LCT10001463

ESMO-ECLU Conference Lugano, 5 July, 2007: 

ESMO-ECLU Conference Lugano, 5 July, 2007 Clinical Cancer Prevention – a New Dimension of Oncology Prof. Dr. med. Hans-Jörg Senn Tumor-Center ZeTuP (Detection, Treatment + Prevention) and St.Gallen International Oncology Conferences St.Gallen, Switzerland

Greetings from the Monastic University-City St.Gallen (Historic, Cultural and Medical Center of Eastern Switzerland): 

Greetings from the Monastic University-City St.Gallen (Historic, Cultural and Medical Center of Eastern Switzerland)

„Silver-Tower“ in St.Gallen: Home of Tumor-Center ZeTuP + St.Gallen Oncology Conferences: 

„Silver-Tower“ in St.Gallen: Home of Tumor-Center ZeTuP + St.Gallen Oncology Conferences

Projected Worldwide Cancer Figures I(WHO, 2004): 

Projected Worldwide Cancer Figures I (WHO, 2004)

Projected Worldwide Cancer Figures II(WHO, 2004): 

Projected Worldwide Cancer Figures II (WHO, 2004) Are we prepared and able to cope with this increasing burden on a world-wide scale in view of: The general increase of age in our populations? The rising cancer incidence also in large „third world countries, where neoplasias were not prevalent until recently? The unfortunately still rising epidemic of smoking and other potentially cancerogenic life style evolutions The rising costs of new cancer treatments?

Rising Cure Rates of Selected Neoplastic Diseases:But Limitations are Obvious for Solid Tumors: 

Rising Cure Rates of Selected Neoplastic Diseases: But Limitations are Obvious for Solid Tumors Many Solid Tumors (GI, Lung, Kidney, etc) of Adults !

Options of Clinical Cancer Prevention: 

Options of Clinical Cancer Prevention Primary Cancer Prevention: Prevention of cancer induction by successfull elimina-tion of causes and/or promoters of carcinogenesis (incl. chemo- and bio-prevention). Secondary Cancer Prevention: Increasing cure rates by successfull early detection and early treatment (screening and early detection). Tertiary Cancer Prevention: Increasing cure rates by successfull prevention of relapse and dissemination (adjuvant systemic therapy).

„More Cure“ by more Prevention in Oncology? I: 

„More Cure“ by more Prevention in Oncology? I Tertiary Cancer-Prevention: (Adjuvant Systemic Therapy) Malignant Lymphomas (RT + ChT) Acute Leukemias (ChT + BMT oder SCT) Breast Cancer Germinal Cancers of Testis and Ovary ENT-Tumors, and others

The Pre-Clinical Rationale of Adjuvant „Curative“ Tumor-Chemotherapy (Skipper, 1967): 

The Pre-Clinical Rationale of Adjuvant „Curative“ Tumor-Chemotherapy (Skipper, 1967) 1967:

Increase of Cure Rate by Adjuvant Chemotherapyin Operable Stage 1 Testicular Cancer: 

Increase of Cure Rate by Adjuvant Chemotherapy in Operable Stage 1 Testicular Cancer

Longterm Survival Benefit by Adjuvant Systemic Treatment after mastectomy for breast cancer: 

Longterm Survival Benefit by Adjuvant Systemic Treatment after mastectomy for breast cancer ChT+HT ChT+HT

Adjuv. Systemic Chemotherapy: Did it really change the History of Breast Cancer?: 

Adjuv. Systemic Chemotherapy: Did it really change the History of Breast Cancer? Hypothesis: Adjuvant systemic therapy in operable breast cancer patients has significantly changed the outcome and survival of this disease. This has been extensively validated in >190 clinical trials by >40 study groups. These „curative“ adjuvant therapies do not only get more and more effective, but also more and more expensive (e.g. Herceptin, Erlotinib, etc.). Do they soon get unaffordable for all, who would need them? And they have their technical limits (sec. resistance!)

10th St. Gallen International Conference „Primary Therapy of Breast Cancer“ 14-17 March, 2007: 

10th St. Gallen International Conference „Primary Therapy of Breast Cancer“ 14-17 March, 2007 www.oncoconferences.ch

Slide14: 

OS DFS Molecular Genetics – Cancer-Risk- and Prognosis- Determination by „Genetic Mapping“ (Breast Cancer) Sorlie T. et al, PNSA, 2005 OS

„More Cure“ by more Prevention in Oncology? II: 

„More Cure“ by more Prevention in Oncology? II Secondary Cancer-Prevention (Screening, Early Detection) Cervical Cancer Breast Cancer(s) Colorectal Cancers ENT-Cancers Skin Cancers, incl. Melanoma Prostate Cancer ??

Inevitable Conditions for Successful Secondary Cancer Prevention Programs: 

Inevitable Conditions for Successful Secondary Cancer Prevention Programs A long pre-cancerous stage of tumor-evolution (silent period) over years Adequate knowledge about the main risk factors A target organ, which is easily accessible and made visible (skin,ENT-region, breast, cervix, etc.) One or several tested and evidence-based technical screening methods (smears, x-ray, endoscopy, etc) The acceptance of respective programs by the medical profession – and the public risk population The necessary health-political vision and the money to conduct such screening programs over long time

Rising Probability of Breast Cancer with Increassing Age (USA, ACS-Data 2003): 

Rising Probability of Breast Cancer with Increassing Age (USA, ACS-Data 2003) With 30 Years of Age: 1 of 2525 Women With 40 Years of Age: 1 of 214 Women With 50 Years of Age: 1 of 50 Women ! With 60 Years of Age: 1 of 14 Women !! With 70 Years of Age: 1 of 10 Women !! (Lifetime-risk in the general population, without any additional risk factors except age)

Slide18: 

Breast Cancer in Europe: North – South Gradient ! Red: Highest mortality! Blue: Lowest Mortality Yellow: Lesser Mortality Switzerland: Each Year 1‘600 Breast-Ca Death 5‘300 New Cases

Slide19: 

Survival Expectation Largely Dependent on Tumor-Size at Diagnosis of Breast Cancer Fig. 1 Munich Cancer Registry 2002, n = 12‘423 (Hoelzl et al) <2 cm 2-5 cm >5 cm T 4 Expected Survival

Secondary and Tertiary Breast Cancer-Prevention (USA: D. Berry, NEJM 2005): 

Secondary and Tertiary Breast Cancer-Prevention (USA: D. Berry, NEJM 2005)

Slide21: 

Swiss Health Inquiry: Wanner et al., 2000, % Women > 40 Years AR < 35 % 35 - 40 % 41 - 51% < 60% Percentage of Women with at least 2 Mammographies ( Switzerland, 1997-2000 ) 51 - 60 % Pioneer Role Ct. of St.Gallen Austria

Screening for Colorectal Cancers: An Orphan Topic!: 

Screening for Colorectal Cancers: An Orphan Topic! In CRC, probably best evaluated pre-cancerous evolution (the so-called „adenoma-cancer-sequence“) Adequately known risk factors and risk populations (age, HNPCC, Amsterdam-Criteria, etc) Easy (FOB) + complicated/cumbersome (colonoscopy) screening methods Impressive results from many (mostly regional and selected) endoscopic screening trials with significant reduction of morbidity and mortality from CRC! Yet: No „wave of acceptance“ of CRC-Screening within the medical profession and in society. Preventive colonscopy still not reimbursed in basic health insurance in most European countries

The Exponential Growth of Cancer Treatment Costs during the last 30 Years (USA): Quo Vadis?: 

The Exponential Growth of Cancer Treatment Costs during the last 30 Years (USA): Quo Vadis?

Would more Intelligent Prevention be an Alternative to Prevent Costs and Impeding Rationing in Oncology?: 

Would more Intelligent Prevention be an Alternative to Prevent Costs and Impeding Rationing in Oncology? The expert moderators and speakers at the last (4th) Conference on „Cancer Prevention 2006“ in February 2006 at the University of St.Gallen/Switzerland said „Yes“, in certain cancer types, such as: Breast Cancer (primary + secondary prevention) Colo-Rectal Cancer (prim. + sec. prevention) Cervical Cancer (prim. + sec. prevention) Malignant Melanoma + Other skin cancers Prostate-Cancer (?) (yet controversial !)

„More Cure“ by more Prevention in Oncology? III: 

„More Cure“ by more Prevention in Oncology? III Primary Cancer Prevention: (Lifestyle, Chemo-Prevention) Breast Cancer Cervical Cancer (Vaccination) Colorectal Cancer ENT-Cancers Prostate Cancer (?)

Estrogen-Serum Levels and Risk of Breast Cancer: 

Estrogen-Serum Levels and Risk of Breast Cancer Known for years, that women with the highest circulating estrogen serum levels have higher rates of developing breast cancer R. Doll and J. Cuzick, Int. J. Cancer, 1992

Breast-Cancer Lifetime-Risk in Gene-Carriers (BRCI-1): 

Breast-Cancer Lifetime-Risk in Gene-Carriers (BRCI-1)

Percentage of Genetic and Familial Breast Cancer in Western Europe = ca. 20%: 

Percentage of Genetic and Familial Breast Cancer in Western Europe = ca. 20% Special need for counceling („family cancer clinic“) and special target individuals for primary (chemo)prevention trials!

Increasing Possibilities of Interfering with the Growth of Human Breast Cancer: 

Estrogen- Biosynthesis Tumor-Cells Nucleus Increasing Possibilities of Interfering with the Growth of Human Breast Cancer LHRH-Agonists LH-RH-Agonists

Prevention of Recurrences and of Contralateral Second Breast Cancers by TAM: 

Prevention of Recurrences and of Contralateral Second Breast Cancers by TAM

Slide31: 

Odds ratio (log scale) .5 1 1.5 Combined Exemestane MA-17 Italian ATAC Contralateral Breast Cancer-Ca-Incidence in Studies with Adjuvant Aromatase-Inhibitors (ANA, LET, EXE) ARNO/ABCSG Cuzick et al, Lancet, 2004

Chemo-Prevention-Trials with TAM (RAL) in Women with High-Risk of Breast Cancer: 

Chemo-Prevention-Trials with TAM (RAL) in Women with High-Risk of Breast Cancer USA-Trial: 13‘400 Women 8 y. Reducing breast- (NSABP-P1) cancer incidence by 49%! Internat. Trial: 7‘200 Women 6 y. Reducing Incidence (IBIS-1, inkl. CH) 34%, but sideeffects Italy-Trial 5‘400 Women 8 y. Reducing Incidence only in HRT-Women UK Pilot-Trial: 2500 Women 9 y. No sign. difference, (Royal Marsden) (Selection?) STAR-Trial: 12‘400 Women <3 y. Reducing Incidence (TAM vs. RAL by 37%, RAL equal NSABP-P2) TAM (+/-)

Slide33: 

Survey of All Chemo-Prevention-Studies With Tamoxifen (J. Cuzick et al, Lancet, 2004) Odds ratio .3 .5 .68 1 1.5 IBIS-1

IBIS-II Breast Cancer-Prevention-Trial(Anastrozole vs. Tamoxifen resp. Placebo): 

IBIS-II Breast Cancer-Prevention-Trial (Anastrozole vs. Tamoxifen resp. Placebo) Stratum I (Prevention-Trial): Anastrozole x 5 years 6000 Women at risk R (Age 40-70y) Placebo x 5 years Stratum II (DCIS-Trial) Anastrozole x 5 years 4000 Women (op.) R (Age 40-70y) Tamoxifen x 5 years

IBIS-II-Studie: A Global Affaire !(Study-Center in London/UK, more than 23 Countries): 

IBIS-II-Studie: A Global Affaire ! (Study-Center in London/UK, more than 23 Countries)

There is a Large Palette of Potential Chemopreventive Agents in Oncology Waiting for Adequate Trials: 

There is a Large Palette of Potential Chemopreventive Agents in Oncology Waiting for Adequate Trials New SERM‘s (Raloxifen, Lozoxyfen, etc.) Breast Cancer Aromatase Inhibitors (Letrozole, Exe) Breast Cancer Fenritinide (+ other Retinoids) Breast, ENT Aspirin (Cheap + Easy…) Colon, Breast Cox-2-Inhibitors (But cardiac problems!) Breast, Prostate Finasteride (Questions!) Prostate-Ca Statins (?) Colorectal + other Vaccinations (?, except Cervical Ca) Diverse Ca Targeted Drugs (MAB‘s, TKI, VEGF-I) Breast, Colon,+ other Cancers „Natural Agents“ (multitude!) No EB-data

Futuristic molecular-biological Intervention-Palette for Tumor-Chemo- resp. Bio-Prevention: 

Futuristic molecular-biological Intervention-Palette for Tumor-Chemo- resp. Bio-Prevention

The Changing Face of „Oncology in the Future“: 

The Changing Face of „Oncology in the Future“ „An important paradigm-shift is presently taking place in Oncology: From the „Detect and Destroy“ Strategy of the past century to the „Target and Control“ – and the „Prevent“– Strategy of the 21st century! What a Challenge for Science, Industry and Medicine“! (Andrew von Eschenbach - Present Director of NCI-USA in Bethesda, MD at the Opening Ceremony, ASCO-2003 Meeting, Orlando/Florida)

What is the place of Medical Oncologists in Clinical Cancer Prevention?: 

What is the place of Medical Oncologists in Clinical Cancer Prevention? Their place should be at the „fore-front“ of clinical cancer prevention, in trials and daily routine. Are medical oncologists of Europe in centers, officies and in training prepared to meet these new needs? I fear, they are not (yet). But they should become pioneers and leaders in the field – instead of leaving prevention issues primarily to gynecologists, urologists, radiologists, and to the general practitioners! Are we ready to take up the challenge – as a profess-ional society? As individual physicians?

For more Infos: www.oncoconferences.ch: 

For more Infos: www.oncoconferences.ch 5th International Conference on Cancer Prevention 2008 Advances in Molecular and Clinical Aspects of Cancer Prevention (Among others, co-organized and supported by ESMO 6 – 8 March, 2008 University of St.Gallen, Switzerland

Thank you for your kind attention !: 

Thank you for your kind attention ! The End (s.d.g.)