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Expression of DNA Damage Response Molecules PARP1, γH2AX, BRCA1, and BRCA2 Predicts Poor Survival of Breast Carcinoma Patients.

Park SH, Noh SJ, Kim KM, Bae JS, Kwon KS, Jung SH, Kim JR, Lee H, Chung MJ, Moon WS, Kang MJ, Jang KY - Transl Oncol (2015)

Bottom Line: In addition, the combined expressional pattern of BRCA1, BRCA2, PARP1, and γH2AX (CSbbph) was an additional independent prognostic predictor for OS (P < .001) and RFS (P < .001).The 10-year OS rate was 95% in the CSbbph-low (CSbbph scores 0 and 1) subgroup, but that was only 35% in the CSbbph-high (CSbbph score 4) subgroup.This study has demonstrated that the individual and combined expression patterns of PARP1, γH2AX, BRCA1, and BRCA2 could be helpful in determining an accurate prognosis for BCA patients and for the selection of BCA patients who could potentially benefit from anti-PARP1 therapy with a combination of genotoxic chemotherapeutic agents.

View Article: PubMed Central - PubMed

Affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA, USA.

No MeSH data available.


Related in: MedlinePlus

Kaplan-Meier survival analysis according to the expression of PARP1, γH2AX, BRCA1, and BRCA2 in the subpopulations of BCAs. (A) OS and RFS in 169 BCA patients who received adjuvant chemotherapy. (B) OS and RFS in 166 BCA patients who received postoperative endocrine therapy. (C) OS and RFS in 33 triple-negative (HER2−/ER−/PR−) BCA patients.
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f0010: Kaplan-Meier survival analysis according to the expression of PARP1, γH2AX, BRCA1, and BRCA2 in the subpopulations of BCAs. (A) OS and RFS in 169 BCA patients who received adjuvant chemotherapy. (B) OS and RFS in 166 BCA patients who received postoperative endocrine therapy. (C) OS and RFS in 33 triple-negative (HER2−/ER−/PR−) BCA patients.

Mentions: Thereafter, we did further survival analysis of the subpopulation of BCA patients who received adjuvant chemotherapy or endocrine therapy. Among the 169 BCA patients who received systemic adjuvant chemotherapy, the expression of HER2, PR, BRCA1 (log-rank, OS, P = .011; RFS, P = .009), BRCA2 (log-rank, OS, P < .001; RFS, P < .001), PARP1 (log-rank, OS, P < .001; RFS, P < .001), and γH2AX (log-rank, OS, P < .001; RFS, P < .001) was significantly associated with shorter OS and RFS (Figure 2A). Older age of the patients and higher tumor stage were associated with shorter OS. Among the 166 BCA patients who received postoperative endocrine therapy, the age, histologic grade, and the expression of HER2, PR, BRCA1 (log-rank, OS, P = .009; RFS, P = .009), BRCA2 (log-rank, OS, P < .001; RFS, P < .001), PARP1 (log-rank, OS, P < .001; RFS, P < .001), and γH2AX (log-rank, OS, P < .001; RFS, P < .001) were significantly associated with both OS and RFS (Figure 2B).


Expression of DNA Damage Response Molecules PARP1, γH2AX, BRCA1, and BRCA2 Predicts Poor Survival of Breast Carcinoma Patients.

Park SH, Noh SJ, Kim KM, Bae JS, Kwon KS, Jung SH, Kim JR, Lee H, Chung MJ, Moon WS, Kang MJ, Jang KY - Transl Oncol (2015)

Kaplan-Meier survival analysis according to the expression of PARP1, γH2AX, BRCA1, and BRCA2 in the subpopulations of BCAs. (A) OS and RFS in 169 BCA patients who received adjuvant chemotherapy. (B) OS and RFS in 166 BCA patients who received postoperative endocrine therapy. (C) OS and RFS in 33 triple-negative (HER2−/ER−/PR−) BCA patients.
© Copyright Policy - CC BY-NC-ND
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4562981&req=5

f0010: Kaplan-Meier survival analysis according to the expression of PARP1, γH2AX, BRCA1, and BRCA2 in the subpopulations of BCAs. (A) OS and RFS in 169 BCA patients who received adjuvant chemotherapy. (B) OS and RFS in 166 BCA patients who received postoperative endocrine therapy. (C) OS and RFS in 33 triple-negative (HER2−/ER−/PR−) BCA patients.
Mentions: Thereafter, we did further survival analysis of the subpopulation of BCA patients who received adjuvant chemotherapy or endocrine therapy. Among the 169 BCA patients who received systemic adjuvant chemotherapy, the expression of HER2, PR, BRCA1 (log-rank, OS, P = .011; RFS, P = .009), BRCA2 (log-rank, OS, P < .001; RFS, P < .001), PARP1 (log-rank, OS, P < .001; RFS, P < .001), and γH2AX (log-rank, OS, P < .001; RFS, P < .001) was significantly associated with shorter OS and RFS (Figure 2A). Older age of the patients and higher tumor stage were associated with shorter OS. Among the 166 BCA patients who received postoperative endocrine therapy, the age, histologic grade, and the expression of HER2, PR, BRCA1 (log-rank, OS, P = .009; RFS, P = .009), BRCA2 (log-rank, OS, P < .001; RFS, P < .001), PARP1 (log-rank, OS, P < .001; RFS, P < .001), and γH2AX (log-rank, OS, P < .001; RFS, P < .001) were significantly associated with both OS and RFS (Figure 2B).

Bottom Line: In addition, the combined expressional pattern of BRCA1, BRCA2, PARP1, and γH2AX (CSbbph) was an additional independent prognostic predictor for OS (P < .001) and RFS (P < .001).The 10-year OS rate was 95% in the CSbbph-low (CSbbph scores 0 and 1) subgroup, but that was only 35% in the CSbbph-high (CSbbph score 4) subgroup.This study has demonstrated that the individual and combined expression patterns of PARP1, γH2AX, BRCA1, and BRCA2 could be helpful in determining an accurate prognosis for BCA patients and for the selection of BCA patients who could potentially benefit from anti-PARP1 therapy with a combination of genotoxic chemotherapeutic agents.

View Article: PubMed Central - PubMed

Affiliation: Division of Gynecologic Oncology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA, USA.

No MeSH data available.


Related in: MedlinePlus