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The Role of Chemoprevention in the Prevention of Breast Cancer

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Atypical Breast Proliferative Lesions and Benign Breast Disease

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Abstract

Breast cancer is the second leading cause of cancer death among women in the United States. Annually, over 1 million breast biopsies are performed. While most of these biopsies result in benign findings, nearly 10% of breast biopsies will result in a diagnosis of a high-risk lesion conferring an elevated risk of future breast cancer. Estimates suggest that 2 million women in the United States and 500,000 women in the United Kingdom are eligible and have favorable cost-benefit profiles for the prophylactic use of breast cancer prevention medications. Despite the consistent data demonstrating that prevention medications reduce breast cancer risk, mean uptake and adherence to these medications in eligible patients remain low.

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References

  1. Freedman AN, Graubard BI, Rao SR, McCaskill-Stevens W, Ballard-Barbash R, Gail MH. Estimates of the number of US women who could benefit from tamoxifen for breast cancer chemoprevention. J Natl Cancer Inst. 2003;95(7):526–32.

    Article  CAS  Google Scholar 

  2. Moyer VA. Medications to decrease the risk for breast cancer in women: recommendations from the U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. Practice Guideline Research Support, U.S. Gov’t, P.H.S. 2013;159(10):698–708.

    PubMed  Google Scholar 

  3. Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, 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. [Clinical Trial Multicenter Study Randomized Controlled Trial Research Support, U.S. Gov’t, P.H.S.]. 1998;90(18):1371–88.

    Article  CAS  Google Scholar 

  4. King TA, Pilewskie M, Muhsen S, Patil S, Mautner SK, Park A, et al. Lobular carcinoma in situ: a 29-year longitudinal experience evaluating clinicopathologic features and breast cancer risk. J Clin Oncol. [Evaluation Studies Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. 2015;33(33):3945–52.

    Article  Google Scholar 

  5. Pruthi S, Heisey R, Bevers T. Personalized assessment and management of women at risk for breast cancer in North America. Womens Health (Lond). [Review]. 2015;11(2):213–23; quiz 23–4.

    Article  CAS  Google Scholar 

  6. Vogel VG, Costantino JP, Wickerham DL, Cronin WM, Cecchini RS, Atkins JN, 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 (Phila). [Comparative Study Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, U.S. Gov’t, P.H.S.]. 2010;3(6):696–706.

    Article  CAS  Google Scholar 

  7. Statistics NCfH. Use of mammography among women aged 40 and over, by selected characteristics. Hyattsville: U.S.Government Printing Office; 2016. [cited 2017 October 1, 2017]; Available from: http://www.cdc.gov/nchs/hus/contents2016.htm#070

    Google Scholar 

  8. Neal L, Sandhu NP, Hieken TJ, Glazebrook KN, Mac Bride MB, Dilaveri CA, et al. Diagnosis and management of benign, atypical, and indeterminate breast lesions detected on core needle biopsy. Mayo Clin Proc. [Comparative Study Review]. 2014;89(4):536–47.

    Article  Google Scholar 

  9. Walia S, Ma YL, Lu J, Lang JE, Press MF. Pathology and current management of borderline breast epithelial lesions. Am J Hematol Oncol. 2017;13(8):24–31.

    Google Scholar 

  10. Black MM, Barclay TH, Cutler SJ, Hankey BF, Asire AJ. Association of atypical characteristics of benign breast lesions with subsequent risk of breast cancer. Cancer. 1972;29(2):338–43.

    Article  CAS  Google Scholar 

  11. Degnim AC, Visscher DW, Berman HK, Frost MH, Sellers TA, Vierkant RA, et al. Stratification of breast cancer risk in women with atypia: a Mayo cohort study. J Clin Oncol. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, Non-P.H.S. 2007;25(19):2671–7.

    Article  Google Scholar 

  12. Hartmann LC, Degnim AC, Santen RJ, Dupont WD, Ghosh K. Atypical hyperplasia of the breast – risk assessment and management options. N Engl J Med. Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t. 2015;372(1):78–89.

    Article  Google Scholar 

  13. Hartmann LC, Radisky DC, Frost MH, Santen RJ, Vierkant RA, Benetti LL, et al. Understanding the premalignant potential of atypical hyperplasia through its natural history: a longitudinal cohort study. Cancer Prev Res (Phila). [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. 2014;7(2):211–7.

    Article  CAS  Google Scholar 

  14. Hartmann LC, Sellers TA, Frost MH, Lingle WL, Degnim AC, Ghosh K, et al. Benign breast disease and the risk of breast cancer. N Engl J Med. 2005;353(3):229–37.

    Article  CAS  Google Scholar 

  15. Menes TS, Kerlikowske K, Lange J, Jaffer S, Rosenberg R, Miglioretti DL. Subsequent breast cancer risk following diagnosis of atypical ductal hyperplasia on needle biopsy. JAMA Oncol. 2017;3(1):36–41.

    Article  Google Scholar 

  16. Morrow M, Schnitt SJ, Norton L. Current management of lesions associated with an increased risk of breast cancer. Nat Rev Clin Oncol. 2015;12(4):227–38.

    Article  Google Scholar 

  17. Page DL, Dupont WD, Rogers LW, Rados MS. Atypical hyperplastic lesions of the female breast – a long-term follow-up-study. Cancer. 1985;55(11):2698–708.

    Article  CAS  Google Scholar 

  18. Page DL, Schuyler PA, Dupont WD, Jensen RA, Plummer WD, Simpson JF. Atypical lobular hyperplasia as a unilateral predictor of breast cancer risk: a retrospective cohort study. Lancet. 2003;361:125. 2003 Jun 7;361(9373):1994–1998.

    Article  Google Scholar 

  19. Worsham MJ, Abrams J, Raju U, Kapke A, Lu M, Cheng JF, et al. Breast cancer incidence in a cohort of women with benign breast disease from a multiethnic, primary health care population. Breast J. 2007;13(2):115–21.

    Article  Google Scholar 

  20. Maximov PY, Lee TM, Jordan VC. The discovery and development of selective estrogen receptor modulators (SERMs) for clinical practice. Curr Clin Pharmacol. [Comparative Study Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, Non-P.H.S. Review]. 2013;8(2):135–55.

    Article  CAS  Google Scholar 

  21. Mocellin S, Pilati P, Briarava M, Nitti D. Breast cancer chemoprevention: a network ,meta-analysis of randomized controlled trials. J Natl Cancer Inst. [Meta-Analysis]. 2016;108(2):djv318.

    Article  Google Scholar 

  22. Jordan VC, Robinson SP. Species-specific pharmacology of antiestrogens – role of metabolism. FASEB J. 1987;46(5):1870–4.

    CAS  Google Scholar 

  23. Wijayaratne AL, McDonnell DP. The human estrogen receptor-alpha is a ubiquitinated protein whose stability is affected differentially by agonists, antagonists, and selective estrogen receptor modulators. J Biol Chem. [Research Support, U.S. Gov’t, P.H.S.]. 2001;276(38):35684–92.

    Article  CAS  Google Scholar 

  24. Harper MJ, Walpole AL. A new derivative of triphenylethylene: effect on implantation and mode of action in rats. J Reprod Fertil. 1967;13(1):101–19.

    Article  CAS  Google Scholar 

  25. Powles TJ, Hardy JR, Ashley SE, Farrington GM, Cosgrove D, Davey JB, et al. A pilot trial to evaluate the acute toxicity and feasibility of tamoxifen for prevention of breast-cancer. Br J Cancer. 1989;60(1):126–31.

    Article  CAS  Google Scholar 

  26. 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. [Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2007;99(4):283–90.

    Article  CAS  Google Scholar 

  27. Fisher B, Costantino JP, Wickerham DL, Cecchini RS, Cronin WM, Robidoux A, 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. [Randomized Controlled Trial Research Support, N.I.H., Extramural]. 2005;97(22):1652–62.

    Article  CAS  Google Scholar 

  28. Cuzick J, Sestak I, Cawthorn S, Hamed H, Holli K, Howell A, et al. Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. Lancet Oncol. [Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2015;16(1):67–75.

    Article  CAS  Google Scholar 

  29. Visvanathan K, Hurley P, Bantug E, Brown P, Col NF, Cuzick J, et al. Use of pharmacologic interventions for breast cancer risk reduction: American Society of Clinical Oncology clinical practice guideline. J Clin Oncol. [Review]. 2013;31(23):2942–62.

    Article  Google Scholar 

  30. Cummings SR, Eckert S, Krueger KA, Grady D, Powles TJ, Cauley JA, 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. [Clinical Trial Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 1999;281(23):2189–97.

    Article  CAS  Google Scholar 

  31. Cauley JA, Norton L, Lippman ME, Eckert S, Krueger KA, Purdie DW, et al. Continued breast cancer risk reduction in postmenopausal women treated with Raloxifene: 4-year results from the MORE trial. Multiple outcomes of Raloxifene evaluation. Breast Cancer Res Treat. [Clinical Trial Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2001;65(2):125–34.

    Article  CAS  Google Scholar 

  32. Riggs BL, Hartmann LC. Selective estrogen-receptor modulators – mechanisms of action and application to clinical practice. N Engl J Med. [Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, P.H.S. Review]. 2003;348(7):618–29.

    Article  CAS  Google Scholar 

  33. Vogel VG. The NSABP Study of Tamoxifen and Raloxifene (STAR) trial. Expert Rev Anticancer Ther. [Review]. 2009;9(1):51–60.

    Article  CAS  Google Scholar 

  34. Mirkin S, Pickar JH. Selective estrogen receptor modulators (SERMs): a review of clinical data. Maturitas. [Review]. 2015;80(I):52–7.

    Article  CAS  Google Scholar 

  35. LaCroix AZ, Powles T, Osborne CK, Wolter K, Thompson JR, Thompson DD, et al. Breast cancer incidence in the randomized PEARL trial of Lasofoxifene in postmenopausal osteoporotic women. J Natl Cancer Inst. Randomized Controlled Trial Research Support, Non-U.S. Gov’t. 2010;102(22):1706–15.

    Article  CAS  Google Scholar 

  36. Suh N, Glasebrook AL, Palkowitz AD, Bryant HU, Burris LL, Starling JJ, et al. Arzoxifene, a new selective estrogen receptor modulator for chemoprevention of experimental breast cancer. Cancer Res. 2001;61(23):8412–5.

    CAS  PubMed  Google Scholar 

  37. Cummings SR, McClung M, Reginster JY, Cox D, Mitlak B, Stock J, et al. Arzoxifene for prevention of fractures and invasive breast cancer in postmenopausal women. J Bone Miner Res. [Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2011;26(2):397–404.

    Article  CAS  Google Scholar 

  38. Goss PE, Ingle JN, Ales-Martinez JE, Cheung AM, Chlebowski RT, Wactawski-Wende J, et al. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med. [Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2011;364(25):2381–91.

    Article  CAS  Google Scholar 

  39. Goss PE, Ingle JN, Pritchard KI, Ellis MJ, Sledge GW, Budd GT, et al. Exemestane versus Anastrozole in postmenopausal women with early breast cancer: NCIC CTG MA.27 – a randomized controlled phase III trial. J Clin Oncol. [Clinical Trial, Phase III Comparative Study Historical Article Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. 2013;31(11):1398–404.

    Article  CAS  Google Scholar 

  40. Cuzick J, Sestak I, Forbes JF, Dowsett M, Knox J, Cawthorn S, et al. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. Lancet. [Multicenter Study Randomized Controlled Trial Research Support, Non-U.S. Gov’t]. 2014;383(9922):1041–8.

    Article  CAS  Google Scholar 

  41. Dowling RJO, Zakikhani M, Fantus IG, Pollak M, Sonenberg N. Metformin inhibits mammalian target of rapamycin-dependent translation initiation in breast cancer cells. Cancer Res. 2007;67(22):10804–12.

    Article  CAS  Google Scholar 

  42. Goodwin PJ, Stambolic V. Obesity and insulin resistance in breast cancer – chemoprevention strategies with a focus on metformin. Breast. 2011;20:S31–S5.

    Article  Google Scholar 

  43. Zakikhani M, Dowling R, Fantus IG, Sonenberg N, Pollak M. Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells. Cancer Res. 2006;66(21):10269–73.

    Article  CAS  Google Scholar 

  44. Christopoulos PF, Msaouel P, Koutsilieris M. The role of the insulin-like growth factor-1 system in breast cancer. Mol Cancer. 2015;15:14.

    Google Scholar 

  45. Kleinberg DL, Axelrod D, Smith J, Singh B, Lesser M, Ameri P, et al. Breast cancer chemoprevention by IGF-I inhibition in women with atypical hyperplasia of the breast: A phase 1/2 proof of principle trial [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research. San Diego: Philadelphia (PA); 2014. AACR; Cancer Res 2014;74(19 Suppl): Abstract nr CT306. https://doi.org/10.1158/1538-7445.AM2014-CT306.

    Article  Google Scholar 

  46. Smith J, Axelrod D, Singh B, Kleinberg D. Prevention of breast cancer: the case for studying inhibition of IGF-1 actions. Ann Oncol. 2011;22:i50–i2.

    Article  Google Scholar 

  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. [Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t]. 2006;6:27.

    Article  Google Scholar 

  48. Masferrer JL, Leahy KM, Koki AT, Zweifel BS, Settle SL, Woerner BM, et al. Antiangiogenic and antitumor activities of cyclooxygenase-2 inhibitors. Cancer Res. 2000;60(5):1306–11.

    CAS  PubMed  Google Scholar 

  49. Wang DZ, DuBois RN. Cyclooxygenase-2: a potential target in breast cancer. Semin Oncol. 2004;31(1):64–73.

    Article  CAS  Google Scholar 

  50. Aktas B, Sorkin M, Pusztai L, Hofstatter EW. Uptake of exemestane chemoprevention in postmenopausal women at increased risk for breast cancer. Eur J Cancer Prev. 2016;25(1):3–8.

    Article  CAS  Google Scholar 

  51. Coopey SB, Mazzola E, Buckley JM, Sharko J, Belli AK, Kim EMH, et al. The role of chemoprevention in modifying the risk of breast cancer in women with atypical breast lesions. Breast Cancer Res Treat. 2012;136(3):627–33.

    Article  CAS  Google Scholar 

  52. Ropka ME, Keim J, Philbrick JT. Patient decisions about breast cancer chemoprevention: a systematic review and meta-analysis. J Clin Oncol. [Research Support, N.I.H., Extramural Review]. 2010;28(18):3090–5.

    Article  Google Scholar 

  53. Smith SG, Sestak I, Forster A, Partridge A, Side L, Wolf MS, et al. Factors affecting uptake and adherence to breast cancer chemoprevention: a systematic review and meta-analysis. Ann Oncol. [Meta-Analysis Research Support, Non-U.S. Gov’t Review]. 2016;27(4):575–90.

    Article  CAS  Google Scholar 

  54. Freedman AN, Yu B, Gail MH, Costantino JP, Graubard BI, Vogel VG, et al. Benefit/risk assessment for breast cancer chemoprevention with raloxifene or tamoxifen for women age 50 years or older. J Clin Oncol. [Research Support, N.I.H., Extramural Research Support, N.I.H., Intramural Research Support, U.S. Gov’t, P.H.S.]. 2011;29(17):2327–33.

    Article  CAS  Google Scholar 

  55. Hermel DJ, Wood ME, Chun J, Rounds T, Sands M, Schwartz S, et al. Multi-institutional evaluation of women at high risk of developing breast cancer. Clin Breast Cancer. 2017;17(6):427–32.

    Article  Google Scholar 

  56. Smith SG, Side L, Meisel SF, Horne R, Cuzick J, Wardle J. Clinician-reported barriers to implementing breast cancer chemoprevention in the UK: a qualitative investigation. Public Health Genomics. [Multicenter Study]. 2016;19(4):239–49.

    Article  Google Scholar 

  57. Land SR, Walcott FL, Liu Q, Wickerham DL, Costantino JP, Ganz PA. Symptoms and QOL as predictors of chemoprevention adherence in NRG oncology/NSABP trial P-1. J Natl Cancer Inst. [Clinical Trial, Phase III Multicenter Study Randomized Controlled Trial Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov’t Research Support, U.S. Gov’t, Non-P.H.S.]. 2016;108(4).

    Google Scholar 

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Authors and Affiliations

  1. Department of Surgery, Mayo Clinic, Jacksonville, FL, USA

    Jinny Gunn, E. Alexa Elder & Sarah McLaughlin

  2. Section of Surgical Oncology, Jacksonville, FL, USA

    Sarah McLaughlin

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  1. Jinny Gunn
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  2. E. Alexa Elder
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  3. Sarah McLaughlin
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Correspondence to Sarah McLaughlin .

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Editors and Affiliations

  1. Samuel Oschin Comprehensive Cancer Inst, Cedars-Sinai Medical Center, Los Angeles, CA, USA

    Farin Amersi

  2. School of Medicine, University of Washington School of Medicine, Seattle, WA, USA

    Kristine Calhoun

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Gunn, J., Alexa Elder, E., McLaughlin, S. (2018). The Role of Chemoprevention in the Prevention of Breast Cancer. In: Amersi, F., Calhoun, K. (eds) Atypical Breast Proliferative Lesions and Benign Breast Disease . Springer, Cham. https://doi.org/10.1007/978-3-319-92657-5_10

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  • DOI: https://doi.org/10.1007/978-3-319-92657-5_10

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