Background. Several randomized trials demonstrated aromatase inhibitors (AI) superiority in terms of disease-free survival (DFS) compared to tamoxifen treatment for postmenopausal hormone receptor-positive breast cancer (BC) patients. Anyway, AI toxicity profile is a concern due to estrogen suppression. Pivotal trials demonstrated a significant bone mineral density (BMD) loss due to AI, with a consistent 5-year risk of bone fractures, thus impacting on patients9 quality of life. Bisphosphonates represent an effective treatment in postmenopausal osteoporosis fractures prevention. However, an adequate patient9s selection for adjuvant bisphosphonates treatment during AI endocrine therapy is still a challenge. Final results of BONADIUV trial presented at San Antonio Breast cancer Symposium in 2016 showed that treatment with ibandronate, as compared to placebo, significantly improved BMD change in osteopenic women treated with adjuvant AI, and consistently protected patients9 bone loss. We present the secondary 5-year analysis on survival outcomes of the trial. Patients and methods. The BONADIUV trial is a single-blind, randomized, placebo-controlled phase 2 study designed to evaluate the impact of ibandronate treatment on BMD in osteopenic women taking AI. Between January 2011 and May 2014, 171 osteopenic patients (lumbar spine [LS] and/or trochanter -1 Results. At the database cutoff time for the present analysis on May 4, 2018, median follow up was 63.3 months (mean 61.2; range 2.7-87.3) for whole series, 64.9 months (range 33.8-84.0) for the placebo arm, and 62.2 months (range 24.2-87.3) for the ibandronate arm. Ten patients in the placebo group and 17 patients in the ibandronate group withdrew the allocated arm before any follow up data collection, and so were excluded from the analysis, performed on 144 patients (72 patients per arm). At the database cutoff time, the OS rate was 97.2% in the placebo group and 100% in the ibandronate arm. We observed four loco-regional relapse (three in the placebo arm, one in the ibandronate arm; p=0.33), three distant metastases (none in the placebo arm, three in the ibandronate arm; p=0.075), and three contralateral BC (one in the placebo arm, two in the ibandronate arm; p=0.65). The number of iDFS events did not differ between groups: four in the placebo group and six in the ibandronate group (p=0.56). Up to data cutoff, two deaths have occurred; none in the placebo arm and two in the ibandronate arm (p=0.15). The OS rate did not differ between arms. Conclusions. The secondary analysis of survival outcomes showed no difference between arms in terms of OS and iDFS rates. Further large investigations and mature follow-up from the published ones are awaited. Citation Format: Meattini I, Scotti V, Desideri I, Saieva C, Visani L, Salvestrini V, Cecchini S, De Feo ML, Mariotti M, Olmetto E, Delli Paoli C, Francolini G, Bernini M, Orzalesi L, Sanchez L, Nori J, Bianchi S, Livi L. Oral ibandronate for osteopenic breast cancer patients receiving adjuvant aromatase inhibitors: secondary 5-year survival outcomes analysis of the single-center phase 2 BONADIUV trial [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 P4-16-04.

Abstract Background. Several randomized trials demonstrated aromatase inhibitors (AI) superiority in terms of disease-free survival compared to tamoxifen treatment for postmenopausal hormone receptor-positive breast cancer (BC) patients. Anyway AI toxicity profile due to estrogen suppression is a concern. Pivotal trials demonstrated a significant bone mineral density (BMD) loss due to AI, with a consistent risk of fractures, thus impacting on patients' quality of life. Bisphosphonates represent an effective treatment in postmenopausal osteoporosis fractures prevention. Several studies demonstrated that upfront bisphosphonates therapy prevents bone loss in postmenopausal women receiving adjuvant AI for early-stage BC. However an adequate patients selection for adjuvant bisphosphonates treatment during AI endocrine therapy is still a challenge. We present the final results of the BONADIUV trial, a single-blind, randomized, placebo-controlled phase 2 study designed to evaluate the impact of ibandronate treatment on BMD in osteopenic women taking AI. Methods. Between January 2011 and May 2014, 561 patients underwent a baseline BMD assessment before starting AI as planned adjuvant treatment. Overall 171 osteopenic patients (lumbar spine [LS] and/or trochanter -1< T-score <-2.5), were randomized in a 1:1 ratio to receive either placebo or oral monthly ibandronate (150 mg). All patients receive oral supplementation of calcium and vitamin D3. Study duration was 2 years. Exclusion criteria were: premenopausal status at time of randomization; comorbidities with increased risk of osteoporosis; body mass index <18; chronic use of steroids; previous use of bisphosphonates; psychiatric disorders. Primary endpoint was the mean BMD difference between the two arms at a 2-year follow up. ClinicalTrials.gov identifier: NCT02616744. A total of 72 patients per arm of treatment were needed to obtain an 85% statistical power in order to detect a 2% BMD mean difference between the two arms. Considering a 10% dropout, at least 158 patients were required. Results. A total of 171 patients were randomized in the study. Overall 27 patients (15.8%) withdrew the protocol (17 ibandronate vs 10 placebo arm): the final analysis was performed on 144 patients (72 patients per arm). P-value from Wilcoxon test showed no significant difference between arms at baseline both for LS (p=0.94) and trochanter (p=0.83). At 2-year, osteopenic patients treated with ibandronate gained +18.7% and +15.5% at the LS and trochanter BMD, respectively. Patients treated with placebo lost -13.3% at the LS, and gained +2.9% at the trochanter. Trochanter p-value from covariance analysis showed a mean BMD change significantly in favor of ibandronate arm at 1-year (p=0.012), and borderline at 2-year (p=0.087). Concerning LS, the mean BMD change was significantly in favor of ibandronate arm both at 1-year (p=0.002) and 2-year (p<0.0001). Conclusions. Final results of our study showed that treatment with ibandronate, as compared to placebo, improved BMD change in osteopenic women treated with adjuvant AI, and consistently protected patients' bone loss. Citation Format: Livi L, Saieva C, Desideri I, Scotti V, De Luca Cardillo C, Carta G, Cecchini S, Orzalesi L, Sanchez LJ, Casella D, Bernini M, Nori J, Bianchi S, De Feo ML, Meattini I. A single-blind, randomized, placebo-controlled phase II study to evaluate the impact of oral ibandronate on bone mineral density in osteopenic breast cancer patients receiving adjuvant aromatase inhibitors: Final results of the single-center BONADIUV trial [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P2-09-12.

Objectives: To evaluate the efficacy and safety of Gamma Knife Radiosurgery (GKRS) in the treatment of single and multiple brain metastases.Patients and methods: From October 2012 to June 2014 106 patients were treated with Radiosurgery (RS) for brain metastases at University of Florence. 77 out of 106 patients had a radiological follow up and their data were analyzed. The target was defined as the enhancing lesion. The prescription dose was defined depending on tumor volume and tumor location. Each patient performed an MRI one month after GKRS for the first three months and every 3 months thereafter. Overall survival was calculated from the day of RS until death. Local recurrence (LR) was defined as radiologic growth of the irradiated lesion, while distant brain recurrence (DBR) was the evidence of brain lesion outside the previous irradiated field. Both the LR and DBR were calculated from the RS till the day of radiological evidence of relapse. The correlations within patient and disease characteristics and the outcomes of survival and disease control were analyzed.Results: Mean follow up was 7.2 +/- 4.8 months (range: 2.4-22.8 months). At the time of analysis 21 patients (273%) were dead. The overall survival (OS) at 1 year was 74%. On univariate Cox Regression analysis female gender (p = 0.043, HR: 0.391, 95% CI: 0.157-0.972) and age >65 years (p = 0.003 HR: 4.623, 95% CI: 1.687-12.663) were predictive for survival. On multivariate analysis, age older than 65 years (p = 0.005HR: 4.254, 95% CI: 1.544-11.721) was confirmed as associated with worsened overall survival. 19 patients (24.7%) had recurrence in the radiosurgery field. The median time to local failure was 4.8 +/- 2.0 months (range: 1.8-9.4 months) from GKRS. On Cox Regression univariate analysis, the only factor associated with higher risk of local failure was a number of treated lesions more than 4 (p = 0.015, HR: 3.813, 95% CI: 1.298-11.202), no significant parameters were found at the multivariate analysis. The median time to develop distant brain failure was 6 +/- 4.32 months (range: 1.08-21.6 months). Median distant brain control was 74% at 1 year. None of the factors analyzed was statistically significant for the distant brain relapse. The radiosurgery treatment was well tolerated. One patient treated for seven metastases developed seizures 8 h after GKRS, he was treated with steroids and anticonvulsants. One patient had radiologic evidence of radionecrosis without any neurological symptoms.Conclusions: In well-performing patients with stable systemic disease radiosurgery can be performed as an exclusive treatment for brain metastases. Younger patients could have a greater benefit from the RS, on the other hand our finding confirm no correlation between the survival outcome and the number of lesions treated. (C) 2015 Elsevier B.V. All rights reserved.

Introduction: Aromatase inhibitors (AIs) are the adjuvant treatment of choice in postmenopausal women with early, hormone receptor-positive breast cancer (BC), because they produce improved disease-free survival rates compared with tamoxifen. Progressive bone loss and subsequent fractures are associated with adjuvant AIs, administered either alone or sequentially after tamoxifen in postmenopausal women with early BC. Recent findings of NSABP B-34 also suggest that bisphosphonates might have anticancer benefits for older postmenopausal women. We present the “BONADIUV” trial, a single-blind, randomized, placebo-controlled study designed to evaluate the impact of bisphosphonate treatment on bone mineral density (BMD) in women taking AIs. Methods: At this time, we enrolled 116 patients (of 190 planned patients) at Florence University (Radiotherapy Unit Department) treated with adjuvant AIs and affected by early BC and osteopenia. We assessed BMD every year and hematic and urinary calcemia, phosphoremia, parathormon, magnesemia, vitamin D, urinary pyridinoline and telopepitde-C every 6 months, until 2 years. Arm A consisted of AIs plus oral ibandronate (150 mg, monthly); Arm B consisted of AIs plus placebo. All patients were treated with calcium and vitamin D supplementation. Primary endpoint was evaluation of ibandronate efficacy in BMD reduction. Secondary endpoints were ibandronate patient's compliance, FRAX® index evaluation, ibandronate safety and bone turn-over markers. Results: At a median follow-up of 12 months (range 6-24), median age in Arm A was 60 (range 47-65) years (59 enrolled patients) and 60 (range 49-65) years in Arm B (57 enrolled patients). Basal Vitamin D was 21.1 ng/mL in Arm A and 37.0 ng/mL in Arm B; at 12 months basal Vitamin D was 25.2 ng/mL in Arm A and 26.3 ng/mL in Arm B. Compliance to ibandronate assumption was optimal. Concerning FRAX® index, at time of analyses we observed a significant improving in Arm A group (median ten years probability hip fracture reduction between 5 and 10%). Conclusions: Preliminary results of our single-blind, randomized, placebo-controlled study in women taking adjuvant AIs showed that the majority of patients had basal hypovitaminosis D. A good drug safety and an improvement of FRAX® index in the experimental Arm were shown; longer follow-up is needed. Disclosure: All authors have declared no conflicts of interest.

BACKGROUND:The dislocation of the malignant cells along the needle tract during breast cancer (BC) diagnosis has been demonstrated by several studies. However, the published experiences that relate the diagnostic technique with sentinel node (SN) involvement are few and controversial. The aim of our analysis was to evaluate the impact of different techniques for preoperative BC biopsy among prognostic factors of metastases occurrence in SN. MATERIALS AND METHODS:We reviewed the institutional clinical database of our Center. A total of 674 patients were diagnosed between February 1999 and December 2006 with invasive BC. SN metastases classification followed the 2002 American Joint Committee on Cancer (AJCC) TNM pathological staging: macrometastases, micrometastases, isolated tumor cells or negative. Only macrometastases and micrometastases were considered positive. Concerning fine-needle aspiration cytology, we used disposable needles of the size of 21-27 G. For percutaneous biopsy we used cutting needle type "tru-cut"; the Gauge needle ranged between 14 and 20. RESULTS:At univariate analysis of specific parameters using positive SN as outcome, percutaneous diagnostic technique did not affect significantly the SN positivity (p = 0.60). At multivariate models only central quadrant lesion (p = 0.005) and lymph vascular invasion (LVI) presence (p < 0.0001) maintained the statistical significance as risk factor for positive SN status. Polytomic logistics models showed that only LVI maintained the statistical significance both for prediction of micrometastases and macrometastases. CONCLUSIONS:Our analysis showed that different techniques used for BC diagnosis did not influence SN status.