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Accelerating progress in early triple-negative breast cancer: A viewpoint on antibody-drug conjugates, back from St Gallen breast cancer conference 2021.

ABSTRACT: Metastatic triple-negative breast cancer (mTNBC) is associated with an aggressive disease course, and limited treatment options. The recent accelerated drug development in the space of mTNBC has been driven by a precision-medicine approach, with the potential to deliver more personalized treatments and result in better outcomes. Antibody-drug conjugates (ADCs) have introduced a novel paradigm in the space of mTNBC, leading to the approval of the first targeted agent in this setting. The research and development of ADCs comes in parallel with the identification of tumor-specific targets of pharmacological interest. As a result, ADCs bring the potential for agnostic treatment delivery-across multiple histology types, and theranostically, by coupling tumor-antigen identification and treatment, as a continuum. In this perspective, recent progress in ADCs development for early and mTNBC are outlined, in the trade-off of patient selection, tumor specificity, precise drug delivery, potent payloads safety and quality of life.

SUBMITTER: Trapani D

PROVIDER: S-EPMC9097802 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Accelerating progress in early triple-negative breast cancer: A viewpoint on antibody-drug conjugates, back from St Gallen breast cancer conference 2021.

Trapani Dario D Curigliano Giuseppe G

Breast (Edinburgh, Scotland) 20211213

Metastatic triple-negative breast cancer (mTNBC) is associated with an aggressive disease course, and limited treatment options. The recent accelerated drug development in the space of mTNBC has been driven by a precision-medicine approach, with the potential to deliver more personalized treatments and result in better outcomes. Antibody-drug conjugates (ADCs) have introduced a novel paradigm in the space of mTNBC, leading to the approval of the first targeted agent in this setting. The research ...[more]

PMID: 34920925

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Project description:The 17th St Gallen International Breast Cancer Consensus Conference in 2021 was held virtually, owing to the global COVID-19 pandemic. More than 3300 participants took part in this important bi-annual critical review of the 'state of the art' in the multidisciplinary care of early-stage breast cancer. Seventy-four expert panelists (see Appendix 1) from all continents discussed and commented on the previously elaborated consensus questions, as well as many key questions on early breast cancer diagnosis and treatment asked by the audience. The theme of this year's conference was 'Customizing local and systemic therapies.' A well-organized program of pre-recorded symposia, live panel discussions and real-time panel voting results drew a worldwide audience of thousands, reflecting the far-reaching impact of breast cancer on every continent. The interactive technology platform allowed, for the first time, audience members to ask direct questions to panelists, and to weigh in with their own vote on several key panel questions. A hallmark of this meeting was to focus on customized recommendations for treatment of early-stage breast cancer. There is increasing recognition that the care of a breast cancer patient depends on highly individualized clinical features, including the stage at presentation, the biological subset of breast cancer, the genetic factors that may underlie breast cancer risk, the genomic signatures that inform treatment recommendations, the extent of response before surgery in patients who receive neoadjuvant therapy, and patient preferences. This customized approach to treatment requires integration of clinical care between patients and radiology, pathology, genetics, and surgical, medical and radiation oncology providers. It also requires a dynamic response from clinicians as they encounter accumulating clinical information at the time of diagnosis and then serially with each step in the treatment plan and follow-up, reflecting patient experiences and treatment response.

Project description:PurposeHuman epidermal growth factor receptor 2 (HER2)-positive luminal B type comprises estrogen receptor (ER)-positive and HER2-positive cancers, and HER2-negative luminal B type comprises ER-positive cancers showing a Ki-67 labeling index ?14% or progesterone receptor (PR) expression of <20% according to the St. Gallen consensus 2013. The current study aimed to classify intrinsic subtypes according to the St. Gallen consensus 2013 and determine the differences in clinicopathological parameters and survival outcomes among the molecular types, especially among the luminal types.MethodsAssessment of molecular types was performed for 267 invasive ductal carcinomas. The differences in clinicopathological parameters, disease-free survival (DFS), and overall survival (OS) among the molecular types were analyzed.ResultsThe luminal B type was the most prevalent, at 44.9%, followed by the luminal A, triple-negative (including basal-like type), and HER2 type, at 21.7%, 18.7%, and 14.6%, respectively. There were statistically significant differences in size (p=0.003), nodal status (p=0.046), histologic grade (p<0.001), p53 (p<0.001) and cyclooxygenase 2 (COX-2) positivity (p=0.002), recurrence (p=0.001) and death rates (p=0.036), DFS (p=0.002), and OS (p=0.039) among the molecular types. Significant differences in size (p=0.009), nodal metastasis (p=0.019), histologic grade (p<0.001), p53 positivity (p=0.001), and PR expression (p<0.001) were noted between the luminal A and B types. Among the luminal B type cancers, the distributions of ER and PR scores showed significant differences (p=0.003, p=0.003). p53 positivity in the luminal B type cancers was related to shortened DFS (p=0.034). In luminal type cancers, COX-2 positivity was related to longer DFS (p=0.026).ConclusionDifferent management guidelines should be considered for the luminal A and luminal B breast cancer types. Positive p53 expression in luminal B type cancers and negative COX-2 expression in luminal type cancers seem to be related to poor clinical outcome.

Project description:The 14th St Gallen International Breast Cancer Conference (2015) reviewed substantial new evidence on locoregional and systemic therapies for early breast cancer. Further experience has supported the adequacy of tumor margins defined as 'no ink on invasive tumor or DCIS' and the safety of omitting axillary dissection in specific cohorts. Radiotherapy trials support irradiation of regional nodes in node-positive disease. Considering subdivisions within luminal disease, the Panel was more concerned with indications for the use of specific therapies, rather than surrogate identification of intrinsic subtypes as measured by multiparameter molecular tests. For the treatment of HER2-positive disease in patients with node-negative cancers up to 1 cm, the Panel endorsed a simplified regimen comprising paclitaxel and trastuzumab without anthracycline as adjuvant therapy. For premenopausal patients with endocrine responsive disease, the Panel endorsed the role of ovarian function suppression with either tamoxifen or exemestane for patients at higher risk. The Panel noted the value of an LHRH agonist given during chemotherapy for premenopausal women with ER-negative disease in protecting against premature ovarian failure and preserving fertility. The Panel noted increasing evidence for the prognostic value of commonly used multiparameter molecular markers, some of which also carried prognostic information for late relapse. The Panel noted that the results of such tests, where available, were frequently used to assist decisions about the inclusion of cytotoxic chemotherapy in the treatment of patients with luminal disease, but noted that threshold values had not been established for this purpose for any of these tests. Multiparameter molecular assays are expensive and therefore unavailable in much of the world. The majority of new breast cancer cases and breast cancer deaths now occur in less developed regions of the world. In these areas, less expensive pathology tests may provide valuable information. The Panel recommendations on treatment are not intended to apply to all patients, but rather to establish norms appropriate for the majority. Again, economic considerations may require that less expensive and only marginally less effective therapies may be necessary in less resourced areas. Panel recommendations do not imply unanimous agreement among Panel members. Indeed, very few of the 200 questions received 100% agreement from the Panel. In the text below, wording is intended to convey the strength of Panel support for each recommendation, while details of Panel voting on each question are available in supplementary Appendix S2, available at Annals of Oncology online.

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Accelerating progress in early triple-negative breast cancer: A viewpoint on antibody-drug conjugates, back from St Gallen breast cancer conference 2021.

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Accelerating progress in early triple-negative breast cancer: A viewpoint on antibody-drug conjugates, back from St Gallen breast cancer conference 2021.

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