Breast Cancer Prevention: Current Approaches and Future Directions

Edward R Sauter, Edward R Sauter

Abstract

The topic of breast cancer prevention is very broad. All aspects of the topic, therefore, cannot be adequately covered in a single review. The objective of this review is to discuss strategies in current use to prevent breast cancer, as well as potential approaches that could be used in the future. This review does not discuss early detection strategies for breast cancer, including breast cancer screening. The breast is the most common site among women worldwide of noncutaneous cancer. Many clinical and genetic factors have been found to increase a woman's risk of developing the disease. Current strategies to decrease a woman's risk of developing breast cancer include primary prevention, such as avoiding tobacco, exogenous hormone use and excess exposure to ionizing radiation, maintaining a normal weight, exercise, breastfeeding, eating a healthy diet and minimizing alcohol intake. Chemoprevention medications are available for those at high risk, though they are underutilized in eligible women. Mastectomy and/or bilateral oophorectomy are reasonable strategies for women who have deleterious mutations in genes that dramatically increase the risk of developing cancer in either breast. There are a variety of strategies in development for the prevention of breast cancer. Personalized approaches to prevent breast cancer that are being developed focus on advances in precision medicine, knowledge of the immune system and the tumor microenvironment and their role in cancer development. Advances in our understanding of how breast cancer develops are allowing investigators to specifically target populations who are most likely to benefit. Additionally, prevention clinical trials are starting to evaluate multi-agent cancer prevention approaches, with the hope of improved efficacy over single agents. Finally, there is a push to increase the use of chemopreventive agents with proven efficacy, such as tamoxifen and raloxifene, in the prevention of breast cancer.

Keywords: Breast cancer; DNA; RNA; biomarkers; carbohydrates; proteins.

Conflict of interest statement

Conflict of Interest: No conflict of interest was declared by the author.

References

    1. DeSantis CE, Ma J, Sauer AG, Newman LA, Jemal A. Breast cancer statistics, 2017, racial disparity in mortality by state. CA Cancer J Clin. 2017;67:439–448. .
    1. WHO. Breast cancer: prevention and control. WHO publication on cancer 2013. Available from:
    1. Steele CB, Thomas CC, henley SJ, Massetti GM, Galuska DA, Agurs-Collins T, Puckett M, Richardson LC. Vital signs: trends in incidence of cancers associated with overweight and obesity-United States, 2005–2014. MMWR Morb Mortal Wkly Rep. 2017;66:1052–1058. .
    1. Pankow JS, Vachon CM, Kuni CC, King RA, Arnett DK, Grabrick DM, Rich SS, Anderson VE, Sellers TA. Genetic analysis of mammographic breast density in adult women: evidence of a gene effect. J Natl Cancer Inst. 1997;89:549–556. .
    1. Haars G, van Noord PA, van Gils CH, Grobbee DE, Peeters PH. Measurements of breast density: no ratio for a ratio. Cancer Epidemiol Biomarkers Prev. 2005;14:2634–2640. .
    1. Gail MH, Mai PL. Comparing breast cancer risk assessment models. J Natl Cancer Inst. 2010;102:665–668. .
    1. Crew KD, Albain KS, Hershman DL, Unger JM, Lo SS. How do we increase uptake of tamoxifen and other anti-estrogens for breast cancer prevention. NPJ Breast Cancer. 2017;3:20. .
    1. Surgeons ASoB. Consensus guideline on hereditary genetic testing for patients with and without breast cancer. 2017
    1. Silvestri V, Barrowdale D, Mulligan AM, Neuhausen SL, Fox S, Karlan BY, Mitchell G, James P, Thull DL, Zorn KK, Carter NJ, Nathanson KL, Domchek SM, Rebbeck TR, Ramus SJ, Nussbaum RL, Olopade OI, Rantala J, Yoon SY, Caligo MA, Spugnesi L, Bojesen A, Pedersen IS, Thomassen M, Jensen UB, Toland AE, Senter L, Andrulis IL, Glendon G, Hulick PJ, Imyanitov EN, Greene MH, Mai PL, Singer CF, Rappaport-Fuerhauser C, Kramer G, Vijai J, Offit K, Robson M, Lincoln A, Jacobs L, Machackova E, Foretova L, Navratilova M, Vasickova P, Couch FJ, Hallberg E, Ruddy KJ, Sharma P, Kim SW. Male breast cancer in BRCA1 and BRCA2 mutation carriers: pathology data from the Consortium of Investigators of Modifiers of BRCA1/2. Breast Cancer Res. 2016;18:15. .
    1. Brinton LA, Cook MB, McCormack V, Johnson KC, Olsson H, Casagrande JT, Cooke R, Falk RT, Gapstur SM, Gaudet MM, Gaziano JM, Gkiokas G, Guénel P, Henderson BE, Hollenbeck A, Hsing AW, Kolonel LN, Isaacs C, Lubin JH, Michels KB, Negri E, Parisi D, Petridou ET, Pike MC, Riboli E, Sesso HD, Snyder K, Swerdlow AJ European Rare Cancer Study Group. Trichopoulos D, Ursin G, van den Brandt PA, Van Den Eeden SK, Weiderpass E, Willett WC, Ewertz M, Thomas DB. Anthropometric and hormonal risk factors for male breast cancer: male breast cancer pooling project results. J Natl Cancer Inst. 2014;106:djt465. .
    1. WHO. Media center: fact sheet 2017, October. Obesity overweight.
    1. UK Cr. Diet and breast cancer. 2017. Available from: .
    1. Picon-Ruiz M, Morata-Tarifa C, Valle-Goffin JJ, Friedman ER, Slingerland JM. Obesity and adverse breast cancer risk and outcome: Mechanistic insights and strategies for intervention. CA Cancer J Clin. 2017;67:378–397. .
    1. Ogden CL, Carroll MD, Fryar CD, Flegal KM. Prevalence of obesity among adults and youth: United States, 2011–2014. NCHS Data Brief. 2015;219:1–8.
    1. Yang L, Colditz GA. Prevalence of Overweight and Obesity in the United States, 2007–2012. JAMA Intern Med. 2015;175:1412–1413. .
    1. Battaglini CL, Mills RC, Phillips BL, Lee JT, Story CE, Nascimento MG, Hackney AC. Twenty-five years of research on the effects of exercise training in breast cancer survivors: A systematic review of the literature. World J Clin Oncol. 2014;5:177–190. .
    1. Wu Y, Zhang D, Kang S. Physical activity and risk of breast cancer: a meta-analysis of prospective studies. Breast Cancer Res Treat. 2013;137:869–882. .
    1. NC Institute. Causes and prevention of cancer. 2017. Available from: .
    1. Shield KD, Soerjomataram I, Rehm J. Alcohol use and breast cancer: a critical review. Alcohol Clin Exp Res. 2016;40:1166–1181. .
    1. Gaudet MM, Gapstur SM, Sun J, Diver WR, Hannan LM, Thun MJ. Active smoking and breast cancer risk: original cohort data and meta-analysis. J Natl Cancer Inst. 2013;105:515–525. .
    1. AC Society. Menopausal hormone therapy and cancer risk. 2017. Available from: .
    1. Komen SG. About breast cancer and birth control pills. 2017. .
    1. Morch LS, Skovlund CW, Hannaford PC, Iversen L, Fielding S, Lidegaard O. Contemporary Hormonal Contraception and the Risk of Breast Cancer. N Engl J Med. 2017;377:2228–2239. .
    1. Kleinerman RA. Cancer risks following diagnostic and therapeutic radiation exposure in children. Pediatr Radiol. 2006;36( Suppl 2):121–125. .
    1. UNSCEAR. The United Nations Scientific Committee on the Effects of Atomic Radiation. Health Phys. 2000;79:314.
    1. Merry G, Miglioretti D, Lee C, Johnson E, Smith-Bindman R. Breast cancer risks from medical imaging including computed tomography (CT) and nuclear medicine among females enrolled in a large integrated health care system. RSNA Abstracts 2012, LL-HPS-TU3A.
    1. Moskowitz CS, Chou JF, Wolden SL, Bernstein JL, Malhotra J, Novetsky Friedman D, Mubdi NZ, Leisenring WM, Stovall M, Hammond S, Smith SA, Henderson TO, Boice JD, Hudson MM, Diller LR, Bhatia S, Kenney LB, Neglia JP, Begg CB, Robison LL, Oeffinger KC. Breast cancer after chest radiation therapy for childhood cancer. J Clin Oncol. 2014;32:2217–2223. .
    1. NC Institute. Surveillance, Epidemiology, and End Results Program. 2017. Cancer stat facts: female breast cancer.
    1. Qin W, Zhang K, Kliethermes B, Ruhlen RL, Browne EP, Arcaro KF, Sauter ER. Differential expression of cancer associated proteins in breast milk based on age at first full term pregnancy. BMC Cancer. 2012;12:100. .
    1. Chung M, Chang HR, Bland KI, Wanebo HJ. Younger women with breast carcinoma have a poorer prognosis than older women. Cancer. 1996;77:97–103.
    1. Braun S, Vogl FD, Naume B, Janni W, Osborne MP, Coombes RC, Schlimok G, Diel IJ, Gerber B, Gebauer G, Pierga JY, Marth C, Oruzio D, Wiedswang G, Solomayer EF, Kundt G, Strobl B, Fehm T, Wong GY, Bliss J, Vincent-Salomon A, Pantel K. A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med. 2005;353:793–802. .
    1. Stuebe AM, Willett WC, Xue F, Michels KB. Lactation and incidence of premenopausal breast cancer: a longitudinal study. Arch Intern Med. 2009;169:1364–1371. .
    1. Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah M, Cronin WM, Vogel V, Robidoux A, Dimitrov N, Atkins J, Daly M, Wieand S, Tan-Chiu E, Ford L, Wolmark N. 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. .
    1. Cuzick J, Sestak I, Cawthorn S, Hamed H, Holli K, Howell A, Forbes JF IBIS-I Investigators. Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. Lancet Oncol. 2015;16:67–75. .
    1. Vogel VG, Costantino JP, Wickerham DL, Cronin WM, Cecchini RS, Atkins JN, Bevers TB, Fehrenbacher L, Pajon ER, Jr, Wade JL, 3rd, Robidoux A, Margolese RG, James J, Lippman SM, Runowicz CD, Ganz PA, Reis SE, McCaskill-Stevens W, Ford LG, Jordan VC, Wolmark N 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. .
    1. Visvanathan K, Hurley P, Bantug E, Brown P, Col NF, Cuzick J, Davidson NE, Decensi A, Fabian C, Ford L, Garber J, Katapodi M, Kramer B, Morrow M, Parker B, Runowicz C, Vogel VG, 3rd, Wade JL, Lippman SM. Use of pharmacologic interventions for breast cancer risk reduction. J Clin Oncol. 2013;31:2942–2962. .
    1. Goss PE, Ingle JN, Alés-Martínez JE, Cheung AM, Chlebowski RT, Wactawski-Wende J, McTiernan A, Robbins J, Johnson KC, Martin LW, Winquist E, Sarto GE, Garber JE, Fabian CJ, Pujol P, Maunsell E, Farmer P, Gelmon KA, Tu D, Richardson H NCIC CTG MAP.3 Study Investigators. Exemestane for breast-cancer prevention in postmenopausal women. N Engl J Med. 2011;364:2381–2391. .
    1. Cuzick J, Sestak I, Forbes JF, Dowsett M, Knox J, Cawthorn S, Saunders C, Roche N, Mansel RE, von Minckwitz G, Bonanni B, Palva T, Howell A IBIS-II investigators. Anastrozole for prevention of breast cancer in high-risk postmenopausal women (IBIS-II): an international, double-blind, randomised placebo-controlled trial. Lancet. 2014;383:1041–1048. .
    1. Komen SG. Hyperplasia and breast cancer risk. 2017. Available from: .
    1. Sharko J, Belli AK, Kim EMH, Polufriaginof F, Parmigiani G, Garber JE, Smith BL, Gadd MA, Specht MC, Guidi AJ, Roche CA, Hughes KS. Clarifying the risk of breast cancer in women with atypical breast lesions. Cancer Res. 2011;71 Abstract nr S4-4.
    1. King TA, Pilewskie M, Muhsen S, Patil S, Mautner SK, Park A, Oskar S, Guerini-Rocco E, Boafo C, Gooch JC, De Brot M, Reis-Filho JS, Morrogh M, Andrade VP, Sakr RA, Morrow M. Lobular Carcinoma in Situ: A 29-Year Longitudinal Experience Evaluating Clinicopathologic Features and Breast Cancer Risk. J Clin Oncol. 2015;33:3945–3952. .
    1. Hartmann LC, Radisky DC, Frost MH, Santen RJ, Vierkant RA, Benetti LL, Tarabishy Y, Ghosh K, Visscher DW, Degnim AC. Understanding the premalignant potential of atypical hyperplasia through its natural history: a longitudinal cohort study. Cancer Prev Res (Phila) 2014;7:211–217. .
    1. Degnim AC, Dupont WD, Radisky DC, Vierkant RA, Frank RD, Frost MH, Winham SJ, Sanders ME, Smith JR, Page DL, Hoskin TL, Vachon CM, Ghosh K, Hieken TJ, Denison LA, Carter JM, Hartmann LC, Visscher DW. Extent of atypical hyperplasia stratifies breast cancer risk in 2 independent cohorts of women. Cancer. 2016;122:2971–2978. .
    1. White J. Breast density and cancer risk: what is the relationship? J Natl Cancer Inst. 2000;92:443. .
    1. Cuzick J, Warwick J, Pinney E, Warren RM, Duffy SW. Tamoxifen and breast density in women at increased risk of breast cancer. J Natl Cancer Inst. 2004;96:621–628. .
    1. Vierkant RA, Degnim AC, Radisky DC, Visscher DW, Heinzen EP, Frank RD, Winham SJ, Frost MH, Scott CG, Jensen MR, Ghosh K, Manduca A, Brandt KR, Whaley DH, Hartmann LC, Vachon CM. Mammographic breast density and risk of breast cancer in women with atypical hyperplasia: an observational cohort study from the Mayo Clinic Benign Breast Disease (BBD) cohort. BMC Cancer. 2017;17:84. .
    1. Surgeons ASoB. Performance and practice guidelines for mastectomy. 2015. Available from: .
    1. Surgeons ASoB: Five things physicians and patients should question. Available from: . Choosing Wisely 2016.
    1. Phillips KA, Milne RL, Rookus MA, Daly MB, Antoniou AC, Peock S, Frost D, Easton DF, Ellis S, Friedlander ML, Buys SS, Andrieu N, Noguès C, Stoppa-Lyonnet D, Bonadona V, Pujol P, McLachlan SA, John EM, Hooning MJ, Seynaeve C, Tollenaar RA, Goldgar DE, Terry MB, Caldes T, Weideman PC, Andrulis IL, Singer CF, Birch K, Simard J, Southey MC, Olsson HL, Jakubowska A, Olah E, Gerdes AM, Foretova L, Hopper JL. Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. J Clin Oncol. 2013;31:3091–3099. .
    1. Metcalfe KA. Oophorectomy for breast cancer prevention in women with BRCA1 or BRCA2 mutations. Womens Health (Lond) 2009;5:63–68. .
    1. Guillem JG, Wood WC, Moley JF, Berchuck A, Karlan BY, Mutch DG, Gagel RF, Weitzel J, Morrow M, Weber BL, Giardiello F, Rodriguez-Bigas MA, Church J, Gruber S, Offit K ASCO; SSO. ASCO/SSO review of current role of risk-reducing surgery in common hereditary cancer syndromes. J Clin Oncol. 2006;24:4642–4660. .
    1. NC Institute. NCI-Match Trial (Molecular Analysis for Therapy Choice) 2017. Available from: .
    1. Kensler TW, Spira A, Garber JE, Szabo E, Lee JJ, Dong Z, Dannenberg AJ, Hait WN, Blackburn E, Davidson NE, Foti M, Lippman SM. Transforming Cancer Prevention through Precision Medicine and Immuneoncology. Cancer Prev Res (Phila) 2016;9:2–10. .
    1. Lam S, Mandrekar SJ, Gesthalter Y, Allen Ziegler KL, Seisler DK, Midthun DE, Mao JT, Aubry MC, McWilliams A, Sin DD, Shaipanich T, Liu G, Johnson E, Bild A, Lenburg ME, Ionescu DN, Mayo J, Yi JE, Tazelaar H, Harmsen WS, Smith J, Spira AE, Beane J, Limburg PJ, Szabo E Cancer Prevention Network. A Randomized Phase IIb Trial of myo-Inositol in Smokers with Bronchial Dysplasia. Cancer Prev Res (Phila) 2016;9:906–914. .
    1. Services DoHaH. Pre-Cancer Atlas (PCA) Research Centers. 2017. RFA-CA-17-035.
    1. Chiang CJ, Yang YW, You SL, Lai MS, Chen CJ. Thirty-year outcomes of the national hepatitis B immunization program in Taiwan. JAMA. 2013;310:974–976. .
    1. Kimura T, McKolanis JR, Dzubinski LA, Islam K, Potter DM, Salazar AM, Schoen RE, Finn OJ. MUC1 vaccine for individuals with advanced adenoma of the colon: a cancer immunoprevention feasibility study. Cancer Prev Res (Phila) 2013;6:18–26. .
    1. Mittendorf EA, Clifton GT, Holmes JP, Schneble E, van Echo D, Ponniah S, Peoples GE. Final report of the phase I/II clinical trial of the E75 (nelipepimut-S) vaccine with booster inoculations to prevent disease recurrence in high-risk breast cancer patients. Ann Oncol. 2014;25:1735–1742. .
    1. Disis ML, Gad E, Herendeen DR, Lai VP, Park KH, Cecil DL, O’Meara MM, Treuting PM, Lubet RA. A multiantigen vaccine targeting neu, IGFBP-2, and IGF-IR prevents tumor progression in mice with preinvasive breast disease. Cancer Prev Res (Phila) 2013;6:1273–1282. .
    1. Samadder NJ, Neklason D, Kanth P, Byrne KR, Samowitz W, Jasperson K, Kohlmann W, Gammon A, Champine M, Nathan D, Boucher KM, Greene T, Pappas L, Fang JC, Valentine JF, Hagedorn C, Jones D, Tavtigian SV, Done MW, Berry T, Smith L, Larson M, Martineau L, Sample D, Christenson C, Keener M, Strait EG, McKinnon W, Greenblatt MS, Lynch PM, Burt RW, Kuwada SK. Effect of COX and EGFR inhibition on duodenal neoplasia in familial adenomatous polyposis: a randomized placebo-controlled trial. Gastroenterology. 2015;4:S93–S94. .
    1. Ropka ME, Keim J, Philbrick JT. Patient decisions about breast cancer chemoprevention: a systematic review and meta-analysis. J Clin Oncol. 2010;28:3090–3095. .
    1. Smith SG, Sestak I, Forster A, Partridge A, Side L, Wolf MS, Horne R, Wardle J, Cuzick J. Factors affecting uptake and adherence to breast cancer chemoprevention: a systematic review and meta-analysis. Ann Oncol. 2016;27:575–590. .
    1. Jin J, Sklar GE, Min Sen Oh V, Chuen Li S. Factors affecting therapeutic compliance: A review from the patient’s perspective. Ther Clin Risk Manag. 2008;4:269–286. .
    1. Mocellin S, Pilati P, Briarava M, Nitti D. Breast Cancer Chemoprevention: A Network Meta-Analysis of Randomized Controlled Trials. J Natl Cancer Inst. 2016;108 .
    1. Lee O, Page K, Ivancic D, Helenowski I, Parini V, Sullivan ME, Margenthaler JA, Chatterton RT, Jr, Jovanovic B, Dunn BK, Heckman-Stoddard BM, Foster K, Muzzio M, Shklovskaya J, Skripkauskas S, Kulesza P, Green D, Hansen NM, Bethke KP, Jeruss JS, Bergan R, Khan SA. A randomized phase II presurgical trial of transdermal 4-hydroxytamoxifen gel versus oral tamoxifen in women with ductal carcinoma in situ of the breast. Clin Cancer Res. 2014;20:3672–3682. .

Source: PubMed

3
S'abonner