Low-Dose Tamoxifen in Noninvasive Breast Neoplasia: Long-Term Results From an Individual-Participant Data Pooled Analysis

PURPOSE: Tamoxifen 20 mg once-daily reduces the risk of breast cancer recurrence after ductal carcinoma in situ (DCIS), but its use is limited by adverse effects. Lower doses may be effective, but benefit durability and differences according to menopausal status and site of recurrence remain uncertain. METHODS: We conducted an individual-participant pooled analysis of three clinical studies involving women with estrogen receptor-positive or unknown DCIS, microinvasive carcinoma, or high-risk breast lesions. Participants received low-dose tamoxifen (5 mg once daily or 10 mg once-every other day for 2-5 years) or a control intervention. The primary end point was breast cancer-free interval, defined as the first occurrence of any ipsilateral or contralateral invasive breast cancer, DCIS, regional recurrence, or distant recurrence. Hazard ratios (HRs) were estimated with mixed-effects Cox models accounting for between-study variability. RESULTS: = .01). In postmenopausal women, breast cancer events occurred in 40 of 335 receiving low-dose tamoxifen versus 93 of 401 controls (HR, 0.51 [95% CI, 0.35 to 0.73]), with a 10-year absolute reduction of 11.2%. Among premenopausal women, no significant reduction was observed (HR, 0.90 [95% CI, 0.70 to 1.17]), although contralateral breast cancer was reduced (HR, 0.45 [95% CI, 0.26 to 0.76]). Serious adverse events were infrequent and similar between groups. CONCLUSION: Low-dose tamoxifen was associated with a sustained reduction in breast cancer events, with differences by menopausal status and site of event. These findings support endocrine dose de-escalation to improve the benefit-risk profile of preventive therapy in DCIS and high-risk lesions.

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Journal
Journal of Clinical Oncology
Published
2026-05-31
DOI
https://doi.org/10.1200/jco-26-00841
Primary Topic
Breast Cancer Treatment Studies
Type
article
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article

Low-Dose Tamoxifen in Noninvasive Breast Neoplasia: Long-Term Results From an Individual-Participant Data Pooled Analysis

Berta Sousa, Matteo Puntoni, Francesco Millo, Davide Serrano et al.
Journal of Clinical Oncology
Breast Cancer Treatment Studies
article

Low-Dose Tamoxifen in Noninvasive Breast Neoplasia: Long-Term Results From an Individual-Participant Data Pooled Analysis

Berta Sousa, Matteo Puntoni, Francesco Millo, Davide Serrano, Matteo Lazzeroni, Patrizia Serra, Márcio Debiasi, Gaetano Aurilio, Alessio Carbone, Maria Digennaro, Katia Cagossi, Roberta Rizzo, Tania Buttiron Webber, Bernardo Bonanni, Giuseppe Aprile, Harriet Johansson, Sara Gandini, Elisa Gallerani, Aliana Guerrieri-Gonzaga, Pedro Gouveia, Laura Cortesi, Andrea DeCensi, Livia Giordano
article en

Abstract

PURPOSE: Tamoxifen 20 mg once-daily reduces the risk of breast cancer recurrence after ductal carcinoma in situ (DCIS), but its use is limited by adverse effects. Lower doses may be effective, but benefit durability and differences according to menopausal status and site of recurrence remain uncertain. METHODS: We conducted an individual-participant pooled analysis of three clinical studies involving women with estrogen receptor-positive or unknown DCIS, microinvasive carcinoma, or high-risk breast lesions. Participants received low-dose tamoxifen (5 mg once daily or 10 mg once-every other day for 2-5 years) or a control intervention. The primary end point was breast cancer-free interval, defined as the first occurrence of any ipsilateral or contralateral invasive breast cancer, DCIS, regional recurrence, or distant recurrence. Hazard ratios (HRs) were estimated with mixed-effects Cox models accounting for between-study variability. RESULTS: = .01). In postmenopausal women, breast cancer events occurred in 40 of 335 receiving low-dose tamoxifen versus 93 of 401 controls (HR, 0.51 [95% CI, 0.35 to 0.73]), with a 10-year absolute reduction of 11.2%. Among premenopausal women, no significant reduction was observed (HR, 0.90 [95% CI, 0.70 to 1.17]), although contralateral breast cancer was reduced (HR, 0.45 [95% CI, 0.26 to 0.76]). Serious adverse events were infrequent and similar between groups. CONCLUSION: Low-dose tamoxifen was associated with a sustained reduction in breast cancer events, with differences by menopausal status and site of event. These findings support endocrine dose de-escalation to improve the benefit-risk profile of preventive therapy in DCIS and high-risk lesions.

Journal of Clinical Oncology
Champalimaud Foundation (PT), University of Modena and Reggio Emilia (IT), University of Parma (IT), Ente Ospedaliero Ospedali Galliera (IT), Azienda Ospedaliera Citta' della Salute e della Scienza di Torino (IT), Azienda Sanitaria Unità Locale di Reggio Emilia (IT), Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IT), Azienda Ospedaliero Universitaria Ospedali Riuniti (IT), Ospedale Santa Maria della Misericordia di Udine (IT), Azienda Socio Sanitaria Territoriale Lariana (IT), Istituto Tumori Bari (IT), California Adaptive Rowing Program (US), Ospedale San Bortolo (IT), Aziende Socio Sanitarie Territoriale dei Sette Laghi, European Institute of Oncology (IT)
Good health and well-being
Openalex Percentile: Top 7%
Breast Cancer Treatment Studies
DOISourceOpenAlex
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