M. Schmidt (Amsterdam, Netherlands)
Netherlands Cancer Institute/Antoni van Leeuwenhoek hospital (NKI-AVL)Author Of 1 Presentation
- Y. Wang (Amsterdam, Netherlands)
- E. Rosenberg (Amsterdam, Netherlands)
- G. Dackus (Utrecht, Netherlands)
- A. Broeks (Amsterdam, Netherlands)
- S. Cornelissen (Amsterdam, Netherlands)
- P. Van Diest (Utrecht, Netherlands)
- M. Hauptmann (Brandenburg, Germany)
- N. Ter Hoeve (Utrecht, Netherlands)
- V. De Jong (Amsterdam, Netherlands)
- K. Jozwiak (Brandenburg, Germany)
- E. Koop (Apeldoorn, Netherlands)
- P. Nederlof (Amsterdam, Netherlands)
- M. Opdam (Amsterdam, Netherlands)
- S. Siesling (Utrecht, Netherlands)
- N. Stathonikos (Utrecht, Netherlands)
- A. Voogd (Maastricht, Netherlands)
- W. Vreuls (Nijmegen, Netherlands)
- M. Kok (Amsterdam, Netherlands)
- S. Linn (Amsterdam, Netherlands)
- M. Schmidt (Amsterdam, Netherlands)
9P - BRCA1 promoter methylation confers a more favorable prognosis to systemically untreated young triple-negative breast cancer patients than tumor BRCA1 mutation
Abstract
Background
The prognoses of systemically treated, triple-negative breast cancer (TNBC) patients with a pathogenic tumor BRCA1 mutation (tBRCA1m) or BRCA1 promoter methylation (BRCA1 PM) have been widely studied. However, the prognosis for systemically untreated women remains unknown. This study investigates the prognosis of systemically untreated young N0 TNBC patients according to tumor BRCA1 status.
Methods
Dutch women aged < 40 years, diagnosed with TanyN0M0 TNBC between 1989 and 2000 were selected from the Netherlands Cancer Registry. In that era, N0 patients were considered low risk and not given (neo)adjuvant systemic therapy. We analyzed tBRCA1m and BRCA1 PM using DNA from formalin-fixed paraffin-embedded tumor tissues. We built Cox and competing risk regression models, for invasive disease-free survival (iDFS), and distant recurrence-free survival (DRFS) with secondary primary tumors (SPTs) as competing events. Both models were adjusted for tumor characteristics and locoregional treatment.
Results
For 373 patients, tBRCA1m and BRCA1 PM status were available. Of these, 28% had pathogenic tBRCA1m, 36% had BRCA1 PM and the rest were classified as BRCA1 dual-negative. Compared to patients with BRCA1 dual-negative tumors, patients with BRCA1 PM had a favorable iDFS (adjusted hazard ratio [aHR] = 0.66, 95% confidence interval [CI] = 0.45 – 0.98) but similar DRFS (subdistribution hazard ratio [sHR] = 0.86, 95% CI = 0.50 – 1.46), while patients with tBRCA1m had poorer iDFS (aHR = 1.86, 95% CI = 1.30 – 2.65) and also similar DRFS (sHR = 1.04, 95% CI = 0.61 – 1.76). Furthermore, patients with BRCA1 PM had lower risk for SPTs (sHR = 0.38, 95% CI = 0.17 – 0.83), while patients with tBRCA1m had higher risk (sHR = 3.12, 95% CI = 1.79 – 5.45).
Conclusions
Although tBRCA1m and BRCA1 PM both cause BRCA1 gene inactivation, the iDFS differed significantly between systemically untreated young TNBC patients with these tumor types. This can be mainly attributed to substantially different risk for SPTs. Interventions to prevent SPTs, such as contralateral prophylactic mastectomy or secondary chemoprevention, should be considered for young tBRCA1m TNBC patients.
Legal entity responsible for the study
Netherlands Cancer Institute.
Funding
Dutch Cancer Society (KWF), A Sister's Hope, Vrienden UMCU, Agilent.
Disclosure
M. Kok: Advisory/Consultancy, Research grant/Funding (institution), Outside the submitted work, M. Kok is a advisory board member: BMS; Advisory/Consultancy, Research grant/Funding (institution), Outside the submitted work, M. Kok is a advisory board member: Roche; Research grant/Funding (institution), Outside the submitted work: AZ; Advisory/Consultancy, M. Kok is a advisory board member: MSD; Advisory/Consultancy, M. Kok is a advisory board member: Daiichi. S.C. Linn: Research grant/Funding (institution), Receives grants during the conduct of the study: ZonMw; Research grant/Funding (institution), Receives grants during the conduct of the study: A Sister's Hope; Advisory/Consultancy, Research grant/Funding (institution), Outside the submitted study: AstraZeneca; Advisory/Consultancy, Research grant/Funding (institution), Outside the submitted study: Cergentis; Advisory/Consultancy, Travel/Accommodation/Expenses, Outside the submitted study: IBM; Advisory/Consultancy, Research grant/Funding (institution), Outside the submitted study: Pfizer; Advisory/Consultancy, Research grant/Funding (institution), Travel/Accommodation/Expenses, Outside the submitted study: Roche; Research grant/Funding (institution), Outside the submitted study: Eurocept-pharmaceuticals; Research grant/Funding (institution), Outside the submitted study: Novartis; Research grant/Funding (institution), Travel/Accommodation/Expenses, Outside the submitted study: Tesaro (now owned by GSK); Research grant/Funding (institution), Outside the submitted study and non-financial support such as study drug: Immunomedics; Research grant/Funding (institution), Outside the submitted study: Agendia; Travel/Accommodation/Expenses, Outside the submitted study: Bayer; Advisory/Consultancy, Travel/Accommodation/Expenses, Outside the submitted study: Daiichi Sankyo; Research grant/Funding (institution), Outside the submitted study: Genentech. All other authors have declared no conflicts of interest.