Abstract P5-15-03: Bisphosphonate use and breast cancer recurrence risk in the QUILT cohort
Authors: Korde LA , Doody DR , Malone KE 
Published: May 2016

Abstract
Background: Women with breast cancer are often prescribed bisphosphonates (BP) for treatment or prevention of osteoporosis. Clinical trials designed to assess the effect of BP on risk of recurrence in women with breast cancer have produced conflicting results. Several randomized studies and a recent meta-analysis suggested that a protective effect of BP is limited to postmenopausal women. Current data have not definitively addressed the utility of BP in patients with ER-positive vs. ER-negative disease.
Methods: We examined use of BP for non-cancer therapy in the QUILT cohort study. The analysis included 1813 women diagnosed with invasive breast cancer at ages 45 to 79 in 1993-1999. Data collection was via medical record review, in-person interview and the Cancer Surveillance System, a population-based registry in the NCI SEER program. Cox proportional hazards regression methods were used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for the association between BP use and outcome. Analyses were adjusted for age and year of diagnosis.
Results: Mean age at diagnosis of study participants was 64.2 years. Eighty-four percent were postmenopausal at diagnosis; 86% had estrogen receptor positive disease; 16.7% used a BP after diagnosis of breast cancer. Among women with any BP use, 91% had a diagnosis of osteopenia or osteoporosis. Mean duration of BP use after BC diagnosis was 35.2 months; 90% of BP users took alendronate. Ever use (2+ months) of BP was associated with a significant decreased risk of any breast cancer event (local recurrence, distant recurrence, or second primary breast cancer; HR 0.65; 95% CI 0.47-0.90). Within users, there was a trend toward lower risk with longer duration of use (p=0.096, see Table 1).
Association between BP use and any breast cancer event (by duration of use)Duration of bisphosphonate useNo event n (%)Any event n (%)Hazard ratio (95% CI)None/Less than 1 mo1070 (70.8)441 (29.2)1.00 (ref)2 mo to &lt;1 yr40 (76.9)12 (23.1)0.82 (0.46-1.45)1 yr to &lt;3 yrs89 (82.4)19 (17.6)0.76 (0.48-1.20)3+ yrs131 (92.3)11 (7.7)0.44 (0.24-0.81)
Though the number of events was smaller, similar effects were seen for each event type (distant recurrence: HR=0.62, 95% CI 0.37-1.06; local recurrence: HR=0.62, 95% CI 0.26-1.44; second primary breast cancer: HR= 0.75, 95% CI 0.47-1.18). Stratification by menopausal status showed a decreased risk of recurrence with BP use for both pre or peri- and postmenopausal women (pre/perimenopausal: HR = 0.34, 95% CI 0.12-0.94; postmenopausal: HR=0.72, 95% CI 0.51-1.01). BP use was protective in both women with ER positive (HR=0.64, 95% CI 0.0.45-0.91) and ER negative (HR=0.46, 95% CI 0.16-1.27) disease.
Conclusion: In this study, we observed a decreased risk of locoregional recurrence, distant recurrence, and second primary breast cancer with BP use after a diagnosis of invasive breast cancer. This effect was seen in pre and postmenopausal women, and for both ER positive and ER negative disease. Women in this cohort were prescribed primarily oral BP for treatment or prevention of osteoporosis. Additional prospective studies of adjuvant BP use should focus on women with low bone density regardless of menopausal status, and should include patients with both ER-positive and ER-negative disease.
Citation Format: Korde LA, Doody DR, Malone KE. Bisphosphonate use and breast cancer recurrence risk in the QUILT cohort. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-15-03.