When should Tamoxifen (tamoxifen citrate) be used for chemoprophylaxis in breast cancer?

Tamoxifen for Breast Cancer Chemoprophylaxis

Tamoxifen (20 mg daily for 5 years) should be discussed as a chemoprevention option for women aged 35 years or older with a 5-year projected absolute breast cancer risk ≥1.66% according to the NCI Breast Cancer Risk Assessment Tool, or with lobular carcinoma in situ (LCIS). 1, 2

Patient Selection Criteria

• Tamoxifen is FDA-approved for reducing invasive breast cancer risk in high-risk women, defined as those with a 5-year predicted risk of breast cancer ≥1.67% as calculated by the Gail Model 2
• Tamoxifen specifically reduces the risk of estrogen receptor (ER)-positive breast cancers but does not prevent ER-negative breast cancers 1
• Risk factors that should prompt consideration of tamoxifen chemoprophylaxis include:
  • Age ≥35 years with family history of breast cancer 1
  • History of atypical ductal hyperplasia 1
  • History of LCIS 1
  • Multiple breast biopsies 1
  • Early menarche, late first live birth, or nulliparity 1

Risk Assessment

• The NCI Breast Cancer Risk Assessment Tool (Gail model) should be used to identify women with a 5-year risk ≥1.66% 1
• Risk should be calculated periodically as a woman's risk increases throughout her lifetime 1
• The risk-benefit ratio is most favorable for women with higher breast cancer risk and lower risk of adverse effects 1

Contraindications and Precautions

• Tamoxifen is contraindicated in women with:
  • History of deep vein thrombosis or pulmonary embolism 1
  • History of stroke or transient ischemic attack 1
  • During prolonged immobilization 1
  • Pregnancy or women who may become pregnant 1
  • Nursing mothers 1

Optimal Candidates

• The balance of benefits and harms is most favorable for:
  • Women in their 40s at increased breast cancer risk without predisposition to thromboembolic events 1
  • Women in their 50s at increased breast cancer risk without predisposition to thromboembolic events and without a uterus 1
  • Women with a personal history of atypical hyperplasia or LCIS 1

Potential Benefits

• Tamoxifen reduces the risk of invasive breast cancer by approximately 44% in high-risk women 2
• The risk reduction benefit continues for at least 10 years after the 5-year treatment period 1
• Tamoxifen reduces the risk of contralateral breast cancer in BRCA1 and BRCA2 mutation carriers 3
• Low-dose tamoxifen (5 mg daily for 3 years) has also shown efficacy in preventing recurrence in women with intraepithelial neoplasia with fewer side effects 4

Potential Risks

• Increased risk of endometrial cancer, particularly in women over 50 years 1, 2
• Increased risk of thromboembolic events (deep vein thrombosis, pulmonary embolism) 1
• Other side effects include hot flashes and cataracts 2, 5

Clinical Considerations

• Despite proven efficacy, uptake of tamoxifen for chemoprevention remains low (approximately 1% of eligible women), primarily due to concerns about adverse effects 6, 5
• Approximately 46% of women discontinue tamoxifen before completing the recommended 5-year course 5
• The number needed to treat to prevent one case of breast cancer is approximately 22 in 5 years and 14 in 10 years 4
• Family physician recommendation significantly influences a woman's decision to take tamoxifen 6

Common Pitfalls to Avoid

• Failing to reassess breast cancer risk periodically as risk increases with age 1
• Recommending tamoxifen to women over 60 years without careful consideration of thromboembolic risk 1
• Not discussing the specific benefits and risks with each patient based on her individual risk factors 1
• Overlooking the long-term protective effect that continues after the 5-year treatment period 1

In summary, tamoxifen chemoprophylaxis should be considered for women at increased risk of breast cancer, with the greatest benefit seen in younger women without contraindications. The decision should be based on a careful assessment of individual breast cancer risk and potential for adverse effects.