Inherited Mutations in 17 Breast Cancer Susceptibility Genes Among a Large Triple-Negative Breast Cancer Cohort Unselected for Family History of Breast Cancer

Couch, Fergus J.; Hart, Steven N.; Sharma, Priyanka; Toland, Amanda E.; Wang, Xianshu; Miron, Penelope; Olson, Janet E.; Godwin, Andrew K.; Pankratz, V. Shane; Olswold, Curtis; Slettedahl, Seth W.; Hallberg, Emily; Guidugli, Lucia; Davila, Jaime; Beckmann, Matthias W.; Janni, Wolfgang; Rack, Brigitte; Ekici, Arif B.; Slamon, Dennis J.; Konstantopoulou, Irene; Fostira, Florentia; Vratimos, Athanassios; Fountzilas, George; Pelttari, Liisa M.; Tapper, William; Durcan, Lorraine; Cross, Simon S.; Pilarski, Robert; Shapiro, Charles L.; Klemp, Jennifer R.; Yao, Song; Garber, Judy E.; Cox, Angela; Brauch, Hiltrud; Ambrosone, Christine B.; Nevanlinna, Heli; Yannoukakos, Drakoulis; Slager, Susan L.; Vachon, Celine M.; Eccles, Diana; Fasching, Peter A.

doi:10.1200/jco.2014.57.1414

Cited by 556 publications

(533 citation statements)

References 42 publications

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“…Mutations in the BRIP1 gene seem to be more frequent in women with early-onset BC and triple-negative BC 108 . About 1% of patients with early-onset or familial BC carry a deleterious mutation 103 .…”

Section: Brip1mentioning

confidence: 99%

Molecular Biology In Young Women With Breast Cancer: From Tumor Gene Expression To Dna Mutations

Gómez-Flores-Ramos¹,

Castro-Sánchez

Peña-Curiel

et al. 2017

RIC

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Young women with breast cancer (YWBC) represent roughly 15% of breast cancer (BC) cases in Latin America and other developing regions. Breast tumors occurring at an early age are more aggressive and have an overall worse prognosis compared to breast tumors in postmenopausal women. The expression of relevant proliferation biomarkers such as endocrine receptors and human epidermal growth factor receptor 2 appears to be unique in YWBC. Moreover, histopathological, molecular, genetic, and genomic studies have shown that YWBC exhibit a higher frequency of aggressive subtypes, differential tumor gene expression, increased genetic susceptibility, and specific genomic signatures, compared to older women with BC. This article reviews the current knowledge on tumor biology and genomic signatures in YWBC.

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Section: Brip1mentioning

confidence: 99%

Molecular Biology In Young Women With Breast Cancer: From Tumor Gene Expression To Dna Mutations

Gómez-Flores-Ramos¹,

Castro-Sánchez

Peña-Curiel

et al. 2017

RIC

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“…In women testing negative for BRCA1 and BRCA2 mutations, multi-gene germline sequencing identifies up to another 10% of patients with pathogenic mutations [21]. Recently, a large study of multi-gene germline testing in over 1,800 unselected patients with TNBC demonstrated that overall mutation rate was 14.6% with 8.5% having mutations in BRCA1, 2.7% in BRCA2 and an additional 3.7% with mutations in other genes such as PALB2 (1.2%), BRIP1, BARD1, and RAD51C among others [22]. Cancers arising in these genetic backgrounds are hypothesized to have HR DNA repair defects and therefore may have similar chemosensitivity to DNA-damaging therapies as BRCA1/2 mutation carriers [4,23].…”

Section: Germline Hr Pathway Mutations Beyond Brca1 and Brca2 As Hr Dmentioning

confidence: 99%

Homologous recombination deficiency and host anti-tumor immunity in triple-negative breast cancer

Telli

Stover

Loi

et al. 2018

Breast Cancer Res Treat

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Purpose Triple-negative breast cancer (TNBC) is associated with worse outcomes relative to other breast cancer subtypes. Chemotherapy remains the standard-of-care systemic therapy for patients with localized or metastatic disease, with few biomarkers to guide benefit. Methods We will discuss recent advances in our understanding of two key biological processes in TNBC, homologous recombination (HR) DNA repair deficiency and host anti-tumor immunity, and their intersection. Results Recent advances in our understanding of homologous recombination (HR) deficiency, including FDA approval of PARP inhibitor olaparib for BRCA1 or BRCA2 mutation carriers, and host anti-tumor immunity in TNBC offer potential for new and biomarker-driven approaches to treat TNBC. Assays interrogating HR DNA repair capacity may guide treatment with agents inducing or targeting DNA damage repair. Tumor infiltrating lymphocytes (TILs) are associated with improved prognosis in TNBC and recent efforts to characterize infiltrating immune cell subsets and activate host anti-tumor immunity offer promise, yet challenges remain particularly in tumors lacking pre-existing immune infiltrates. Advances in these fields provide potential biomarkers to stratify patients with TNBC and guide therapy: induction of DNA damage in HR-deficient tumors and activation of existing or recruitment of host anti-tumor immune cells. Importantly, these advances provide an opportunity to guide use of existing therapies and development of novel therapies for TNBC. Efforts to combine therapies that exploit HR deficiency to enhance the activity of immune-directed therapies offer promise. Conclusions HR deficiency remains an important biomarker target and potentially effective adjunct to enhance immunogenicity of 'immune cold' TNBCs.

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“…One study was excluded from this review despite the high number of patients, because the authors chose to study only 36 known pathogenic mutations in the selected HBOC genes [14]. The highest number of patients included was 10030, most of whom had HBOC, although one study was limited to unselected TNBC patient [31] and another one to OC [29]. Two studies included exclusively patients previously tested negatively for BRCA1/2 mutations [25,27].…”

Section: Discussionmentioning

confidence: 99%

The transfer of multigene panel testing for hereditary breast and ovarian cancer to healthcare: What are the implications for the management of patients and families?

Lizard¹,

Eliade²,

Skrzypski

et al. 2016

JCO

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Until recently, the molecular diagnosis of hereditary breast and ovarian cancer (HBOC) was mostly based on BRCA1/2 testing. Next generation sequencing and the recent discovery of new genes involved in HBOC now permit the transfer of genomic capture targeting multiple candidate genes from research to clinical use. However, the implications for the management of patients and their families have not been extensively studied, in particular since some of these genes are not well-established cancer predisposing genes. We studied 583 consecutive patients from Burgundy

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Inherited Mutations in 17 Breast Cancer Susceptibility Genes Among a Large Triple-Negative Breast Cancer Cohort Unselected for Family History of Breast Cancer

Cited by 556 publications

References 42 publications

Molecular Biology In Young Women With Breast Cancer: From Tumor Gene Expression To Dna Mutations

Molecular Biology In Young Women With Breast Cancer: From Tumor Gene Expression To Dna Mutations

Homologous recombination deficiency and host anti-tumor immunity in triple-negative breast cancer

The transfer of multigene panel testing for hereditary breast and ovarian cancer to healthcare: What are the implications for the management of patients and families?

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