P2-17-08: rospective Study of Aromatase Inhibitor Induced Bone Loss and Lipid Levels in Early Postmenopausal (PM) Hormone Receptor Positive (HR+) Breast Cancer (BC) Patients Treated with Adjuvant Letrozole Extended beyond 5 Years (yrs).

Introduction/Aim: Adjuvant treatment with aromatase inhibitors (AI) is associated with accelerated bone loss and increase in lipid levels. The effectiveness and tolerance of extended treatment with AI beyond 5 years is currently under investigation. In the SOLE study, five years of continuous (C) extended letrozole is compared to interrupted therapy (9 months on, 3 months off letrozole) after 5 yrs of tamoxifen, AI or sequential hormonal therapy. We have evaluated the bone mineral density and lipid levels during the extended use of letrozole beyond 5 yrs in a cohort of patients included in the SOLE study. Patients and methods: Postmenopauzal women with HR+ BC, receiving extended continuous (C) or intermittent (I) letrozole for 5 yrs after 5 yrs of tamoxifen, 5 yrs of an AI, or switch therapy within the first 5 years, were included. Bone mineral density was measured at the lumbar spine (L2-4) and total hip BMD (g/cm 2 ), by dual energy X-ray absorptiometry (DXA). The mean percentage change in BMD at 12, 36 and 60 months (mths) was compared between the C and I treatment with letrozole and with baseline values. Differences between the treatment groups were assessed by the independent samples T test. We also compared the evolution ofthe serum lipid levels in both arms. Results: Thirty two patients (pts) were included with a mean age of 62 yrs (+/− 8.7 yrs). Thirty pts were valuable because of missing baseline DXA values in 2. In their first 5 years of adjuvant letrozole, prior to inclusion in the current study, twenty three pts had a mean percentage decrease of −0,76 (13,25 SD) and 7 pts who had received preventive zoledronate in the ZOFAST study, had a mean percentage increase in BMD of 4,4 (6,08 SD). Currently 12 pts receiving the continuous letrozole are evaluable after a first one year extension of adjuvant letrozole. They had a mean percentage increase in BMD for the lumbar spine of 1.8 (3.3 SD), and a mean percentage increase in BMD for the hip of 0.85 (SD 1.93). Eight pts included in the intermittent arm are evaluable. They experience a mean percentage decrease in BMD for the lumbar spine of −0.32(2.7 SD) and a mean decrease in BMD for the hip of −2.9(SD 3.6) The difference between the two treatment groups was not significant for the lumbar spine measurements (p=0.14), but it was significant for the hip (p=0.02). The mean fasting cholesterol levels at 12 months in the C arm (12pts) was 228mg/dl (24.4 SD) and in the I arm (11pts) was 225,5mg/dl(32,3 SD) (p=0.37). Conclusion: This is the first prospective BMD and lipid follow-up study during adjuvant letrozole extended beyond 5 yrs in PM early breast cancer pts. After the first year of extended intake of continuous or intermittent letrozole a possible difference in bone mineral density between the two arms is emerging, but the two groups are too small to make final conclusions. An updated longer follow-up on more patients will be presented. After one year no differential effect on cholesterol levels has been observed. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P2-17-08.