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.
authors.affiliation: Divisions of Cancer Prevention and Genetics, European Institute of Oncology Milan, Italy.
authors.forename: Aliana
authors.initials: A
authors.lastname: Guerrieri-Gonzaga
authors.affiliation: Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, United Kingdom.
authors.forename: Ivana
authors.initials: I
authors.lastname: Sestak
authors.affiliation: Divisions of Cancer Prevention and Genetics, European Institute of Oncology Milan, Italy.
authors.forename: Matteo
authors.initials: M
authors.lastname: Lazzeroni
authors.affiliation: Divisions of Cancer Prevention and Genetics, European Institute of Oncology Milan, Italy.
authors.forename: Davide
authors.initials: D
authors.lastname: Serrano
authors.affiliation: Epidemiology and Biostatistics, European Institute of Oncology Milan, Italy.
authors.forename: Nicole
authors.initials: N
authors.lastname: Rotmensz
authors.affiliation: Divisions of Cancer Prevention and Genetics, European Institute of Oncology Milan, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Cazzaniga
authors.affiliation: Divisions of Cancer Prevention and Genetics, European Institute of Oncology Milan, Italy.
authors.forename: Clara
authors.initials: C
authors.lastname: Varricchio
authors.affiliation: Pathology, European Institute of Oncology Milan, Italy.|University of Milan, School of Medicine, Milan, Italy.
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Pruneri
authors.affiliation: Radiotherapy, European Institute of Oncology Milan, Italy.
authors.forename: Maria Cristina
authors.initials: MC
authors.lastname: Leonardi
authors.affiliation: University of Milan, School of Medicine, Milan, Italy.|Radiotherapy, European Institute of Oncology Milan, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Orecchia
authors.affiliation: Breast Surgery, European Institute of Oncology Milan, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Galimberti
authors.affiliation: Divisions of Cancer Prevention and Genetics, European Institute of Oncology Milan, Italy.
authors.forename: Bernardo
authors.initials: B
authors.lastname: Bonanni
authors.affiliation: Divisions of Cancer Prevention and Genetics, European Institute of Oncology Milan, Italy.|Centre for Cancer Prevention, Wolfson Institute of Preventive Medicine, Queen Mary University of London, United Kingdom.|Division of Medical Oncology, E.O. Ospedali Galliera, Genoa, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: DeCensi
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000008:administration & dosage* / Q000627:therapeutic use; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000188:drug therapy* / Q000532:radiotherapy / Q000601:surgery; D003131:Combined Modality Therapy; D005260:Female; D006801:Humans; D015412:Mastectomy, Segmental; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology*; D011960:Receptors, Estrogen / Q000378:metabolism; D016019:Survival Analysis; D013629:Tamoxifen / Q000008:administration & dosage* / Q000627:therapeutic use; D016896:Treatment Outcome
chemical_list: D018931:Antineoplastic Agents, Hormonal; D011960:Receptors, Estrogen; D013629:Tamoxifen
keywords: ductal carcinoma in situ; local neoplasm recurrence; low-dose tamoxifen