Is it worth continuing tamoxifen (Selective Estrogen Receptor Modulator) for 10 years versus 5 years after breast surgery for hormone receptor-positive breast cancer?

From the Guidelines

Continuing tamoxifen for 10 years is recommended over 5 years for patients with hormone receptor-positive breast cancer, as it reduces the risk of recurrence and breast cancer-related mortality, despite increased side effects. The decision to extend tamoxifen therapy should be individualized, taking into account the patient's specific recurrence risk, tolerance of the medication, menopausal status, and quality of life concerns 1. For women with higher-risk disease, such as positive lymph nodes or larger tumors, the additional 5 years of tamoxifen can reduce recurrence risk by about 3-5% and breast cancer mortality by about 2-3% 1. Some key points to consider when deciding to extend tamoxifen therapy include:

• The risk of recurrence during years 5 to 14 was 21.4% for patients receiving tamoxifen versus 25.1% for controls, with an absolute recurrence reduction of 3.7% 1
• The reduction in risk of recurrence was 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
• The most important adverse effects noted in all patients in the ATLAS trial after 10 years of tamoxifen treatment were an increased risk for endometrial cancer and pulmonary embolism 1
• Premenopausal women generally derive more benefit from extended therapy than postmenopausal women, for whom aromatase inhibitors might be preferred if they become postmenopausal during treatment 1. The standard tamoxifen dose is 20mg daily, taken at the same time each day, with or without food, and annual gynecological exams are recommended during tamoxifen therapy to monitor for endometrial changes. When considering extended therapy, the patient's oncologist should evaluate their specific recurrence risk, tolerance of the medication, menopausal status, and quality of life concerns, and weigh the modest reduction in recurrence risk against the impact of continued side effects on their quality of life.

From the FDA Drug Label

In the NSABP B-14 trial, in which patients were randomized to tamoxifen 20 mg/day for 5 years vs placebo and were disease-free at the end of this 5 year period were offered rerandomization to an additional 5 years of tamoxifen or placebo. With 4 years of follow-up after this rerandomization, 92% of the women that received 5 years of tamoxifen were alive and disease-free, compared to 86% of the women scheduled to receive 10 years of tamoxifen (p = 0. 003). Overall survivals were 96% and 94%, respectively (p = 0.08). Results of the B-14 study suggest that continuation of therapy beyond 5 years does not provide additional benefit.

Continuation of Tamoxifen Therapy

• The NSABP B-14 trial suggests that continuing tamoxifen therapy beyond 5 years does not provide additional benefit in terms of disease-free survival and overall survival.
• The study found that 92% of women who received 5 years of tamoxifen were alive and disease-free, compared to 86% of women who received 10 years of tamoxifen.
• The results indicate that 5 years of tamoxifen therapy may be sufficient for hormone receptor-positive breast cancer patients after breast surgery. 2

From the Research

Tamoxifen Therapy Duration

The decision to continue tamoxifen therapy for 10 years versus 5 years after breast surgery for hormone receptor-positive breast cancer depends on various factors, including the patient's age, lymph node status, and overall health.

• A study published in 2016 3 found that extended hormonal therapy with tamoxifen for more than 5 years improved disease-free survival (DFS) and overall survival (OS) in hormone receptor-positive breast cancer patients, particularly those under 40 years old or with lymph node metastasis.
• Another study published in 2023 4 investigated the effects of extending anastrozole treatment to 10 years and found that continuing adjuvant anastrozole for an additional 5 years after 5 years of initial treatment improved DFS, although no difference in overall survival was observed.
• In contrast, a study published in 1996 5 found that the benefit from 5 years of tamoxifen therapy persists through 10 years of follow-up, but no additional advantage is obtained from continuing tamoxifen therapy for more than 5 years.

Comparison of Tamoxifen and Aromatase Inhibitors

• A patient-level meta-analysis published in 2015 6 compared aromatase inhibitors versus tamoxifen in early breast cancer and found that aromatase inhibitors reduce recurrence rates by about 30% compared to tamoxifen while treatments differ, but not thereafter.
• A review published in 2003 7 discussed the role of aromatase inhibitors as adjuvant therapy for hormone receptor-positive breast cancer and found that they have equivalent or superior efficacy to tamoxifen in the treatment of metastatic breast cancer.

Key Considerations

• The decision to continue tamoxifen therapy for 10 years versus 5 years should be individualized based on the patient's specific characteristics and medical history.
• Patients with high-risk features, such as young age or lymph node metastasis, may benefit from extended tamoxifen therapy.
• Aromatase inhibitors may be a suitable alternative to tamoxifen for some patients, particularly those with contraindications to tamoxifen or those who experience adverse effects.