Annals of Oncology Advance Access originally published online on May 4, 2006
Annals of Oncology 2006 17(7):1065-1071; doi:10.1093/annonc/mdl047
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© 2006 European Society for Medical Oncology
Fifteen-year results of a randomized phase III trial of fenretinide to prevent second breast cancer
1 European Institute of Oncology, Milan, Italy; 2 Istituto Nazionale per lo Studio e la Cura dei Tumori, Milan, Italy; 3 E.O. Ospedali Galliera, Genoa, Italy; 4 Fondazione S. Maugeri, Pavia, Italy; 5 Institute of Medical Statistics and Biometry, University of Milan, Italy; 6 Department of Pharmacology, Dartmouth Medical School, Hanover, NH, USA
* Correspondence to: Prof. U. Veronesi, Scientific Director, European Institute of Oncology, Via G. Ripamonti, 435 – 20141 Milan, Italy. Tel: +39 02 57489221; Fax: +39 02 57489210; E-mail: umberto.veronesi{at}ieo.it
Purpose: The synthetic retinoid fenretinide administered for 5 years for prevention of second breast cancer showed no difference after a median of 8 years, but a possible reduction in premenopausal women. We conducted a long-term analysis in a subgroup of women who were regularly followed up in a single center.
Patients and methods: We analyzed data after a median follow-up of 14.6 years (IQ range, 12.3–16.3 years) from 1739 women aged 30–70 (872 in the fenretinide arm and 867 in the observation arm), representing 60% of the initial cohort of 2867 women. The main efficacy endpoint was second primary breast cancer (contralateral or ipsilateral).
Results: The number of second breast cancers was 168 in the fenretinide arm and 190 in the control arm (hazard ratio = 0.83, 95% CI, 0.67–1.03). There were 83 events in the fenretinide arm and 126 in the observation arm in premenopausal women (HR = 0.62, 95% CI, 0.46–0.83), and 85 and 64 events in postmenopausal women (HR = 1.23, 95% CI, 0.63–2.40). The younger were the women, the greater was the risk reduction associated with fenretinide, which attained 50% in women aged 40 years or younger and disappeared after age 55 (P-age*treatment interaction = 0.023). There was no difference in cancers in other organs, distant metastases or survival.
Conclusions: Fenretinide induces a significant risk reduction of second breast cancer in premenopausal women, which is remarkable at younger ages, and persists several years after treatment cessation. Since adverse events are limited, a trial in young women at high-risk is warranted.
Key words: breast neoplasms, chemoprevention, fenretinide, clinical trial
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