing genomic instability. HR also repairs DNA lesions caused by platinums and PARP inhibitors. Triple Negative Breast Cancers (TNBC) harbour sub-populations with BRCA1/2 mutations, hypothesised to be especially platinum sensitive. Putative “BRCAness” subgroups may also be especially platinum sensitive. We assessed carboplatin and mechanistically distinct docetaxel in a phase-III trial in unselected advanced TNBC. A pre-specified programme enabled biomarker-treatment interaction analyses in gBRCA-BC and “BRCAness” subgroups: tumour BRCA1 methylation; BRCA1 mRNA-low; HR deficiency mutational signatures and basal phenotypes. Primary endpoint was objective response rate (ORR). In the unselected population (376 patients; 188 carboplatin, 188 docetaxel) carboplatin was not more active than docetaxel (ORR: 31.4v34.0; p=0.66). In contrast in patients with gBRCA-BC carboplatin had double the ORR compared to docetaxel (68%v33%), test for biomarker-treatment interaction (p=0.01). No treatment interaction was observed for BRCA1 methylation, BRCA1 mRNA-low status or a Myriad-HRD mutation signature assay. Significant treatment interaction with basal-like subtype was driven by high docetaxel response in the non-basal subgroup. Patients with advanced TNBC benefit from BRCA1/2 mutation characterization, but not BRCA1 methylation or Myriad-HRD analysis, informing platinum choices. Basal-like gene expression analysis may also influence treatment choices.
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                Author and article information

                Contributors
                Journal
                J Oncol
                J Oncol
                JO
                Journal of Oncology
                Hindawi
                1687-8450
                1687-8469
                2020
                28 November 2020
                : 2020
                : 9645294
                Affiliations
                Medical Oncology Unit, IRCCS Istituto Tumori “Giovanni Paolo II”, Bari, Italy
                Author notes

                Academic Editor: Ozkan Kanat

                Author information
                https://orcid.org/0000-0003-0670-7747
                Article
                10.1155/2020/9645294
                7719522
                c94f0508-ad10-4bb9-a33f-74b699b5efc8
                Copyright © 2020 Vito Lorusso et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 6 May 2020
                : 5 October 2020
                : 11 November 2020
                Funding
                Funded by: Eisai
                Categories
                Review Article

                Oncology & Radiotherapy
                Oncology & Radiotherapy

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