From the Guidelines
Extended adjuvant tamoxifen therapy beyond 5 years is recommended for women with hormone receptor-positive breast cancer, as it reduces the risk of recurrence and breast cancer-related mortality, as demonstrated by the ATLAS trial 1. The ATLAS trial, a high-quality study published in 2024, showed that extending adjuvant treatment to 10 years reduced the risk of relapse and breast cancer-related mortality in patients with ER-positive disease 1. Key findings from the ATLAS trial include:
- A reduction in the risk of recurrence during years 5 to 14, with an absolute recurrence reduction of 3.7% 1
- A greater reduction in risk of progression, possibly due to a “carryover effect,” with a reduction in risk of recurrence of 0.90 (95% CI, 0.79–1.02) during 5 to 9 years of tamoxifen treatment and 0.75 (0.62–0.90) after 10 years of treatment 1
- Decreases in the incidence of contralateral breast cancer and reduced mortality after completion of 10 years of treatment with tamoxifen 1 However, extended therapy is associated with increased risks, including:
- Endometrial cancer
- Pulmonary embolism The decision to extend therapy should balance these risks against the recurrence risk reduction benefits, considering the patient's age, comorbidities, and tolerance of the first 5 years of treatment. The standard dose of tamoxifen remains 20mg daily, and patients should be monitored for side effects, including endometrial cancer risk, thromboembolic events, and vasomotor symptoms. The benefit of extended therapy appears most pronounced in patients with higher initial recurrence risk, while those with very low-risk disease may not gain significant advantage from the additional 5 years.
From the FDA Drug Label
Results of the B-14 study suggest that continuation of therapy beyond 5 years does not provide additional benefit. A Scottish trial of 5 years of tamoxifen vs. indefinite treatment found a disease-free survival of 70% in the five-year group and 61% in the indefinite group, with 6.2 years median follow-up (HR = 1.27,95% CI: 0. 87 to 1.85).
The efficacy of extended adjuvant Tamoxifen therapy beyond 5 years in breast cancer patients is not supported by the available data.
- The NSABP B-14 trial found no additional benefit with continuation of therapy beyond 5 years 2.
- A Scottish trial also found no significant difference in disease-free survival between 5 years of tamoxifen and indefinite treatment 2. No benefit is seen with extended use of tamoxifen beyond 5 years.
From the Research
Efficacy of Extended Adjuvant Tamoxifen Therapy
- The efficacy of extended adjuvant Tamoxifen therapy beyond 5 years in breast cancer patients has been studied in several clinical trials 3, 4, 5, 6.
- A study published in 2017 found that extending adjuvant endocrine therapy using up to 10 years of treatment can provide a small absolute benefit in reducing the risk of late relapse in hormone receptor-positive disease 3.
- Another study published in 2008 found that letrozole, an aromatase inhibitor, improved disease-free survival and overall survival when compared with placebo as extended adjuvant treatment after 5 years of tamoxifen 4.
- A 2013 study found that both initial aromatase inhibitor therapy and switching/sequential tamoxifen followed by an aromatase inhibitor are associated with longer disease- and relapse-free survival versus 5 years of tamoxifen alone 5.
- A meta-analysis published in 2016 found that aromatase inhibitors alone or sequentially combined with tamoxifen improved disease-free survival and overall survival compared with tamoxifen or placebo 6.
Comparison with Aromatase Inhibitors
- Aromatase inhibitors have been shown to have superior efficacy over tamoxifen in the metastatic, neoadjuvant, and adjuvant settings, and to improve outcome as extended adjuvant therapy following 5 years of tamoxifen 4, 6.
- A study published in 2011 found that raloxifene and tamoxifen reduce the risk of ER-positive invasive breast cancer with equal efficacy, but raloxifene is associated with a lower risk of thromboembolic disease, benign uterine conditions, and cataracts than tamoxifen in postmenopausal women 7.