BRCAness as a prognostic indicator in patients with early breast cancer

Liu, Lei; Matsunaga, Yuki; Tsurutani, Junji; Akashi‐Tanaka, Sadako; Masuda, Hiroko; Ide, Yoshimi; Hashimoto, Rikako; Inuzuka, Mayuko; Watanabe, Chie; Taruno, Kanae; Sawada, Terumasa; Okuyama, Hiromi; Ata, Arisa; Kuwayama, Takashi; Nakayama, Sadayoshi; Tonouchi, Yumi; Nakamura, Seigo

doi:10.1038/s41598-020-78016-8

Cited by 15 publications

(7 citation statements)

References 29 publications

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“…BRCA1 and BRCA2 are tumor suppressor genes with a fundamental role in DNA repair through the homologous recombination pathway [61]. Germline mutations in these genes are associated with an increased risk of developing breast and ovarian cancer [62], with the mean cumulative breast cancer risk at 80 years of age for BRCA1 and BRCA2 genes being 72% and 69%, respectively [3].…”

Section: P53mentioning

confidence: 99%

Biomarkers in Breast Cancer: An Old Story with a New End

Alves

Meira

Merigueti

et al. 2023

Genes

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Breast cancer is the second most frequent cancer in the world. It is a heterogeneous disease and the leading cause of cancer mortality in women. Advances in molecular technologies allowed for the identification of new and more specifics biomarkers for breast cancer diagnosis, prognosis, and risk prediction, enabling personalized treatments, improving therapy, and preventing overtreatment, undertreatment, and incorrect treatment. Several breast cancer biomarkers have been identified and, along with traditional biomarkers, they can assist physicians throughout treatment plan and increase therapy success. Despite the need of more data to improve specificity and determine the real clinical utility of some biomarkers, others are already established and can be used as a guide to make treatment decisions. In this review, we summarize the available traditional, novel, and potential biomarkers while also including gene expression profiles, breast cancer single-cell and polyploid giant cancer cells. We hope to help physicians understand tumor specific characteristics and support decision-making in patient-personalized clinical management, consequently improving treatment outcome.

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Section: P53mentioning

confidence: 99%

Biomarkers in Breast Cancer: An Old Story with a New End

Alves

Meira

Merigueti

et al. 2023

Genes

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“…For instance, somatic mutations of homologous recombination repair (HRR) genes such as ATM, ATR, PALB2 and RAD51 cause BRCAness [ 3 ]. BRCAness was reported to predict response to anticancer agents [ 4 ]. Since poly ADP-ribose polymerase (PARP) is also essential in DNA repair, PARP inhibitors (PARPis) cause synthetic lethality in tumors with BRCA1 and/or BRCA2 germline mutations and are used for ovarian, prostate, pancreatic, and breast cancer.…”

Section: Introductionmentioning

confidence: 99%

Development of a novel BRCAness score that predicts response to PARP inhibitors

Oshi

Gandhi

et al. 2022

Biomark Res

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Background BRCAness is a characteristic feature of homologous recombination deficiency (HRD) mimicking BRCA gene mutation in breast cancer. We hypothesized that a measure to quantify BRCAness that causes synthetic lethality in BRCA mutated tumors will identify responders to PARP inhibitors. Methods A total of 6753 breast cancer patients from 3 large independent cohorts were analyzed. A score was generated by transcriptomic profiling using gene set variation analysis algorithm on 34 BRCA1-mutation related genes selected by high AUC levels in ROC curve between BRCA1 mutation and wildtype breast cancer. Results The score was significantly associated with BRCA1 mutation, high mutation load and intratumoral heterogeneity as expected, as well as with high HRD, DNA repair and MKi67 expression regardless of BRCA mutations. High BRCAness tumors enriched not only DNA repair, but also all five Hallmark cell proliferation-related gene sets. High BRCAness tumors were significantly associated with higher cytolytic activity and with higher anti-cancerous immune cell infiltration. Not only did the breast cancer cell lines with BRCA-mutation show high score, but even the other cells in human breast cancer tumor microenvironment were contributing to the score. The BRCAness score was the highest in triple-negative breast cancer consistently in all 3 cohorts. BRCAness was associated with response to chemotherapy and correlated strongly with response to PARP inhibitor in both triple-negative and ER-positive/HER2-negative breast cancer. Conclusions We established a novel BRCAness score using BRCA-mutation-related gene expressions and found that it associates with DNA repair and predicts response to PARP inhibitors regardless of BRCA mutation.

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“…In NACT subgroup analysis, clinical response rate for taxane-based regimen was significantly lower in BRCAness patients (58.3% vs. 77.8%, p = 0.041). Authors concluded that BRCAness may suggest resistance to taxane-based CT [134]. Similarly, in the just above-mentioned study [133] the 50% inhibitory concentration of docetaxel was higher in BRCA mutant and BRCAness cell lines than their counterparts.…”

Section: Brcanessmentioning

confidence: 85%

Molecular Mechanisms, Biomarkers and Emerging Therapies for Chemotherapy Resistant TNBC

Scatena

Ghilli

Bargagna

et al. 2022

IJMS

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Triple-negative breast cancer (TNBC) is associated with high recurrence rates, high incidence of distant metastases, and poor overall survival (OS). Taxane and anthracycline-containing chemotherapy (CT) is currently the main systemic treatment option for TNBC, while platinum-based chemotherapy showed promising results in the neoadjuvant and metastatic settings. An early arising of intrinsic or acquired CT resistance is common and represents the main hurdle for successful TNBC treatment. Numerous mechanisms were uncovered that can lead to the development of chemoresistance. These include cancer stem cells (CSCs) induction after neoadjuvant chemotherapy (NACT), ATP-binding cassette (ABC) transporters, hypoxia and avoidance of apoptosis, single factors such as tyrosine kinase receptors (EGFR, IGFR1), a disintegrin and metalloproteinase 10 (ADAM10), and a few pathological molecular pathways. Some biomarkers capable of predicting resistance to specific chemotherapeutic agents were identified and are expected to be validated in future studies for a more accurate selection of drugs to be employed and for a more tailored approach, both in neoadjuvant and advanced settings. Recently, based on specific biomarkers, some therapies were tailored to TNBC subsets and became available in clinical practice: olaparib and talazoparib for BRCA1/2 germline mutation carriers larotrectinib and entrectinib for neurotrophic tropomyosin receptor kinase (NTRK) gene fusion carriers, and anti-trophoblast cell surface antigen 2 (Trop2) antibody drug conjugate therapy for heavily pretreated metastatic TNBC (mTNBC). Further therapies targeting some pathologic molecular pathways, apoptosis, miRNAS, epidermal growth factor receptor (EGFR), insulin growth factor 1 receptor (IGF-1R), and androgen receptor (AR) are under investigation. Among them, phosphatidylinositol 3 kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) and EGFR inhibitors as well as antiandrogens showed promising results and are under evaluation in Phase II/III clinical trials. Emerging therapies allow to select specific antiblastics that alone or by integrating the conventional therapeutic approach may overcome/hinder chemoresistance.

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BRCAness as a prognostic indicator in patients with early breast cancer

Cited by 15 publications

References 29 publications

Biomarkers in Breast Cancer: An Old Story with a New End

Biomarkers in Breast Cancer: An Old Story with a New End

Development of a novel BRCAness score that predicts response to PARP inhibitors

Molecular Mechanisms, Biomarkers and Emerging Therapies for Chemotherapy Resistant TNBC

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