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Ductal Intraepithelial Neoplasia: Postsurgical Outcome for 1,267 Women Cared for in One Single Institution over 10 Years

^aCancer Prevention and Genetics, ^bEpidemiology and Biostatistics, ^cPathology, ^dBreast Surgery, ^eMedical Oncology, and ^fRadiotherapy, European Institute of Oncology, Milan, Italy; ^gDepartment of Statistics, University of Milan-Bicocca, Milan, Italy; ^hUniversity of Milan School of Medicine, Milan, Italy; ⁱUniversity of Rome Tor Vergata School of Oncology, Rome, Italy; ^jDivision of Medical Oncology, Galliera Hospital, Genoa, Italy ^kScientific Directorate, European Institute of Oncology, Milan, Italy

Key Words. Intraepithelial neoplasia • Tamoxifen • Chemoprevention • Radiotherapy

Correspondence: Correspondence: Andrea Decensi, M.D., Division of Medical Oncology, Galliera Hospital, Mura Le Capuccine 14, 16128 Genoa, Italy. Telephone: 39-0105634501; Fax: 39-01057481090; e-mail: andrea.decensi{at}galliera.it

Received September 10, 2008; accepted for publication January 28, 2009.

Disclosures: Aliana Guerrieri-Gonzaga: None; Edoardo Botteri: None; Nicole Rotmensz: None; Fabio Bassi: None; Mattia Intra: None; Davide Serrano: None; Giuseppe Renne: None; Alberto Luini: None; Massimiliano Cazzaniga: None; Aaron Goldhirsch: None; Marco Colleoni: None; Giuseppe Viale: None; Giovanni Ivaldi: None; Vincenzo Bagnardi: None; Matteo Lazzeroni: None; Andrea Decensi: None; Umberto Veronesi: None; Bernardo Bonanni: None

The content of this article has been reviewed by independent peer reviewers to ensure that it is balanced, objective, and free from commercial bias.

Introduction. Diagnosis of breast ductal intraepithelial neoplasia (DIN) has increased over the last decades, but proper postsurgical treatment remains controversial. We analyzed risk factors and treatment outcome in a large series of women treated at one institution.

Methods. Women undergoing surgery for DIN at the European Institute of Oncology between 1996 and 2005, with follow-up until December 2006, were included.

Results. We evaluated the postsurgical treatment outcome of 974 and 293 patients who underwent breast-conserving surgery (BCS) or mastectomy, respectively. The 5-year cumulative incidence of breast cancer (BC) events was 11.8%, with a significant trend according to age (from 43% in women <36 years to 8% in women >65 years).

Among the 727 BCS patients with DIN2–DIN3 histology, 414 (57%) received radiotherapy (RT), and they were both younger and with worse prognostic factors than the 313 patients who did not receive it. In these groups, the adjusted hazard ratio (HR) for RT versus non-RT was 0.40 (95% confidence interval [CI], 0.26–0.63).

Among the 691 BCS patients with estrogen receptor (ER)⁺ disease, 329 (48%) received low-dose tamoxifen (either 5 mg/day or 20 mg once a week) and they were younger than the 362 who did not receive it. In these groups, the adjusted HR for tamoxifen versus no tamoxifen was 0.68 (95% CI, 0.43–1.07), and the HR was 0.55 (95% CI, 0.32–0.97) after excluding human epidermal growth factor receptor (HER)2/neu-overexpressing DIN.

Conclusions. BC events were more frequent in young patients. RT was associated with a lower incidence of BC events. Low-dose tamoxifen was associated with a lower incidence of BC events in patients with ER⁺ disease when HER-2 was not overexpressed. Further prospective studies should confirm our observations.

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