Review Article

Year: 2017│Volume:5│Issue-1

Prophylactic Mastectomy: A boon or bane?

Kalaivani Annadurai1, Geetha Mani2, Raja Danasekaran2

1Associate Professor, 22Assistant Professors; Department of Community Medicine, Shri Sathya Sai Medical College & Research Institute, Kancheepuram district, Tamil Nadu

Corresponding Author:

Associate professor, department of Community Medicine,
Shri Sathya Sai Medical College & Research Institute,
Ammapettai village-603108
Thiruporur, Kancheepuram district, Tamil Nadu, India.
Mobile no.9500029829, Email address:


Globally, breast cancer is the second most common cancer next only to lung cancer and a major public health challenge to women’s health. Worldwide, breast cancer affects 1.3 million women every year which represents 23% of all cancers in women. It is estimated that by 2030 the global burden of breast cancer will increase to over 2 million new cases per year. Unlike other cancers, breast cancer is treatable if detected at an early stage. Management of women who carry a high lifetime risk for breast cancer is always an issue of debate. A number of risk-reducing treatment options with varying efficacy exist, including regular surveillance, chemoprevention, and prophylactic surgery. Prophylactic mastectomy (PM) or Risk reducing mastectomy (RRM) remains a controversial procedure as a preventive tool against breast cancer. More women are opting for prophylactic mastectomy as a risk reducing strategy for breast cancer. Prophylactic mastectomy is appropriate only for a small proportion of women who are at high risk for breast cancer. Patient misconceptions about recurrence risk and fear have been implicated in the increase in prophylactic procedures. Other possible reasons for the rise in prophylactic mastectomy are highly sensitive breast cancer screening methods, which diagnose breast cancer at earlier stages, and improved breast reconstruction techniques. With this background this paper aims to analyze the pros and cons of preventive mastectomy.

Key words: Prophylactic mastectomy, Risk reducing strategy, breast cancer.


Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer death among females worldwide. An estimated 1.38 million women across the world were diagnosed with breast cancer in 2008, accounting for nearly a quarter (23%) of all cancers diagnosed in women and represented 11% of total cancer in men and women.1The rapid development of genetic counseling clinics and better diagnostic techniques for hereditary cancers has dramatically led to the rise in statistics of women at risk and requiring prophylaxis. A number of risk-reducing treatment options with varying efficacy exist, including regular surveillance, chemoprevention, and prophylactic surgery.2Prophylactic surgeries include prophylactic mastectomy and prophylactic salphingo-oopherectomy. More women are opting to have their breasts removed to reduce the risk of cancer. Unfortunately many women who overestimate the risk of developing breast cancer undergo unnecessary surgery. There by, prophylactic mastectomy remains a controversial risk reduction measure for breast cancer.

What is prophylactic mastectomy?

Prophylactic mastectomy or Preventive mastectomy (PM) (or risk-reducing mastectomy) is the surgical removal of one or both breasts to prevent or reduce the risk of breast cancer in women who are at high risk of developing the disease.3It is of three types: total mastectomy, subcutaneous mastectomy and skin sparing mastectomy. Total mastectomy involves the removal of entire breast along with nipple. In Subcutaneous mastectomy, breast tissues are removed leaving the nipple intact. In skin sparing mastectomy, most of the skin over the breast (other than the nipple and areola) is left intact. Preventive mastectomy may be bilateral or contra lateral. It can be done along with oopherectomy, and with or without the reconstruction of breast.

Criteria for prophylactic mastectomy:

Eligibility criteria for prophylactic mastectomy are based on one of the following categories:

Uptake of prophylactic surgery:

There was a wide variation in uptake of prophylactic surgery worldwide. In a recent survey, the largest uptake of prophylactic mastectomy with breast reconstruction was found in the United States of America (36.3%).5 Average age at the time of prophylactic mastectomy/breast reconstruction among high-risk women was found to be 35-46 years (range 20-73).6-10 And they were significantly younger and with higher educational level.11,12 Mutation carriers among PM acceptors ranges from 13 to 100 % and other breast cancer risk carriers were in between 55-100%, and the majority of women who underwent PM did not have personal history of breast cancer (92-100%).7, 9,13,14 Majority (63-100%) of the high-risk women had opted for breast reconstruction after prophylactic mastectomy7,8,14,15 and 14-63% of women who underwent prophylactic mastectomy also opted for prophylactic salphingo oopherectomy.9,16,17

Increasing prophylactic mastectomy rates:

Prophylactic mastectomy with reconstruction is becoming an increasingly popular choice among women accepting for PM. Most women who are diagnosed with cancer in one breast have a very low risk of developing cancer in their other breast. Patient fear is one of the main motivational factors for prophylactic surgery without truly examining the actual chances of developing cancer.

Accepting prophylactic mastectomy was highly a personal decision. Factors that determine the high risk women to consider for prophylactic surgeries are fear, over estimation of perceived risk, personal characteristics features including her experience with cancer within her family; her role and responsibilities in her nuclear family; her values; her experiences with the medical system; and her misconception about cancer risk. Other possible reasons for the rise in prophylactic mastectomy are more sensitive breast cancer screening methods, which diagnose breast cancer at earlier stages, increased awareness, insurance coverage, underestimation of the extent of this major surgery and improved breast reconstruction techniques. High-visibility celebrities with breast cancer who have chosen to have prophylactic mastectomies are also playing an important factor for choosing the surgery.

Worry about breast cancer and perceived risk were independent predictors of prophylactic mastectomy.18-20Parenthood also plays an important role in the selection of PM. Meijers-Heijboer HJ et al reported that 61% of women with children selected risk reducing mastectomy compared with 14% women without children (odds ratio-9.43; Confidence Interval-1.92 TO 46.4;P=.006).21 Yi M et al reported that majority of patients (72%) chose to undergo contralateral PM for the following reasons: a family history of breast cancer, difficulty in surveillance, and fear of developing another breast cancer.22 An increasing trend for prophylactic mastectomy was observed. The rate of increase in prophylactic mastectomy ranges from 20% to 188%.11,12,23-25 Adherence to published consensus guidelines for the indications of prophylactic mastectomy was observed to be 97.6%.26

Among unaffected women waiting for genetic report, the rate of consideration for prophylactic mastectomy, if BRCA found to be positive varies from 19 to 23%.27,28 At the same time among unaffected high risk women, consideration range from 3 to 55%.21,29 These broad differences might be due to difference in sample size, assessment strategies ,different follow up preferences, cultural differences, differences in health-services delivery systems, differences in medical specialties which facilitated the discussions of follow-up options, or differences in the type of follow-up information provided. Many women overestimate their risk. Studies have reported that women overestimate their breast cancer risk both in genetics clinics and in general practice.30

Perceptions after surgery:

Women who undergo prophylactic bilateral mastectomy have an exaggerated perception of their breast cancer risk before surgery. About 70-100% of women who underwent prophylactic mastectomy were satisfied with the surgery7,8,10,14,31,32 and 5% reported regrets for choosing the surgery as an option.31 Generally, 48-55% of all women felt less sexually attractive after prophylactic mastectomy7,33 and 32-69% of them experienced untoward changes in their sexual relationship9,32,33 Changes in the sexual relationship seemed independent of type of PM or presence or absence of breast reconstruction.32 Around 12-53% of the women reported adverse effects on the appearance of their body i.e. were self-conscious about their appearance, felt less physically attractive, were dissatisfied with their body, as a result of prophylactic mastectomy 6,7,10,32,33 and an equal proportion of women reported a change in feelings of feminity.6,7 Dissatisfaction with the surgical scars was reported by a third to almost half of all women (33-44%) who underwent the surgery.7,33 Moreover, women without breast reconstruction were less satisfied with their bodies than women with breast reconstruction.7,32 But Brandberg Y et al. reported that majority of the women were satisfied with their surgery, but a considerable proportion reported feelings of depression and some impact on their sexuality.33

Complications of prophylactic mastectomy

It includes pain, bleeding, infection, development of scar tissue, cutaneous necrosis, capsular contractures, hematoma, implant rupture and implant malposition. Cutaneous necrosis and capsular contractures were observed in approximately 30% of cases, especially when the glandular tissue has been removed close to the dermis.34 Jose Abel de la Pen˜a-Salcedo et al reported that capsular contracture was found in 6.25% of women who underwent PM, hematoma was observed in 3.12% women, and 1.56% had infection.35 Overall one third of all women were having complications of prophylactic mastectomy.36

Efficacy of prophylactic mastectomy:

Average gain in life expectancy ranges from 2.8 to 11.7 years depends upon her cancer risks and her age.37,38 Gain in life expectancy declined with the age of the woman at the time of surgery. Gain was minimal for women aged 60 years and older. It was demonstrated that risk reducing mastectomy was cost effective compared to other medical interventions. The incremental cost per life year saved, ranges from $800 to $73,755 depends upon age and other risk status.39

Table 1: Efficacy of Prophylactic mastectomy (PM)

To View the Source

Most studies concur that prophylactic mastectomy provides upto 100% reduction.

Ethical issues in prophylactic mastectomy:

The procedures do not completely eradicate cancer risk because, often, not all the tissues at risk are removed. It is also important to keep in mind that prophylactic mastectomy doesn’t guarantee a cancer-free future. There are four main ethical issues. First of all, it’s a risky condition, not a disease for which surgery is a prophylactic option. Having one or both breasts removed is a major surgery. Some encourage the surgery as a protective measure, while others believe that there is no sufficient evidence to support its benefits. Secondly, the cause of the risk is a genetic factor and some might argue about genetic ‘exceptionalism’. Thirdly, there is no organ as, connected to feminity, sensuality, sexuality, adulthood and motherhood as the breast. Lastly, making tough and complex choices requires assistance from ethics. Areas of agreement: Among ethical principles, western countries often rely on autonomy. Area of controversy: In France during 1998, national recommendations set a list of criteria to fulfill, reducing autonomy.45

Alternative risk reduction strategies:

These include regular surveillance and chemoprevention. Regular surveillance includes monthly breast self-examinations, clinical breast examination, periodic mammograms (conventional or digital), automated whole breast ultrasound, molecular breast imaging and Magnetic Resonance Imaging (MRI). Newer imaging techniques such as digital tomosynthesis, positron emission mammography, Vibro-acoustography, breast computerized tomography and 3D whole breast ultrasound are under evaluation. Chemo-preventions using Tamoxifen or Raloxifene like medication are used to reduce the breast cancer risk.

Table 2: Summary of alternate risk reduction strategies

To View the Source

Each risk reduction measure is having its own merits and demerits. Relying on single method is also not currently indicated in any literature.

Genetic counseling:

Before prophylactic mastectomy, efforts must be made to correct any overestimation of risk and also to allay excessive anxiety through genetic counseling. This counseling should include the ascertainment of medical and family histories, determination and communication of cancer risk, assessment of risk perception, education regarding the genetics of breast cancer and the necessary follow-up. Psychological assessment may also be warranted. The genetic counselor should provide an individualized estimate of a woman’s risk of breast cancer and discuss other preventive options. And the woman should be encouraged to take her time to consider a decision. Reports from Van Dijk et al19 states that before the counseling, 83% of the low-risk women overestimated their risk and after counseling 56% overestimated their risk. Perceived risk was found to be decreased after the counseling session.


Prophylactic mastectomy is becoming an increasingly frequent procedure. There is plenty of evidence that prophylactic mastectomy lowers the risk of breast cancer in at least 95% of the high-risk population. Although prophylactic mastectomy may be appropriate in women at high risk of developing breast cancer, it is perhaps less so in those who have a moderately increased risk. Such moderate-risk women are likely to get benefit from interventions aimed at reducing breast cancer anxiety and correction of exaggerated breast cancer risk perceptions. Cancer risk assessment is an important decision-making tool for women considering irreversible risk-reducing surgery. So, proper risk assessment and genetic counseling is necessary to make a correct decision for those at increased risk of breast cancer.


  1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. GLOBOCAN 2008 v1.2, Cancer Incidence and Mortality Worldwide: IARC CancerBase No. 10 [Internet]. Lyon, France: International Agency for Research on Cancer, 2010. Available from: Last accessed on 14th July 2016.

  2. Burke W, Daly M, Garber J, Botkin J, Kahn MJ, Lynch P, McTiernan A, et al. Recommendations for follow-up care of individuals with an inherited predisposition to cancer. II. BRCA1 and BRCA2. JAMA 1997;77:997-1003.

  3. Singletary SE. Techniques in surgery: Therapeutic and prophylactic mastectomy. In: Harris JR, Lippman ME, Morrow M, Osborn CK, editors. Diseases of the Breast. 3rd ed. Philadelphia: Lippincott Williams and Wilkins, 2004.

  4. Lostumbo L, Carbine NE, Wallace J. Prophylactic mastectomy for the prevention of breast cancer. Cochrane Database of Systematic Reviews 2010, Issue 11.

  5. Metcalfe KA, Birenbaum-Carmeli D, Lubinski J, Gronwald J, Lynch H, Moller P et al. International variation in rates of uptake of preventive options in BRCA1 and BRCA2 mutation carriers. Int J Cancer 2008; 122: 2017-22.

  6. Frost MH, Schaid DJ, Sellers TA, Slezak JM, Arnold PG, Woods JE, et al. Long-term satisfaction and psychological and social function following bilateral prophylactic mastectomy. JAMA. 2000; 284: 319-24.

  7. Hopwood P, Lee A, Shenton A, Baildam A, Brain A, Lalloo F, et al. Clinical follow-up after bilateral risk reducing prophylactic mastectomy: mental health and body image outcomes. Psycho-Oncology 2000; 9: 462-72.

  8. Josephson U, Wickman M, Sandelin K. Initial experiences of women from hereditary breast cancer families after bilateral prophylactic mastectomy: a retrospective study. Eur J Surg Oncol 2000; 26: 351-6.

  9. Lodder LN, Frets PG, Trijsburg RW, Meijers-Heijboer EJ, Klijn JG, Seynaeve C et al. One year follow-up of women opting for presymptomatic testing for BRCA1 and BRCA2: emotional impact of the test outcome and decisions on risk management (surveillance or prophylactic surgery). Breast Cancer Res Treat 2002; 73: 97-112.

  10. Metcalfe KA, Semple JL, Narod SA. Satisfaction with breast reconstruction in women with bilateral prophylactic mastectomy: a descriptive study. Plast Reconstr Surg 2004; 114: 360-6.

  11. Jones NB, Wilson J, Kotur L, Stephens J, Farrar WB, Agnese DM. Contralateral prophylactic mastectomy for unilateral breast cancer: an increasing trend at a single institution. Ann Surg Oncol.2009;16:2691-6

  12. Tuttle TM, Jarosek S, Habermann EB, Arrington A, Abraham A, Morris TJ et al. Increasing Rates of Contralateral Prophylactic Mastectomy Among Patients With Ductal Carcinoma In Situ J. Clin. Oncology 2009;27:1362-7

  13. Meijers-Heijboer EJ, Brekelmans CTM, Menke-Pluymers, M, Seynaeve C, Baalbergen A, Burger C et al. Use of Genetic Testing and Prophylactic Mastectomy and Oophorectomy in Women with Breast or Ovarian Cancer from Families with a BRCA1 or BRCA2 Mutation. J Clin Oncol 2003; 21: 1675-81.

  14. Geiger AM, Nekhlyudov L, Herrinton LJ, Rolnick SJ, Greene SM, West CN et al. Quality of life after bilateral prophylactic mastectomy.Annals of Surgical Oncology 2007; 14: 686-94.

  15. Bebbington Hatcher M, Fallowfield L, A'Hern R. The psychosocial impact of bilateral prophylactic mastectomy: prospective study using questionnaires and semistructured interviews. BMJ 2001; 322:1-6.

  16. Madalinska JB, Hollenstein J, Bleiker E, van Beurden M, Valdimarsdottir HB, Massuger LF et al. Quality-of-life effects of prophylactic salpingooophorectomy versus gynecologic screening among women at increased risk of hereditary ovarian cancer. J Clin Oncol 2005; 23: 6890-8.

  17. Madalinska JB, van Beurden M, Bleiker EMA, Valdimarsdottir HB, Brandsma LL, Massuger LF,et al. Predictors of prophylactic bilateral salpingooophorectomy compared with gynecologic screening use in BRCA1/2 mutation carriers. J Clin Oncol 2007; 25: 301-7.

  18. Yi M, Hunt KK, Arun BK, Bedrosian I, Barrera AG, Do KA et al. Factors affecting the decision of breast cancer patients to undergo contralateral prophylactic mastectomy. Cancer Prev Res 2010;3:1026.

  19. Van Dijk S, van Dijk S, Otten W, Zoeteweij MW, Timmermans DRM, van Asperen CJ, Breuning MH et al. Genetic counseling and the intention to undergo prophylactic mastectomy: effects of a breast cancer risk assessment British Journal of Cancer.2003; 88, 1675–81.

  20. Kelly A, Metcalfe, Steven A. Narod. Breast Cancer Risk Perception Among Women Who Have Undergone Prophylactic Bilateral Mastectomy. JNCI J Natl Cancer Inst .2002;94:1564-9.

  21. Meijers-Heijboer HJ, van Geel B, van Putten WL, Henzen-Logmans SC, Seynaeve C, Menke-Pluymers MB et al. Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med 2001;345:159–64.

  22. Yi M, Meric-Bernstam F, Middleton LP, Arun BK, Bedrosian I, Babiera GV, et al. Predictors of contralateral breast cancer in patients with unilateral breast cancer undergoing contralateral prophylactic mastectomy. Cancer.2009;115:962-71.

  23. Tuttle TM, Habermann EB, Grund EH, Morris TJ, Virnig BA. Increasing use of contralateral prophylactic mastectomy for breast cancer patients: A trend toward more aggressive surgical treatment. J Clin Oncol 2007;25:5203–9.

  24. Sorbero ME, Dick AW, Beckjord EB, Ahrendt G. Diagnostic breast magnetic resonance imaging and contralateral prophylactic mastectomy. Ann Surg Oncol 2009;16:1597–605.

  25. Stucky CC, Gray RJ, Wasif N, Dueck AC, Pockaj BA. Increase in contralateral prophylactic mastectomy: Echoes of a bygone era? Surgical trends for unilateral breast cancer. Ann Surg Oncol 2010;17:330-7.

  26. Hoover DJ, Paragi PR, Santoro E, Schafer S, Chamberlain RS. Prophylactic mastectomy in high risk patients: a practice-based review of the indications. Do we follow guidelines? Breast Dis. 2010;31:19-27.

  27. Eisinger F, Julian-Reynier C, Sobol H, Stoppa-Lyonnet D, Lasset C, Nogues C. Acceptability of prophylactic mastectomy in cancer-prone women. JAMA 2000;283:202–3.

  28. Meiser B, Butow P, Friedlander M, Schnieden V, Gattas M, Kirk J et al. Intention to undergo prophylactic bilateral mastectomy in women at increased risk of developing hereditary breast cancer. J Clin Oncol 2000;18:2250–7.

  29. Lerman C, Narod S, Schulman K, Hughes C, Gomez-Caminero A, Bonney G et al. BRCA1 testing in families with hereditary breast–ovarian cancer. A prospective study of patient decision making and outcomes. JAMA 1996;275:1885–92.

  30. Watson M, Duvivier V, Wade Walsh M, Ashley S, Davidson J, Papaikonomou M, et al. Family history of breast cancer: what do women understand and recall about their genetic risk? J Med Genet 1998;35:731–8.

  31. Borgen PI, Hill AD, Tran KN, Van Zee KJ, Massie MJ, Payne D, et al. Patient regrets after bilateral prophylactic mastectomy. Ann Surg Oncol.1998; 5: 603-6.

  32. Metcalfe KA, Esplen MJ, Goel V, Narod SA. Psychosocial functioning in women who have undergone bilateral prophylactic mastectomy. Psycho-Oncology 2004; 13: 14-25.

  33. Brandberg Y, Sandelin K, Erikson S, Jurell G, Liljegren A, Lindblom A et al. Psychological reactions, quality of life, and body image after bilateral prophylactic mastectomy in women at high risk for breast cancer: a prospective 1-year follow up study. J Clin Oncol 2008; 26: 3943-9.

  34. Pennisi VR, Capozzi A. Subcutaneous mastectomy data: a final statistical analysis of 1500 patients. Aesth Plast Surg 1989;13, 15-21.

  35. Jose Abel de la Pena-Salcedo, Miguel Angel Soto-Miranda, Jose Fernando Lopez-Salguero. Prophylactic Mastectomy: Is It Worth It? Aesth Plast Surg 2012;36:140-8.

  36. Heemskerk-Gerritsen BAM, Brekelmans CTM, Menke-Pluymers MBE, van Geel AN, Tilanus-Linthorst MMA, Bartels CCM et al. Prophylactic mastectomy in BRCA1/2 mutation carriers and women at risk of hereditary breast cancer: long-term experiences at the Rotterdam Family Cancer Clinic. Ann Surg Oncol 2007; 14: 3335-44.

  37. Grann VR, Jacobson JS, Whang W, Hershman D, Heitjan DF, Antman KH, et al. Prevention with tamoxifen or other hormones versus prophylactic surgery in BRCA1/2-positive women: a decision analysis. Cancer J Sci Am 2000;6:13–20.

  38. Van Roosmalen MS, Verhoef LC, Stalmeier PF, Hoogerbrugge N, van Daal WA. Decision analysis of prophylactic surgery or screening for BRCA mutation carriers: a more prominent role for oophorectomy. J Clin Oncol.2002; 20:2092–100

  39. Anderson K, Jacobson JS, Heitjan DF, Zivin JG, Hershman D, Neugut AI, et al. Cost-effectiveness of preventive strategies for women with a BRCA1 or a BRCA2 mutation. Ann Intern Med. 2006;144:397-406.

  40. Kaas, R, Verhoef S, Wesseling J, Rookus, MA, Oldenburg HS, Peeters, MJV et al. Prophylactic mastectomy in BRCA1 and BRCA2 mutation carriers: very low risk for subsequent breast cancer. Ann Surg. 2010;251:488-92.

  41. Domchek SM, Friebel TM, Singer CF, Evans DG, Lynch HT, Isaacs C et al. Association of risk reducing surgery in BRCA1 or BRCA 2 mutation carriers with cancer risk and mortality. JAMA. 2010;304:967-975.

  42. Heemskerk-Gerritsen BA, Menke-Pluijmers MB, Jager A, Tilanus-Linthorst MM, Koppert LB, Obdeijn IM et al. Substantial breast cancer risk reduction and potential survival benefit after bilateral mastectomy when compared with surveillance in healthy BRCA1 and BRCA2 mutation carriers: a prospective analysis. Ann Oncol. 2013;24:2029-35

  43. Skytte, AB, Crüger D, Gerster M, Laenkholm AV, Lang C, Brøndum-Nielsen K et al. Breast cancer after bilateral risk-reducing mastectomy. Clin Genet. 2011;79:431-7.

  44. Arver B, Isaksson K, Atterhem H, Baan A, Bergkvist L, Brandberg Y,et al. Bilateral prophylactic mastectomy in Swedish women at high risk of breast cancer: a national survey. Ann Surg. 2011;253:1147-54.

  45. Eisinger F. Prophylactic mastectomy: ethical issues. Br Med Bull. 2007; 81-82: 7-19.

  46. Kösters J.P, Gøtzsche P.C. Regular Self-Examination or Clinical Examination for Early Detection of Breast Cancer; Int. J. Epidemiol. 2008; 37: 1217-1219.

  47. Bobo JK, Lee NC, Thames SF. Findings from 752 081 clinical breast examinations reported to a national screening program from 1996 through 1998. J Natl Cancer Inst 2000; 92: 971–976.

  48. 48.
  49. Alexander FE, Anderson TJ, Brown HK, Forrest APM, Hepburn W, Kirkpatrick AE et al. The Edinburgh randomised trial of breast cancer screening: results after 10 years of follow-up. Br J Cancer 1994;70:542–8.

  50. Shapiro S. Periodic screening for breast cancer: the HIP Randomized Controlled Trial. Health Insurance Plan. J Natl Cancer Inst Monogr 1997;22: 27–30.

  51. Fracheboud J, de Koning HJ, Beemsterboer PM, Boer R, Hendriks JH, Verbeek AL et al. Nation-wide breast cancer screening in The Netherlands: results of initial and subsequent screening 1990-1995. National Evaluation Team for Breast Cancer Screening. Int J Cancer 1998; 75: 694–698.
  52. Breen N, Yabroff KR, Meissner HI. What proportion of breast cancers are detected by mammography in the United States? Cancer Detect Prev 2007;31:220-4.

  53. 52.
  54. Kuhl CK, Schrading S, Leutner CC, Morakkabati-Spitz N, Wardelmann E, Fimmers R. et al. Mammography, Breast Ultrasound, and Magnetic Resonance Imaging for Surveillance of Women at High Familial Risk for Breast Cancer. J Clin Oncol 2005;23:8469-76.

  55. Fisher B, Costantino J P, Wickerham D L, Redmond C K, Kavanah M, Cronin W 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: 1371–88.

  56. Veronesi U, Maisonneuve P, Costa A, Sacchini V, Maltoni C, Robertson C et al. Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomized trial. Lancet 1998; 352: 93–7.

  57. King MC, Wieand S, Hale K, Lee M, Walsh T, Owens K, Tait J et al. Tamoxifen and breast cancer incidence among women with inherited mutations in BRCA1 and BRCA2. JAMA 2001; 286: 2251–6.

  58. 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. JAMA 1999; 281: 2189–97. Erratum JAMA 1999;282: 2124.

  59. World health organization. EMRO Technical Publications Series 30. Guidelines for the early detection and screening of breast cancer. 2006. Available from Accessed on 21st August 2016.