Benefit of low-dose tamoxifen in a large observational cohort of high risk ER positive breast DCIS

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Abstract

Low-dose tamoxifen has comparable antiproliferative effect to the standard dose of 20 mg/day in biomarker trials, but its clinical efficacy remains unclear. We assessed the effect of low-dose tamoxifen on ipsilateral recurrence in ductal carcinoma in situ (DCIS) patients treated in a referral Institution between 1996 and 2008. Following conserving surgery, women received radiotherapy and/or low-dose tamoxifen upon clinical judgment and patient preferences. Cox regression analyses were used with and without confounding factors. Among 1,091 women with DCIS and median age 53 years (IQR: 46–62), 544 (49.9%) received radiotherapy. Of the 833 women with oestrogen receptor (ER) positive DCIS, 467 (56.1%) received low-dose tamoxifen. After a median of 7.7 years, 235 ipsilateral recurrences and 62 contralateral breast tumors were observed. Low-dose tamoxifen significantly decreased any breast event (HR = 0.70, 95% CI: 0.54–0.91) and ipsilateral DCIS recurrence (HR = 0.66, 95% CI: 0.49–0.88), but not ipsilateral invasive recurrence or contralateral tumors. Radiotherapy showed a large significant reduction for any breast event (HR = 0.55, 95% CI: 0.42–0.72). Tamoxifen was more effective on all breast events in women aged >50 years than in women aged ≤50 (HR = 0.51, 95% CI: 0.33–0.77 versus HR = 0.84, 95% CI: 0.60–1.18, p-interaction = 0.03). Age ≤50 years, positive margins, high Ki67, high grade and low BMI were independent predictors of ipsilateral recurrence. No increase of endometrial cancers and fewer deaths (p = 0.015) were observed on tamoxifen. Low-dose tamoxifen seems to be safe and effective in reducing ipsilateral recurrence in ER positive DCIS in women aged >50 years. A randomized trial is underway to confirm these findings.

Original languageEnglish
Pages (from-to)2127-2134
Number of pages8
JournalInternational Journal of Cancer
Volume139
Issue number9
DOIs
Publication statusPublished - Nov 1 2016

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Carcinoma, Intraductal, Noninfiltrating
Tamoxifen
Recurrence
Breast
Radiotherapy
Breast Carcinoma In Situ
Patient Preference
Endometrial Neoplasms
Estrogen Receptors
Referral and Consultation
Biomarkers
Regression Analysis
Breast Neoplasms

Keywords

  • ductal carcinoma in situ
  • local neoplasm recurrence
  • low-dose tamoxifen

ASJC Scopus subject areas

  • Medicine(all)
  • Oncology
  • Cancer Research

Cite this

@article{75a589181e214e99b7080b6eaa96dfde,
title = "Benefit of low-dose tamoxifen in a large observational cohort of high risk ER positive breast DCIS",
abstract = "Low-dose tamoxifen has comparable antiproliferative effect to the standard dose of 20 mg/day in biomarker trials, but its clinical efficacy remains unclear. We assessed the effect of low-dose tamoxifen on ipsilateral recurrence in ductal carcinoma in situ (DCIS) patients treated in a referral Institution between 1996 and 2008. Following conserving surgery, women received radiotherapy and/or low-dose tamoxifen upon clinical judgment and patient preferences. Cox regression analyses were used with and without confounding factors. Among 1,091 women with DCIS and median age 53 years (IQR: 46–62), 544 (49.9{\%}) received radiotherapy. Of the 833 women with oestrogen receptor (ER) positive DCIS, 467 (56.1{\%}) received low-dose tamoxifen. After a median of 7.7 years, 235 ipsilateral recurrences and 62 contralateral breast tumors were observed. Low-dose tamoxifen significantly decreased any breast event (HR = 0.70, 95{\%} CI: 0.54–0.91) and ipsilateral DCIS recurrence (HR = 0.66, 95{\%} CI: 0.49–0.88), but not ipsilateral invasive recurrence or contralateral tumors. Radiotherapy showed a large significant reduction for any breast event (HR = 0.55, 95{\%} CI: 0.42–0.72). Tamoxifen was more effective on all breast events in women aged >50 years than in women aged ≤50 (HR = 0.51, 95{\%} CI: 0.33–0.77 versus HR = 0.84, 95{\%} CI: 0.60–1.18, p-interaction = 0.03). Age ≤50 years, positive margins, high Ki67, high grade and low BMI were independent predictors of ipsilateral recurrence. No increase of endometrial cancers and fewer deaths (p = 0.015) were observed on tamoxifen. Low-dose tamoxifen seems to be safe and effective in reducing ipsilateral recurrence in ER positive DCIS in women aged >50 years. A randomized trial is underway to confirm these findings.",
keywords = "ductal carcinoma in situ, local neoplasm recurrence, low-dose tamoxifen",
author = "Aliana Guerrieri-Gonzaga and Ivana Sestak and Matteo Lazzeroni and Davide Serrano and Nicole Rotmensz and Massimiliano Cazzaniga and Clara Varricchio and Giancarlo Pruneri and Leonardi, {Maria Cristina} and Roberto Orecchia and Viviana Galimberti and Bernardo Bonanni and Andrea DeCensi",
year = "2016",
month = "11",
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language = "English",
volume = "139",
pages = "2127--2134",
journal = "International Journal of Cancer",
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T1 - Benefit of low-dose tamoxifen in a large observational cohort of high risk ER positive breast DCIS

AU - Guerrieri-Gonzaga, Aliana

AU - Sestak, Ivana

AU - Lazzeroni, Matteo

AU - Serrano, Davide

AU - Rotmensz, Nicole

AU - Cazzaniga, Massimiliano

AU - Varricchio, Clara

AU - Pruneri, Giancarlo

AU - Leonardi, Maria Cristina

AU - Orecchia, Roberto

AU - Galimberti, Viviana

AU - Bonanni, Bernardo

AU - DeCensi, Andrea

PY - 2016/11/1

Y1 - 2016/11/1

N2 - Low-dose tamoxifen has comparable antiproliferative effect to the standard dose of 20 mg/day in biomarker trials, but its clinical efficacy remains unclear. We assessed the effect of low-dose tamoxifen on ipsilateral recurrence in ductal carcinoma in situ (DCIS) patients treated in a referral Institution between 1996 and 2008. Following conserving surgery, women received radiotherapy and/or low-dose tamoxifen upon clinical judgment and patient preferences. Cox regression analyses were used with and without confounding factors. Among 1,091 women with DCIS and median age 53 years (IQR: 46–62), 544 (49.9%) received radiotherapy. Of the 833 women with oestrogen receptor (ER) positive DCIS, 467 (56.1%) received low-dose tamoxifen. After a median of 7.7 years, 235 ipsilateral recurrences and 62 contralateral breast tumors were observed. Low-dose tamoxifen significantly decreased any breast event (HR = 0.70, 95% CI: 0.54–0.91) and ipsilateral DCIS recurrence (HR = 0.66, 95% CI: 0.49–0.88), but not ipsilateral invasive recurrence or contralateral tumors. Radiotherapy showed a large significant reduction for any breast event (HR = 0.55, 95% CI: 0.42–0.72). Tamoxifen was more effective on all breast events in women aged >50 years than in women aged ≤50 (HR = 0.51, 95% CI: 0.33–0.77 versus HR = 0.84, 95% CI: 0.60–1.18, p-interaction = 0.03). Age ≤50 years, positive margins, high Ki67, high grade and low BMI were independent predictors of ipsilateral recurrence. No increase of endometrial cancers and fewer deaths (p = 0.015) were observed on tamoxifen. Low-dose tamoxifen seems to be safe and effective in reducing ipsilateral recurrence in ER positive DCIS in women aged >50 years. A randomized trial is underway to confirm these findings.

AB - Low-dose tamoxifen has comparable antiproliferative effect to the standard dose of 20 mg/day in biomarker trials, but its clinical efficacy remains unclear. We assessed the effect of low-dose tamoxifen on ipsilateral recurrence in ductal carcinoma in situ (DCIS) patients treated in a referral Institution between 1996 and 2008. Following conserving surgery, women received radiotherapy and/or low-dose tamoxifen upon clinical judgment and patient preferences. Cox regression analyses were used with and without confounding factors. Among 1,091 women with DCIS and median age 53 years (IQR: 46–62), 544 (49.9%) received radiotherapy. Of the 833 women with oestrogen receptor (ER) positive DCIS, 467 (56.1%) received low-dose tamoxifen. After a median of 7.7 years, 235 ipsilateral recurrences and 62 contralateral breast tumors were observed. Low-dose tamoxifen significantly decreased any breast event (HR = 0.70, 95% CI: 0.54–0.91) and ipsilateral DCIS recurrence (HR = 0.66, 95% CI: 0.49–0.88), but not ipsilateral invasive recurrence or contralateral tumors. Radiotherapy showed a large significant reduction for any breast event (HR = 0.55, 95% CI: 0.42–0.72). Tamoxifen was more effective on all breast events in women aged >50 years than in women aged ≤50 (HR = 0.51, 95% CI: 0.33–0.77 versus HR = 0.84, 95% CI: 0.60–1.18, p-interaction = 0.03). Age ≤50 years, positive margins, high Ki67, high grade and low BMI were independent predictors of ipsilateral recurrence. No increase of endometrial cancers and fewer deaths (p = 0.015) were observed on tamoxifen. Low-dose tamoxifen seems to be safe and effective in reducing ipsilateral recurrence in ER positive DCIS in women aged >50 years. A randomized trial is underway to confirm these findings.

KW - ductal carcinoma in situ

KW - local neoplasm recurrence

KW - low-dose tamoxifen

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