Benefits of Tamoxifen on Overall Survival (OS) and Progression-Free Survival (PFS) for DCIS
Tamoxifen, when used as an adjuvant therapy in patients with ductal carcinoma in situ (DCIS), primarily aims to reduce the risk of recurrence rather than directly impacting overall survival (OS) or progression-free survival (PFS). Here are some key findings from studies:
– Risk Reduction: Tamoxifen reduces the risk of ipsilateral (same breast) and contralateral (opposite breast) breast cancer by 30% to 50% following local therapy for DCIS[5].
– Disease-Free Survival: In women who received breast-conserving surgery (BCS) and radiation, the addition of tamoxifen resulted in a 95.0% five-year disease-free survival rate, which is comparable to the 95.6% rate for those who underwent mastectomy[2].
– Impact on Recurrence: The NSABP B-24 trial demonstrated a 31% reduction in all breast cancer recurrences with tamoxifen use after lumpectomy and radiation[5].
Tamoxifen Dosing, Side Effects, and Duration
Dosing
– Standard Dose: The typical dose for tamoxifen is 20 mg per day, usually taken for five years[6].
– Low-Dose Options: Low-dose tamoxifen regimens, such as 5 mg/day or 10 mg every other day, have been explored to reduce side effects while still providing some protective benefits[6][7].
– It does not significantly impact overall survival, its role in reducing recurrence makes it a valuable component of adjuvant therapy.
Side Effects
– Common Side Effects: These include hot flashes, irregular periods, and vaginal discharge[4].
– Serious Risks: Tamoxifen carries a black box warning for uterine malignancies, pulmonary embolism, and stroke, especially in patients at high risk[4].
– Other Effects: Patients may experience peripheral edema, mood changes, nausea, and skin rashes, among others[4].
Duration
– Typical Duration: Tamoxifen is generally prescribed for five years as part of adjuvant therapy for DCIS[5][7].
Uterine malignancies and thromboembolic events:
Serious and life-threatening events from the use of tamoxifen include uterine malignancies, stroke, and pulmonary embolism. Fatal cases of each type of event have occurred.
Incidence rates per 1,000 woman-years for these events were estimated from the National Surgical Adjuvant Breast and Bowel Project (NSABP) P-1 trial in women at high risk for breast cancer:
- Endometrial adenocarcinoma: 2.20 for tamoxifen versus 0.71 for placebo
- Uterine sarcoma: 0.17 for tamoxifen versus 0.04 for placebo
- Stroke: 1.43 for tamoxifen versus 1.00 for placebo.
- Pulmonary embolism: 0.75 for tamoxifen versus 0.25 for placebo
Discuss the potential benefits of tamoxifen versus the potential risks of these serious events with women at high risk for breast cancer and women with ductal carcinoma in situ (DCIS) considering tamoxifen to reduce the risk of developing breast cancer. For most patients already diagnosed with breast cancer, the benefits of tamoxifen outweigh its risks.
Citations:
[1] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3341142/
[2] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915783/
[3] https://www.breastcancer.org/treatment/hormonal-therapy/tamoxifen
[4] https://www.ncbi.nlm.nih.gov/books/NBK532905/
[5] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999067/
[6] https://link.springer.com/article/10.1007/s40265-024-02010-x
[7] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10500726/
[8] https://www.nature.com/articles/s41392-024-01779-3
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Adjuvant Tamoxifen (pre-menopausal in early stage breast cancer)
The efficacy of 5 years of adjuvant tamoxifen in premenopausal women with early-stage breast cancer has been well established through meta-analyses conducted by the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). These analyses have shown that 5 years of tamoxifen reduces the risk of breast cancer recurrence by nearly 40% and breast cancer mortality by 30% over 15 years of follow-up in women with estrogen receptor-positive disease, regardless of age or use of chemotherapy. More recent clinical trials have evaluated extending the duration of tamoxifen beyond 5 years, as well as incorporating ovarian suppression. The ATLAS and aTTom trials demonstrated a further reduction in recurrence and mortality with 10 years versus 5 years of tamoxifen. Additionally, trials like SOFT and TEXT have shown improved outcomes with the addition of ovarian suppression to tamoxifen or an aromatase inhibitor compared to tamoxifen alone in higher-risk premenopausal women.
References:
Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). (2011). Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials. The Lancet, 378(9793), 771-784.
Davies, C., Pan, H., Godwin, J., Gray, R., Arriagada, R., Raina, V., … & Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group. (2013). Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial. The Lancet, 381(9869), 805-816.
Francis, P. A., Regan, M. M., Fleming, G. F., Láng, I., Ciruelos, E., Bellet, M., … & SOFT Investigators and International Breast Cancer Study Group. (2015). Adjuvant ovarian suppression in premenopausal breast cancer. New England Journal of Medicine, 372(5), 436-446.
Pagani, O., Regan, M. M., Walley, B. A., Fleming, G. F., Colleoni, M., Láng, I., … & TEXT and SOFT Investigators and International Breast Cancer Study Group. (2014). Adjuvant exemestane with ovarian suppression in premenopausal breast cancer. New England Journal of Medicine, 371(2), 107-118.