USPSTF Guidance: When to Use Medication to Reduce Breast Cancer Risk

CLINICAL ACTIONS:

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 (2019) 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 (Grade B – offer or provide this service).

  • 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)
    • 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.

SYNOPSIS:

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 above a certain 5-year risk threshold cut-off (see thresholds below).  An individualized approach which integrates personal and family medical history is used to determine the best risk reduction approach.

KEY POINTS:

  • 5-year risk threshold cut-offs:
    • USPSTF recommends 3% (1/33) risk of breast cancer in next 5 years
    • ASCO recommends 1.66% (1/60) risk of breast cancer in the next 5 years
  • Medication options recommended by the USPSTF include

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

  • SERMs such as Tamoxifen and Raloxifene can significantly reduce risk of ‘estrogen receptor positive’ breast cancer
  • Aromatase inhibitors are also appropriate
    • NCCN: Risk-reduction agents for women age ≥35 years and older
      • Tamoxifen for premenopausal women only
      • Tamoxifen, raloxifene, anastrozole, or exemestane may be used in postmenopausal women
    • ACOG: Tamoxifen and raloxifene may be considered for risk reduction of breast cancer in women with BRCA genetic mutations
      • Raloxifene only in postmenopausal women
      • Aromatase an alternative in women who cannot use tamoxifen
      • Monitor women on tamoxifen for endometrial hyperplasia (see ‘Related ObG Topics’ below)
    • AAFP: Supports the USPSTF recommendation
  • 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

Use of pharmacologic interventions for breast cancer risk reduction: American Society of Clinical Oncology clinical practice guideline

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