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Efficacy of Risk-Reducing Mastectomy on Overall Survival in BRCA1/2-associated Breast Cancer patients BAM Heemskerk-Gerritsen, MJ Hooning, CJ van Asperen,

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Presentation on theme: "Efficacy of Risk-Reducing Mastectomy on Overall Survival in BRCA1/2-associated Breast Cancer patients BAM Heemskerk-Gerritsen, MJ Hooning, CJ van Asperen,"— Presentation transcript:

1 Efficacy of Risk-Reducing Mastectomy on Overall Survival in BRCA1/2-associated Breast Cancer patients BAM Heemskerk-Gerritsen, MJ Hooning, CJ van Asperen, MGEM Ausems, M Collée, L Jansen, M Kets, K Keymeulen, HEJ Meijers-Heijboer, TAM van Os, HFA Vasen, L Koppert, M Rookus, C Seynaeve Hereditary Breast/Ovarian cancer study group (HEBON), The Netherlands

2 Background BRCA1/2-associated unilateral breast cancer patients:
20 – 60% risk contralateral breast cancer (CBC) Risk-reducing mastectomy (RRM): CBC risk-reduction >90% Survival benefit?? no evidence in literature for BRCA1/2 Presented by: Annette (B.A.M.) Heemskerk-Gerritsen

3 Aim To investigate the efficacy of risk-reducing mastectomy (RRM) on overall survival in BRCA1/2 mutation carriers with a history of unilateral breast cancer. Presented by: Annette (B.A.M.) Heemskerk-Gerritsen

4 Patients Nationwide cohort study of the Hereditary Breast/Ovarian cancer group, the Netherlands (HEBON) Presented by: Annette (B.A.M.) Heemskerk-Gerritsen

5 Patients Inclusion criteria: Proven BRCA1/2 mutation carrier
Nationwide cohort study of the Hereditary Breast/Ovarian cancer group, the Netherlands (HEBON) Inclusion criteria: Proven BRCA1/2 mutation carrier First BC diagnosis 1/1/1980 – 12/31/2011 No CBC, ovarian cancer or distant metastases before DNA testing Contralateral breast tissue in situ Presented by: Annette (B.A.M.) Heemskerk-Gerritsen

6 Person-years of observation (PYO) in Control ( ) and
Statistical analysis 1. COX analysis with RRM as time-dependent variable START RRM END First BC + 2 years or DNA testing First BC + 2 years Date of death (all causes) or last contact or 31/12/2012 Person-years of observation (PYO) in Control ( ) and RRM ( ) group 2. Kaplan-Meier survival curve Presented by: Annette (B.A.M.) Heemskerk-Gerritsen

7 Results Characteristics Characteristics RRM CONTROL N 239 (42%)
326 (58%) Median yrs after first BC 11.5 11.6 BRCA1 79% 76% BRCA2 21% 24% Characteristics Presented by: Annette (B.A.M.) Heemskerk-Gerritsen

8 Results Characteristics Characteristics RRM CONTROL N 239 (42%)
326 (58%) Median yrs after first BC 11.5 11.6 BRCA1 79% 76% BRCA2 21% 24% First BC Median age * 38 ( ) 42 ( ) * Significant difference Characteristics Presented by: Annette (B.A.M.) Heemskerk-Gerritsen

9 Results Characteristics Characteristics RRM CONTROL N 239 (42%)
326 (58%) Median yrs after first BC 11.5 11.6 BRCA1 79% 76% BRCA2 21% 24% First BC Median age * 38 ( ) 42 ( ) DCIS/T1 63% 60% N0 64% Poor differentiation 80% 77% * Significant difference Characteristics Presented by: Annette (B.A.M.) Heemskerk-Gerritsen

10 Results Characteristics Characteristics RRM CONTROL N 239 (42%)
326 (58%) Median yrs after first BC 11.5 11.6 BRCA1 79% 76% BRCA2 21% 24% First BC Median age * 38 ( ) 42 ( ) DCIS/T1 63% 60% N0 64% Poor differentiation 80% 77% ER negative 62% PR negative 68% 70% Her2 negative 94% 96% * Significant difference Characteristics Presented by: Annette (B.A.M.) Heemskerk-Gerritsen

11 No differences in tumor characteristics
Results Characteristics RRM CONTROL N 239 (42%) 326 (58%) Median yrs after first BC 11.5 11.6 BRCA1 79% 76% BRCA2 21% 24% First BC Median age * 38 ( ) 42 ( ) No differences in tumor characteristics * Significant difference Characteristics Presented by: Annette (B.A.M.) Heemskerk-Gerritsen

12 Results Characteristics Characteristics RRM CONTROL N 239 (42%)
326 (58%) Adjuvant treatment first BC Chemotherapy * 66% 50% Endocrine therapy 19% 16% * Significant difference Characteristics Presented by: Annette (B.A.M.) Heemskerk-Gerritsen

13 Results Characteristics Characteristics RRM CONTROL N 239 (42%)
326 (58%) Adjuvant treatment first BC Chemotherapy * 66% 50% Endocrine therapy 19% 16% Risk-reducing salpingo-oophorectomy * 80% 69% Ovarian cancer 2% 4% * Significant difference Characteristics Presented by: Annette (B.A.M.) Heemskerk-Gerritsen

14 Results Characteristics Characteristics RRM CONTROL N 239 (42%)
326 (58%) Adjuvant treatment first BC Chemotherapy * 66% 50% Endocrine therapy 19% 16% Risk-reducing salpingo-oophorectomy * 80% 69% Ovarian cancer 2% 4% Contralateral BC * 20% * Significant difference Characteristics Presented by: Annette (B.A.M.) Heemskerk-Gerritsen

15 Person-years of observation
Results Cox After RRM the risk of dying is reduced Person-years of observation Deaths Mortality rate 1 Hazard Ratio (95% CI) Control 2666 56 21.0 Ref. RRM 1837 18 9.8 0.46 ( ) 2 0.55 ( ) 3 1 per 1000 person-years of observation 2 univariate analysis 3 adjusted for risk-reducing salpingo-oophorectomy Presented by: Annette (B.A.M.) Heemskerk-Gerritsen

16 Results Kaplan-Meier RRM improves 15-year overall survival 90% 81% 93%
89% Presented by: Annette (B.A.M.) Heemskerk-Gerritsen

17 Strengths Limitations Prospective study design Large sample size
Long follow-up Limitations No randomized study No data on breast cancer-specific survival Limited numbers of BRCA2 mutation carriers Presented by: Annette (B.A.M.) Heemskerk-Gerritsen

18 Conclusions RRM improves overall survival in BRCA1/2-associated BC patients who remained free of distant metastases 2 years after first BC RRM reduces contralateral BC risk More research warranted on prediction model Presented by: Annette (B.A.M.) Heemskerk-Gerritsen

19 Acknowledgments b.heemskerk-gerritsen@erasmusmc.nl AMC, Amsterdam
CM Aalfs NKI, Amsterdam FBL Hoogervorst FE van Leeuwen MK Schmidt T Mooij J de Lange R Wijnands VUMC, Amsterdam Q Waisfisz M Adank UMCG, Groningen GH de Bock MJE Mourits JC Oosterwijk LUMC, Leiden TCTEF van Cronenburg R Tollenaar P Devilee STOET, Leiden HFA Vasen MUMC, Maastricht MJ Blok E Gómez-Garcia UMCN, Nijmegen AR Mensenkamp EMC, Rotterdam C van Deurzen IM Obdeijn A Jager P Bos J Blom C Crepin UMCU, Utrecht RB van der Luijt HJGD van den Bongard Presented by: Annette (B.A.M.) Heemskerk-Gerritsen

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