Journal Article Ahead of print
PubMed: 42218652 DOI: 10.1200/JCO-26-00841
Low-Dose Tamoxifen in Noninvasive Breast Neoplasia: Long-Term Results From an Individual-Participant Data Pooled Analysis.
J Clin Oncol
Authors: Sara Gandini, Aliana Guerrieri-Gonzaga, Davide Serrano, Roberta Rizzo, Matteo Lazzeroni, Matteo Puntoni, Tania Buttiron Webber, Gaetano Aurilio, Harriet Johansson, Alessio Carbone, Livia Giordano, Maria Digennaro, Laura Cortesi, Francesco Millo, Katia Cagossi, Giuseppe Aprile, Patrizia Serra, Elisa Gallerani, Marcio Debiasi, Berta Sousa, Pedro Gouveia, Bernardo Bonanni, Andrea DeCensi
Affiliations
- Department of Experimental Oncology, IEO, European Institute of Oncology IRCCS, Milan, Italy.
- Division of Cancer Prevention and Genetics, IEO, European Institute of Oncology, IRCCS, Milan, Italy.
- Clinical and Epidemiological Research Unit, University Hospital of Parma, Parma, Italy.
- Medical Oncology Unit, EO Ospedali Galliera, Genoa, Italy.
- CPO-Piedmont-AOU Città della Salute e della Scienza, Turin, Italy.
- IRCCS, Istituto Tumori "Giovanni Paolo II", Bari, Italy.
- Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy.
- UOC Oncologia, Azienda USL-IRCCS Reggio Emilia, Reggio Emilia, Italy.
- Ospedali Riuniti ASL - Ospedale SS Antonio e Margherita, Tortona (AL), Italy.
- Oncology and Palliative Care Unit, Civil Hospital Carpi, USL, Carpi, Italy.
- Department of Oncology, San Bortolo General Hospital, Azienda ULSS8 Berica, Vicenza, Italy.
- Department of Oncology, Academic Hospital of Udine ASUFC, Udine, Italy.
- IRCCS Istituto Romagnolo per lo Studio dei Tumori "Dino Amadori"-IRST S.r.l. Meldola (FC), Italy.
- Aziende Socio Sanitarie Territoriale dei Sette Laghi, Varese, Italy.
- Breast Department, Champalimaud Clinical Centre, Lisbon, Portugal.
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
Among 1,545 women included with a median follow-up of 9.4 years, low-dose tamoxifen reduced breast cancer events overall, with evidence of treatment heterogeneity according to menopausal status (P = .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.
MeSH
Breast Neoplasms, Neoplasms, Carcinoma, Intraductal, Noninfiltrating, Breast, Therapeutics, Wounds And Injuries, Tamoxifen