The BRCA1/BRCA2/Rad51 complex is a prognostic and predictive factor in early breast cancer

Söderlund, Karin; Skoog, Lambert; Fornander, Tommy; Askmalm, Marie Stenmark

doi:10.1016/j.radonc.2007.06.012

Cited by 55 publications

(45 citation statements)

References 59 publications

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“…In the study conducted by Söderlund et al, the patients with low expression of the BRCA1/BRCA2/Rad51 complex had more local recurrences, high histologic grade, and good response to radiotherapy compared to patients with high expression of the complex 126 . The polymorphism 135G > C in the RAD51 gene showed functional effects and was associated with the expression of the complex.…”

Section: Predictive and Prognostic Genetic Variantsmentioning

confidence: 95%

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: Predictive and Prognostic Genetic Variantsmentioning

confidence: 95%

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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“…Two separate studies on the same dataset, consisting of an RCT in which breast cancer patients were randomized between CMF or local radiotherapy used IHC to measure expression of firstly, BRCA1, BRCA2, and RAD51, and secondly, MRE11, NBS1, RAD50, and ATM [174,175]. It was found that patients with tumors with low RAD51 expression or with high expression of nuclear ATM or RAD50 benefited significantly from radiotherapy compared to CMF, while no differential benefit was seen in patients with tumors expressing high RAD51 or low ATM/RAD50 (no significant test for interaction) [174,175]. While the RAD51 data was consistent with the hypothesis that lack of RAD51 corresponds to impaired DNA repair and sensitivity to radiotherapy [174], the ATM/RAD50 data are counterintuitive [175].…”

Section: Hr Genesmentioning

confidence: 99%

Genomic instability in breast and ovarian cancers: translation into clinical predictive biomarkers

Vollebergh

Jonkers

Linn

2011

Cell. Mol. Life Sci.

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Breast and ovarian cancer are among the most common malignancies diagnosed in women worldwide. Together, they account for the majority of cancer-related deaths in women. These cancer types share a number of features, including their association with hereditary cancer syndromes caused by heterozygous germline mutations in BRCA1 or BRCA2. BRCA-associated breast and ovarian cancers are hallmarked by genomic instability and high sensitivity to DNA double-strand break (DSB) inducing agents due to loss of error-free DSB repair via homologous recombination (HR). Recently, poly(ADP-ribose) polymerase inhibitors, a new class of drugs that selectively target HR-deficient tumor cells, have been shown to be highly active in BRCA-associated breast and ovarian cancers. This finding has renewed interest in hallmarks of HR deficiency and the use of other DSB-inducing agents, such as platinum salts or bifunctional alkylators, in breast and ovarian cancer patients. In this review we discuss the similarities between breast and ovarian cancer, the hallmarks of genomic instability in BRCA-mutated and BRCA-like breast and ovarian cancers, and the efforts to search for predictive markers of HR deficiency in order to individualize therapy in breast and ovarian cancer.

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“…A similar role for S6K2 cannot be excluded, however, the impact on radiosensitivity appear to be mainly connected to the 17q21-23 amplicon. Of note, the RAD51C gene is located about 1 Mb from S6K1, and the RAD51 DNA repair family has in both in vivo and in vitro studies been related to a poor sensitivity of radiation-induced apoptosis [46][47][48][49].…”

Section: Treatment Predictionmentioning

confidence: 99%

Clinical potential of the mTOR targets S6K1 and S6K2 in breast cancer

Pérez-Tenorio

Karlsson

Waltersson

et al. 2010

Breast Cancer Res Treat

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Aim: The Mammalian Target of Rapamycin (mTOR) and its substrates S6K1 and S6K2 regulate cell growth, proliferation and metabolism through translational control. RPS6KB1 (S6K1) and RPS6KB2 (S6K2) are situated in the commonly amplified 17q21-23 and 11q13regions. S6K1 amplification and protein overexpression have earlier been associated with a worse outcome in breast cancer, but information regarding S6K2 is scarce. The aim of this study was to evaluate the prognostic and treatment predictive relevance of S6K1/S6K2 gene amplification, as well as S6K2 protein expression in breast cancer. Results: S6K1 amplification/gain was detected in 10.7%/21.4% and S6K2 amplification/gain in 4.3%/21.3% of the tumors. S6K2 protein was detected in the nucleus (38%) and cytoplasm (76%) of the tumor cells. S6K1 amplification was significantly associated with HER2 gene amplification and protein expression. S6K2 amplification correlated significantly with high S6K2 mRNA levels, ER+ status and CCND1 amplification. S6K1 and S6K2 gene amplification was associated with a worse prognosis independent of HER2 and CCND1. S6K2 gain and nuclear S6K2 expression was related to an improved benefit from tamoxifen among patients with ER+ respectively ER+/PgR+ tumors. In the ER+/PgR-subgroup, nuclear S6K2 rather indicated decreased tamoxifen responsiveness. S6K1 amplification predicted reduced benefit from radiotherapy.Conclusions: This is the first study showing that S6K2 amplification and overexpression, like S6K1 amplification, have prognostic and treatment predictive significance in breast cancer.

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The BRCA1/BRCA2/Rad51 complex is a prognostic and predictive factor in early breast cancer

Cited by 55 publications

References 59 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

Genomic instability in breast and ovarian cancers: translation into clinical predictive biomarkers

Clinical potential of the mTOR targets S6K1 and S6K2 in breast cancer

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