Of great interest are the single nucleotide polymorphisms (SNIPs) that individually have minor effects of risk but are common. Some women will have several of these SNIPs to have an impact on their breast cancer risk, especially in combination with mammographic density and other known factors. An assessment of how SNIPs might improve risk assessment among high-risk women is needed for better targeting of preventive therapy. In a recent study, Cuzick et al evaluated a panel of 15 SNIPs and found that they are useful for refining risk estimates in women at high risk of developing breast cancer.52

In conclusion, there are many options for the prevention of ER-positive breast cancer, specifically in postmenopausal women who can be given a SERM or an AI. For premeno­pausal women, only tamoxifen can be potentially used as a preventive agent as AIs are not indicated in this group of women. It remains unclear how to prevent the incidence of ER-negative breast cancer, which occurs mostly in premeno­pausal women, and more research is needed to specifically target this unsolved matter.


Continue Reading


Disclosure

The author reports no conflicts of interest in this work.


Ivana Sestak, Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, Charterhouse Square, London, UK. 


References

1. Ferlay J, Soerjomataram I, Ervik M, et al. GLOBOCAN 2012 v1.0, Cancer Incidence and Mortality Worldwide: IARC CancerBase No 11 [Internet]. Lyon: International Agency for Research on Cancer; 2013.

2. Cuzick J. Aromatase inhibitors for breast cancer prevention. J Clin Oncol. 2005;23:1636–1643.

3. Tseng M, Weinberg CR, Umbach DM, Longnecker MP. Calculation of population attributable risk for alcohol and breast cancer (United States). Cancer Causes Control. 1999;10:119–123.

4. Sestak I, Cuzick J. Breast cancer chemoprevention. Oncol Rev. 2008;2: 221–226.

5. Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer Trialists’ Collaborative Group. Lancet. 1998;351: 1451–1467.

6. Cuzick J, Powles T, Veronesi U, et al. Overview of the main outcomes in breast-cancer prevention trials. Lancet. 2003;361:296–300.

7. Powles T, Eeles R, Ashley S, et al. Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial. Lancet. 1998;352:98–101.

8. Powles TJ, Ashley S, Tidy A, Smith IE, Dowsett M. Twenty-year follow-up of the Royal Marsden randomized, double-blinded tamox­ifen breast cancer prevention trial. J Natl Cancer Inst. 2007;99:283–290.

9. Cuzick J, Forbes J, Edwards R, et al. First results from the International Breast Cancer Intervention Study (IBIS-I): a randomised prevention trial. Lancet. 2002;360:817–824.

10. Cuzick J, Forbes JF, Sestak I, et al. Long-term results of tamoxifen prophylaxis for breast cancer – 96-month follow-up of the randomized IBIS-I trial. J Natl Cancer Inst. 2007;99:272–282.

11. Veronesi U, Maisonneuve P, Rotmensz N, et al. Tamoxifen for the prevention of breast cancer: late results of the Italian Randomized Tamoxifen Prevention Trial among women with hysterectomy. J Natl Cancer Inst. 2007;99:727–737.

12. Veronesi U, Maisonneuve P, Sacchini V, et al. Tamoxifen for breast can­cer among hysterectomised women. Lancet. 2002;359:1122–1124.

13. Fisher B, Costantino JP, Wickerham DL, 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.

14. Fisher B, Costantino JP, Wickerham DL, 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.

15. Veronesi U, Maisonneuve P, Costa A, et al. Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study. Lancet. 1998;352:93–97.

16. Cuzick J, Sestak I, Bonanni B, et al. Selective oestrogen receptor modulators in prevention of breast cancer: an updated meta-analysis of individual participant data. Lancet. 2013;381:1827–1834.

17. Cummings SR, Eckert S, Krueger KA, 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.

18. Martino S, Cauley JA, Barrett-Connor E, 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.

19. Barrett-Connor E, Mosca L, Collins P, et al. Effects of raloxifene on cardiovascular events and breast cancer in postmenopausal women. N Engl J Med. 2006;355:125–137.

20. Vogel VG, Costantino JP, Wickerham DL, et al. 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(23):2727–2741.

21. Cummings SR, Ensrud K, Delmas PD, et al. Lasofoxifene in postmeno­pausal women with osteoporosis. N Engl J Med. 2010;362:686–696.

22. Cummings SR, McClung M, Reginster JY, et al. Arzoxifene for prevention of fractures and invasive breast cancer in postmenopausal women. J Bone Miner Res. 2011;26:397–404.

23. NICE: Familial Breast Cancer; 2013. Available from: guidance.nice.org.uk/cg164 NICE.

24. Richards JA, Petrel TA, Brueggemeier RW. Signaling pathways regu­lating aromatase and cyclooxygenases in normal and malignant breast cells. J Steroid Biochem Mol Biol. 2002;80:203–212.

25. Baum M, Budzar AU, Cuzick J, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early breast cancer: first results of the ATAC randomised trial. Lancet. 2002;359:2131–2139.

26. Boccardo F, Rubagotti A, Puntoni M, et al. Switching to anastrozole versus continued tamoxifen treatment of early breast cancer: preliminary results of the Italian Tamoxifen Anastrozole Trial. J Clin Oncol. 2005;23:5138–5147.

27. Coates AS, Keshaviah A, Thürlimann B, et al. Five years of letrozole compared with tamoxifen as initial adjuvant therapy for postmenopausal women with endocrine-responsive early breast cancer: update of study BIG 1-98. J Clin Oncol. 2007;25:486–492.

28. Coombes RC, Hall E, Gibson LJ, et al. A randomized trial of exemestane after two to three years of tamoxifen therapy in postmenopausal women with primary breast cancer. N Engl J Med. 2004;350:1081–1092.

29. Goss PE, Ingle JN, Martino S, et al. A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med. 2003;349:1793–1802.

30. Jakesz R, Jonat W, Gnant M, et al. Switching of postmenopausal women with endocrine-responsive early breast cancer to anastrozole after 2 years’ adjuvant tamoxifen: combined results of ABCSG trial 8 and ARNO 95 trial. Lancet. 2005;366:455–462.

31. Mamounas E, Jeong J-H, Wickerham DL, et al. Benefit from exemestane (EXE) as extended adjuvant therapy after 5 years of tamoxifen (TAM): intent-to-treat analysis of NSABP B-33. Breast Cancer Res Treat. 2006;100:S22.

32. Baum M, Buzdar A, Cuzick J, et al. Anastrozole alone or in combination with tamoxifen versus tamoxifen alone for adjuvant treatment of postmenopausal women with early-stage breast cancer: results of the ATAC (Arimidex, Tamoxifen Alone or in Combination) trial efficacy and safety update analyses. Cancer. 2003;98:1802–1810.

33. Arimidex, Tamoxifen Alone or in Combination (ATAC) Trialists’ Group, Forbes JF, Cuzick J, et al. Effect of anastrozole and tamoxifen as adjuvant treatment for early-stage breast cancer: 100-month analysis of the ATAC trial. Lancet Oncol. 2008;9:45–53.

34. Howell A, Cuzick J, Baum M, et al. 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.

35. Dowsett M, Cuzick J, Ingle J, et al. Meta-analysis of breast cancer outcomes in adjuvant trials of aromatase inhibitors versus tamoxifen. J Clin Oncol. 2010;28:509–518.

36. Goss PE, Ingle JN, Alés-Martínez JE, et al. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med. 2011;364: 2381–2391.

37. Cuzick J, Sestak I, Forbes JF, et al. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an inter­national, double-blind, randomised placebo-controlled trial. Lancet. 2014;383(9922):1041–1048.

38. Chlebowski RT, Col N. Bisphosphonates and breast cancer prevention. Anticancer Agents Med Chem. 2012;12:144–150.

39. Rennert G, Pinchev M, Rennert HS. Use of bisphosphonates and risk of postmenopausal breast cancer. J Clin Oncol. 2010;28:3577–3581.

40. Terry MB, Gammon MD, Zhang FF, et al. Association of frequency and duration of aspirin use and hormone receptor status with breast cancer risk. JAMA. 2004;291:2433–2440.

41. Holmes MD, Chen WY, Li L, Hertzmark E, Spiegelman D, Hankinson SE. Aspirin intake and survival after breast cancer. J Clin Oncol. 2010;28:1467–1472.

42. Li Y, Brasky TM, Nie J, et al. Use of nonsteroidal anti-inflammatory drugs and survival following breast cancer diagnosis. Cancer Epidemiol Biomarkers Prev. 2012;21:239–242.

43. Wald NJ, Morris JK, Law MR. Aspirin in the prevention of cancer. Lancet. 2011;377:1649; author reply 1651–1652.

44. Cuzick J, Warwick J, Pinney E, et al. Tamoxifen-induced reduction in mammographic density and breast cancer risk reduction: a nested case-control study. J Natl Cancer Inst. 2011;103:744–752.

45. Kim J, Han W, Moon HG, et al. Breast density change as a predictive surrogate for response to adjuvant endocrine therapy in hormone receptor positive breast cancer. Breast Cancer Res. 2012;14:R102.

46. Rahme E, Ghosn J, Dasgupta K, Rajan R, Hudson M. Association between frequent use of nonsteroidal anti-inflammatory drugs and breast cancer. BMC Cancer. 2005;5:159.

47. Harris RE, Beebe-Donk J, Alshafie GA. Reduction in the risk of human breast cancer by selective cyclooxygenase-2 (COX-2) inhibitors. BMC Cancer. 2006;6:27.

48. Mazhar D, Ang R, Waxman J. COX inhibitors and breast cancer. Br J Cancer. 2006;94:346–350.

49. Eliassen AH, Colditz GA, Rosner B, Willett WC, Hankinson SE. Serum lipids, lipid-lowering drugs, and the risk of breast cancer. Arch Intern Med. 2005;165:2264–2271.

50. Esserman LJ, Campbell M, Shoemaker M. Breast cancer inhibition by statins. Proc Am Soc Clin Oncol. 2004;2004:97.

51. Murillo G, Peng X, Torres KE, Mehta RG. Deguelin inhibits growth of breast cancer cells by modulating the expression of key members of the Wnt signaling pathway. Cancer Prev Res (Phila). 2009;2:942–950.

52. Cuzick J, Brentnall AR, Segala C, et al. Use of a SNP panel to refine risk estimates in women at high risk of breast cancer: results from two randomized tamoxifen prevention trials. J Clin Oncol. 2014;32(Suppl; abstr 1519).