Fifteen-year results of a randomized phase III trial of fenretinide to prevent second breast cancer

• Published in: Annals of oncology Vol. 17; no. 7; pp. 1065 - 1071
• Main Authors: Veronesi, U., Mariani, L., Decensi, A., Formelli, F., Camerini, T., Miceli, R., Di Mauro, M.G., Costa, A., Marubini, E., Sporn, M.B., De Palo, G.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 01-07-2006; Oxford University Press; Oxford Publishing Limited (England)
• Subjects: Adult; Age Factors; Aged; Anticarcinogenic Agents - therapeutic use; Antineoplastic agents; Biological and medical sciences; breast neoplasms; Breast Neoplasms - drug therapy; Breast Neoplasms - epidemiology; Breast Neoplasms - pathology; chemoprevention; clinical trial; Female; fenretinide; Fenretinide - therapeutic use; Follow-Up Studies; Gynecology. Andrology. Obstetrics; Humans; Mammary gland diseases; Medical sciences; Middle Aged; Neoplasm Recurrence, Local - prevention & control; Neoplasms, Second Primary - epidemiology; Pharmacology. Drug treatments; Postmenopause; Premenopause; Risk; Tumors; clinical trial; fenretinide; chemoprevention; breast neoplasms; Antineoplastic agent; Phase III trial; Human; Fenretinide; Chemoprophylaxis; Breast tumor; Retinoid; Breast cancer; Malignant tumor; Prevention; Mammary gland diseases; Chemotherapy; Randomization; Treatment; Second cancer; Clinical trial
• ISSN: 0923-7534; 1569-8041
• DOI: 10.1093/annonc/mdl047

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.