The prognostic value of BRCA1 promoter methylation in early stage triple negative breast cancer

Sharma, Priyanka; Stecklein, Shane R.; Kimler, Bruce F.; Sethi, Geetika; Petroff, Brian K.; Phillips, Teresa A.; Tawfik, Ossama; Godwin, Andrew K.; Jensen, Roy A.

doi:10.7243/2049-7962-3-2

Cited by 55 publications

(53 citation statements)

References 50 publications

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“…IPV has consistently been associated with increased self-perceived stress including symptoms of post-traumatic stress disorder (PTSD) among women with [4] and without cancer [8]. Convincing epidemiologic and clinical evidence now links chronic stress, depression and cancer progression [9–11]. Stressed individuals are more likely to smoke, excessively consume alcohol, and become obese; all three stress responses are associated with chronic inflammation which may influence cancer risk.…”

Section: Introductionmentioning

confidence: 99%

Intimate partner violence and women’s cancer quality of life

Coker

Follingstad

Garcia

et al. 2016

Cancer Causes Control

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Purpose Because Intimate partner violence (IPV) may disproportionately impact women’s quality of life (QOL) when undergoing cancer treatment, women experiencing IPV were hypothesized to have (a) more symptoms of depression or stress and (b) lower QOL as measured with the Functional Assessment of Cancer Therapy (FACT-B) and Functional Assessment of Chronic Illness Therapy-Spiritual Well-being (FACIT-SP) Scales relative to those never experiencing IPV. Methods Women, ages 18–79, who were included in one of two state cancer registries from 2009–2015 with a recent incident, primary, invasive biopsy-confirmed cancer diagnosis were recruited and asked to complete a phone interview, within 12 months of diagnosis. This interview measured IPV by timing (current and past) and type (physical, sexual, psychological), socio-demographics, and health status. Cancer registries provided consenting women’s cancer stage, site, date of diagnosis, and age. Results In this large cohort of 3,278 women who completed a phone interview, 1,221 (37.3%) disclosed lifetime IPV (10.6% sexual, 24.5% physical, and 33.6% psychological IPV). Experiencing IPV (particularly current IPV) was associated with poorer cancer-related QOL defined as having more symptoms of depression and stress after cancer diagnosis and lower FACIT-SP and FACT scores than women not experiencing IPV and controlling for confounders including demographic factors, cancer stage, site and number of comorbid conditions. Current IPV was more strongly associated with poorer QOL. When compared with those experiencing past IPV (and no IPV), women with cancer who experienced current IPV had significantly higher depression and stress symptoms scores and lower FACIT-SP and FACT-G scores indicating poorer QOL for all domains. While IPV was not associated with being diagnosed at a later cancer stage, current IPV was significantly associated with having more than one comorbid physical conditions at interview (adjusted rate ratio = 1.35; 95% confidence interval: 1.19–1.54) and particularly for women diagnosed with cancer when <55 years of age. Conclusions Current and past IPV were associated with poorer mental and physical health functioning among women recently diagnosed with cancer. Including clinical IPV screening may improve women’s cancer-related quality of life.

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Section: Introductionmentioning

confidence: 99%

Intimate partner violence and women’s cancer quality of life

Coker

Follingstad

Garcia

et al. 2016

Cancer Causes Control

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“…It is estimated that if these factors beyond germline BRCA mutations are comprehensively evaluated, 50%-60% of TNBC will demonstrate HR deficiency or BRCAness, making it an attractive selection and response biomarker for DNA-damaging therapy, such as platinum compounds and PARPi (Fig. 2) [58,68,80,81,85]. It is speculated that DNA-damaging therapy may be most active in tumors with germline BRCA mutations and in BRCA wild-type tumors that harbor the BRCAness phenotype.…”

Section: Homologous Recombination Defects and Dna-damaging Therapymentioning

confidence: 99%

“…To this end, development and clinical evaluation of platforms to identify markers of BRCAness have been a subject of intense investigation, especially in TNBC, a subtype thoughtto beenriched for BRCAness [58,[79][80][81][82][83]. Approximately 10%-20% of TNBCs harbor detectable germline BRCA1/2 mutations [12, 22, 24, 61,84].…”

Section: Homologous Recombination Defects and Dna-damaging Therapymentioning

confidence: 99%

Biology and Management of Patients With Triple-Negative Breast Cancer

2016

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Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancers and is associated with poor long-term outcomes compared with other breast cancer subtypes. Because of the lack of approved targeted therapy, at present chemotherapy remains the mainstay of treatment for early and advanced disease. TNBC is enriched for germline BRCA mutation, providing a foundation for the use of this as a biomarker to identify patients suitable for treatment with DNA-damaging agents. Inherited and acquired defects in homologous recombination DNA repair, a phenotype termed "BRCAness," may be present in a large proportion of TNBC cases, making it an attractive selection and response biomarker for DNAdamaging therapy. Triple-negative breast cancer is a diverse entity for which additional subclassifications are needed.Increasing understanding of biologic heterogeneity of TNBC has provided insight into identifying potentially effective systemic therapies, including cytotoxic and targeted agents. Numerous experimental approaches are under way, and several encouraging drug classes, such as immune checkpoint inhibitors, poly(ADP-ribose) polymerase inhibitors, platinum agents, phosphatidylinositol-3-kinase pathway inhibitors, and androgen receptor inhibitors, are being investigated in TNBC. Molecular biomarker-based patient selection in early-phase trials has the potential to accelerate development of effective therapies for this aggressive breast cancer subtype. TNBC is a complex disease, and it is likely that several different targeted approaches will be needed to make meaningful strides in improving the outcomes. The Oncologist 2016;21:1050-1062Implications for Practice: Triple-negative breast cancer (TNBC) is an aggressive subtype that is associated with poor outcomes.This article reviews clinical features and discusses the molecular diversity of this unique subtype. Current treatment paradigms, the role ofgermline testing, and platinum agents in TNBC are reviewed. Results and observations from pertinent clinical trials with potential implications for patient management are summarized.This article also discusses the clinical development and ongoing clinical trials of novel promising therapeutic agents in TNBC.

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“…The incidence of BRCA1 promoter methylation in breast cancer tissues is significantly higher (up to 82.1%) than in non-cancerous tissues 62, 63, 64, 65 , and gene methylation status is inversely correlated with BRCA1 mRNA expression 63, 65, 66 . BRCA1 promoter methylation is also correlated with decreased overall survival and disease-free survival for triple-negative and basal-like breast cancer 62, 66 . Methylation of promoters of upstream UBLs or cooperating factors governs expression of genes including HACE1, RNF180, CHIP, KEAP1 and PARK1.…”

Section: Promoter Hypermethylationmentioning

confidence: 98%

Dysregulation of ubiquitin ligases in cancer

Ronai

2015

Drug Resistance Updates

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Ubiquitin ligases are critical components of the ubiquitin proteasome system (UPS), which governs fundamental processes regulating normal cellular homeostasis, metabolism, and cell cycle in response to external stress signals and DNA damage. Among multiple steps of the UPS system required to regulate protein ubiquitination and stability, UBLs define specificity, as they recognize and interact with substrates in a temporally- and spatially-regulated manner. Such interactions are required for substrate modification by ubiquitin chains, which marks proteins for recognition and degradation by the proteasome, or alters their subcellular localization or assembly into functional complexes. UBLs are often deregulated in cancer, altering substrate availability or activity in a manner that can promote cellular transformation. Such deregulation can occur at the epigenetic, genomic, or post-translational levels. Alterations in UBL can be used to predict their contributions, affecting tumor suppressors or oncogenes in select tumors. Better understanding of mechanisms underlying UBL expression and activities is expected to drive the development of next generation modulators that can serve as novel therapeutic modalities. This review summarizes our current understanding of UBL deregulation in cancer and highlights novel opportunities for therapeutic interventions.

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The prognostic value of BRCA1 promoter methylation in early stage triple negative breast cancer

Cited by 55 publications

References 50 publications

Intimate partner violence and women’s cancer quality of life

Intimate partner violence and women’s cancer quality of life

Biology and Management of Patients With Triple-Negative Breast Cancer

Dysregulation of ubiquitin ligases in cancer

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