Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Local and Contralateral Recurrence in Breast Intraepithelial Neoplasia

Andrea DeCensi, Matteo Puntoni, Aliana Guerrieri-Gonzaga, Silvia Caviglia, Franca Avino, Laura Cortesi, Cristiana Taverniti, Maria Grazia Pacquola, Fabio Falcini, Marcella Gulisano, Maria Digennaro, Anna Cariello, Katia Cagossi, Graziella Pinotti, Matteo Lazzeroni, Davide Serrano, Daniela Branchi, Sara Campora, Marilena Petrera, Tania Buttiron WebberLuca Boni, Bernardo Bonanni

Research output: Contribution to journalArticle

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Abstract

PURPOSE: Tamoxifen administered for 5 years at 20 mg/d is effective in breast cancer treatment and prevention, but toxicity has limited its broad use. Biomarker trials showed that 5 mg/d is not inferior to 20 mg/d in decreasing breast cancer proliferation. We hypothesized that a lower dose given for a shorter period could be as effective in preventing recurrence from breast intraepithelial neoplasia but have a lower toxicity than the standard dose. PATIENTS AND METHODS: We conducted a multicenter randomized trial of tamoxifen, 5 mg/d or placebo administered for 3 years after surgery in women with hormone-sensitive or unknown breast intraepithelial neoplasia, including atypical ductal hyperplasia and lobular or ductal carcinoma in situ. The primary end point was the incidence of invasive breast cancer or ductal carcinoma in situ. RESULTS: Five hundred women 75 years of age or younger were included. After a median follow-up of 5.1 years (interquartile range, 3.9-6.3 years), there were 14 neoplastic events with tamoxifen and 28 with placebo (11.6 v 23.9 per 1,000 person-years; hazard ratio, 0.48; 95% CI, 0.26 to 0.92; P = .02), which resulted in a 5-year number needed to treat of 22 (95% CI, 20 to 27). Tamoxifen decreased contralateral breast events by 75% (three v 12 events; hazard ratio, 0.25; 95% CI, 0.07 to 0.88; P = .02). Patient-reported outcomes were not different between arms except for a slight increase in frequency of daily hot flashes with tamoxifen (P = .02). There were 12 serious adverse events with tamoxifen and 16 with placebo, including one deep vein thrombosis and one stage I endometrial cancer with tamoxifen and one pulmonary embolism with placebo. CONCLUSION: Tamoxifen at 5 mg/d for 3 years can halve the recurrence of breast intraepithelial neoplasia with a limited toxicity, which provides a new treatment option in these disorders.

Original languageEnglish
Pages (from-to)1629-1637
Number of pages9
JournalJournal of clinical oncology : official journal of the American Society of Clinical Oncology
Volume37
Issue number19
DOIs
Publication statusPublished - Jul 1 2019

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Tamoxifen
Breast
Randomized Controlled Trials
Placebos
Recurrence
Carcinoma, Intraductal, Noninfiltrating
Neoplasms
Breast Neoplasms
Hot Flashes
Numbers Needed To Treat
Endometrial Neoplasms
Pulmonary Embolism
Venous Thrombosis
Multicenter Studies
Arm
Biomarkers
Hormones
Incidence
Therapeutics

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Local and Contralateral Recurrence in Breast Intraepithelial Neoplasia. / DeCensi, Andrea; Puntoni, Matteo; Guerrieri-Gonzaga, Aliana; Caviglia, Silvia; Avino, Franca; Cortesi, Laura; Taverniti, Cristiana; Pacquola, Maria Grazia; Falcini, Fabio; Gulisano, Marcella; Digennaro, Maria; Cariello, Anna; Cagossi, Katia; Pinotti, Graziella; Lazzeroni, Matteo; Serrano, Davide; Branchi, Daniela; Campora, Sara; Petrera, Marilena; Buttiron Webber, Tania; Boni, Luca; Bonanni, Bernardo.

In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology, Vol. 37, No. 19, 01.07.2019, p. 1629-1637.

Research output: Contribution to journalArticle

DeCensi, A, Puntoni, M, Guerrieri-Gonzaga, A, Caviglia, S, Avino, F, Cortesi, L, Taverniti, C, Pacquola, MG, Falcini, F, Gulisano, M, Digennaro, M, Cariello, A, Cagossi, K, Pinotti, G, Lazzeroni, M, Serrano, D, Branchi, D, Campora, S, Petrera, M, Buttiron Webber, T, Boni, L & Bonanni, B 2019, 'Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Local and Contralateral Recurrence in Breast Intraepithelial Neoplasia', Journal of clinical oncology : official journal of the American Society of Clinical Oncology, vol. 37, no. 19, pp. 1629-1637. https://doi.org/10.1200/JCO.18.01779
DeCensi, Andrea ; Puntoni, Matteo ; Guerrieri-Gonzaga, Aliana ; Caviglia, Silvia ; Avino, Franca ; Cortesi, Laura ; Taverniti, Cristiana ; Pacquola, Maria Grazia ; Falcini, Fabio ; Gulisano, Marcella ; Digennaro, Maria ; Cariello, Anna ; Cagossi, Katia ; Pinotti, Graziella ; Lazzeroni, Matteo ; Serrano, Davide ; Branchi, Daniela ; Campora, Sara ; Petrera, Marilena ; Buttiron Webber, Tania ; Boni, Luca ; Bonanni, Bernardo. / Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Local and Contralateral Recurrence in Breast Intraepithelial Neoplasia. In: Journal of clinical oncology : official journal of the American Society of Clinical Oncology. 2019 ; Vol. 37, No. 19. pp. 1629-1637.
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T1 - Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Local and Contralateral Recurrence in Breast Intraepithelial Neoplasia

AU - DeCensi, Andrea

AU - Puntoni, Matteo

AU - Guerrieri-Gonzaga, Aliana

AU - Caviglia, Silvia

AU - Avino, Franca

AU - Cortesi, Laura

AU - Taverniti, Cristiana

AU - Pacquola, Maria Grazia

AU - Falcini, Fabio

AU - Gulisano, Marcella

AU - Digennaro, Maria

AU - Cariello, Anna

AU - Cagossi, Katia

AU - Pinotti, Graziella

AU - Lazzeroni, Matteo

AU - Serrano, Davide

AU - Branchi, Daniela

AU - Campora, Sara

AU - Petrera, Marilena

AU - Buttiron Webber, Tania

AU - Boni, Luca

AU - Bonanni, Bernardo

PY - 2019/7/1

Y1 - 2019/7/1

N2 - PURPOSE: Tamoxifen administered for 5 years at 20 mg/d is effective in breast cancer treatment and prevention, but toxicity has limited its broad use. Biomarker trials showed that 5 mg/d is not inferior to 20 mg/d in decreasing breast cancer proliferation. We hypothesized that a lower dose given for a shorter period could be as effective in preventing recurrence from breast intraepithelial neoplasia but have a lower toxicity than the standard dose. PATIENTS AND METHODS: We conducted a multicenter randomized trial of tamoxifen, 5 mg/d or placebo administered for 3 years after surgery in women with hormone-sensitive or unknown breast intraepithelial neoplasia, including atypical ductal hyperplasia and lobular or ductal carcinoma in situ. The primary end point was the incidence of invasive breast cancer or ductal carcinoma in situ. RESULTS: Five hundred women 75 years of age or younger were included. After a median follow-up of 5.1 years (interquartile range, 3.9-6.3 years), there were 14 neoplastic events with tamoxifen and 28 with placebo (11.6 v 23.9 per 1,000 person-years; hazard ratio, 0.48; 95% CI, 0.26 to 0.92; P = .02), which resulted in a 5-year number needed to treat of 22 (95% CI, 20 to 27). Tamoxifen decreased contralateral breast events by 75% (three v 12 events; hazard ratio, 0.25; 95% CI, 0.07 to 0.88; P = .02). Patient-reported outcomes were not different between arms except for a slight increase in frequency of daily hot flashes with tamoxifen (P = .02). There were 12 serious adverse events with tamoxifen and 16 with placebo, including one deep vein thrombosis and one stage I endometrial cancer with tamoxifen and one pulmonary embolism with placebo. CONCLUSION: Tamoxifen at 5 mg/d for 3 years can halve the recurrence of breast intraepithelial neoplasia with a limited toxicity, which provides a new treatment option in these disorders.

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