For Physicians. By Physicians.™

Professional Recommendations for Use Pharmacologic Interventions to Reduce Breast Cancer Risk


Both USPSTF and ASCO have released guidance on the use of medications to reduce breast cancer risk in women who meet a certain risk threshold. The USPSTF guidance is in alignment with ASCO in the recommendation of aromatase inhibitors, along with tamoxifen and raloxifene, as drugs suitable for use as risk-reducing medications for women at increased risk for breast cancer and at low risk for adverse medication effect (USPSTF Grade B – offer or provide this service). Based on data review, the USPSTF and ASCO determined that certain medications have the potential to reduce the risk of estrogen receptor positive breast cancer by almost 50% in women. An individualized approach which integrates personal and family medical history is used to determine the best risk reduction approach.

USPSTF Recommendations

Risk Assessment 

  • All patients should initially be assessed to determine if they are at high risk for breast cancer and if so, appropriate referral should be considered in the following circumstances
    • Personal history of breast cancer, LCIS or DCIS
    • Personal history of mantle radiation for Hodgkin’s lymphoma
    • Personal or family history suggestive of high risk for pathogenic variants in BRCA1, BRCA2 and other high or intermediate risk genes that may cause heritable cancer syndromes
  • If patients do not meet the above high-risk criteria, an absolute 5-year risk score can be calculated using a validated assessment tool (see ‘Learn More – Primary Sources’ below; both publicly available)
    • Offer pharmacologic interventions if at least 3% (1/33) risk of breast cancer in next 5 years
      • Gail or Breast Cancer Surveillance Consortium (BCSC) Risk Calculator for women who are ≥ 35 years of age are validated 5-year risk assessment tools
      • BCSC Risk Calculator includes field for breast density
  • Alternatives to the above as per the USPSTF, clinicians may consider a combination of risk factors including (but not limited to)

Age 65 years or older with 1 first-degree relative with breast cancer

45 years or older with more than 1 first-degree relative with breast cancer or 1 first-degree relative who developed breast cancer before age 50 years

40 years or older with a first-degree relative with bilateral breast cancer

Presence of atypical ductal or lobular hyperplasia or lobular carcinoma in situ on a prior biopsy.

Medication Options 

Tamoxifen, raloxifene, and aromatase inhibitors all reduce primary breast cancer risk in postmenopausal women

Use of raloxifene and aromatase inhibitors is indicated only in postmenopausal women

Only tamoxifen is indicated for risk-reduction of primary breast cancer in premenopausal women

ASCO Recommendations

Risk Assessment

  • Women with 1 or more factors are most likely to benefit from endocrine therapy risk reduction
    • Prior diagnosis of atypical hyperplasia or lobular carcinoma in situ
    • 5-year risk by the NCI Breast Cancer Risk Assessment Tool of at least 3%
    • 10-year risk by the IBIS/Tyrer Cuzick Risk Calculator of 5% or higher
    • Relative risk of 2X or greater than the average for age group if age 45-69
    • Relative risk of 4X or greater than the average for age group if age 40-44

Medication Options

  • Postmenopausal women at elevated risk: Prescribe daily for 5 years
    • Anastrozole 1 mg
    • Tamoxifen 20 mg
    • Raloxifene 60 mg
    • Exemestane 25 mg
  • Premenopausal
    • Tamoxifen 20 mg/day for 5 years in women who are at least 35 years old and have completed childbearing


  • 5-year risk assessment is not appropriate as an initial assessment in high risk families
    • Referral to genetic counseling should be made if there is a significant family history of cancers including non-breast malignancies, such as colon, ovarian and uterine
    • Paternal family history of breast and other cancers is critical in this setting and requires a multiple generation pedigree analysis
    • See “USPSTF Guidelines for Primary Care Clinicians: BRCA-Related Cancer Risk Assessment” in Related ObG Topics below
  • USPSTF recommends against the use of medications to reduce breast cancer risk in women ≥ 35 who are not at increased risk (Grade D – discourage the use of this service)

Harms Associated with Risk Reduction Medications

  • Tamoxifen and raloxifene are associated with small to moderate harms
    • Increased risk for VTE
      • Tamoxifen > raloxifene | Greater risk in older women
    • Tamoxifen increases risk for endometrial cancer (not raloxifene)
    • Hot flashes common with both
  • Aromatase inhibitors are associated with small to moderate harms including
    • Hot flashes | GI symptoms | MSK pain | Possible cardiovascular events (e.g., stroke)
    • May increase risk of fractures

Learn More – Primary Sources:

USPSTF: Breast Cancer Medications for Risk Reduction

ASCO: Use of Endocrine Therapy for Breast Cancer Risk Reduction

NIH Breast Cancer Risk Assessment Tool (Gail)

Breast Cancer Surveillance Consortium Risk Calculator

Locate a Genetic Counselor or Genetics services:

Genetic Services Locator-ACMG

Genetic Services Locator-NSGC

Genetic Services Locator-CAGC

USPSTF Guidelines for Primary Care Clinicians: BRCA-Related Cancer Risk Assessment


USPSTF released updated guidelines (2019) to help primary care professionals identify women who would benefit from further genetic counseling and testing for BRCA1 and BRCA2. Two major changes from previous USPSTF recommendations address the inclusion of two additional patient groups: (1) women with previous breast cancer or ovarian cancer who are considered cancer-free; (2) the explicit inclusion of ancestry.

The USPSTF recommends that primary care clinicians, using an “appropriate brief familial risk assessment tool” should screen women with  

  • Personal or family history of breast, ovarian, tubal, or peritoneal cancer or
  • Ancestry associated with BRCA1/2 gene mutation

The USPSTF document further states that

Women with a positive result on the risk assessment tool should receive genetic counseling and, if indicated after counseling, genetic testing. (Grade B – The USPSTF recommends the service. There is high certainty that the net benefit is moderate or there is moderate certainty that the net benefit is moderate to substantial)

Note: A patient with a family member with known BRCA1/2 pathogenic variant should also be referred to genetic counseling

For women whose personal or family history or ancestry is not associated with potential harmful BRCA1/2 gene mutations

The USPSTF recommends against routine risk assessment, genetic counseling, or genetic testing (Grade D – The USPSTF recommends against the service. There is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits)

Appropriate Familial Risk Assessment Tools

Note: NCCN and ACMG/ NSGC also have guidelines regarding when to refer women for genetic counseling (see ‘Learn More – Primary Sources’ below for links to these sites) | ACOG recommends that “Genetic counseling is recommended before initiation of genetic testing and can be performed by an obstetrician–gynecologist (or other gynecologic care provider) who has expertise in cancer genetics or by a genetic counselor”


  • BRCA1/2 pathogenic variants
    • Occur in an estimated 1/300 to 1/500 women and account for the following percent of cancer cases
      • Breast cancer: 5% to 10%
      • Ovarian cancer: 15%
    • Significantly increase cancer risk breast cancer: 45% to 65% (cumulative age 70)
    • Significantly increase ovarian, fallopian tube, or peritoneal cancer risk (cumulative age 70)
      • BRCA1: 39% 
      • BRCA2: 10% to 17%

Note: See ‘BRCA1 & BRCA2 Mutations: What Are the Risks for Developing Breast and Ovarian Cancer?’ in ‘Related ObG Topics’ below

  • NCCN and other professional bodies recommend offering BRCA testing to any women with ovarian cancer
    • 15% of women with epithelial ovarian cancer will have a pathogenic variant in BRCA1/2
  • NCCN also recommends that all individuals with pancreatic cancer be offered BRCA1/2 testing along with other related genes associated with this malignancy
  • 2.5% (1/40) individuals of Ashkenazi Jewish heritage (unselected – i.e. do not need high risk family history) will have one of the 3 founder BRCA1/2 variants vs 0.1% in the general population
    • Founder pathogenic variants: BRCA1 185delAG | BRCA1 5382insC | BRCA2 6174delT
    • 90% of pathogenic BRCA1/2 pathogenic variants belong to one of the 3 founder mutations
    • NCCN updated its guidance (December 2019) and now states that testing for the 3 founder mutations can be ‘considered’ in an AJ individual without personal cancer history | Ideally testing should be offered within a longitudinal study, but if such a study is not readily available, the test may be provided if there is pre-test and education and post-test counseling available
  • Multigene Panel Testing: USPSTF does not endorse the use of multigene panel testing beyond BRCA1/2, due to limited data regarding clinical utility
    • Benefit of multigene panels: Will detect variants associated with other cancers that are seen in conjunction with breast cancer, for example
      • Pancreatic cancer | Prostate cancer | Melanoma
    • Risks associated with multigene panels: While multigene panel testing offers more comprehensive coverage of other important genes there is additional risk for
      • Identifying variants of uncertain significance (VUS)
      • Clinical follow-up may not be well defined  
    • Pre and post genetic counseling may be especially beneficial for those offered multigene panel testing
    • Note: ACOG does address multigene panels and finds that “Genetic testing may be performed using a panel of multiple genes through next-generation sequencing technology” | Heritable cancer syndromes may overlap such that a strong family history for ovarian cancer may be the result of a pathogenic variant in BRCA1/2 or genes associated with Lynch Syndrome
  • This USPSTF guidance specifically addresses women and not men
    • Metastatic prostate cancer
      • BRCA1/2 found in 6% of metastatic prostate | NCCN therefore considers this pathology an indication for genetic counseling and BRCA1/2 testing
  • Population addressed in this current USPSTF guideline: Higher risk only and, therefore, may benefit from genetic counseling regarding BRCA1/2
    • USPSTF has another guideline specific to average risk population
      • All women at average risk (i.e., not at higher risk for BRCA1/2) should have a 5-year breast cancer risk assessment to determine if they may benefit from chemoprophylaxis (e.g., tamoxifen, raloxifene or aromatase inhibitor)
      • These risk assessment tools are different than those described above and focus on breast density, prior history of breast atypia etc. (See ‘Related ObG Topics below)
  • New treatments (not addressed in this guidance)
    • Knowledge of BRCA status has implications for treatment
    • Poly (ADP-ribose) polymerase (PARP) inhibitors block an enzyme involved in DNA damage repair
    • FDA has approved PARP inhibitors for treatment of BRCA-associated metastatic breast and ovarian cancers, and other cancers in various pharmaceutical pipelines  

Learn More – Primary Sources:

USPSTF Recommendation Statement: Risk Assessment, Genetic Counseling, and Genetic Testing for BRCA-Related Cancer

Editorial: Broadening Criteria for BRCA1/2 Evaluation: Placing the USPSTF Recommendation in Context

Editorial: USPSTF Recommendations for BRCA1 and BRCA2 Testing in the Context of a Transformative National Cancer Control Plan

PARP inhibitors for BRCA1/2-mutated and sporadic ovarian cancer: current practice and future directions

Hereditary Cancer Evaluation in 2019—a Rapidly Evolving Landscape

BRCAPROLYTE: A Two-Stage Approach to Genetic Risk Assessment in Primary Care

NCCN GUIDELINES FOR DETECTION, PREVENTION, & RISK REDUCTION: Genetic/Familial High-Risk Assessment: Breast, Ovarian and Pancreatic (free but requires sign-up)

Addendum: A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment (see Table 1 in original article)

ACOG Practice Bulletin 182: Hereditary Breast and Ovarian Cancer Syndrome

ACOG Committee Opinion 793: Hereditary Cancer Syndromes and Risk Assessment

Locate a Genetic Counselor or Genetics services:

Genetic Services Locator-ACMG

Genetic Services Locator-NSGC

Genetic Services Locator-CAGC

Mammography Guidelines for Average-Risk Women


Professional organizations continue to release evidence based guidance on mammography, with ACP the latest to provide updated recommendations. While required frequency and starting age may differ, they all emphasize shared decision making with patients, which entails counseling about uncertainty, risk/benefit and related patient values.


  • Appears to decrease breast cancer mortality by 15 to 20%
    • Studies demonstrate varying magnitude
    • ACS (RCT data): Relative risk 0.80-0.82
    • Recent data from the Canadian National Breast Screening Study did not show decrease when comparing mammography to controls, perhaps due to more recent improvements in treatments but does not take in to account advances in imaging
  • Reduces advanced cancer (although no evidence regarding advanced cancer treatment)
    • USPSTF evidence review in women > 50 years of age: Relative risk 0.62 (95% CI, 0.46 – 0.83)
  • May increase life expectancy (ACS systematic review) but could not quantitate


False Positives (additional images and benign biopsies)

  • USPSTF review 10 yr cumulative false positive rate
    • Annual: 61% false positive / 7% require biopsy
    • Every 2 years: 42% false positive / 5% require biopsy
  • ACS review of the same data
    • Increased risk of false positive with dense breasts among women 40-49
    • Callbacks minimized if prior films available

Anxiety and Distress

  • May persist even if follow-up is normal
  • Financial concerns as patient may be responsible for paying for additional tests


  • USPSTF review identified mammography as being a painful procedure
  • Follow-up procedures may also result in pain

Overdiagnosis and Overtreatment

  • Overdiagnosis is defined as detecting a cancer that would have remained indolent and not become apparent without screening
  • Overtreatment is defined as treatment for an overdiagnosed cancer
  • Difficult to discern actual number of overdiagnosed cancers
    • USPSTF review suggests 10.7% – 22.7% based on RCT data
    • 1/8 cancers will be overdiagnosed
  • Inclusion of Ductal Carcinoma in Situ may impact data
  • Other organizations such as ACS make the point that certain assumptions may not be verifiable in addition to bias in methodology and design


  • USPSTF using modelling but not direct studies of radiation exposure estimates 2 per 100,000 deaths among women 50-59 yrs due to mammography screening
  • Other models in women 40-74 yrs suggest 125 cases of breast cancer and 25 cancer deaths due to radiation exposure, but 986 cancer deaths prevented



  • Start Age
    • Recommend at age 50
    • Offer from age 40 (shared decision making)
  • Screening Interval
    • Every 1 or 2 years (shared decision making)
  • Stop Age
    • Age 75
    • > 75 shared decision making including overall health and longevity


  • Start Age
    • Recommend at 50 years | Consider 40 years if patient desires
  • Screening Interval: Every 2 years until 74 years
  • Stop Age
    • ≥ 75 years:  Insufficient evidence to recommend for/against


  • Start Age
    • Recommend at age 45 years | Consider 40 years if patient desires
  • Screening Interval
    • 45 – 50 years: annual
    • ≥55 years: Every 2 years or can choose annual
  • Stop Age
    • Continue if good health and life expectancy >10 years


  • Start Age
    • Recommend at 40 years
  • Screening Interval: Annual
  • Stop Age
    • “Screening should continue past age 74 without an upper age limit, unless severe comorbidities limit life expectancy or ability to accept treatment.

Note: ACR updated guidelines to include transgender patients stating “Annual screening at age 40 is recommended for transfeminine (male-to-female) patients who have used hormones for ≥5 years, as well as for transmasculine (female-to-male) patients who have not had mastectomy” 


  • Start Age
      • Recommended at 50 years
    • 40-49 years: Discuss risks vs benefits and patient preference (“potential harms outweigh the benefits for most women” in this age bracket )
  • Screening Interval: Every 2 years
  • Stop Age
    • Screening not recommended for women ≥75
    • Life expectancy ≤10 years


  • Start Age
    • Recommend at 50 years
  • Screening Interval
    • Every 2 years
  • Stop Age
    • ≥ 75 years:  Insufficient evidence to recommend for/against


  • Start Age
    • Recommend at 40 years
  • Screening Interval: Annual
  • Stop Age
    • Upper age limit not yet established
  • Consider comorbidities that may impact life expectancy (≤10 years)

Canadian Task Force on Preventative Healthcare

  • Start Age
    • Recommend not to screen women 40 to 49 years (conditional recommendation; low-certainty evidence)
  • Screening Interval
    • Every 2 to 3 years
    • 50 to 69 years: “Conditional on the relative value that a woman places on possible benefits and harms from screening (conditional recommendation; very low-certainty evidence)”
    • 50 to 59 years: 1333 women is the number needed to screen (NNS) to prevent one death from breast cancer (95% CI, 909 to 2857)
    • 60-69 years: NNS is 1087 (95% CI, 741 to 2325)
    • 70-74 years: NNS is 645 (95% CI, 441 to 1389)
  • Stop Age
    • No evidence found regarding harms vs benefits of screening ≥75 years

Note: The Canadian Task Force did not make any significant change from the previous guideline, however certainty of evidence – now ‘very low- to low-certainty’ was downgraded based on serious concerns of previous study bias

American Society of Breast Surgeons

  • Start Age
    • Non-dense breasts (A and B density): 3D preferred modality | Age 40 | No need for supplemental imaging
    • Dense breasts (C and D density): 3D preferred modality | Age 40 | Consider supplemental imaging
  • Screening Interval
    • Annual
  • Stop Age
    • When life expectancy is <10 years


  • Clinical Breast Examination (CBE)
    • ACOG & NCCN: Offer every 1 to 3 years for women 25 to 39 years and annually for ≥ 40 years
    • USPSTF & AAFP: Insufficient evidence to recommend for or against
    • ACS, ACP & Canadian Task Force on Preventative Healthcare: Not recommended
    • WHO: CBE may be of benefit for women age 50 to 69 years with poor access to healthcare resources 
  • Most professional organizations find insufficient evidence to recommend adjunctive screening using breast ultrasonography, MRI, Digital Breast Tomosynthesis, or other method in the setting of a normal mammogram and no other risk factors

Learn More – Primary Sources:

ACOG Practice Bulletin 179: Breast Cancer Risk Assessment and Screening in Average-Risk Women

Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement

Twenty five year follow-up for breast cancer incidence and mortality of the Canadian National Breast Screening Study: randomised screening trial

Canadian Task Force: Recommendations on screening for breast cancer in women aged 40–74 years who are not at increased risk for breast cancer

Breast Cancer Screening Recommendations Inclusive of All Women at Average Risk: Update from the ACR and Society of Breast Imaging

Breast Cancer Screening for Women at Average Risk: 2015 Guideline Update From the American Cancer Society

Screening for Breast Cancer in Average-Risk Women: A Guidance Statement From the American College of Physicians

AAFP: Summary of Recommendations for Clinical Preventative Services

NCCN Guidelines: Breast Cancer Screening and Diagnosis

ASBrS: Position Statement on Screening Mammography

Radiation-Induced Breast Cancer Incidence and Mortality from Digital Mammography Screening: A Modeling Study 

WHO position paper on mammography screening