Skip to main content
Erschienen in: Journal of Cancer Research and Clinical Oncology 9/2014

01.09.2014 | Original Article – Cancer Research

BRCA1 promoter methylation is a marker of better response to platinum–taxane-based therapy in sporadic epithelial ovarian cancer

verfasst von: T. Ignatov, H. Eggemann, S. D. Costa, A. Roessner, T. Kalinski, A. Ignatov

Erschienen in: Journal of Cancer Research and Clinical Oncology | Ausgabe 9/2014

Einloggen, um Zugang zu erhalten

Abstract

Background

The aim of the current study was to investigate the role of BRCA1 promoter methylation as predictive factor of response to platinum–taxane-based therapy in sporadic ovarian cancer.

Patients and methods

BRCA1 promoter methylation was analyzed in 42 sporadic epithelial ovarian cancers. The results were validated in a second cohort of 137 ovarian cancer patients.

Results

BRCA1 promoter methylation was observed in 35.7 % of patients in the first group and in 33.6 % in the second group. BRCA1 promoter methylation was associated with significant increase in median progression-free survival (PFS) of ovarian cancer patients receiving adjuvant platinum–taxane-based chemotherapy (P = 0.008). Multivariate analysis revealed that BRCA1 promoter methylation remains a favorable factor in regard to PFS (HR 0.52; 95 % CI 0.32–0.85, P = 0.009) after adjustment for other prognostic factors. Under the patients with recurrent disease, BRCA1 promoter methylation was associated with significant longer median PFS of 18.5 months in comparison with 12.8 months PFS for patients without BRCA1 promoter methylation.

Conclusions

BRCA1 promoter methylation is predictive for better response to platinum–taxane-based therapy in EOC.
Literatur
Zurück zum Zitat Boyd J, Sonoda Y, Federici MG, Bogomolniy F, Rhei E, Maresco DL, Saigo PE, Almadrones LA, Barakat RR, Brown CL, Chi DS, Curtin JP, Poynor EA, Hoskins WJ (2000) Clinicopathologic features of BRCA-linked and sporadic ovarian cancer. JAMA 17:2260–2265CrossRef Boyd J, Sonoda Y, Federici MG, Bogomolniy F, Rhei E, Maresco DL, Saigo PE, Almadrones LA, Barakat RR, Brown CL, Chi DS, Curtin JP, Poynor EA, Hoskins WJ (2000) Clinicopathologic features of BRCA-linked and sporadic ovarian cancer. JAMA 17:2260–2265CrossRef
Zurück zum Zitat Buller RE, Shahin MS, Geisler JP, Zogg M, De Young BR, Davis CS (2002) Failure of BRCA1 dysfunction to alter ovarian cancer survival. Clin Cancer Res 5:1196–1202 Buller RE, Shahin MS, Geisler JP, Zogg M, De Young BR, Davis CS (2002) Failure of BRCA1 dysfunction to alter ovarian cancer survival. Clin Cancer Res 5:1196–1202
Zurück zum Zitat Carser JE, Quinn JE, Michie CO, O’Brien EJ, McCluggage WG, Maxwell P, Lamers E, Lioe TF, Williams AR, Kennedy RD, Gourley C, Harkin DP (2011) BRCA1 is both a prognostic and predictive biomarker of response to chemotherapy in sporadic epithelial ovarian cancer. Gynecol Oncol 3:492–498CrossRef Carser JE, Quinn JE, Michie CO, O’Brien EJ, McCluggage WG, Maxwell P, Lamers E, Lioe TF, Williams AR, Kennedy RD, Gourley C, Harkin DP (2011) BRCA1 is both a prognostic and predictive biomarker of response to chemotherapy in sporadic epithelial ovarian cancer. Gynecol Oncol 3:492–498CrossRef
Zurück zum Zitat Catteau A, Morris JR (2002) BRCA1 methylation: a significant role in tumour development? Semin Cancer Biol 12(5):359–371PubMedCrossRef Catteau A, Morris JR (2002) BRCA1 methylation: a significant role in tumour development? Semin Cancer Biol 12(5):359–371PubMedCrossRef
Zurück zum Zitat Chaudhry P, Srinivasan R, Patel FD (2009) Utility of gene promoter methylation in prediction of response to platinum-based chemotherapy in epithelial ovarian cancer (EOC). Cancer Investig 8:877–884CrossRef Chaudhry P, Srinivasan R, Patel FD (2009) Utility of gene promoter methylation in prediction of response to platinum-based chemotherapy in epithelial ovarian cancer (EOC). Cancer Investig 8:877–884CrossRef
Zurück zum Zitat Chetrit A, Hirsh-Yechezkel G, Ben David Y, Lubin F, Friedman E, Sadetzki S (2008) Effect of BRCA1/2 mutations on long-term survival of patients with invasive ovarian cancer: the national Israeli study of ovarian cancer. J Clin Oncol 1:20–25CrossRef Chetrit A, Hirsh-Yechezkel G, Ben David Y, Lubin F, Friedman E, Sadetzki S (2008) Effect of BRCA1/2 mutations on long-term survival of patients with invasive ovarian cancer: the national Israeli study of ovarian cancer. J Clin Oncol 1:20–25CrossRef
Zurück zum Zitat Guendel I, Carpio L, Pedati C, Schwartz A, Teal C, Kashanchi F, Kehn-Hall K (2010) Methylation of the tumor suppressor protein, BRCA1, influences its transcriptional cofactor function. PLoS One 6:e11379CrossRef Guendel I, Carpio L, Pedati C, Schwartz A, Teal C, Kashanchi F, Kehn-Hall K (2010) Methylation of the tumor suppressor protein, BRCA1, influences its transcriptional cofactor function. PLoS One 6:e11379CrossRef
Zurück zum Zitat Harter P, Hilpert F, Mahner S, Heitz F, Pfisterer J, du BA (2010) Systemic therapy in recurrent ovarian cancer: current treatment options and new drugs. Expert Rev Anticancer Ther 1:81–88CrossRef Harter P, Hilpert F, Mahner S, Heitz F, Pfisterer J, du BA (2010) Systemic therapy in recurrent ovarian cancer: current treatment options and new drugs. Expert Rev Anticancer Ther 1:81–88CrossRef
Zurück zum Zitat Ignatov T, Poehlmann A, Ignatov A, Schinlauer A, Costa SD, Roessner A, Kalinski T, Bischoff J (2013) BRCA1 promoter methylation is a marker of better response to anthracycline-based therapy in sporadic TNBC. Breast Cancer Res Treat 2:205–212CrossRef Ignatov T, Poehlmann A, Ignatov A, Schinlauer A, Costa SD, Roessner A, Kalinski T, Bischoff J (2013) BRCA1 promoter methylation is a marker of better response to anthracycline-based therapy in sporadic TNBC. Breast Cancer Res Treat 2:205–212CrossRef
Zurück zum Zitat Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics, 2009. CA Cancer J Clin 4:225–249CrossRef Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics, 2009. CA Cancer J Clin 4:225–249CrossRef
Zurück zum Zitat Knudson AG Jr (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 4:820–823CrossRef Knudson AG Jr (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 4:820–823CrossRef
Zurück zum Zitat Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 5182:66–71CrossRef Miki Y, Swensen J, Shattuck-Eidens D, Futreal PA, Harshman K, Tavtigian S, Liu Q, Cochran C, Bennett LM, Ding W (1994) A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 5182:66–71CrossRef
Zurück zum Zitat Quinn JE, Carser JE, James CR, Kennedy RD, Harkin DP (2009) BRCA1 and implications for response to chemotherapy in ovarian cancer. Gynecol Oncol 1:134–142CrossRef Quinn JE, Carser JE, James CR, Kennedy RD, Harkin DP (2009) BRCA1 and implications for response to chemotherapy in ovarian cancer. Gynecol Oncol 1:134–142CrossRef
Zurück zum Zitat Senturk E, Cohen S, Dottino PR, Martignetti JA (2010) A critical re-appraisal of BRCA1 methylation studies in ovarian cancer. Gynecol Oncol 2:376–383CrossRef Senturk E, Cohen S, Dottino PR, Martignetti JA (2010) A critical re-appraisal of BRCA1 methylation studies in ovarian cancer. Gynecol Oncol 2:376–383CrossRef
Zurück zum Zitat Shilpa V, Bhagat R, Premalata CS, Pallavi VR, Ramesh G, Krishnamoorthy L (2014) BRCA1 promoter hypermethylation and protein expression in ovarian carcinoma-an Indian study. Tumour Biol 35:4277–4284PubMedCrossRef Shilpa V, Bhagat R, Premalata CS, Pallavi VR, Ramesh G, Krishnamoorthy L (2014) BRCA1 promoter hypermethylation and protein expression in ovarian carcinoma-an Indian study. Tumour Biol 35:4277–4284PubMedCrossRef
Zurück zum Zitat Stefansson OA, Villanueva A, Vidal A, Marti L, Esteller M (2012) BRCA1 epigenetic inactivation predicts sensitivity to platinum-based chemotherapy in breast and ovarian cancer. Epigenetics 11:1225–1229CrossRef Stefansson OA, Villanueva A, Vidal A, Marti L, Esteller M (2012) BRCA1 epigenetic inactivation predicts sensitivity to platinum-based chemotherapy in breast and ovarian cancer. Epigenetics 11:1225–1229CrossRef
Zurück zum Zitat Suijkerbuijk KP, Fackler MJ, Sukumar S, van Gils CH, van Laar T, Van der WE, Vooijs M, van Diest PJ (2008) Methylation is less abundant in BRCA1-associated compared with sporadic breast cancer. Ann Oncol 11:1870–1874CrossRef Suijkerbuijk KP, Fackler MJ, Sukumar S, van Gils CH, van Laar T, Van der WE, Vooijs M, van Diest PJ (2008) Methylation is less abundant in BRCA1-associated compared with sporadic breast cancer. Ann Oncol 11:1870–1874CrossRef
Zurück zum Zitat Swisher EM, Gonzalez RM, Taniguchi T, Garcia RL, Walsh T, Goff BA, Welcsh P (2009) Methylation and protein expression of DNA repair genes: association with chemotherapy exposure and survival in sporadic ovarian and peritoneal carcinomas. Mol Cancer 8:48PubMedCentralPubMedCrossRef Swisher EM, Gonzalez RM, Taniguchi T, Garcia RL, Walsh T, Goff BA, Welcsh P (2009) Methylation and protein expression of DNA repair genes: association with chemotherapy exposure and survival in sporadic ovarian and peritoneal carcinomas. Mol Cancer 8:48PubMedCentralPubMedCrossRef
Zurück zum Zitat Teodoridis JM, Hall J, Marsh S, Kannall HD, Smyth C, Curto J, Siddiqui N, Gabra H, McLeod HL, Strathdee G, Brown R (2005) CpG island methylation of DNA damage response genes in advanced ovarian cancer. Cancer Res 19:8961–8967CrossRef Teodoridis JM, Hall J, Marsh S, Kannall HD, Smyth C, Curto J, Siddiqui N, Gabra H, McLeod HL, Strathdee G, Brown R (2005) CpG island methylation of DNA damage response genes in advanced ovarian cancer. Cancer Res 19:8961–8967CrossRef
Zurück zum Zitat Turner N, Tutt A, Ashworth A (2004) Hallmarks of ‘BRCAness’ in sporadic cancers. Nat Rev Cancer 10:814–819CrossRef Turner N, Tutt A, Ashworth A (2004) Hallmarks of ‘BRCAness’ in sporadic cancers. Nat Rev Cancer 10:814–819CrossRef
Zurück zum Zitat Vencken PM, Kriege M, Hoogwerf D, Beugelink S, van der Burg ME, Hooning MJ, Berns EM, Jager A, Collee M, Burger CW, Seynaeve C (2011) Chemosensitivity and outcome of B. Ann Oncol 6:1346–1352CrossRef Vencken PM, Kriege M, Hoogwerf D, Beugelink S, van der Burg ME, Hooning MJ, Berns EM, Jager A, Collee M, Burger CW, Seynaeve C (2011) Chemosensitivity and outcome of B. Ann Oncol 6:1346–1352CrossRef
Zurück zum Zitat Weberpals JI, Tu D, Squire JA, Amin MS, Islam S, Pelletier LB, O’Brien AM, Hoskins PJ, Eisenhauer EA (2011) Breast cancer 1 (BRCA1) protein expression as a prognostic marker in sporadic epithelial ovarian carcinoma: an NCIC CTG OV.16 correlative study. Ann Oncol 11:2403–2410CrossRef Weberpals JI, Tu D, Squire JA, Amin MS, Islam S, Pelletier LB, O’Brien AM, Hoskins PJ, Eisenhauer EA (2011) Breast cancer 1 (BRCA1) protein expression as a prognostic marker in sporadic epithelial ovarian carcinoma: an NCIC CTG OV.16 correlative study. Ann Oncol 11:2403–2410CrossRef
Zurück zum Zitat Yang D, Khan S, Sun Y, Hess K, Shmulevich I, Sood AK, Zhang W (2011) Association of BRCA1 and BRCA2 mutations with survival, chemotherapy sensitivity, and gene mutator phenotype in patients with ovarian cancer. JAMA 14:1557–1565CrossRef Yang D, Khan S, Sun Y, Hess K, Shmulevich I, Sood AK, Zhang W (2011) Association of BRCA1 and BRCA2 mutations with survival, chemotherapy sensitivity, and gene mutator phenotype in patients with ovarian cancer. JAMA 14:1557–1565CrossRef
Metadaten
Titel
BRCA1 promoter methylation is a marker of better response to platinum–taxane-based therapy in sporadic epithelial ovarian cancer
verfasst von
T. Ignatov
H. Eggemann
S. D. Costa
A. Roessner
T. Kalinski
A. Ignatov
Publikationsdatum
01.09.2014
Verlag
Springer Berlin Heidelberg
Erschienen in
Journal of Cancer Research and Clinical Oncology / Ausgabe 9/2014
Print ISSN: 0171-5216
Elektronische ISSN: 1432-1335
DOI
https://doi.org/10.1007/s00432-014-1704-5

Weitere Artikel der Ausgabe 9/2014

Journal of Cancer Research and Clinical Oncology 9/2014 Zur Ausgabe

Adjuvante Immuntherapie verlängert Leben bei RCC

25.04.2024 Nierenkarzinom Nachrichten

Nun gibt es auch Resultate zum Gesamtüberleben: Eine adjuvante Pembrolizumab-Therapie konnte in einer Phase-3-Studie das Leben von Menschen mit Nierenzellkarzinom deutlich verlängern. Die Sterberate war im Vergleich zu Placebo um 38% geringer.

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

25.04.2024 NSCLC Nachrichten

Das Risiko für Rezidiv oder Tod von Patienten und Patientinnen mit reseziertem ALK-positivem NSCLC ist unter einer adjuvanten Therapie mit dem Tyrosinkinase-Inhibitor Alectinib signifikant geringer als unter platinbasierter Chemotherapie.

Bei Senioren mit Prostatakarzinom auf Anämie achten!

24.04.2024 DGIM 2024 Nachrichten

Patienten, die zur Behandlung ihres Prostatakarzinoms eine Androgendeprivationstherapie erhalten, entwickeln nicht selten eine Anämie. Wer ältere Patienten internistisch mitbetreut, sollte auf diese Nebenwirkung achten.

ICI-Therapie in der Schwangerschaft wird gut toleriert

Müssen sich Schwangere einer Krebstherapie unterziehen, rufen Immuncheckpointinhibitoren offenbar nicht mehr unerwünschte Wirkungen hervor als andere Mittel gegen Krebs.

Update Onkologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.