Options for the primary prevention of breast cancer include risk-reducing agents (hormone therapies) and surgery (mastectomy and salpingo-oophorectomy). These options should be discussed with women at risk for breast cancer, and decisions should be based on shared decision-making.
Women should be advised of healthy lifestyle measures that may reduce their risk, such as limiting alcohol consumption, keeping physically active, maintaining a healthy weight, and, if appropriate, breastfeeding.
Breast cancer risk assessment
Risk assessment should be used to identify women at higher risk, and guide screening, risk reduction strategies, and genetic evaluation.[54]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer risk reduction [internet publication].
https://www.nccn.org/guidelines/category_2
[102]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer screening and diagnosis [internet publication].
https://www.nccn.org/guidelines/category_2
A validated assessment tool may be used to estimate a woman's risk of developing invasive breast cancer:[54]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer risk reduction [internet publication].
https://www.nccn.org/guidelines/category_2
[102]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer screening and diagnosis [internet publication].
https://www.nccn.org/guidelines/category_2
US guidelines recommend clinical assessment by age 25 years for all women.[102]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer screening and diagnosis [internet publication].
https://www.nccn.org/guidelines/category_2
[103]Monticciolo DL, Newell MS, Moy L, et al. Breast cancer screening for women at higher-than-average risk: updated recommendations from the ACR. J Am Coll Radiol. 2023 Sep;20(9):902-14.
http://www.ncbi.nlm.nih.gov/pubmed/37150275?tool=bestpractice.com
[104]Committee on Practice Bulletins - Gynecology. Practice bulletin number 179: breast cancer risk assessment and screening in average-risk women. Obstet Gynecol. 2017 Jul;130(1):e1-16.
http://www.ncbi.nlm.nih.gov/pubmed/28644335?tool=bestpractice.com
[105]Expert Panel on Breast Imaging, Niell BL, Jochelson MS, et al. ACR appropriateness criteria® female breast cancer screening: 2023 update. J Am Coll Radiol. 2024 Jun;21(6s):S126-43.
https://www.jacr.org/article/S1546-1440(24)00260-6/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/38823941?tool=bestpractice.com
Clinical assessment should include risk assessment, counselling on breast awareness and healthy lifestyle, and may include a breast exam.
Risk-reduction options should be discussed with women at increased risk of breast cancer who have a life expectancy ≥10 years, including those who have:[54]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer risk reduction [internet publication].
https://www.nccn.org/guidelines/category_2
[102]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer screening and diagnosis [internet publication].
https://www.nccn.org/guidelines/category_2
[106]Visvanathan K, Fabian CJ, Bantug E, et al. Use of endocrine therapy for breast cancer risk reduction: ASCO clinical practice guideline update. J Clin Oncol. 2019 Nov 20;37(33):3152-65.
https://ascopubs.org/doi/full/10.1200/JCO.19.01472
http://www.ncbi.nlm.nih.gov/pubmed/31479306?tool=bestpractice.com
≥20% lifetime risk of breast cancer calculated using a validated risk assessment tool that is primarily based on family history (e.g., BRCAPro, Tyrer-Cuzick, BOADICEA/CanRisk), or
A history of radiotherapy with exposure to breast tissue between age 10 and 30 years, or
A personal history of lobular carcinoma in situ, or atypical ductal or lobular hyperplasia, or
A strong family history of breast cancer or a known or likely pathogenic variant associated with increased risk for breast cancer (e.g., BRCA1, BRCA2, TP53, PALB2, PTEN, STK11, or CDH1), or
A 5-year breast cancer risk ≥1.7% using Gail's model (age ≥35 years); or 10-year risk of ≥5% using Tyrer-Cuzick model.
Risk-reducing agents
Selective oestrogen receptor modulators (tamoxifen and raloxifene) and aromatase inhibitors (exemestane and anastrozole) are recommended as risk-reducing agents for women aged ≥35 years at increased risk for invasive oestrogen receptor-positive breast cancer.[54]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer risk reduction [internet publication].
https://www.nccn.org/guidelines/category_2
[106]Visvanathan K, Fabian CJ, Bantug E, et al. Use of endocrine therapy for breast cancer risk reduction: ASCO clinical practice guideline update. J Clin Oncol. 2019 Nov 20;37(33):3152-65.
https://ascopubs.org/doi/full/10.1200/JCO.19.01472
http://www.ncbi.nlm.nih.gov/pubmed/31479306?tool=bestpractice.com
[107]US Preventive Services Task Force, Owens DK, Davidson KW, et al. Medication use to reduce risk of breast cancer: US Preventive Services Task Force recommendation statement. JAMA. 2019 Sep 3;322(9):857-67.
https://jamanetwork.com/journals/jama/fullarticle/2749221
http://www.ncbi.nlm.nih.gov/pubmed/31479144?tool=bestpractice.com
[108]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 Sep 16;90(18):1371-88.
http://www.ncbi.nlm.nih.gov/pubmed/9747868?tool=bestpractice.com
[109]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 Nov 16;97(22):1652-62.
https://academic.oup.com/jnci/article/97/22/1652/2521468
http://www.ncbi.nlm.nih.gov/pubmed/16288118?tool=bestpractice.com
[110]Cuzick J, Sestak I, Cawthorn S, et al. Tamoxifen for prevention of breast cancer: extended long-term follow-up of the IBIS-I breast cancer prevention trial. Lancet Oncol. 2015 Jan;16(1):67-75.
https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)71171-4/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/25497694?tool=bestpractice.com
[111]Mocellin S, Goodwin A, Pasquali S. Risk-reducing medications for primary breast cancer: a network meta-analysis. Cochrane Database Syst Rev. 2019 Apr 29;(4):CD012191.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012191.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/31032883?tool=bestpractice.com
[112]Nelson HD, Fu R, Zakher B, Pappas M, et al. Medication use for the risk reduction of primary breast cancer in women: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2019 Sep 3;322(9):868-86.
https://jamanetwork.com/journals/jama/fullarticle/2749220
http://www.ncbi.nlm.nih.gov/pubmed/31479143?tool=bestpractice.com
[
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How do aromatase inhibitors compare with tamoxifen in women with increased risk of breast cancer?/cca.html?targetUrl=https://www.cochranelibrary.com/cca/doi/10.1002/cca.2568/fullShow me the answer
For pre-menopausal women (≥35 years) at increased risk of breast cancer, tamoxifen is recommended. Tamoxifen is teratogenic and should be avoided in pregnancy or in women planning a pregnancy.[54]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer risk reduction [internet publication].
https://www.nccn.org/guidelines/category_2
[106]Visvanathan K, Fabian CJ, Bantug E, et al. Use of endocrine therapy for breast cancer risk reduction: ASCO clinical practice guideline update. J Clin Oncol. 2019 Nov 20;37(33):3152-65.
https://ascopubs.org/doi/full/10.1200/JCO.19.01472
http://www.ncbi.nlm.nih.gov/pubmed/31479306?tool=bestpractice.com
Tamoxifen, raloxifene, exemestane, or anastrozole are options for post-menopausal women.[54]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer risk reduction [internet publication].
https://www.nccn.org/guidelines/category_2
[106]Visvanathan K, Fabian CJ, Bantug E, et al. Use of endocrine therapy for breast cancer risk reduction: ASCO clinical practice guideline update. J Clin Oncol. 2019 Nov 20;37(33):3152-65.
https://ascopubs.org/doi/full/10.1200/JCO.19.01472
http://www.ncbi.nlm.nih.gov/pubmed/31479306?tool=bestpractice.com
Exemestane and anastrozole are not currently approved by the US Food and Drug Administration (FDA) for breast cancer risk reduction.
Risks and benefits of risk-reduction agents should be discussed, including adverse effects and age-dependent risks, and a shared decision made. The National Comprehensive Cancer Network (NCCN) advises that tamoxifen is a superior choice of risk reduction agent for most post-menopausal women. However, consideration of adverse effects may lead to the choice of raloxifene over tamoxifen for some patients.[54]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer risk reduction [internet publication].
https://www.nccn.org/guidelines/category_2
[113]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 Jun 21;295(23):2727-41.
https://jamanetwork.com/journals/jama/fullarticle/203040
http://www.ncbi.nlm.nih.gov/pubmed/16754727?tool=bestpractice.com
[114]Vogel VG, Costantino JP, Wickerham DL, 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). 2010 Jun;3(6):696-706.
https://www.doi.org/10.1158/1940-6207.CAPR-10-0076
http://www.ncbi.nlm.nih.gov/pubmed/20404000?tool=bestpractice.com
NCCN guidelines strongly recommend a risk-reducing agent for patients with atypical hyperplasia (both ductal and lobular types) and lobular carcinoma in situ, who are at high risk of developing invasive breast cancer.[54]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer risk reduction [internet publication].
https://www.nccn.org/guidelines/category_2
The USPSTF specifically recommends against the routine use of risk-reducing agents for women who are not at increased risk for breast cancer.[107]US Preventive Services Task Force, Owens DK, Davidson KW, et al. Medication use to reduce risk of breast cancer: US Preventive Services Task Force recommendation statement. JAMA. 2019 Sep 3;322(9):857-67.
https://jamanetwork.com/journals/jama/fullarticle/2749221
http://www.ncbi.nlm.nih.gov/pubmed/31479144?tool=bestpractice.com
Investigations before starting a risk-reducing agent
Women with an intact uterus require a gynaecological evaluation before starting tamoxifen, to ensure there is no abnormal uterine bleeding that requires further investigation.
Post-menopausal women require an assessment of bone density (dual energy x-ray absorptiometry [DXA]) before treatment and should be offered raloxifene or tamoxifen in preference to aromatase inhibitors if they have low bone mineral density.[54]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer risk reduction [internet publication].
https://www.nccn.org/guidelines/category_2
Women who do not desire risk-reducing therapy should be invited for screening according to national guidelines.
Risk-reducing mastectomy
Risk-reducing mastectomy should be discussed with women who have:[18]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: breast, ovarian, and pancreatic [internet publication].
https://www.nccn.org/guidelines/category_2
[54]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer risk reduction [internet publication].
https://www.nccn.org/guidelines/category_2
[115]Sessa C, Balmaña J, Bober SL, et al. Risk reduction and screening of cancer in hereditary breast-ovarian cancer syndromes: ESMO clinical practice guideline. Ann Oncol. 2023 Jan;34(1):33-47.
https://www.annalsofoncology.org/article/S0923-7534(22)04193-X/fulltext
A known or likely pathogenic genetic variant in a high-penetrance breast cancer susceptibility gene (e.g., BRCA1, BRCA2, TP53, PALB2, PTEN, STK11, or CDH1)
A strong family history
Prior radiotherapy with exposure to breast tissue at aged <30 years.
Prophylactic mastectomy in BRCA carriers is associated with reduced breast cancer incidence and reduced breast cancer mortality.[116]Owens DK, Davidson KW, Krist AH, et al; US Preventive Services Task Force. Risk assessment, genetic counseling, and genetic testing for BRCA-related cancer: US Preventive Services Task Force recommendation statement. JAMA. 2019 Aug 20;322(7):652-65.
https://jamanetwork.com/journals/jama/fullarticle/2748515
http://www.ncbi.nlm.nih.gov/pubmed/31429903?tool=bestpractice.com
Risk-reducing mastectomy is most beneficial when carried out in women aged between 30 and 55 years.[115]Sessa C, Balmaña J, Bober SL, et al. Risk reduction and screening of cancer in hereditary breast-ovarian cancer syndromes: ESMO clinical practice guideline. Ann Oncol. 2023 Jan;34(1):33-47.
https://www.annalsofoncology.org/article/S0923-7534(22)04193-X/fulltext
Women considering surgery should undergo multi-disciplinary evaluation and receive counselling on the potential psychosocial impact of risk-reducing mastectomy. Immediate breast reconstruction is an option for many women undergoing risk-reducing mastectomy.[54]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer risk reduction [internet publication].
https://www.nccn.org/guidelines/category_2
Nipple-sparing mastectomy may be an alternative option to total mastectomy.[115]Sessa C, Balmaña J, Bober SL, et al. Risk reduction and screening of cancer in hereditary breast-ovarian cancer syndromes: ESMO clinical practice guideline. Ann Oncol. 2023 Jan;34(1):33-47.
https://www.annalsofoncology.org/article/S0923-7534(22)04193-X/fulltext
For women who decline risk-reducing mastectomy, risk-reducing agents may be considered, and recommendations for screening of high-risk women should be followed.[18]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: breast, ovarian, and pancreatic [internet publication].
https://www.nccn.org/guidelines/category_2
[115]Sessa C, Balmaña J, Bober SL, et al. Risk reduction and screening of cancer in hereditary breast-ovarian cancer syndromes: ESMO clinical practice guideline. Ann Oncol. 2023 Jan;34(1):33-47.
https://www.annalsofoncology.org/article/S0923-7534(22)04193-X/fulltext
See Screening.
Contralateral prophylactic mastectomy is not recommended for patients diagnosed with unilateral breast cancer, unless they already meet criteria for risk-reducing mastectomy based on high familial or genetic risk.[117]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer [internet publication].
https://www.nccn.org/professionals/physician_gls/default.aspx
One meta-analysis found that there was no absolute reduction in the risk of metachronous contralateral breast cancer in patients who received a contralateral prophylactic mastectomy, compared with those who did not have the procedure. In patients with elevated familial or genetic risk, contralateral prophylactic mastectomy significantly decreased the risk of metachronous contralateral breast cancer, compared with no procedure, but there was no improvement in breast cancer mortality or overall survival.[118]Fayanju OM, Stoll CR, Fowler S, et al. Contralateral prophylactic mastectomy after unilateral breast cancer: a systematic review and meta-analysis. Ann Surg. 2014 Dec;260(6):1000-10.
http://www.ncbi.nlm.nih.gov/pubmed/24950272?tool=bestpractice.com
Risk-reducing salpingo-oophorectomy
While risk-reducing mastectomy has been found to decrease breast cancer risk by >90% in high-risk patients, the role of risk-reducing bilateral salpingo-oophorectomy (RRSO) in reducing the risk of breast cancer remains uncertain.[119]Rebbeck TR, Friebel T, Lynch HT, et al. Bilateral prophylactic mastectomy reduces breast cancer risk in BRCA1 and BRCA2 mutation carriers: the PROSE Study Group. J Clin Oncol. 2004 Mar 15;22(6):1055-62.
https://ascopubs.org/doi/10.1200/JCO.2004.04.188
http://www.ncbi.nlm.nih.gov/pubmed/14981104?tool=bestpractice.com
[120]Hartmann LC, Schaid DJ, Woods JE, et al. Efficacy of bilateral prophylactic mastectomy in women with a family history of breast cancer. N Engl J Med. 1999 Jan 14;340(2):77-84.
https://www.nejm.org/doi/full/10.1056/NEJM199901143400201
http://www.ncbi.nlm.nih.gov/pubmed/9887158?tool=bestpractice.com
[121]Meijers-Heijboer H, van Geel B, van Putten WL, et al. Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation. N Engl J Med. 2001 Jul 19;345(3):159-64.
https://www.nejm.org/doi/full/10.1056/NEJM200107193450301
http://www.ncbi.nlm.nih.gov/pubmed/11463009?tool=bestpractice.com
[122]Kauff ND, Domchek SM, Friebel TM, et al. Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: a multicenter, prospective study. J Clin Oncol. 2008 Mar 10;26(8):1331-7.
https://ascopubs.org/doi/10.1200/JCO.2007.13.9626
http://www.ncbi.nlm.nih.gov/pubmed/18268356?tool=bestpractice.com
[123]Domchek SM, Friebel TM, Singer CF, et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA. 2010 Sep 1;304(9):967-75.
https://jamanetwork.com/journals/jama/fullarticle/186510
http://www.ncbi.nlm.nih.gov/pubmed/20810374?tool=bestpractice.com
[124]Eleje GU, Eke AC, Ezebialu IU, et al. Risk-reducing bilateral salpingo-oophorectomy in women with BRCA1 or BRCA2 mutations. Cochrane Database Syst Rev. 2018 Aug 24;(8):CD012464.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012464.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/30141832?tool=bestpractice.com
[125]Heemskerk-Gerritsen BA, Seynaeve C, van Asperen CJ, et al. Breast cancer risk after salpingo-oophorectomy in healthy BRCA1/2 mutation carriers: revisiting the evidence for risk reduction. J Natl Cancer Inst. 2015 Mar 18;107(5):djv033.
http://www.ncbi.nlm.nih.gov/pubmed/25788320?tool=bestpractice.com
[126]Terry MB, Daly MB, Phillips KA, et al. Risk-reducing oophorectomy and breast cancer risk across the spectrum of familial risk. J Natl Cancer Inst. 2019 Mar 1;111(3):331-4.
https://academic.oup.com/jnci/article/111/3/331/5212812
http://www.ncbi.nlm.nih.gov/pubmed/30496449?tool=bestpractice.com
Early studies in women with BRCA mutations reported a reduction in risk of breast cancer of approximately 50% with RRSO.[122]Kauff ND, Domchek SM, Friebel TM, et al. Risk-reducing salpingo-oophorectomy for the prevention of BRCA1- and BRCA2-associated breast and gynecologic cancer: a multicenter, prospective study. J Clin Oncol. 2008 Mar 10;26(8):1331-7.
https://ascopubs.org/doi/10.1200/JCO.2007.13.9626
http://www.ncbi.nlm.nih.gov/pubmed/18268356?tool=bestpractice.com
[123]Domchek SM, Friebel TM, Singer CF, et al. Association of risk-reducing surgery in BRCA1 or BRCA2 mutation carriers with cancer risk and mortality. JAMA. 2010 Sep 1;304(9):967-75.
https://jamanetwork.com/journals/jama/fullarticle/186510
http://www.ncbi.nlm.nih.gov/pubmed/20810374?tool=bestpractice.com
However, subsequent studies with more robust methodology found no evidence for a protective effect with RRSO.[125]Heemskerk-Gerritsen BA, Seynaeve C, van Asperen CJ, et al. Breast cancer risk after salpingo-oophorectomy in healthy BRCA1/2 mutation carriers: revisiting the evidence for risk reduction. J Natl Cancer Inst. 2015 Mar 18;107(5):djv033.
http://www.ncbi.nlm.nih.gov/pubmed/25788320?tool=bestpractice.com
[126]Terry MB, Daly MB, Phillips KA, et al. Risk-reducing oophorectomy and breast cancer risk across the spectrum of familial risk. J Natl Cancer Inst. 2019 Mar 1;111(3):331-4.
https://academic.oup.com/jnci/article/111/3/331/5212812
http://www.ncbi.nlm.nih.gov/pubmed/30496449?tool=bestpractice.com
One Cochrane review found very low-certainty evidence that RRSO improves survival and lowers breast and ovarian cancer-related mortality in women with BRCA1 and BRCA2 mutations.[124]Eleje GU, Eke AC, Ezebialu IU, et al. Risk-reducing bilateral salpingo-oophorectomy in women with BRCA1 or BRCA2 mutations. Cochrane Database Syst Rev. 2018 Aug 24;(8):CD012464.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD012464.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/30141832?tool=bestpractice.com
For women with variants associated with ovarian and breast cancer, guidelines recommend RRSO for ovarian and breast cancer risk reduction at age 35-40 years, upon completion of childbearing, in women with BRCA mutation.[18]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: breast, ovarian, and pancreatic [internet publication].
https://www.nccn.org/guidelines/category_2
[54]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: breast cancer risk reduction [internet publication].
https://www.nccn.org/guidelines/category_2
BRCA2 variants are associated with later ovarian cancer onset, and consideration may be given to delaying RRSO until age 40-45 years in these patients. For women with a BRIP1, RAD51C, or RAD51D mutation, RRSO is recommended at age 45-50 years. RRSO may be considered at age >45 years in women with a PALB2 mutation. Discussions should start earlier if there is a family history of early-onset ovarian cancer.[18]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: breast, ovarian, and pancreatic [internet publication].
https://www.nccn.org/guidelines/category_2
[115]Sessa C, Balmaña J, Bober SL, et al. Risk reduction and screening of cancer in hereditary breast-ovarian cancer syndromes: ESMO clinical practice guideline. Ann Oncol. 2023 Jan;34(1):33-47.
https://www.annalsofoncology.org/article/S0923-7534(22)04193-X/fulltext
Women considering surgery should undergo multidisciplinary evaluation and receive counselling on the potential psychosocial impact of RRSO, including consideration of reproductive wishes and advice on premature menopause for women who are pre-menopausal.[18]National Comprehensive Cancer Network. NCCN clinical practice guidelines in oncology: genetic/familial high-risk assessment: breast, ovarian, and pancreatic [internet publication].
https://www.nccn.org/guidelines/category_2
[115]Sessa C, Balmaña J, Bober SL, et al. Risk reduction and screening of cancer in hereditary breast-ovarian cancer syndromes: ESMO clinical practice guideline. Ann Oncol. 2023 Jan;34(1):33-47.
https://www.annalsofoncology.org/article/S0923-7534(22)04193-X/fulltext