Coexistent Loss of the Expressions of BRCA1 and p53 Predicts Poor Prognosis in Triple-Negative Breast Cancer

Kim, Min Chong; Choi, Jung Eun; Lee, Soo Jung; Bae, Young Kyung

doi:10.1245/s10434-016-5307-z

Cited by 15 publications

(15 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The loss of BRCA1 expression was observed in about 20% of patients and was correlated with a poor prognosis in this study. These findings are consistent with those of previous reports [ 17 , 18 ], although no association was noted between the resistance to taxanes and the loss of BRCA1 expression in this study. The EMT phenotype is considered to be related to chemoresistance.…”

Section: Discussionsupporting

confidence: 94%

See 1 more Smart Citation

CD44v9 as a poor prognostic factor of triple-negative breast cancer treated with neoadjuvant chemotherapy

et al. 2018

View full text Add to dashboard Cite

show abstract

Section: Discussionsupporting

confidence: 94%

“…Among DNA repair-related genes, low expression of BRCA1 or “BRCAness” features is correlated with taxane resistance [ 14 – 16 ] and a poor prognosis, specifically TNBC [ 17 , 18 ]. Regarding EMT, we previously reported that vimentin, the major EMT-related factors, is poor prognostic factors for TNBC [ 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

CD44v9 as a poor prognostic factor of triple-negative breast cancer treated with neoadjuvant chemotherapy

et al. 2018

View full text Add to dashboard Cite

show abstract

“…We examined p53 expression in 156 cases of TNBC and found it was positive in 71.3% of cases, which was in consistent with reported positivity rates of p53 expression (56% to 71%) in TNBC [ 22 ]. Although the association between p53 and clinical features varies in studies, we found that histologic grade was the only variable correlated with p53 expression.…”

Section: Discussionsupporting

confidence: 86%

“…Although various methodological and clinical settings have been applied to explore p53 status for predicting therapy response and patients’ outcomes, results are contradictory [ 20 ]. Missense mutation of P53 gene induces stable detectable mutant p53 protein, whereas truncating P53 gene mutations yields unstable p53 proteins that cannot be detected by IHC [ 21 , 22 ]. Besides, wildtype p53 may accumulate in cells resulted from DNA damage or binding to other proteins and thus show strong immunoreactivity [ 21 , 23 ].…”

Section: Discussionmentioning

confidence: 99%

P53 and Ki-67 as prognostic markers in triple-negative breast cancer patients

et al. 2017

View full text Add to dashboard Cite

Triple-negative breast cancer (TNBC) is an aggressive subgroup of breast cancer lack of effective target therapy. This study was to investigate the prognostic role of p53 and Ki-67 in 156 cases of TNBC patients. Logistic regression analysis was used to examine the association between clinical parameters and recurrence. Univariate and multivariate analyses were used to examine the association between clinical characteristics and disease-free survival (DFS) or overall survival (OS). Survival analyses using the Kaplan-Meier method were performed to examine the association between p53/Ki-67 and DFS and OS. Our data showed that p53 was positive in 71.3% and the Ki-67 high index was in 82.8% of TNBC. Elevated p53 and Ki-67 were associated with histological grade. The tumor size, lymph node involvement, and p53 expression are associated with risk of recurrence. Tumor size, lymph node involvement, family history, Ki-67 and p53 are independent variables associated with either DFS or OS. TNBC patients with positive p53 or Ki-67 high index or family history of cancer have a significant association with worse prognosis. This study suggests that p53, Ki-67 and family history are useful prognostic markers in TNBC.

show abstract

“…Furthermore, there is a strong association between BCCIP negativity and normal p53 status, or p53 mutant status with a normal level of BCCIP (Table 1 , p = 0.0018, χ 2 test). This is in contrast to the breast cancers of BRCA1 deficiency, which are often associated with p53 mutations [ 5 , 8 – 10 , 41 ]. We also examined BCCIP expression in 12 cases of TNBC with BRCA1 mutations, and found that only one of the 12 cases was BCCIP negative (8%), which is significantly less frequent than in sporadic TNBC (49%, p = 0.0073, χ 2 test).…”

Section: Resultsmentioning

confidence: 94%

Roles of BCCIP deficiency in mammary tumorigenesis

Droz-Rosario

Liu

et al. 2017

Breast Cancer Res

View full text Add to dashboard Cite

BackgroundDysregulated DNA repair and cell proliferation controls are essential driving forces in mammary tumorigenesis. BCCIP was originally identified as a BRCA2 and CDKN1A interacting protein that has been implicated in maintenance of genomic stability, cell cycle regulation, and microtubule dynamics. The aims of this study were to determine whether BCCIP deficiency contributes to mammary tumorigenesis, especially for a subset of breast cancers with 53BP1 abnormality, and to reveal the mechanistic implications of BCCIP in breast cancer interventions.MethodsWe analyzed the BCCIP protein level in 470 cases of human breast cancer to determine the associations between BCCIP and 53BP1, p53, and subtypes of breast cancer. We further constructed a unique BCCIP knockdown mouse model to determine whether a partial BCCIP deficiency leads to spontaneous breast cancer formation.ResultsWe found that the BCCIP protein level is downregulated in 49% of triple-negative breast cancer and 25% of nontriple-negative breast cancer. The downregulation of BCCIP is mutually exclusive with p53 mutations but concurrent with 53BP1 loss in triple-negative breast cancer. In a K14-Cre-mediated conditional BCCIP knockdown mouse model, we found that BCCIP downregulation causes a formation of benign modules in the mammary glands, resembling the epidermal inclusion cyst of the breast. However, the majority of these benign lesions remain indolent, and only ~ 10% of them evolve into malignant tumors after a long latency. This tumor progression is associated with a loss of 53BP1 and p16 expression. BCCIP knockdown did not alter the latency of mammary tumor formation induced by conditional Trp53 deletion.ConclusionsOur data suggest a confounding role of BCCIP deficiency in modulating breast cancer development by enhancing tumor initiation but hindering progression. Furthermore, secondary genetic alternations may overcome the progression suppression imposed by BCCIP deficiency through a synthetic viability mechanism.Electronic supplementary materialThe online version of this article (doi:10.1186/s13058-017-0907-5) contains supplementary material, which is available to authorized users.

show abstract

Coexistent Loss of the Expressions of BRCA1 and p53 Predicts Poor Prognosis in Triple-Negative Breast Cancer

Abstract: Combined expression patterns of BRCA1 and p53 could serve as useful prognostic markers in TNBC.

Cited by 15 publications

References 32 publications

CD44v9 as a poor prognostic factor of triple-negative breast cancer treated with neoadjuvant chemotherapy

CD44v9 as a poor prognostic factor of triple-negative breast cancer treated with neoadjuvant chemotherapy

P53 and Ki-67 as prognostic markers in triple-negative breast cancer patients

Roles of BCCIP deficiency in mammary tumorigenesis

Contact Info

Product

Resources

About