Hormone receptor-positive, human epidermal growth factor receptor 2-negative (HR+/HER2-) early breast cancer (EBC) is the most common breast cancer subtype and encompasses a biologically heterogeneous group of tumours. Endocrine therapy (ET) remains the cornerstone of treatment, but decisions regarding chemotherapy, cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors, and bone-modifying agents must be tailored to tumour biology, clinical stage, and menopausal status. REAL Canadian Breast Cancer Alliance (REAL Alliance), a pan-Canadian group of breast cancer specialists, convened to develop national clinical consensus recommendations for the systemic management of HR+/HER2- EBC. Using a structured consensus process, 28 recommendations were endorsed, spanning neoadjuvant and adjuvant systemic therapy, surgical considerations, and use of bisphosphonates. Key recommendations include the selective use of neoadjuvant chemotherapy for high-risk or locally advanced disease; genomic testing to guide chemotherapy decisions, particularly in postmenopausal patients; ET as the foundation of adjuvant therapy with intensification using CDK4/6 inhibitors in higher-risk patients; and adjuvant bisphosphonates in postmenopausal women to reduce recurrence and improve survival. These consensus recommendations provide practical, evidence-based guidance to support individualized, patient-centred management of HR+/HER2- EBC in the Canadian context.

Thirty years after its landmark approval, PEGylated liposomal doxorubicin (PLD, Doxil®) remains one of the most influential examples of how drug delivery technologies can reshape cancer therapy. By altering the pharmacokinetics and tissue distribution of doxorubicin, PLD improved the tolerability of conventional anthracycline therapy to enable a more manageable treatment experience for patients. Despite these advantages, PLD demonstrated non-superior efficacy compared with free drug in select clinical trials, contributing to mixed perceptions regarding the clinical impact of nanomedicine platforms. In this Perspective, we revisit the clinical and translational legacy of PLD to examine nanomedicine's broader implications for oncology drug delivery. Using PLD as a case study, we discuss how translational gaps between preclinical promise and clinical performance have shaped perceptions of nanomedicine. We further highlight how conventional evaluation frameworks may undervalue important benefits delivered by nanotherapeutics. Improvements in tolerability and reductions in "time toxicity" - the time patients spend managing treatment and its consequences - are rarely quantified in clinical evaluation, suggesting that the value of nanomedicine platforms may be systematically underestimated within current clinical and reimbursement paradigms. Addressing this disconnect requires a broader framework for evaluating therapeutic benefit in oncology drug delivery. By reflecting on the experience of PLD, this Perspective argues for better integration of patient-centered outcomes when assessing nanomedicine technologies. In doing so, we aim to stimulate discussion on how the field can better align research priorities, clinical evaluation, and reimbursement considerations with the needs and experiences of patients.

Human epidermal growth factor receptor 2-positive (HER2+) breast cancer is an aggressive subtype associated with a poor prognosis when not optimally treated. Over the past year, major advances—including results from DESTINY-Breast05, DESTINY-Breast09, DESTINY-Breast11, PATINA, and long-term APHINITY follow-up—have changed the treatment landscape regarding the place in therapy of antibody–drug conjugates and the optimal sequencing of systemic therapies. These developments prompted the need for updated evidence-informed consensus recommendations to support consistent, high-quality care across Canada. Research Excellence, Active Leadership Canadian Breast Cancer Alliance (REAL Alliance), comprising clinical-academic oncologists from across Canada and Breast Cancer Canada, updated its 2024 HER2+ recommendations through a modified Delphi process with up to three rounds of anonymous voting. Consensus was defined a priori as ≥75% agreement. This 2025 update incorporates new data in early-stage, metastatic, and central nervous system-involved disease, including revisions to neoadjuvant and adjuvant treatment pathways and expanded guidance on the clinical use of antibody–drug conjugates.

Triple-negative breast cancer (TNBC) has been associated with a poorer prognosis than other subtypes, due to its more aggressive behaviour. Since 2020, significant advances in locoregional and systemic therapy have improved outcomes for patients with TNBC, but the implementation of these treatments remains inconsistent across Canada. There is, therefore, a critical need for evidence-informed, consensus-driven guidance to support the integration of new therapies into practice. Research Excellence, Active Leadership Canadian Breast Cancer Alliance (REAL Alliance), a pan-Canadian group of breast cancer specialists and Breast Cancer Canada, a patient advocacy organization, convened to develop national clinical consensus recommendations for the management of breast cancer. Through a selective literature review and modified Delphi process of national experts in the fields of medical oncology, radiation oncology, surgical oncology and pharmacy, REAL Alliance developed national consensus recommendations for the management of TNBC. The result is a set of 23 recommendations: four overall general recommendations, 11 in early-stage TNBC, and eight in metastatic TNBC. These recommendations are intended for oncology healthcare professionals, and are intended to guide evidence-informed, consistent care across Canada.

BACKGROUND:Granulocyte colony-stimulating factors (G-CSFs), including filgrastim and pegfilgrastim, are associated with bone pain, potentially impacting treatment adherence. This study hypothesized that a 5-day regimen of filgrastim would result in less bone pain than single-dose pegfilgrastim in patients receiving chemotherapy for early breast cancer. METHODS:In this multicenter, open-label, randomized controlled trial, patients requiring prophylactic G-CSF during chemotherapy were randomly assigned 1:1 to receive either 5-day filgrastim or pegfilgrastim. The primary outcome was patient-reported bone pain, assessed as area under the curve of daily pain scores (0 = no pain to 10 = worst pain) over the first 5 days following G-CSF in cycle 1. Secondary outcomes included bone pain in cycles 2-4, febrile neutropenia, hospitalizations, chemotherapy delays, dose reductions, early discontinuations, chemotherapy-related deaths, health-related quality of life, and health-care resource utilization. RESULTS:From June 2021 to March 2023, a total of 233 patients were randomly assigned, with 219 analyzed (110 filgrastim and 109 pegfilgrastim) after excluding those who withdrew before receiving treatment. Adjusting for stratification factors and prespecified baseline covariates using repeated measures linear regression, the mean area under the curve (0-40) for cycle 1 bone pain was 10.2 (11.2) for 5-day filgrastim and 10.2 (9.81) for pegfilgrastim, with an adjusted mean difference of 0.70 (95% confidence interval = 1.62 to 3.02; P = .556). Although no clinically significant differences were observed in most secondary outcomes, the 5-day filgrastim group exhibited a numerically higher incidence of febrile neutropenia (6.4% vs 0.9%, P = .065) and hospitalization (10.0% vs 3.7%, P = .106). CONCLUSION:There was no significant difference in bone pain between 5-day filgrastim and pegfilgrastim.

Pathogenic variants in breast cancer predisposition genes are associated with poor clinical outcomes but also offer an opportunity for more individualized therapeutic pathways. Given increasing knowledge, improvements in germline genetic testing efficiency, and the availability of novel systemic targeted treatment options, the importance of appropriately identifying patients for testing has never been greater. A pan-Canadian expert working group (EWG) consisting of 10 healthcare professionals (HCPs) was convened to review recent international guidelines for germline genetic testing in breast cancer and develop Canadian recommendations. The group identified four clinical questions to address which patients should undergo testing, what approaches should be used, how patients should be counselled, and what steps are needed for implementation. In response to these questions, the EWG agreed upon 12 recommendations that emphasized broader incorporation of germline genetic testing and more standardized, streamlined testing and counselling approaches. The group also offered multiple suggestions to support effective and equitable implementation across Canada. These recommendations provide guidance for HCPs and represent a call to action for the Canadian government and other organizations to support genetic testing pathways, drug access, and ultimately improved outcomes for patients with breast cancer and their families.

Cyclin-dependent kinase (CDK)4/6 inhibitors have become a key component of adjuvant treatment for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) early breast cancer who are at high risk of recurrence. The addition of abemaciclib and ribociclib to standard endocrine therapy has demonstrated clinically meaningful improvements in invasive disease-free survival, supported by the monarchE and NATALEE trials, respectively. With expansion of patient eligibility for CDK4/6 inhibitors, multidisciplinary coordination among medical oncologists, surgeons, nurses, pharmacists, and other health care providers is critical to optimizing patient identification, monitoring, and management of adverse events. This expert guidance document provides practical recommendations for implementing adjuvant CDK4/6 inhibitor therapy in routine clinical practice, incorporating insights from multiple specialties and with patient advocacy representation. Key considerations include patient selection based on clinical trial data, treatment duration, dosing schedules, adverse event profiles, monitoring requirements, drug–drug interactions, and patient-specific factors such as tolerability, cost, and quality of life. This guidance aims to support Canadian clinicians in effectively integrating CDK4/6 inhibitors into clinical practice, ensuring optimal patient outcomes through a multidisciplinary and patient-centric approach.

Background: Breast cancer (BC) care faces challenges in early detection, timely diagnosis and comprehensive management. Disparities persist, with underserved populations facing the greatest barriers. Addressing these requires policies that support consistent, evidence-based practices and enhance healthcare capacity and technology advancements. This document presents the development of the Breast Cancer Care Quality Index (BCCQI), supported by evidence to promote equitable care and improve BC outcomes globally, and discusses its adoption as a strategic tool within National Cancer Control Plans. Methods: A two-part methodology identified challenges in BC care and defined dimensions, targets and indicators for the BCCQI, aligned with the World Health Organization Global Breast Cancer Initiative. A literature review and analysis of existing United Nations (UN) frameworks informed the initial structure of the index, which was later refined through expert feedback from a multidisciplinary panel representing diverse backgrounds and geographies. Findings: The BCCQI is organised into four dimensions, comprising 10 targets and 23 indicators to guide the development of country-specific roadmaps. It should promote progress across key domains: health equity, patient centricity, universal access, care quality and treatment effectiveness. The Index is conceived as a dynamic tool, continuously refined through real-world application and emerging evidence. Interpretation: Despite the previous initiatives, progress has been slow, likely due to practical details and country-specific guidance remaining limited due to scarce real-world evidence. Promoting national ownership and empowering action aligned with local challenges and opportunities, a flexible, strategic framework may help address these gaps.

BACKGROUND:Immune checkpoint inhibitors (ICIs) are increasingly used to treat various cancers. Their use may result in immune-related adverse events, including psoriasis. When managing psoriasis, induced or exacerbated by an ICI, there are concerns regarding immunosuppression from systemic agents for the treatment of psoriasis (saPs) and the potential impact on ICI efficacy. No direct, high-level evidence exists to address these concerns. OBJECTIVE:To address clinically relevant questions regarding the management of ICI-mediated psoriasis (ICI-Ps) with saPs. METHODS:We convened a multidisciplinary panel of 15 international specialists in dermatology, oncology, immunology, and rheumatology. A Delphi process defined clinical concerns related to the systemic treatment of ICI-Ps, focusing on the potential of saPs to impact ICI effectiveness. The saPs considered included biologics targeting tumour necrosis factor, interleukin (IL)-17, IL-12/23 and IL-23, traditional systemic therapies (cyclosporine, methotrexate), small molecules targeting phosphodiesterase-4 or tyrosine kinase 2, systemic retinoids (acitretin), and systemic corticosteroids. A systematic review of the literature was supplemented with evidence supporting an inference-based methodology to derive conclusions on the use of systemic therapies in patients with ICI-Ps. The specialist panel rated the strength of the conclusions using a probabilistic scale. RESULTS:After reviewing the totality of direct and indirect evidence, we drafted inference-based conclusions and ascribed a level of support, focusing on the potential impact of saPs on ICI efficacy. This work provides a structured framework informing healthcare professional and patient discussions on the risks and benefits of using saPs in patients with cancer who experience ICI-Ps. CONCLUSIONS:Although there is no direct evidence, we support the following conclusions: saPs may be used to treat ICI-Ps without an appreciable loss of ICI effectiveness. Generally, it is not necessary to interrupt ICI therapy. When available, non-steroid saPs are preferred over systemic corticosteroids for the treatment of psoriasis.

Concerns exist regarding increased toxicities, including endocrine therapy toxicity, with concurrent radiation and endocrine therapy in early breast cancer (EBC). We present a pragmatic, randomized trial comparing concurrent versus sequential endocrine and radiotherapy in hormone-responsive EBC. In this multicenter trial, patients were randomized to receive adjuvant endocrine therapy concurrent with, or sequential to, radiotherapy. The primary outcome was change in endocrine therapy toxicity from baseline to 3 months post radiotherapy using the Functional Assessment of Cancer Therapy-Endocrine Symptom (FACT-ES) score. From September 2019 to January 2021, 133 patients were randomized to concurrent endocrine and radiotherapy, and 127 to sequential treatment. Most patients were post-menopausal (72.7%, 189/260) with stage 1 disease (65.8%, 171/260). Tamoxifen was the endocrine therapy of choice for 69.6% (181/260) of patients, and an aromatase inhibitor for the remainder. The median total radiation dose and fractions were 40.1 Gray (range 26-50) and 15 fractions (range 5-25), respectively. For the primary outcome of change in endocrine therapy toxicity per FACT-ES scores from baseline to 3 months post radiotherapy, no significant difference was found between the groups (median [range] = -4.9 (-82, 38.8) for concurrent and -5.1 (-42, 40) for sequential, p = 0.87). This is the first trial to investigate the impact of concurrent versus sequential adjuvant endocrine and radiotherapy on endocrine therapy-related toxicities. The findings provide further support to allow the optimal timing of radiation and endocrine therapy to be tailored for the individual patient.

Patient access to new oncology drugs in Canada is only possible after navigating multiple sequential systemic checkpoints for national regulatory approval, health technology assessment (HTA) and collective government price negotiation. These steps delay access and prevent health care providers from being able to prescribe optimal therapy. Eighteen Canadian oncology clinicians from the medicine, nursing and pharmacy professions met to develop consensus recommendations for defining reasonable government performance standards around process and timeliness to improve Canadian cancer patients’ access to best care. A modified Delphi methodology was used to identify consensus on 30 questions involving five themes: accountability, disparities, endpoints, timeliness, and cost-effectiveness. It was agreed that greater transparency is required across regulatory and HTA processes. Health professionals in oncology are frustrated for their patients because they are unable to deliver the modern guideline-supported therapies they want to provide due to delays in approval or funding. Canadian health care providers request improvements in timely access to life-saving therapeutics in line with other comparator countries. Clinicians expect urgent improvements in Canadian health systems to give our patients their best chance of survival.

Abstract Background. Interventions to improve tolerability and adherence to endocrine therapy (ET) are critical to the global improvement of breast cancer (BC) survivorship. The optimal time of day to take ET in terms of quality of life, side effects and adherence is unknown. This study compared a morning dose versus an evening dose of ET in patients with early-stage BC (EBC). Methods. In this pragmatic, open-label, multicenter trial, patients with hormone receptor-positive (HR+) EBC were randomized (1:1) to receive either a morning dose (within 1 hour of the patient wake up time) or an evening dose of ET (within 1 hour of patient bedtime). The primary endpoint was endocrine toxicity/tolerability measured by the change in total Functional Assessment of Cancer Therapy-Endocrine Subscale (FACT-ES) score from baseline (commencement of ET) to 12 weeks. The secondary endpoints included: ET toxicity/tolerability and quality of life (FACT-ES and FACT-B) from baseline to 4, 8, 12 and 52 weeks, non-persistence or non-adherence, and patient timing preference. Results. Between June 2021 and March 2022, 245 eligible patients were randomized, 122 to morning (122/245, 49.8%) and 123 to evening (123/245, 50.2%) dosing. Mean age was 61 [standard deviation (sd) 11.9], 181 patients (73.9%) were postmenopausal, 188 (76.7%) received tamoxifen, 58 (23.7%) received an aromatase inhibitor and 22 (9%) received luteinizing hormone-releasing hormone. The mean changes in the FACT-ES score from baseline to 12 weeks following the beginning of ET were -2.0 (sd=14.3) vs -5.4 (sd=16.8) in the morning vs evening arms respectively (Wilcoxon two-sample rank sum test p-value=0.22). Also, the proportion of patients with a clinically important increase (Fisher’s exact test p-value=0.54 0.89) or decrease (p-value= 0.89) in FACT-ES Scores was not statistically different between the arms. At 52 weeks, the mean changes in the FACT-ES score from baseline were -2.5 (sd=18.8) vs -4.8 (sd=15.5) in the morning vs evening arms respectively (p-value=0.23). There was no statistical difference in FACT-ES and FACT-B scores over the 52 weeks of the study. At 12 weeks, 94.5% (69/79) vs 98.7% (78/79) were still taking the ET (p-value=0.2), whereas at 52 weeks, 92.1% (58/63) vs 85.4% (41/48) were still taking ET (p-value=0.36), in the morning vs evening arms respectively. Also, 13.7% (10/73) vs 7.6% (6/79) and 3.2% (2/62) vs 12.5% (6/48) interrupted their ET at least once, in the morning vs evening arms, at 12 and 52 weeks respectively. At week 52, 57.9% (62/107) in the morning arm vs 13.5% (14/104) in the evening arm strongly preferred an ET morning dose, whereas 7.5% (8/107) vs 42.3% (44/104) strongly preferred an ET evening dose. No significant preference changes were observed in dose timing from baseline to week 52 (p-value=0.081). Conclusions. These results suggest no significant difference in quality of life or adherence if ET is taken in the morning or in the evening. Patients should be reassured that they can take ET at their preferred time. Clinical Trial Registration: NCT04864405 Table 1. Mean changes between FACT scores at 12 weeks and 52 weeks from baseline for patients receiving ET morning vs evening dose. A positive value indicates the FACT score increased over time. FACT ES: Endocrine Subscale; FACT B: breast Citation Format: Marie-France Savard, Mohammed Ibrahim, Gregory Pond, Deanna Saunders, Lisa Vandermeer, Lesley Fallowfield, Terry Ng, Arif Awan, Sandeep Sehdev, Ana-Alicia Beltran-Bless, Mark Clemons. A Pragmatic Randomized Trial Comparing Morning versus Evening Dosing of Endocrine Therapy for Early Breast Cancer: Final Results (REaCT-CHRONO Study) [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-11-12.

Countries face challenges in paying for new drugs. High prices are driven in part by exploding drug development costs, which, in turn, are driven by essential but excessive regulation. Burdensome regulation also delays drug development, and this can translate into thousands of life-years lost. We need system-wide reform that will enable less expensive, faster drug development. The speed with which COVID-19 vaccines and AIDS therapies were developed indicates this is possible if governments prioritize it. Countries also differ in how they value drugs, and generally, those willing to pay more have better, faster access. Canada is used as an example to illustrate how “incremental cost-effectiveness ratios” (ICERs) based on measures such as gains in “quality-adjusted life-years” (QALYs) may be used to determine a drug’s value but are often problematic, imprecise assessments. Generally, ICER/QALY estimates inadequately consider the impact of patient crossover or long post-progression survival, therapy benefits in distinct subpopulations, positive impacts of the therapy on other healthcare or societal costs, how much governments willingly might pay for other things, etc. Furthermore, a QALY value should be higher for a lethal or uncommon disease than for a common, nonlethal disease. Compared to international comparators, Canada is particularly ineffective in initiating public funding for essential new medications. Addressing these disparities demands urgent reform.

Abstract Background: Granulocyte colony stimulating factor (G-CSF) such as filgrastim (FIL) or pegfilgrastim (PEG) significantly reduces the risk of febrile neutropenia (FN) and treatment-related hospitalization in patients with early breast cancer receiving chemotherapy. However, patients receiving G-CSF can experience clinically significant bone pain. Previous studies examining post-GCSF bone pain were mostly based on physician pain assessment and compared mixed doses (30/60/100 μg/kg) of PEG vs. FIL (5μg/kg/day or 300 μg/day) given for 7 to 14 days. Based on a randomized non-inferiority study, 5 days of FIL is considered non-inferior to 10 days of FIL to prevent FN and hospitalizations and is frequently used in patients receiving chemotherapy for breast cancer. Patient-reported bone pain after 5 days of FIL vs. single dose of PEG has never been compared in a prospective randomized study and has important implications for patient and physician treatment preferences. Methods: In this multicenter, open-label trial, patients receiving neo-/adjuvant chemotherapy for early-stage breast cancer requiring primary FN prophylaxis with G-CSF were randomized 1:1 to either 5 days of FIL (300 μg or 480μg if ≥ 90 kg) or 1 day of PEG (6 mg) with each cycle of chemotherapy. The primary endpoint was bone pain using area under the curve (AUC) of the daily pain score from days 1-5 (AUC score 0 to 40) during cycle 1. We used linear regression adjusting for stratification factors [cancer center (2 centers) and chemotherapy regimen (taxane (TAX) or anthracycline (ANTH)-based during cycle 1] and prespecified baseline covariates: age, pain, and use of pain medications pre-chemotherapy. Supportive analysis of bone pain across cycles 1 to 4 was conducted using repeated linear regression. Key secondary endpoints included incidence of FN, hospitalizations, chemotherapy delay, dose-reduction or discontinuation, and chemotherapy-related deaths. Results: From June 2021 to March 2023, 233 patients were enrolled, with 217 patients (108 FIL/109 PEG) in the intention-to-treat analysis; 16 (7.4%) patients were excluded because of incomplete follow-up. Participants were mean age 55.6 years; almost exclusively female (99.1%), on chemotherapy regimen TAX 57% vs. ANTH 43%, had mean baseline pain score 1.12, and prevalence of pain medication use pre-chemotherapy was acetaminophen 14.7%, non-steroidal anti-inflammatory drugs (NSAIDs) 6.0% and opioids 3.2%. Characteristics were balanced between arms (Table 1). After repeated measures linear regression adjusted for age, chemotherapy regimen, baseline pain, and use of pain medications pre-chemotherapy, mean AUC for bone pain at cycle 1 was 10.94 for FIL and 10.12 for PEG (mean difference 0.82; 95% CI: -1.59, 3.23; p = 0.516). There was no significant difference between arms across treatment cycles (interaction p = 0.785; mean time-averaged difference 0.28; 95% CI: -1.75, 2.32). Across cycles 1 to 4, mean peak pain over 5 days post-GCSF was 3.27 vs. 3.41 (p=0.700); frequency of bone pain during first 8 days (pain score > 0) was 52.5% vs. 51.3%; p=0.358, and mean frequency of severe pain (pain score ≥ 5) was 17.5% vs. 15.2%; p=0.014 for FIL vs. PEG, respectively. The incidence of FN [4.6% vs. 0%, absolute difference 4.6% (95% CI: -0.3%, 9.5%; p=0.069)] and hospitalization [FN and non-FN related: 10.2% vs. 1.8%, absolute difference of 8.4% (95% CI: 1.2%, 15.5%; p=0.021)] was higher in the FIL group. There were no significant differences in chemotherapy delay (13% vs. 11%; p=0.815), dose reduction (14.8% vs. 14.7%; p=0.999), early discontinuation (8.3% vs. 5.5%; p=0.580), or chemotherapy-related death (0.9% vs. 0%; p=0.996) in the FIL vs. PEG groups, respectively. Conclusion: There was no difference in patient-reported bone pain after 5 days of FIL or PEG, even after controlling for important clinical factors. Importantly, the study observed higher rates of FN and hospitalizations in patients receiving FIL for 5 days only. Table 1 Baseline Characteristics Citation Format: Terry Ng, Yuxin Zhang, Carol Stober, Jennifer Shamess, Natalie Mills, Stuart Nicholls, Mohammed Ibrahim, Daniel Davoudpour, Christopher Armiento, Marie-France Savard, Moira Rushton, Arif Awan, Sandeep Sehdev, John Hilton, Xinni Song, Rakesh Goel, Fiona Macdonald, Kelly Daigle, Lisa Vandermeer, Monica Taljaard, Mark Clemons. REaCT 5G: A randomized study comparing bone pain after 5 days of filgrastim or one day of pegfilgrastim for primary febrile neutropenia prophylaxis during neo-/adjuvant chemotherapy for early breast cancer [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-12-12.