Abstract P4-15-06: Low dose tamoxifen lowers recurrences after mastectomy for in situ neoplasia. Ten-year results of a monoinstitutional study
Authors: Guerrieri-Gonzaga A , Gandini S , Serrano D , Lazzeroni M , Pruneri G , Varricchio C , Cazzaniga M , Leonardi MC , Galimberti V , Viale G , De Censi A , Bonanni B 
Published: February 2018

Abstract
There is no agreement upon the need of a preventive treatment after breast mastectomy for in situ neoplasia. Low-dose tamoxifen (5 mg/day) has comparable antiproliferative effect than the standard dose of 20 mg/day in biomarker trials and has been shown to halve ipsilateral recurrence in a large cohort of postmenopausal ER positive DCIS treated with breast conserving surgery (Guerrieri-Gonzaga et al., Int J Cancer 2016).
Here we investigated the effect of low dose tamoxifen in patients treated with mastectomy for an in situ neoplasia and followed-up in a single Institution for a median of 10 years.
Our cohort consists of 404 consecutive premenopausal (n=281) or postmenopausal (n=123) women who underwent unilateral mastectomy at the European Institute of Oncology (IEO), with or without nipple preservation, between 1996 and 2011. Patients had a diagnosis of pure LCIS (n=12) or ER positive (ER&gt;1%) DCIS (n=363) or both (n=29) and were treated with tamoxifen 5 mg/day (n=162) or no treatment (n=242) upon medical judgment, patient preference and/or clinical trial assignment. The main subject and tumor characteristics are reported in table 1.
Patient and tumor characteristics No tam (n=242)Low dose tam (n=162)P-valueMedian age, years (IQR)46 (41, 54)47 (42, 51)0.65Premenopausal status (n, %)160 (66)121 (75)0.07Median BMI (kg/m2, IQR)22 (20, 25)22 (20, 24)0.7Breast cancer family history (%)29320.44Histology (LCIS, DCIS, both; %)4/92/42/86/120.01Grading (G1,G2,G3;%)11/59/2918/61/200.04Median ER (%, IQR)90 (70, 95)90 (80, 95)0.005Median PgR (%, IQR)40 (5, 80)68 (25, 90)0.0002Median Ki67 (%, IQR)15 (10, 23)14 (10, 20)0.03Radiotherapy (n, %)95 (39)76 (47)0.13
After a median follow-up of 10 years (range 4-21 years) and a median low dose tamoxifen treatment of 4.9 years (IQR 2.7, 5.0), a total of 85 events were observed (28 in situ, 40 invasive breast cancers, 3 metastatic diseases, 12 other primary cancers, 2 deaths). A total of 36 ipsilateral breast events (23 versus 13 in the no tam versus tam group, respectively), 32 contralateral breast events (22 versus 10 in the no tam versus tam, respectively) and 17 other events (11 versus 6 in the no tam versus tam, respectively) occurred. Overall, eleven deaths (3%) occurred and no endometrial cancers were observed. A time-dependent competing risk model was applied for tamoxifen use and we have shown that low-dose tamoxifen was associated with a 48% reduction on all breast events (adjusted HR=0.52, 95% CI: 0.31–0.88, p=0.01), adjusting for radiotherapy and age.
Although limited by the observational nature of the study, we show for the first time that treatment with low dose tamoxifen is effective and safe in women who underwent mastectomy for non-invasive breast neoplasms and should be taken into consideration as a risk reduction strategy for premenopausal and postmenopausal women with breast intraepithelial neoplasia.
Citation Format: Guerrieri-Gonzaga A, Gandini S, Serrano D, Lazzeroni M, Pruneri G, Varricchio C, Cazzaniga M, Leonardi MC, Galimberti V, Viale G, De Censi A, Bonanni B. Low dose tamoxifen lowers recurrences after mastectomy for in situ neoplasia. Ten-year results of a monoinstitutional study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-15-06.