Primärprävention des Mammakarzinoms – State of the Art

Einige Faktoren, die das Brustkrebsrisiko erhöhen, wie Übergewicht, körperliche Inaktivität, hoher Alkoholkonsum, Diabetes oder Hormonersatztherapie, können durch Änderungen des Lebensstils günstig beeinflusst werden. Bei erhöhtem Risiko aufgrund nicht modifizierbarer Risikofaktoren, wie höheres Lebensalter, hereditäre Brustkrebsformen, Kinderlosigkeit, frühe Menarche oder späte Menopause, kann nach individueller Nutzen-Risiko-Abwägung eine medikamentöse (Tamoxifen, Raloxifen, Aromatasehemmer) oder chirurgische (bilaterale Mastektomie) Primärprävention in Betracht gezogen werden. Der Stellenwert anderer medikamentöser Interventionen, z. B. mit nicht-steroidalen Antirheumatika, Vitamin D oder Antidiabetika ist bisher noch nicht ausreichend geklärt. Da medikamentöse und chirurgische Primärprävention gleichbedeutend mit einer Therapie gesunder Frauen mit lediglich statistisch erhöhtem Risiko ist, kann eine entsprechende Entscheidung nur gemeinsam mit der betroffenen Frau nach sorgfältiger Nutzen-Risiko-Bewertung getroffen werden.

Some risk factors for breast cancer like obesity, sedentary lifestyle, diabetes, alcohol abuse or hormone replacement therapy are modifiable by lifestyle interventions. In women highly at risk with non modifiable risk factors, like age, hereditary risks, nulliparity, early onset of menarche or delayed menopause, the use of substances like tamoxifen, raloxifene or aromatase inhibitors may be considered after evaluation of the risks and benefits. In hereditary forms of breast cancer (like BRCA 1, 2 mutations) bilateral mastectomy reduces the risk considerably. The benefit of interventions like non steroidal anti inflammatory drugs, vitamin D or antidiabetics remains unclear. As preventive medication and surgery means treatment of healthy women at only statistically elevated risk, the decision must be discussed with the patient considering risks and benefits in a shared decision-making process.

Key words

breast cancer prevention - risk assessment - risk reduction - chemoprevention - lifestyle interventions

• Literatur

• 1 Bevers TB et al. Breast Cancer Risk Reduction. J Natl Compr Canc Netw 2010; 8: 1112-1146
• 2 Fisher B et al. Tamoxifen for Prevention of Breast Cancer. J Natl Cancer Inst 1998; 90: 1371-1388
• 3 Fisher B et al. Tamoxifen for the prevention of breast cancer: current status of the National Surgical Adjuvant Breast and Bowel Project P-1 study. J Natl Cancer Inst 2005; 97: 1652-1662
• 4 Powles TJ et al. Twenty-year follow-up of the Royal Marsden randomized, double-blinded tamoxifen breast cancer prevention trial. J Natl Cancer Inst 2007; 99: 283-290
• 5 Ropka ME et al. Patient decisions about breast cancer chemoprevention. J Clin Oncol 2010; 28: 3090-3095
• 6 Cummings SR et al. The Effect of Raloxifene on Risk of Breast Cancer in Postmenopausal Women. JAMA 1999; 281: 2189-2197
• 7 Martino S et al. Continuing outcomes relevant to Evista: breast cancer incidence in postmenopausal osteoporotic women in a randomized trial of raloxifene. J Natl Cancer Inst 2004; 96: 1751-1761
• 8 Vogel VG et al. Effects of Tamoxifen vs Raloxifene on the Risk of developing Invasive Breast Cancer and other Disease Outcomes. JAMA 2006; 295: 2727-2741
• 9 Vogel VG et al. Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: Preventing breast cancer. Cancer Prev Res 2010; 3: 696-706
• 10 Freedman AN et al. Benefit/Risk Assessment for Breast Cancer Chemoprevention with Raloxifene or Tamoxifen for Women Age 50 Years or older. J Clin Oncol 2011; 29: 2327-2333
• 11 Bushnell CD, Goldstein LB. Risk of ischemic stroke with tamoxifen treatment for breast cancer: a meta-analysis. Neurology 2004; 63: 1230-1233
• 12 Braithwaite RS et al. Meta-analysis of vascular and neoplastic events associated with tamoxifen. J Gen Intern Med 2003; 18: 937-947
• 13 Goss PE et al. Exemestane for breast cancer prevention in postmenopausal women. N Engl J Med 2011; 364: 2381-2391
• 14 Pollak M. Metformin and other Biguanides in Oncology. Cancer Prev Res 2010; 3: 1060-1065
• 15 Landman GW et al. Metformin associated with Lower Cancer Mortality in Type 2 Diabetes. Diabetes Care 2010; 33: 322-326
• 16 Zhao YS et al. Association between NSAIDs use and breast cancer risk: a systematic review and meta-analysis. Breast Cancer Res Treat 2009; 117: 141-150
• 17 Seshasai SRK et al. Effect of Aspirin on Vascular and Nonvascular Outcomes. Arch Intern Med online 09.01.2012; 628-628
• 18 Holmes MD et al. Aspirin Intake and Survival after Breast Cancer. J Clin Oncol 2010; 28: 1467-1472
• 19 Hartmann LC et al. Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N Engl J Med 1999; 340: 77-84
• 20 Hartmann LC et al. Efficacy of bilateral prophylactic mastectomy in BRCA1 and BRCA2 gene mutation carriers. J Natl Cancer Inst 2001; 93: 1633-1637
• 21 Hamm RM, Lawler F, Scheid D. Prophylactic mastectomy in women with a high risk of breast cancer. N Engl J Med 1999; 340: 1837-1839
• 22 National Institutes of Health. Optimizing Energy Balance to Reduce the Cancer Burden. NIH Publication 03-5446 2003;
• 23 World Cancer Research Fund, American Institute for Cancer Research. Food, nutrition, physical activity, and the prevention of cancer: a global perspective. Washington DC: AICR; 2007
• 24 Barnes BE et al. Population attributable risk of invasive postmenopausal breast cancer and breast cancer subtypes for modifiable and non-modifiable risk factors. Cancer Epidemiology 2011; 35: 345-352
• 25 Mahoney MC et al. Opportunities and strategies for breast cancer prevention through risk reduction. Cancer J Clin 2008; 58: 347-371
• 26 Eliassen AH et al. Adult weight change and risk of postmenopausal breast cancer. JAMA 2006; 296: 193-201
• 27 Giovannucci E et al. Diabetes and Cancer: A Consensus Report. Diabetes Care 2010; 33: 1674-1685
• 28 Barone BB et al. Long-term all Cause Mortality in Cancer Patients with Preexisting Diabetes Mellitus. JAMA 2008; 300: 2754-2764
• 29 Pollak M. Insulin and Insulin-like Growth Factor Signalling in Neoplasia. Nat Rev Cancer 2008; 8: 915-928
• 30 Ballard-Barbash R et al. Physical Activity, Weight Control and Breast Cancer Risk and Survival. J Natl Cancer Inst 2009; 101: 630-643
• 31 Friedenreich CM et al. Sex hormone changes in a year-long exercise intervention among postmenopausal women. J Clin Oncol 2010; 28: 1458-1466
• 32 Kohler S, Leitzmann M. Körperliche Aktivität in der Tumorprävention. FORUM der DKG 2011; 26: 25-30
• 33 Irwin ML et al. Influence of pre- and postdiagnosis Physical Activity on Mortality in Breast Cancer Survivors. J Clin Oncol 2008; 26: 3958-3964
• 34 Holmes MD et al. Physical Activity and Survival after Breast Cancer Diagnosis. JAMA 2005; 293: 2479-2486
• 35 Brennan SF et al. Dietary Patterns and Breast Cancer Risk: a systematic Review and Metaanalysis. Am J Clin Nutr 2010; 91: 1294-1302
• 36 Prentice RL et al. Low-fat Dietary Pattern and Risk of Invasive Breast Cancer. JAMA 2006; 295: 629-642
• 37 Bertone-Johnson ER et al. Plasma 25-hydroxyvitamin D, and 1,25-dihydroxyvitamin D and risk of breast cancer. Cancer Epidemiol Biomarkers Prev 2005; 14: 1991-1997
• 38 Manson JAE, Mayne ST, Clinton SK. Vitamin D and Prevention of Cancer: Ready for Prime Time?. N Engl J Med 2011; 364: 1385-1387
• 39 Terry MB et al. Lifetime alcohol intake and breast cancer risk. Ann Epidemiol 2006; 16: 230-240
• 40 Xue F et al. Cigarette Smoking and the Incidence of Breast Cancer. Arch Intern Med 2011; 171: 125-133
• 41 Rossouw JE et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results from the Women's Health Initiative randomized controlled trial. JAMA 2002; 288: 321-333
• 42 Beral V. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet 2003; 362: 419-427
• 43 Chen WY et al. Unopposed estrogen therapy and the risk of invasive breast cancer. Arch Intern Med 2006; 166: 1027-1032