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

Slides:

Advertisements

Similar presentations

516 (32723) Phase III trial comparing AC (x4)taxane (x4) with taxane (x8) as adjuvant therapy for node-positive breast cancer: Results of N-SAS-BC02.

Advertisements

Chemotherapy Prolongs Survival for Isolated Local or Regional Recurrence of Breast Cancer: The CALOR Trial (Chemotherapy as Adjuvant for Locally Recurrent.

Obesity at Diagnosis Is Associated with Inferior Outcomes in Hormone Receptor Positive Breast Cancer 1 The Impact of Body Mass Index (BMI) on the Efficacy.

The 70-Gene Profile and Chemotherapy Benefit in 1,600 Breast Cancer Patients Bender RA et al. ASCO 2009; Abstract 512. (Oral Presentation)

Laura J. Van ‘t Veer Helen Diller Family Comprehensive Cancer Center University of California, San Francisco Biology of disease Who is at risk for what.

Expression profiles for prognosis and prediction Laura J. Van ‘t Veer The Netherlands Cancer Institute, Amsterdam.

Discordance in Hormone Receptor and HER2 Status in Breast Cancer during Tumor Progression Lindstrom LS et al. Proc SABCS 2010;Abstract S3-5.

Clinical Relevance of HER2 Overexpression/Amplification in Patients with Small Tumor Size and Node-Negative Breast Cancer Curigliano G et al. J Clin Oncol.

Cancer Genetics. Issues Colorectal guidelines – Awaiting publication of coloproctologists guidance – SIGN / QIS update started Breast / ovarian – Breast.

MammaPrint, the story of the 70-gene profile

Introduction MarkerPolymorphisms in CYP2C19 (*2 and *17) assessed by Taqman allelic discrimination ObjectivesTo evaluate the predictive capacity of CYP2C19.

Neoadjuvant versus Adjuvant Systemic Treatment in Breast Cancer: A Meta-Analysis Mauri D, Pavlidis N, Ioannidis J. J Natl Cancer Inst 2005;97(3):

HERA: KEY DESIGN ELEMENTS, RESULTS AND FUTURE PLANS NSABP 17 SEPTEMBER 2005 Brian Leyland-Jones Minda De Gunzberg Professor of Oncology, McGill University,

The Carry-Over Effect of Adjuvant Zoledronic Acid: Comparison of 48- and 62-Month Analyses of ABCSG-12 Suggests the Benefits of Combining Zoledronic Acid.

Dubsky P et al. Proc SABCS 2012;Abstract S4-3.

T Andre, E Quinaux, C Louvet, E Gamelin, O Bouche, E Achille, P Piedbois, N Tubiana-Mathieu, M Buyse and A de Gramont. Updated results at 6 year of the.

Outcome of chemotherapy in synovial sarcoma (sys) patients (pts): review of 15 clinical trials from EORTCc involving advanced sys compared to other Soft.

Snyder D, Heidel RE, Panella T, Bell J, Orucevic A University of Tennessee Medical Center – Knoxville Departments of Pathology, Surgery, and Medicine BREAST.

Trastuzumab plus Adjuvant Chemotherapy for HER2-Positive Breast Cancer: Final Planned Joint Analysis of Overall Survival from NSABP B-31 and NCCTG N9831.

Extended adjuvant treatment with anastrozole: results from the ABCSG Trial 6a R Jakesz, H Samonigg, R Greil, M Gnant, M Schmid, W Kwasny, E Kubista, B.

THE EFFECT OF AGE ON OUTCOME OF SYNOVIAL SARCOMA PATIENTS A DUTCH POPULATION BASED STUDY Myrella Vlenterie, SEJ Kaal, VKY Ho, R Vlenterie, WTA van der.

Vivianne Tjan-Heijnen, MJ Pepels, M de Boer, GF Borm, JA van Dijck, CH van Deurzen, EM Adang, MB Menke- Pluymers, PJ van Diest and P Bult On behalf of.

Postmenopausal breast cancer patients included in the original Stockholm tamoxifen trial (n=2459) Stockholm 2 cohort (n=679) Stockholm 3 cohort (n=1780)

‘Arimidex’, Tamoxifen, Alone or in Combination (ATAC) trial: Completed Treatment Analysis.

Local Recurrence Growth Rate Predicts Outcome In Locally Recurrent Retroperitoneal Liposarcoma James Park, MD, Li-Xuan Qin, PhD, Francesco Prete, MD Murray.

HERA TRIAL: 2 Years versus 1 Year of Trastuzumab After Adjuvant Chemotherapy in Women with HER2-Positive Early Breast Cancer at 8 Years of Median Follow-Up.

Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer Slideset on: Piccart-Gebhart M, Procter M, Leyland- Jones B, et al. Trastuzumab.

2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial Aron Goldhirsch, Richard.

Date of download: 7/7/2016 From: Genetic Risk Assessment and BRCA Mutation Testing for Breast and Ovarian Cancer Susceptibility: Systematic Evidence Review.

Prognostic impact of Ki-67 in Croatian women with early breast cancer (single-institution prospective observational study) Ivan Bilić, Natalija Dedić Plavetić,

Mamounas EP et al. Proc SABCS 2012;Abstract S1-10.

Pathways involved in hereditary breast cancer

Slamon D et al. SABCS 2009;Abstract 62.

Alessandra Gennari, MD PhD

Figure 1. FinHER dataset: distribution of tumor-infiltrating lymphocytes in breast cancer according to the (A) three breast cancer subtypes and (B) HER2.

San Antonio Breast Cancer Symposium. December

Prognostic significance of tumor subtypes in male breast cancer:

R. Michelle Sarin, MD Mentor: Jeffrey Fowler, MD

Conclusions- Discussion

San Antonio Breast Cancer Symposium - December 6-10, 2011 Pre-operative haematological markers and prognosis in early breast cancer Cordiner RL1, Mansell.

Surgical Management of the Breast in Breast Cancer

Prognostic and Predictive Value of the 21-Gene Recurrence Score Assay in Postmenopausal Women with Node-Positive, Estrogen- Receptor-Positive Breast Cancer.

Oncol Res Treat 2016;39: DOI: /

Picture 3. Higher grade tumors are more frequently Ki67 positive

Concurrent chemotherapy and hyperthermia in patients with recurrent cervical cancer after chemoradiation: outcome and survival S.T. Heijkoop1,2; H.C. van.

Clinical outcome after SVR: Veterans Affairs

Marcelo Calil Instituto Brasileiro de Controle do Câncer

European Cooperative Trial in Operable Breast Cancer(ECTO): Improved freedom from progression from adding paclitaxel(T) to doxorubicin(A) followed by CMF.

Benefits of switching postmenopausal women with hormone-sensitive early breast cancer to anastrozole after 2 years adjuvant tamoxifen: Combined results.

Untch M et al. Proc SABCS 2010;Abstract P

EVALUTE THE EFFICACY OF ADJUVANT REGIMEN 3FEC- 3T IN STAGE II BREAST CANCER Hai Phong, 2017 LÊ THU HÀ, Ph.D. Nguyễn Khánh Hà, Dr.

Effect of Obesity on Prognosis after Early Breast Cancer

Background: Gene Expression

Published online September 20, 2017 by JAMA Surgery

Martin M et al. Proc SABCS 2012;Abstract S1-7.

LV5FU2-cisplatin followed by gemcitabine or the reverse sequence in metastatic pancreatic cancer: Preliminary results of a randomized phase III trial (FFCD.

Badwe RA et al. SABCS 2009;Abstract 72.

Cetuximab with chemotherapy as 1st-line treatment for metastatic colorectal cancer: a meta-analysis of the CRYSTAL and OPUS studies according to KRAS.

Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer. A meta-analysis of two randomized trials E Mitry, A Fields,

Treated with Neoadjuvant Therapy

GOCS GRUPO ONCOLÓGICO COOPERATIVO DEL SUR

20-Year Risks of Breast-Cancer Recurrence

Efficacy of BSI-201, a PARP Inhibitor, in Combination with Gemcitabine/Carboplatin (GC) in Triple Negative Metastatic Breast Cancer (mTNBC): Results.

THE LANCET Oncology Volume 19, No. 1, p27–39, January 2018

The SUV on 18F-FDG-PET/CT imaging as an independent predictor for overall survival and disease free survival after hepatectomy of Hepatocellular carcinoma（

Fig. 1. Classification of the Kaplan-Meier curves and Cox survival estimates for the OS of patients using the pSPC in Cohort_C and in the overall population.

Breast cancer BRCA testing protocol

Surgical resection of metachronous liver metastases

Kaplan-Meier survival analysis of p53 mutation in the overall breast tumor series. Kaplan-Meier survival analysis of p53 mutation in the overall breast.

(A). (A). Kaplan-Meier plot of event-free survival in 27 LMNA mutation carriers and 78 DCM control patients. Death, heart transplantation, resuscitation.

Presentation transcript:

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

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

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

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

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

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

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

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 (23 - 72) 42 (24 - 71) * Significant difference Characteristics Presented by: Annette (B.A.M.) Heemskerk-Gerritsen

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 (23 - 72) 42 (24 - 71) DCIS/T1 63% 60% N0 64% Poor differentiation 80% 77% * Significant difference Characteristics Presented by: Annette (B.A.M.) Heemskerk-Gerritsen

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 (23 - 72) 42 (24 - 71) 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

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 (23 - 72) 42 (24 - 71) No differences in tumor characteristics * Significant difference Characteristics Presented by: Annette (B.A.M.) Heemskerk-Gerritsen

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

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

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

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 (0.27-0.79) 2 0.55 (0.32-0.94) 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

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

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

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

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 b.heemskerk-gerritsen@erasmusmc.nl Presented by: Annette (B.A.M.) Heemskerk-Gerritsen