slide1 n.
Download
Skip this Video
Loading SlideShow in 5 Seconds..
THE LATEST ADVANCES IN CLINICAL GENETICS OF HEREDITARY BREAST CANCER PowerPoint Presentation
Download Presentation
THE LATEST ADVANCES IN CLINICAL GENETICS OF HEREDITARY BREAST CANCER

Loading in 2 Seconds...

play fullscreen
1 / 57

THE LATEST ADVANCES IN CLINICAL GENETICS OF HEREDITARY BREAST CANCER - PowerPoint PPT Presentation


  • 163 Views
  • Uploaded on

THE LATEST ADVANCES IN CLINICAL GENETICS OF HEREDITARY BREAST CANCER. J. Lubiński. INTERNATIONAL HEREDITARY CANCER CENTER POMERANIAN MEDICAL UNIVERSITY, SZCZECIN, POLAND. 12 December 2005, Chennai, India.

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'THE LATEST ADVANCES IN CLINICAL GENETICS OF HEREDITARY BREAST CANCER' - gerodi


Download Now An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript
slide1

THE LATEST ADVANCES IN CLINICAL GENETICS OF HEREDITARY BREAST CANCER

J. Lubiński

INTERNATIONAL HEREDITARY CANCER CENTER

POMERANIAN MEDICAL UNIVERSITY, SZCZECIN, POLAND

12 December 2005, Chennai, India

slide2

Lubinski J.1, Górski B.1, Cybulski C.1, Huzarski T.1, Byrski T.1, Gronwald J.1, Jakubowska A.1, Stawicka M.2, Gozdecka-Grodecka S.3, Szwiec M.4, Urbański K.5, Mituś J.5, Marczyk E.5, Dziuba J.1, Wandzel P.6, Surdyka D.7, Haus O.8, Janiszewska H.8, Dębniak T.1, Tołoczko-Grabarek A.1, Mędrek K.1, Masojć B.1, Mierzejewski M.1, Kowalska E.1, Zientek H.9, Pamuła J.9, Metcalfe K.10, Tung N.11, Foulkes WD.12, Offit K.13, Gershoni R.14, Daly M.15, Kim-Sing Ch.16, Olsson H.17, Ainsworth P.18, Eisen A.19, Saal H.20, Friedman E.21, Olopade O.22, Osborne M.23, Weitzel J.24, Lynch H.25, Ghadirian P.26, Sun P.10, Narod SA.10 and Hereditary Breast Cancer Clinical Study Group

1 Department of Genetics and Pathology, International Hereditary Cancer Center, Pomeranian Medical University, Szczecin, Poland

2 Prophylactic and Epidemiology Center, Poznan, Poland

3 Poznan Medical University

4 Regional Oncology Hospital, Opole, Poland

5 Regional Oncology Center, Kraków, Poland

6 Regional Oncology Hospital, Bielsko-Biała, Poland

7 Regional Oncology Hospital, Lublin, Poland

8 Department of Clinical Genetics, Bydgoszcz Medical University, Poland

9 Oncology Center, Gliwice, Poland

10 Centre for Research in Women’s Health, University of Toronto, Canada

11 Beth Israel Deaconess Hospital, Boston, USA

12 Program in Cancer Genetics, Department of Oncology and Human Genetics, McGill University, Montreal, Canada

13 Department of Human Genetics and Medicine, Memorial Sloan-Kettering Cancer Center, New York, USA

14 Institute of Genetics, Rambam Medical Center, Haifa, Israel

15 Division of Population Science, Fox Chase Cancer Center, Philadelphia, USA

16 British Columbia Cancer Agency, Vancouver, British Columbia, Canada

17 The Jubileum Institute, Department of Oncology, Lund University Hospital, Lund, Sweden

18 London Regional Cancer Center, London, Ontario, Canada

19 Toronto Sunnybrook Regional Cancer Centre, Toronto, Canada

20 Hereditary Cancer Program, Division of Human Genetics, Children’s Hospital Medical Center, Cincinnati, USA

21 Oncogenetics Unit, Chaim Sheba Medical Center, Tel-Hashomer, Israel

22 Center for Clinical Cancer Genetics, University of Chicago, Chicago, USA

23 Strang Cancer Prevention Center, New York, USA

24 City of Hope Hospital, Duarte, CA, USA

25 Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, USA

26 Epidemiology Research Unit, Centre hospitalier de l’Université de Montréal (CHUM), Hôtel-Dieu, University of Montreal, Quebec, Canada

slide4

POLAND

- country with high level of genetic homogeneity !

slide7

POLISH FAMILIES WITH STRONG AGGREGATION OF BREAST/OVARIAN CANCERS (n=200)

  • BRCA 1 ~65%
  • BRCA2 ~4%

Górski B. et al. Int. J. Can, 2004

slide8

POLISH PANEL OF BRCA1 MUTATIONS

  • 5382 ins C
  • C 61 G
  • 4153 del A

90% of mutations

Górski B. et al. Int. J. Can, 2004

slide9

BRCA1 MULTIPLEX PCR

possitive controls

patients

5382 insC

5382 insC

4153 delA

(-) DNA

C61G

slide10

BRCA1 FOUNDER MUTATIONS IN POLAND

  • GÓRSKI B. ET AL. - PATENT NO P335917- MULTIPLEX PCR - 50€
slide11

BRCA1 – REGISTRY – SZCZECIN – POLAND

3225 CARRIERS

THE LARGEST REGISTRY IN THE WORLD

Szczecin 7 December 2005

slide14

BRCA1 mutations in patients with breast cancer <51yrs

  • 4780 patients
  • 3629 (75,9%) blood samples
  • 3614 BRCA1 tests
  • 200 (5,5%) mutations
slide17

CANCER RISKS IN FIRST-DEGREE RELATIVES OF BRCA1 MUTATION CARRIERS:

EFFECTS OF MUTATION AND PROBAND DISEASE STATUS

J. Gronwald, JMG 2005

slide18

0.8

C61G

0.7

5382insC

0.6

4153delA

P=0.12

0.5

0.4

0.3

0.2

0.1

0.0

25

30

35

40

45

50

55

60

65

70

75

Age (years)

Cumulativeincidence ofbreast cancerin first-degree relativesby mutation

slide19

0.8

C61G

0.7

5382insC

0.6

4153delA

0.5

P=0.05

0.4

0.3

0.2

0.1

0.0

25

30

35

40

45

50

55

60

65

70

75

Age (years)

Cumulativeincidence ofovarian cancerin first-degree relativesby mutation

slide20

0.8

0.7

Proband Breast Cancer Proband Ovarian Cancer

0.6

0.5

P=0.005

0.4

0.3

0.2

0.1

0.0

25

30

35

40

45

50

55

60

65

70

75

Age (years)

Cumulativeincidence ofbreast cancerin first-degree relativesby cancer siteof the proband

slide21

0.8

0.7

Proband Breast Cancer Proband Ovarian Cancer

0.6

0.5

P=0.98

0.4

0.3

0.2

0.1

0.0

25

30

35

40

45

50

55

60

65

70

75

Age (years)

Cumulativeincidence ofovarian cancerin first-degree relativesby cancer siteof the proband

slide22

A. BRCA1 PROPHYLACTICS

RISK BR OV

  • Oral contraceptives < 30yrs 1.3> 30yrs 0.5
  • Breast feeding > 1 yrs 0.5
  • Later menarche per yr 0.9
  • Tubal ligation 0.5
  • Adnexectomy 0.2 0.05
  • Tamoxifen 0.5
  • Adnexectomy + tamoxifen 0.15
  • Mastectomy 0.01
slide25

TAMOXIFEN AND CONTRALATERAL BREAST CANCER IN BRCA1 AND BRCA2 CARRIERS: AN UPDATE

Gronwald J. et al. Int J Can 2005

slide26

NSABP P1 Results

The efficacy of tamoxifen for breast cancer prevention in BRCA1/2 mutation carriers cannot be determined from P1 data

B. Weber 2005

slide28

HRT after BPO in BRCA1/2 Mutation Carriers

  • 408 BRCA1/2 Mutation Carriers
    • 184 women with BPO (65% took HRT)
    • 224 women without BPO (7% took HRT)
  • Post operative follow up 3.4 years
  • Post BPO breast cancer risk reduction:
    • 68% reduction overall
    • 64% reduction in women who took HRT

Rebbeck et al, JCO in press, 2005

slide29

Hormone replacement therapy appears to be safe after prophylactic adnexectomy in premenopausal BRCA1/BRCA2 mutation carriers

slide30

BRCA1 PROPHYLACTICS

  • Sodium selenite – pilot study

BRCA1 CARRIERS

N = 130 Se

3 Br/Ov Ca

N = 130 (-)

9 Br/Ov Ca

slide31

DETECTION OF EARLY BREAST CANCERS IN BRCA1 MUTATION CARRIERS

USG MAMMOGR. MRI

~20% ~20% ~90%

Narod S. et al. 2003

slide32

Breast cancers with BRCA1 Treatment

10 yrs survival

  • prophylactic adnexectomy  2×
  • tamoxifen  1.5×
  • mastectomy  1.5×
slide34

4% (~200) of BRCA1 carriers among 5000 relatives of women with breast cancer dgn < 50 yrs or ovarian cancer dgn at any age

  • Thanks to geneticists - oncologists from 20 Polish centers!
slide35

POPULATION SCREENING FOR CANCER FAMILY SYNDROMES IN WEST – POMERANIA, POLAND

WEST – POMERANIA HEALTH CARE INS. COMP

FAMILY DOCTORS

IHCC POMERANIAN MEDICAL UNIVERSITY, SZCZECIN

slide36

FAMILY DOCTORS – PROJECT INITIATORS

1. Andrzej Raczyński NPZOZ „Asklepios” Bobolice

2. Jarosław Kopciewicz - SPZOZ Pyrzyce

3. Cygal Lucyna - SZOZ nr 3 Kołobrzeg

4. Krzysztof Jankowiak - NZOZ „Zdrowie” Drawsko Pomorskie

5. Wiesława Fabian - NZOZ Szczecin

6. Józef Dmochowski - ZOZ „Zdrowie” Barwice

7. Paweł Szycko - NZOZ Podimed - Szczecinek.

8. Tadeusz Cieślak - NZOZ - „Hipokrates” - Złocieniec.

slide37

JANUARY 2001 – MAY 2002

  • 1,258 mln questionnaires out of 1,45 mln of inhabitants
  • the first worldwide large screening for hereditary cancers
slide39

BRCA 1

  • MUTATION DETECTION COST 750 €
  • SURVEILLANCE COST 1650 €(USG, MAMMOGRAPHY, FNAB, ADNEXECTOMY, TAMOXIFEN)
  • RISK REDUCTION
    • BREAST 60%  10% (WITHOUT PROPHYLACTIC MASTECTOMY)
    • OVARY 40%  5%
slide40

BRCA 1

  • PROPHYLACTICS:
    • 1 BREAST CA ~5 250 €
    • OVARIAN CA ~4 500 €
  • TREATMENT COST OF BREAST/ OVARIAN CANCER:
    • > 6 000 €
slide41

2000-2003 BRCA1 mutation carriers with breast/ovarian cancers N=50

  • treatment costs 21 428 PLN
  • social security costs 34 086 PLN
  • GP per capita lost 195 071 PLN

250 586 PLN

  • average annual cost 62 646 PLN

Marska N, US 2004

slide43

TWÓJ STYL 2001

  • 5024 BRCA1 tests
  • 198 (3,9%) mutations found
slide44

36.5% - worry

  • 27.0% - shock
  • 22.0% - sadness

TWÓJ STYL BRCA1 carriers unaffected n=632001

slide45

TWÓJ STYL BRCA1 carriers unaffected n=632004

  • 66% - used preventive measures
  • 98% - would recommend testing

Gronwald J. et al. JAMA 2005

slide46

two session counseling is effective for diagnosing BRCA1 carriers in Poland

TWÓJ STYL

Gronwald J. et al. JAMA 2005

slide47

BREAST CANCER GENETIC RISK

GENES

HIGH

MODERATE / LOW

slide50

BREAST CANCER RISKDGN <50 yrs, n=3500

GENES MUTATIONS / POLYMORPHISMS

RR

X3

X2

X1

P16

NOD2

I157T

ex2splice

CHEK2

1100delC

NBS1

BRCA2

BRCA1

0,0

5,0

10,0

15,0

20,0

25,0

30,0

35,0 %

slide53

EU PROJECT

Population specific panels of DNA markers for detection of moderate risk of breast and colon cancers and their market application

slide55

WORKPACKAGES

  • 1: Organization of international network of registries
  • 2: Elaboration ofpopulation specific panels ofDNA markers
  • 3: Market protection of markers by patents
  • 4: Technical optimization ofDNA testing based on established panelsofmarkers
  • 5: Establishment of rules to berespected when proposedtesting is offered
  • 6: Organization ofnetworks ofoutpatient clinics applying developedDNA testing
  • 7: Promotion ofdeveloped DNA testing
slide57

More information:

  • www.hereditarycancer.net
  • e-mail: ihcc@wp.pl
  • phone: +48-91-466-15-32fax: +48-91-466-15-33