Brustkrebsprävention in der klinischen Praxis - Möglichkeiten und Grenzen

C. Tempfer; E. Bentz

doi:10.1055/s-2007-963246

TumorDiagnostik & Therapie, Inhaltsverzeichnis

TumorDiagnostik & Therapie 2007; 28(3): 133-140
DOI: 10.1055/s-2007-963246

Thieme Onkologie aktuell

Georg Thieme Verlag KG Stuttgart · New York

Brustkrebsprävention in der klinischen Praxis - Möglichkeiten und Grenzen

Breast Cancer Prevention in Clinical Practice - Potential and LimitationsC. Tempfer¹ , E. Bentz¹

¹Universitätsklinik für Frauenheilkunde Wien, Klinische Abteilung für gynäkologische Endokrinologie und Sterilitätsbehandlung

Abstract

Zusammenfassung

Brustkrebs ist jene bösartige Erkrankung, mit der der/die in der klinischen Praxis tätige Gynäkologe/in am häufigsten konfrontiert ist. Für folgende präventiv wirksame Interventionen liegen wissenschaftlich verwertbare Daten vor: diätetische Maßnahmen, sportliche Aktivität, Phytoöstrogene, Pharmakoprävention mittels selektiven Östrogenrezeptormodulatoren (SERMs), prophylaktische Chirurgie, sowie Aspirin und Nahrungsergänzungen/Vitamine. Eine bestimmte Diät zur Brustkrebsprävention kann nicht empfohlen werden. Weder eine fettarme noch eine vegetarische oder mediterrane Diät haben nachweislich einen positiven Einfluss auf das Brustkrebsrisiko. Eine fettreduzierte Diät ohne Gewichtsabnahme führt zu keiner Reduktion der Brustkrebsinzidenz. Auf der anderen Seite gibt es eine Reihe von indirekten Hinweisen aus epidemiologischen und tierexperimentellen Daten, dass eine simple aber dauerhafte Reduktion der Gesamtkalorienmenge von etwa 30 % verbunden mit einer BMI-Reduktion die Brustkrebsinzidenz, die Langzeitmorbidität und ‐mortalität reduziert und die Lebensdauer verlängert. Eine Brustkrebsprävention durch Sport ist nicht nachgewiesen, allerdings ist es aufgrund der Datenlage empfehlenswert, dass Frauen zur Brustkrebsprävention eine sportliche Betätigung ausüben, deren Ausmaß zwischen 3 und 5 Wochenstunden beträgt. Eine bestimmte Sportart kann nicht empfohlen werden. Eine Phytoöstrogensupplementierung zur Brustkrebsprävention kann nicht empfohlen werden. Es existiert kein gesicherter Hinweis darauf, dass eine peri- oder postmenopausale Phytoöstrogentherapie das Brustkrebsrisiko beeinflusst. Frauen mit einem erhöhten Brustkrebsrisiko kann eine prophylaktische Therapie mit Tamoxifen angeboten werden. Frauen mit einem unsubstituierten postmenopausalen Serumöstradiolspiegel > 10 pmol/L kann eine Chemoprävention mit Raloxifen angeboten werden. Durch den prophylaktischen Einsatz von Tamoxifen oder Raloxifen kann während der Einnahme die Inzidenz von hormonrezeptorpositiven Mammakarzinomen um 48 % reduziert werden. Eine chirurgische Prävention durch Salpingo-Oophorektomie ist neben Frauen mit hereditärer Brustkrebsbelastung durch BRCA-Mutation auch für Frauen mit einer Verwandten ersten Grades mit Ovarialkarzinom, Frauen nach sporadischem Mammakarzinom und Frauen mit hereditärem Kolonkarzinomsyndrom (HNPCC) empfehlenswert. Die fehlende Wirksamkeit einer brustkrebspräventiven Aspirin- und Vitamin-E-Einnahme wurde in prospektiv-randomisierten Studien nachgewiesen. Für andere Vitamine und Spurenelemente existieren keine prospektiv-randomisierten Daten, die epidemiologischen Studien sind inkonklusiv. Vitamine und Spurenelemente können daher zur Brustkrebsprävention nicht empfohlen werden.

Abstract

The validity of various strategies for breast cancer prevention has been investigated in scientific studies, including studies on dietary changes, physical activity, chemoprevention by selective estrogen receptor modulators (SERMs), prophylactic surgery, and the supplementation of phytoestrogens, aspirin, and vitamins. Epidemiologic and intervention studies were not able to demonstrate a favourable influence of low fat, vegetarian or Mediterranean diets on the risk of developing breast cancer. Experimental evidence, however, does appear to indicate that an increase in life-span, reduced mortality, and reduced cancer incidence occurs in individuals with sustained caloric restriction and body mass index (BMI) reduction. The preventive efficacy of physical activity has not been proven in intervention studies, but epidemiologic evidence consistently suggests that 3 to 5 hours of exercise per week reduces the risk of breast cancer. A supplementation with phytoestrogens has not been demonstrated to protect against breast cancer and cannot be recommended. Women with an elevated risk of breast cancer may use tamoxifen or raloxifen and can expect to reduce the risk of hormone receptor positive breast cancer during drug intake by 48 %. Prophylactic salpingo-oophorectomy (PSO) has been proven beneficial in women at risk for hereditary breast cancer and those with a first degree relative with ovarian cancer. In addition, breast cancer survivors and women at risk for hereditary non-polyposis colon cancer (HNPCC) benefit from PSO and prophylactic hysterectomy and PSO, respectively. Randomized controlled trials have shown that aspirin and vitamin supplementation do not offer protection against breast cancer and these compounds are therefore not recommended.

Schlüsselwörter

Brustkrebs - Prävention - Diät - Chemoprävention

Key words

breast cancer - prevention - diet - chemoprevention

Volltext

Referenzen

Literatur

1 Calle E E, Rodriguez C, Walker-Thurmond K, Thun M J. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U. S. adults. N Engl J Med. 2003; 348 1625-1638
2 Calle E E, Thun M J, Petrelli J M, Rodriguez C, Heath Jr C W. Body-mass index and mortality in a prospective cohort of U. S. adults. N Engl J Med. 1999; 341 1097-1105
3 Van Itallie T B. Obesity: adverse effects on health and longevity. Am J Clin Nutr. 1979; 32 2723-2733
4 Liberopoulos E N, Tsouli S, Mikhailidis D P, Elisaf M S. Preventing type 2 diabetes in high risk patients: an overview of lifestyle and pharmacological measures. Curr Drug Targets. 2006; 7 211-228
5 Manson J E, Stampfer M J, Hennekens C H, Willett W C. Body weight and longevity. A reassessment. JAMA. 1987; 257 353-358
6 Favero A, Franceschi S. Overweight and risk of breast tumor in Italy. Epidemiol Prev. 1998; 22 171-174
7 Wenten M, Gilliland F D, Baumgartner K, Samet J M. Associations of weight, weight change, and body mass with breast cancer risk in Hispanic and non-Hispanic white women. Ann Epidemiol. 2002; 12 435-434
8 Trichopoulou A, Lagiou P, Kuper H, Trichopoulos D. Cancer and mediterranean dietary traditions. Cancer Epidemiol Biomarkers Prev. 2000; 9 869-873
9 Rock C L, Demark-Wahnefried W. Nutrition and survival after the diagnosis of breast cancer: a review of the evidence. J Clin Oncol. 2002; 20 3302-3316
10 Pierce J P, Faerber S, Wright F A, Rock C L, Newman V. et al . Women's Healthy Eating and Living (WHEL) study group. A randomized trial of the effect of a plant-based dietary pattern on additional breast cancer events and survival: the Women's Healthy Eating and Living (WHEL) Study. Control Clin Trials. 2002; 23 728-756
11 Terry P, Jain M, Miller A B, Howe G R, Rohan T E. No association among total dietary fiber, fiber fractions, and risk of breast cancer. Cancer Epidemiol Biomarkers Prev. 2002; 11 1507-1508
12 Smith-Warner S A, Spiegelman D, Yaun S S, Adami H O, Beeson W L. et al . Intake of fruits and vegetables and risk of breast cancer: a pooled analysis of cohort studies. JAMA. 2001; 285 769-776
13 Prentice R L, Caan B, Chlebowski R T, Patterson R, Kuller L H, Ockene J K. Low-fat dietary pattern and risk of invasive breast cancer: the Women's Health Initiative Randomized Controlled Dietary Modification Trial. JAMA. 2006; 295 629-642
14 Mobbs C V, Bray G A, Atkinson R L, Bartke A, Finch C E, Maratos-Flier E, Crawley J N, Nelson J F. Neuroendocrine and pharmacological manipulations to assess how caloric restriction increases life span. J Gerontol A Biol Sci Med Sci. 2001; 56 Spec No 1 34-44
15 Sonntag W E, Lynch C D, Cefalu W T, Ingram R L, Bennett S A, Thornton P L, Khan A S. Pleiotropic effects of growth hormone and insulin-like growth factor (IGF)-1 on biological aging: inferences from moderate caloric-restricted animals. J Gerontol A Biol Sci Med Sci. 1999; 54 B521-B538
16 Roth G S, Mattison J A, Ottinger M A, Chachich M E, Lane M A, Ingram D K. Aging in rhesus monkeys: relevance to human health interventions. Science. 2004; 305 1423-1426
17 Elias S G, Peeters P H, Grobbee D E, Noord P A. The 1944 - 1945 Dutch famine and subsequent overall cancer incidence. Cancer Epidemiol Biomarkers Prev. 2005; 14 1981-1985
18 Michels K B, Ekbom van A. Caloric restriction and incidence of breast cancer. JAMA. 2004; 291 1226-1230
19 Kushi L H, Potter J D, Bostick R M, Drinkard C R, Sellers T A, Gapstur S M, Cerhan J R, Folsom A R. Dietary fat and risk of breast cancer according to hormone receptor status. Cancer Epidemiol Biomarkers Prev. 1995; 4 11-19
20 Friedenreich C M. Physical activity and breast cancer risk: the effect of menopausal status. Exerc Sport Sci Rev. 2004; 32 180-184
21 Gilliland F D, Li Y F, Baumgartner K, Crumley D, Samet J M. Physical activity and breast cancer risk in hispanic and non-hispanic white women. Am J Epidemiol. 2001; 154 442-450
22 McTiernan A, Kooperberg C, White E, Wilcox S, Coates R, Adams-Campbell L L, Woods N, Ockene J. Women's Health Initiative Cohort Study . Recreational physical activity and the risk of breast cancer in postmenopausal women: the Women's Health Initiative Cohort Study. JAMA. 2003; 290 1331-1336
23 Maskarinec G. Breast cancer-interaction between ethnicity and environment. In Vivo. 2000; 14 115-123
24 Yamamoto S, Sobue T, Kobayashi M, Sasaki S, Tsugane S. Japan Public Health Center-Based Prospective Study on Cancer Cardiovascular Diseases Group . Soy, isoflavones, and breast cancer risk in Japan. J Natl Cancer Inst. 2003; 95 906-913
25 De Angelis M, Stossi F, Waibel M, Katzenellenbogen B S, Katzenellenbogen J A. Isocoumarins as estrogen receptor beta selective ligands: Isomers of isoflavone phytoestrogens and their metabolites. Bioorg Med Chem. 2005; 13 6529-6542
26 Horn-Ross P L, John E M, Lee M, Stewart S L, Koo J, Sakoda L C, Shiau A C, Goldstein J, Davis P, Perez-Stable E J. Phytoestrogen consumption and breast cancer risk in a multiethnic population: the Bay Area Breast Cancer Study. Am J Epidemiol. 2001; 154 434-441
27 Russo I H, Russo J. Hormonal approach to breast cancer prevention. J Cell Biochem Suppl . 2000; 34 1-6
28 Peeters P H, Keinan-Boker L, Schouw Y T, Grobbee D E. Phytoestrogens and breast cancer risk. Review of the epidemiological evidence. Breast Cancer Res Treat. 2003; 77 171-183
29 Cuzick van der J, Powles T, Veronesi U, Forbes J, Edwards R, Ashley S, Boyle P. Overview of the main outcomes in breast-cancer prevention trials. Lancet. 2003; 361 296-300
30 Fisher B, Costantino J P, Wickerham D L, Redmond C K, Kavanah M. et al . Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P‐1 Study. J Natl Cancer Inst. 1998; 90 1371-1388
31 Gardner F J, Konje J C, Abrams K R, Brown L J, Khanna S, Al-Azzawi F, Bell S C, Taylor D J. Endometrial protection from tamoxifen-stimulated changes by a levonorgestrel-releasing intrauterine system: a randomised controlled trial. Lancet. 2000; 356 1711-1717
32 Cummings S R, Eckert S, Krueger K A, Grady D, Powles T J. et al . The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA. 1999; 281 2189-2197
33 Cummings S R, Duong T, Kenyon E, Cauley J A, Whitehead M, Krueger K A. Multiple Outcomes of Raloxifene Evaluation (MORE) Trial. Serum estradiol level and risk of breast cancer during treatment with raloxifene. JAMA. 2002; 287 216-220
34 Vogel V G, Costantino J P, Wickerham D L, Cronin W M, Cecchini R S, Atkins J N. et al . National Surgical Adjuvant Breast and Bowel Project (NSABP). Effects of tamoxifen vs. raloxifene on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of Tamoxifen and Raloxifene (STAR) P‐2 trial. JAMA. 2006; 295 2727-2741
35 Veronesi U, Maisonneuve P, Sacchini V, Rotmensz N, Boyle P. Italian Tamoxifen Study Group . Tamoxifen for breast cancer among hysterectomised women. Lancet. 2002; 359 1122-1124
36 Powles T J, Jones A L, Ashley S E, O'Brien M E, Tidy V A, Treleavan J, Cosgrove D, Nash A G, Sacks N, Baum M. et al . The Royal Marsden Hospital pilot tamoxifen chemoprevention trial. Breast Cancer Res Treat. 1994; 31 73-82
37 Cuzick J, Forbes J, Edwards R, Baum M, Cawthorn S, Coates A, Hamed A, Howell A, Powles T. IBIS investigators . First results from the International Breast Cancer Intervention Study (IBIS‐I): a randomised prevention trial. Lancet. 2002; 360 817-824
38 Howell A, Cuzick J, Baum M, Buzdar A, Dowsett M, Forbes J F, Hoctin-Boes G, Houghton J, Locker G Y, Tobias J S. ATAC Trialists' Group . Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial after completion of 5 years' adjuvant treatment for breast cancer. Lancet. 2005; 365 60-62
39 Rebbeck T R, Friebel T, Lynch H T, Neuhausen S L, van't Veer L. et al . Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol. 2004; 22 1055-1062
40 Domchek S M, Friebel T M, Neuhausen S L, Wagner T, Evans G. et al . Mortality after bilateral salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers: a prospective cohort study. Lancet Oncol. 2006; 7 223-229
41 Kerlikowske K, Brown J S, Grady D G. Should women with familial ovarian cancer undergo prophylactic oophorectomy?. Obstet Gynecol. 1992; 80 700-707
42 ACOG . ACOG practice bulletin. Prophylactic oophorectomy. Number 7, September 1999 (replaces Technical Bulletin Number 111, December 1987). Clinical management guidelines for obstetrician-gynecologists. American College of Obstetricians and Gynecologists. Int J Gynaecol Obstet. 1999; 67 193-199
43 Prior P, Waterhouse J A. Multiple primary cancers of the breast and ovary. Br J Cancer. 1981; 44 628-636
44 Schmeler K M, Lynch H T, Chen L M, Munsell M F, Soliman P T. et al . Prophylactic surgery to reduce the risk of gynecologic cancers in the Lynch syndrome. N Engl J Med. 2006; 354 261-269
45 Chow L W, Zhu L, Loo W T, Lui E L. Aberrant methylation of cyclooxygenase-2 in breast cancer patients. Biomed Pharmacother. 2005; 59 S264-S267
46 Timoshenko A V, Chakraborty C, Wagner G F, Lala P K. COX‐2-mediated stimulation of the lymphangiogenic factor VEGF‐C in human breast cancer. Br J Cancer. 2006; 94 1154-1163
47 Cook N R, Lee I M, Gaziano J M, Gordon D, Ridker P M, Manson J E, Hennekens C H, Buring J E. Low-dose aspirin in the primary prevention of cancer: the Women's Health Study: a randomized controlled trial. JAMA. 2005; 294 47-55
48 Duffield-Lillico A J, Dalkin B L, Reid M E, Turnbull B W, Slate E H. et al . Selenium supplementation, baseline plasma selenium status and incidence of prostate cancer: an analysis of the complete treatment period of the Nutritional Prevention of Cancer Trial. BJU Int. 2003; 91 608-612
49 Nissen S B, Tjonneland A, Stripp C, Olsen A, Christensen J, Overvad K, Dragsted L O, Thomsen B. Intake of vitamins A, C, and E from diet and supplements and breast cancer in postmenopausal women. Cancer Causes Control. 2003; 14 695-704
50 Kushi L H, Fee R M, Sellers T A, Zheng W, Folsom A R. Intake of vitamins A, C, and E and postmenopausal breast cancer. The Iowa Women's Health Study. Am J Epidemiol. 1996; 144 165-174
51 Zhang S, Hunter D J, Forman M R, Rosner B A, Speizer F E. et al . Dietary carotenoids and vitamins A, C, and E and risk of breast cancer. J Natl Cancer Inst. 1999; 91 547-556
52 Verhoeven D T, Assen N, Goldbohm R A, Dorant E, 't Veer van P, Sturmans F, Hermus R J, Brandt P A. Vitamins C and E, retinol, beta-carotene and dietary fibre in relation to breast cancer risk: a prospective cohort study. Br J Cancer. 1997; 75 149-155
53 Hunter D J, Manson J E, Colditz G A, Stampfer M J, Rosner van den B. et al . A prospective study of the intake of vitamins C, E, and A and the risk of breast cancer. N Engl J Med. 1993; 329 234-240
54 Rohan T E, Howe G R, Friedenreich C M, Jain M, Miller A B. Dietary fiber, vitamins A, C, and E, and risk of breast cancer: a cohort study. Cancer Causes Control. 1993; 4 29-37
55 Bohlke K, Spiegelman D, Trichopoulou A, Katsouyanni K, Trichopoulos D. Vitamins A, C and E and the risk of breast cancer: results from a case-control study in Greece. Br J Cancer. 1999; 79 23-29
56 Do M H, Lee S S, Jung P J, Lee M H. Intake of dietary fat and vitamin in relation to breast cancer risk in Korean women: a case-control study. J Korean Med Sci. 2003; 18 534-540
57 Moorman P G, Ricciuti M F, Millikan R C, Newman B. Vitamin supplement use and breast cancer in a North Carolina population. Public Health Nutr. 2001; 4 821-827
58 Lee I M, Cook N R, Manson J E, Buring J E, Hennekens C H. Beta-carotene supplementation and incidence of cancer and cardiovascular disease: the Women's Health Study. J Natl Cancer Inst. 1999; 91 2102-2106
59 Albanes D, Heinonen O P, Taylor P R, Virtamo J, Edwards B K. et al . Alpha-Tocopherol and beta-carotene supplements and lung cancer incidence in the alpha-tocopherol, beta-carotene cancer prevention study: effects of base-line characteristics and study compliance. J Natl Cancer Inst. 1996; 88 1560-1570
60 Cook N R, Le I M, Manson J E, Buring J E, Hennekens C H. Effects of beta-carotene supplementation on cancer incidence by baseline characteristics in the Physicians' Health Study (United States). Cancer Causes Control. 2000; 11 617-626
61 Veronesi U, De Palo G, Marubini E, Costa A, Formelli F. et al . Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer. J Natl Cancer Inst. 1999; 91 1847-1856

C. Tempfer

Universitätsklinik für Frauenheilkunde Wien
Klinische Abteilung für gyn. Endokrinologie u. Sterilitätsbehandlung

Währinger Gürtel 18 - 20

1090 Wien

Österreich

eMail: clemens.tempfer@meduniwien.ac.at