19558 Introduction: Osteoporotic fracture represents a major source of morbidity in PmW. Breast cancer patients can be at additional risk because of treatment related estrogen deprivation. The favorable effects of bisphosphonates in osteoporosis and potential reduction of metastases warrant evaluation of ZA in PmW at high risk for breast cancer relapse. We assessed whether ZA 4 mg IV every 12 weeks x 4 doses was associated with an increase in BMD. Secondary objectives included defining ZA’s toxicity profile in this setting, and assessing for differences in overall cancer relapse. Methods: PmW with node positive or stage III breast cancer diagnosed less than 5 years earlier were randomized to ZA or observation. BMD was assessed by dual energy xray absorptiometry (DXA) for all subjects at 0 and 12 months. A toxicity evaluation was performed pre- and post-treatment for patients receiving ZA. Study endpoint occurred when subjects completed the DXAs, had disease progression or declined further treatment. We calculated change in BMD between 0 and 12 months at the L1–4 spine and femur neck. Results: 66 women have enrolled since 2000; 49 women have completed DXAs at 0 and 12 months (observation 23, ZA 26). Median age was 52 (range 40–81 yr), median ECOG performance status was 0 (range 0–1), and most women received concurrent tamoxifen (observation 74%, ZA 61%). Over 12 months, L1–4 spine BMD decreased in the observation arm (-0.006 ± 0.034 g/cm2) and increased in the ZA arm (p<0.001; 0.050 ± 0.042 g/cm2). No significant BMD change occurred at the femur neck. Only three grade 3 events occurred (2 arthralgia, 1 myalgia). Side effects were mild and transient, but as frequent as 87% following dose 1. The most common side effects were fatigue, myalgia and arthralgia. No clinically significant changes in creatinine or calcium occurred. Osteonecrosis of the jaw was not observed. Of the 66 women enrolled, 7 have relapsed (observation 4, ZA 3) but time since diagnosis is less than 10 years for most patients. Conclusions: ZA administered every 12 weeks for 4 doses leads to a statistically and clinically significant change in BMD at the lumbar spine. Toxicity was mild but common. There are as yet no significant differences in cancer relapse. No significant financial relationships to disclose.

Background: To date, the use of anti-androgens in the subset of triple negative breast cancers (TNBC) that express androgen receptor (AR) has shown modest response rates, indicating anti-androgen-resistance in the majority of these tumors. Based on data that Cyclin D kinase (CDK) inhibitors reverse resistance to anti-androgens in prostate cancer cell lines, we hypothesize that the use of CDK inhibition may enhance the activity of anti-androgens in AR-positive TNBC. Methods: Key eligibility include: patients with centrally confirmed AR-positive TNBC, defined as AR expression &gt;0%; 0 to 1 line of prior therapy for metastatic disease; and measurable disease. Patients are treated with bicalutamide 150mg orally once daily plus ribociclib at one of 3 dose levels (see table). Table 1Dose levelBicalutamideRibociclib1150mg orally once daily (D1 to 28)400mg daily (D1 to 21)2150mg orally once daily (D1 to 28)400mg daily (D1 to 28)3150mg orally once daily (D1 to 28)600mg daily (D1 to 21) Results: AR expression was positive by trial criteria in 74% of screened patients. Three patients have been accrued at each dose level. Median age is 56 and 6 and 3 patients were treated in first and second-line settings, respectively. Median AR expression was 50% (range 5 to 75%). Toxicity data is available for 6-patients treated on dose levels 1 and 2. No dose-limiting toxicities were noted. As anticipated with ribociclib, the most common toxicity is neutropenia (1 patient grade 4 and 2 patients grade 3). Two patients experienced grade 3 hypertension and 1 experienced grade 3 lymphopenia. Grade 2 or lower toxicities included fatigue, nausea, hyperglycemia and mucositis. One patient experienced grade 1 QT interval prolongation. Conclusion: The combination of bicalutamide and ribociclib is tolerable without unexpected toxicities. Data on the 3-patients treated at dose level 3 and dose expansion will be included. Phase 2 dosing schedule will be decided based on phase 1 results. Citation Format: Sharifi M, Wisinski KB, Burkard ME, Tevaarwerk AJ, Tamkus D, Chan N, Truica C, Danciu O, Hoskins K, O'Regan RM. Phase I trial of bicalutamide and ribociclib in androgen receptor-positive triple negative breast cancer [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr OT1-02-01.