Abstract A47: Low-dose tamoxifen in the treatment of breast ductal intraepithelial neoplasia: Results of a monoinstitutional observational study on 985 patients

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Abstract Background: Tamoxifen's cost-benefit ratio for breast ductal intraepithelial neoplasia (DIN) is not well established yet. Since low-dose tamoxifen showed a favorable modulation of several breast cancer biomarkers in phase II trials, a mono-institutional cohort of women with DIN treated with low-dose tamoxifen or no systemic treatment was analyzed. Patients and Methods: All consecutive women who underwent surgery at the European Institute of Oncology from 01/01/1999 and 31/12/2007, diagnosed for a DIN with ER positive staining (ER>1%) and followed-up to December 31, 2010 were included in the cohort. The primary endpoint was disease-free survival, calculated from the date of surgery to any local or regional recurrence, contralateral breast cancer (BC), death from BC, or to the last visit date, whatever occurred first. For patients with multiple BC episodes during follow-up, only the first episode was considered in the analysis. Other primaries and non-BC related deaths were considered as competing events. Results: A total of 985patients with a median age of 50 years (range 26–84) were included. Overall, 496 were premenopausal (50%) at diagnosis and 30% of the whole cohort had at least a first or second degree family history of BC. As regards histology, most DIN were solid or cribriform (81%), with a low proliferating index (ki67% <20%, 72%) and with high ER-positive expression immunostaining (91% with ER>50%). Her2 neu was overexpressed in 21% of the cases. Most of the women underwent conservative surgery (78%) and among those, radiotherapy (RT) was given to 45% of the patients. A total of 475 patients with DIN received low-dose tamoxifen as part of institutional guidelines and they were compared with 510 patients with DIN who received no systemic treatment after surgery because of refusal of taking treatment, or because of taking placebo in clinical trials or because of contraindication to tamoxifen use. Relatively to the untreated group, patients receiving low dose tamoxifen tended to be younger and more frequently received RT. Overall, after a median follow-up of 80 months a total of 207 events have been observed: 141 ipsilateral BC (68 infiltrating BC, 73 in situ BC), 35 contralateral BC (21 infiltrating BC, 14 in situ), 31 other primary cancer (including 6 endometrial, 4 lung, 3 bladder, 3 colon and 2 ovarian cancers). A total of 18 deaths have been observed (4 due to BC, 6 for other cancers and 8 for other reasons). Overall, the five year cumulative incidence of DIN-related events was 18.3% in premenopausal women (17.3% in the tamoxifen arm and 20.5% in the untreated arm) and 11.3% in postmenopausal women (8.2% in the tamoxifen arm and 13.3% in the untreated arm). After adjustment for age, BMI, Ki-67%, Her2-neu overexpression, type of surgery and RT, Hazard Ratio (HR) was 0.73 (95%CI 0.49–1.10) and 0.61 (95% CI 0.36–1.00) in premenopausal and postmenopausal patients respectively. In addition, women with ER/PgR >50% DIN who received low dose tamoxifen had a lower incidence of breast events than women who were not treated (HR 0.65; 95% CI, 0.41–1.02) while women with ER/PgR<50% DIN didn't show any protective effect by tamoxifen. Conclusions: Low dose tamoxifen appears to be an active treatment for highly hormone responsive DIN. On the contrary women with low expression ER/PgR DIN do not seem to benefit from tamoxifen. Since at present no standard treatment exists to treat these women, particularly in Europe, where tamoxifen is not registered in women with prior DCIS (DIN 2–3), a multicenter phase III trial is currently ongoing to evaluate the efficacy and the safety of 5 mg/day tamoxifen to reduce breast cancer incidence in women with previous IEN (LIN 2–3 and ER-positive DIN 1b-3). Citation Information: Cancer Prev Res 2011;4(10 Suppl):A47.