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News

08May 2017

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Thesis defense of Alexandra van den Broek: The impact of BRCA1 and BRCA2 germline mutations on breast cancer outcome in young women

Weefselonderzoek

Women with a hereditary mutation in the BRCA1 or BRCA2 gene have a high risk of developing breast cancer. But what do these mutations mean for the survival of these patients after developing breast cancer? This was the central question in the PhD research of Alexandra van den Broek. She will defend her thesis on May 8.

What is unique about Van den Broek's study is the cohort size: she used the data of as many as 6000 Dutch breast cancer patients who developed cancer before the age of 50 and who were treated between 1972 and 2003 in a large number of Dutch hospitals. For all these patients she and colleagues determined the BRCA mutation status using residual tissue that was stored in pathological archives of the hospitals. This allowed her to retrospectively compare patients with a BRCA1 or BRCA2 mutation with breast cancer patients without such a mutation.

The results of this study show that within this historical cohort women with a BRCA1 or BRCA2 mutation had a worse survival compared to patients without a mutation. This was largely explained by the unfavorable characteristics of the breast tumors that arise in patients with these mutations. Women with a BRCA1 or BRCA2 mutation were also at increased risk of developing breast cancer for a second time, in the other breast than the first tumor. This was especially the case for women who developed the first breast cancer before the age of forty years. Women with a BRCA1 mutation were also at increased risk of developing ovarian cancer after the breast cancer, which also explained part of the worse survival of the patients with BRCA1 mutations. Finally, the results show that breast-conserving surgery is also a safe surgical treatment to offer to patients with a BRCA1 or BRCA2 mutation.

The findings in of this study, and the potentially new targeted treatment strategies available for these patients (e.g. PARP inhibitors), emphasize the importance of testing for BRCA1 or BRCA2 mutations in young breast cancer patients, as is the current clinical practice.

This study was financed by the Dutch Cancer Society, the Dutch Genomics Initiative and the European Union (Horizon 2020 program) and was coordinated by the Netherlands Cancer Institute. It was a collaboration between the Albert Schweitzer Hospital (Dordrecht), Diaconessenhuis (Leiden), Elkerliek Hospital (Helmond), Erasmus Medical Center (Rotterdam), Netherlands Comprehensive Cancer Organisation, Leiden University Medical Center (Leiden), Medisch Spectrum Twente (Enschede), Rijnland hospital (Leiden), Netherlands Cancer Institute (Amsterdam), PAMM: laboratory for Pathology en Medical Microbiology (Eindhoven) and the Viecuri Medical Center (Venlo).

Details of the defense:
Alexandra van den Broek's thesis is entitled "The impact of BRCA1 and BRCA2 germline mutations on breast cancer outcome in young women". Her promotors are Flora van Leeuwen and Laura van 't Veer, and co-promotors Marjanka Schmidt en Rob Tollenaar. The public defense ceremony will take place on May 8 at 09:45 in the VU University, Boelelaan 1105 in Amsterdam.

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