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Background: We present the 2-year results of a randomised trial comparing 4- versus 12-weekly bone-targeting agents (BTAs) in patients with bone metastases from breast or castration-resistant prostate cancer (CRPC)., Patients and Methods: Patients with bone metastases from breast or CRPC, who were going to start or were already receiving BTAs, were randomised to 4- or 12-weekly BTA treatment for 2 years. The endpoints were: symptomatic skeletal events (SSE) rates, time to SSEs, toxicity and cost-effectiveness., Results: Of 263 patients (160 breast cancer, 103 CRPC), 133 (50.6%) and 130 (49.4%) were randomised to the 4- and 12-weekly groups, respectively. BTAs included denosumab (56.3%), zoledronate (24.0%) and pamidronate (19.8%). After 2 years, the cumulative incidence rate (95% CI) of SSEs was 32.7% (24.6% to 41.1%) and 28.1% (20.3% to 36.4%) for the 4- and 12-weekly intervention groups respectively. The hazard ratio for time to first SSE was 0.96 (95% CI = 0.63 to 1.47). However, in a post hoc analysis, those patients who had an on-study SSE, there was a small non-statistical increased risk of subsequent SSEs among patients on the 12-weekly dosing arm (HR = 1.14; 95% CI - 0.90-1.44). BTA-related toxicity rates were similar between study arms. A cost-utility analysis showed that 12-weekly BTA is cost-effective from a public payer's perspective., Conclusion: These results in addition to those previously reported for de-escalating zoledronate, would support that de-escalation of commonly used BTAs is a reasonable and economically valid treatment option. While not statistically significant, the increase in subsequent SSEs in the 12-weekly arm requires further exploration., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2021 Published by Elsevier GmbH.)

Purpose: Radiation therapy (RT) and endocrine therapy (ET) are standard treatments for hormone receptor-positive (HR+) breast cancer after breast-conserving surgery (BCS). However, many older patients are at greater risk of treatment-related toxicities and non-cancer related death, and less likely to benefit from these standard treatments. A systematic review was performed evaluating outcomes of omitting RT or ET in older patients aged ≥50 treated with BCS for lower-risk breast cancer., Methods: Medline, Embase, and the Cochrane Register of Controlled Trials were queried from 1980 to April 30th, 2020 for randomized controlled studies (RCTs) and prospective cohort studies (PCSs) evaluating omission of RT and/or ET compared to RT plus ET in patients. Meta-analysis was performed using random-effects models with findings reported as risk ratios (RR) with 95% confidence intervals (CI)., Results: From 3860 citations, 10 prospective studies met eligibility criteria. Omission of RT alone was evaluated in 7 RCTs (n = 4604) and one PCS (n = 667); omission of ET alone was assessed in 1 PCS (n = 271); and omission of either ET or RT was compared to ET plus RT in 1 RCT (n = 495). Adjuvant RT compared to no RT reduced 5- and 10-year in-breast tumor recurrence [5-year: RR 0.16, 95 %CI 0.09-0.27 l 10-year: 0.28, 95 %CI 0.16-0.5], but had no effect on survival [5-year: RR 0.94, 95 %CI 0.77-1.15; 10-year: 1.01, 95 %CI 0.9-1.12]., Conclusion: The current body of evidence suggests that RT can be omitted in older patients with lower-risk disease. However, more trials on the omission of ET are required to better inform treatment decisions., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Purpose: While routine, in-person follow-up of early-stage breast cancer patients (EBC) after completion of initial treatment is common, the COVID-19 pandemic has resulted in unprecedented changes in clinical practice. A systematic review was performed to evaluate the evidence supporting different frequencies of routine follow-up., Methods: MEDLINE and the Cochrane Collaboration Library were searched from database inception to July 16, 2020 for randomized controlled trials (RCTs) and prospective cohort studies (PCS) evaluating different frequencies of routine follow-up. Citations were assessed by pairs of independent reviewers. Risk of Bias (RoB) was assessed using the Cochrane RoB tool for RCTs and the Newcastle-Ottawa Quality Assessment Scale for Cohort Studies. Findings were summarized narratively., Results: The literature search identified 3316 studies, of which 7 (6 RCTs and 1 PCS) were eligible. Study endpoints included; quality of life (QoL; 5 RCTs and 1 PCS), disease free survival (DFS) (1 RCT), overall survival (OS) (1 RCT) and cost-effectiveness (1 RCT). The results showed reduction in follow-up frequency had no adverse effect on: QoL (6 studies, n = 920), DFS (1 trial, n = 472) or OS (1 trial, n = 472), but improved cost-effectiveness (1 trial, n = 472). Four RCTs specifically examined follow-up on-demand versus scheduled follow-up visits and found no statistically significant differences in QoL (n = 544)., Conclusion: While no evidence-based guidelines suggest that follow-up of EBC patients improves DFS or OS, routinely scheduled in-person assessment is common. RCT data suggests that reduced frequency of follow-up has no adverse effects., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Despite the increasing use of adjuvant bisphosphonates for early stage breast cancer (EBC), little is known about the patient experience with such treatments. A patient survey was performed to identify current prescribing practices, perceptions around the role of treatment, the impact of treatment on patients' quality of life, and future trial designs., Methods: EBC patients who had either completed or were currently receiving adjuvant bisphosphonates were sent an anonymized survey. The survey collected information on patient and disease characteristics, bisphosphonate scheduling, compliance, and tolerance. Questions also assessed patient interest in trials of de-escalated bisphosphonate therapy., Results: A total of 255 patients were contacted, with 164 eligible respondents (eligible response rate 164/255, 64.3%). Median patient age was 52 years (range 28 to 82 years). The majority (111/163, 68.1%) were postmenopausal at the time of diagnosis, 23.3% (38/163) were premenopausal, and 7.4% (12/163) were perimenopausal. Most patients (78%) had received chemotherapy. Zoledronate was the most commonly used bisphosphonate (92%), with the majority receiving treatment every 6 months for 3 years (73%). While 66% (107/161) of respondents had experienced side effects with treatment, most had, or expected to, complete treatment (154/163, 94%). Provided there was no detriment in breast cancer outcomes, there was strong interest in future studies of de-escalating adjuvant bisphosphonate therapy., Conclusion: While most patients tolerate their treatment, there is interest in performing trials of de-escalation of these agents., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SMG reports receipt of honorarium from Novartis for insights on management of breast cancer patients. AAA reports Advisory board: Eli Lily, Exact Sciences, Exactis, Novartis, Pfizer, Honoraria: Apotex, Roche, Travel: Roche. BH and MC reports consulting fees from Cornerstone Research, outside the submitted work. GP reports consulting fees from Merck, Astra-Zeneca, Profound Medical, outside of submitted work; honorarium for DSMB membership from Takeda outside of submitted work; a close family member works for Roche Canada Ltd and owns stock in Roche Ltd. All other authors declare no competing interests., (© 2021 The Authors.)

Background: Adjuvant zoledronate is widely used in patients with early stage breast cancer (EBC), but its optimal duration and dosing interval is still unknown. While a single-dose of zoledronate can improve bone density for many years, a proper evaluation of its effects on breast cancer-related outcomes would require a large trial. In this pilot study we evaluated the feasibility of performing such a trial., Methods: Eligible patients with EBC were randomised to receive either one dose of zoledronate or 7 doses (6-monthly dosing for 3 years). Feasibility was assessed by a combination of primary outcomes including: activation of at least 6 Ontario sites within a year, active participation (i.e. approaching eligible patients for study participation) of at least half of the medical oncologists, and enrolment of at least 100 patients across all sites within 9 months of the sixth site being activated., Results: All 6 sites were activated within 1 year and of 47 medical oncologists, 27 (57%) approached patients. Between November 2018 and April 2020, 211 eligible patients were randomised, 106 (50.2%) to a single dose of zoledronate and 105 (49.8%) to 6-monthly dosing. Baseline characteristics of randomised patients included; median age 59 (range 36-88), ER and/or PR positive (85%), Her2 positive (23%), menopausal status (premenopausal [19%], perimenopausal [6.7%] and postmenopausal [74%]) and 74% received neo/adjuvant chemotherapy., Conclusions: All study feasibility endpoints were met in this trial comparing alternative schedules for adjuvant zoledronate. We will now seek funding for performing a larger efficacy trial.Trial registration: NCT03664687., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2020 The Author(s).)

Introduction: Indiscriminate ordering of Oncotype DX (ODX) is expensive and of poor value to patients, physicians, and health care providers. The 3 Magee equations, Gage Algorithm, and University of Tennessee predictive algorithm all use standard clinicopathologic data to provide surrogate ODX scores. In this hypothesis-generating study, we evaluated whether these prognostic scores could be used to identify patients unlikely to benefit from additional ODX testing., Patients and Methods: Retrospective data was collected from 302 patients with invasive ductal breast cancer and available ODX scores. Additional data was available for: Magee equations 1 (212 patients), 2 (299 patients), 3 (212 patients), Gage Algorithm (299 patients), and University of Tennessee predictive algorithm (286 patients). ODX scores were banded according to the TAILORx results., Results: Correlation with ODX scores was between 0.7 and 0.8 (Gage), 0.8 and 0.9 (Magee 2, University of Tennessee predictive algorithm), and > 0.9 (Magee 1 and 3). Magee 3 was the most robust and is proposed as a screening tool: for patients aged ≤ 50 years, ODX testing would be not required if the Magee 3 score was < 14 or ≥ 20; for those aged > 50 years, ODX would not be required if the Magee 3 score was < 18 or ≥ 26. Using these cut-offs, 110 (51.9%) of 212 patients would be deemed as not requiring ODX testing, and 109 (99.1%) of110 patients would be appropriately managed., Conclusions: Use of all formulae, and the Magee 3 equation in particular, are proposed as possible screening tools for ODX testing, resulting in significantly reduced frequency of ODX testing. This requires validation in other populations., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Patients can start endocrine therapy before, concurrently with, or sequentially after radiotherapy. The optimal timing of starting adjuvant endocrine therapy is unknown. This survey was performed to evaluate physician recommendations., Methods: Canadian oncologists were surveyed to evaluate institutional and personal practices regarding the prescription of adjuvant endocrine therapy and radiotherapy. Perspectives regarding the design of a clinical trial to compare concurrent versus sequential therapy, and the optimum end points for such a trial, were also sought., Results: The overall response rate was 30% (65/220), with responses mainly from medical (35/65, 54%) and radiation (28/65, 43%) oncologists. Eighty-four percent of respondents reported an absence of institutional protocols. The majority of physicians (57%, 36/65) identified endocrine therapy provided after radiotherapy as the preferred sequence of treatments. Twenty-two percent (14/65) had no preference, while 21%, (14/65) started endocrine therapy either before or concurrent with radiotherapy. Practice patterns were largely based on the physician's own clinical experience. Thirty-two percent of physicians (21/65) had concerns regarding concurrent endocrine therapy and radiotherapy, including increased adverse effects with endocrine therapy (13/21, 62%), reduced efficacy of radiotherapy (4/21, 19%), reduced compliance with endocrine therapy (3/21, 14%), and increased radiation toxicity (1/21, 5%). Most thought a pragmatic clinical trial addressing this question would help standardize and improve patient care., Conclusion: Decisions around the timing of endocrine therapy and radiotherapy are largely being made on the basis of physicians' personal choices. In the absence of data to support these decisions, appropriately powered trials are needed., (Copyright © 2018 Elsevier Inc. All rights reserved.)