Canadian Oncology Today

The Role of ctDNA in Breast Cancer: Prognosis and Clinical Utility

2025-04-11T14:23:41+00:00

Breast cancer remains the most common cancer among women globally, with significant morbidity and mortality. Current treatment for breast cancer, both in the early stage and metastatic setting, is based on a tumour biopsy and immunohistochemical detection of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor 2 (HER2) expression. Though substantial research has been undertaken over the years to establish new prognostic and predictive biomarkers in breast cancer, most have not demonstrated significant clinical utility. Circulating tumour DNA (ctDNA) is increasingly used across various cancer types for precision medicine. In this article, we discuss the current roles of ctDNA in breast cancer prognosis and its clinical utility in treatment decision-making in early- and advanced-stage settings.

Clinical Considerations for the Management of Advanced PD-L1 ≥50% Non-small Cell Lung Cancer In 2025: Should All Patients Be Treated the Same?

2025-04-11T14:23:40+00:00

Despite advances in the treatment of non‑small cell lung cancer (NSCLC) due to the advent of immunotherapy in the form of immune checkpoint inhibitors (ICI), NSCLC remains the leading cause of cancer-related death in Canada. In addition, multiple first‑line options exist for patients with NSCLC without a sensitizing mutation in epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK), but no head‑to‑head comparisons of first-line treatment regimens have been made in randomized controlled trials. The programmed cell death ligand 1 (PD-L1) tumour proportion score (TPS)—which is derived from immunohistochemistry analysis—emerged as an important biomarker early in the advent of ICI in NSCLC. Approximately 30% of patients with NSCLC have PD-L1 expression in at least 50% of the tumour. This ≥50% threshold was established through retrospective biomarker analyses in pivotal trials, such as the KEYNOTE-001 and KEYNOTE-024 trials, in which patients with higher PD-L1 expression demonstrated superior response rates and overall survival (OS) benefits with immunotherapy compared to chemotherapy. The KEYNOTE-001 trial first identified ≥50% PD-L1 expression as an optimal cut-off for predicting response to pembrolizumab (anti-programmed cell death protein 1 [PD-1] antibody), showing an objective response rate (ORR) of ~45% in this group. Subsequently, the KEYNOTE-024 trial confirmed that patients with PD-L1 ≥50% had significantly improved progression-free survival (PFS) and OS with pembrolizumab than those treated with chemotherapy (hazard ratio [HR] for PFS: 0.50, 95% confidence interval [CI]: 0.37–0.68). Similar findings from the IMpower110 (atezolizumab) and EMPOWER-Lung 1 trials (cemiplimab) reinforced ≥50% PD-L1 TPS as a clinically meaningful biomarker. As a result, ≥50% PD-L1 TPS became an actionable biomarker in regulatory approvals and treatment guidelines, guiding immunotherapy decisions in advanced NSCLC.

Current Approaches and Future Directions for the Treatment of Solid Tumour Brain Metastases

2025-04-11T14:23:38+00:00

Brain metastases (BrM) are most common among patients with metastatic lung cancer, breast cancer, and melanoma. Historically, management of BrM consisted of local treatments with surgical resection and/or radiation therapy, with either whole brain radiation therapy (WBRT) or stereotactic radiosurgery (SRS). Current guidelines recommend SRS as the initial therapy for patients who have up to four BrM, but several studies have demonstrated that upfront SRS may be considered for some patients who have more than four BrM given additional clinical benefits of improved memory function and quality of life compared to WBRT.

Systemic therapies are increasingly understood to cross the blood-brain barrier (BBB) following disruption of its integrity upon BrM development. Disseminated tumour cells intravasate into the circulation and spread hematogenously with a “seed and soil” tropism for the brain that provides a suitable tumour microenvironment. Tumour cells extravasate and increase the permeability of the BBB by decreasing tight junction protein expression, decreasing astrocyte pedicles, reducing pericyte coverage, and increasing neoangiogenesis. The altered integrity of the BBB allows penetration of large drug molecules, such as antibody-drug conjugates (ADCs), which exert their therapeutic effects on BrM by binding to tumour cell-specific epitopes and releasing a cytotoxic payload, even in the absence of radiation. Other therapeutic mechanisms of action include molecular (passive or receptor-mediated transport), physical (radiation or focused ultrasound), direct delivery to the brain (intrathecal or intratumoral), and cell‑mediated (immune cell extravasation) (Figure 1).

The Role of Biomarkers in Upper Gastrointestinal Cancers

2025-04-11T14:23:37+00:00

Upper gastrointestinal (GI) cancers include esophageal, esophagogastric junction, and stomach cancers, which together represent the second leading cause of cancer-related mortality worldwide in both sexes, with approximately 1,100,000 deaths in 2022. The disease is usually diagnosed at an advanced non-curable stage, and conventional chemotherapy treatment is associated with poor prognosis. Advances have been made in the development of new therapies, including immunotherapy and targeted therapies. Biomarker identification has expanded treatment options and guides treatment selection. This article reviews the molecular characterization of GI cancers, which has been the subject of increasing research, and biomarker-targeted agents, representing a continually evolving landscape in upper GI cancers.

Advances in Adjuvant Therapy for High-Risk Breast Cancer: A Canadian Clinical Approach

2025-04-11T14:24:15+00:00

Breast cancer remains the second leading cause of cancer-related death among women in Canada. In early-stage disease, the purpose of adjuvant therapies following surgical resection is to reduce the risk of recurrence. The advent of adjuvant endocrine therapy (ET) significantly reduced breast cancer recurrence and mortality; however, some patients have disease recurrence even 20 years after initial diagnosis. Therefore, several advancements have been made to optimize cure rates and improve outcomes. As a heterogeneous disease, breast cancer outcomes are impacted by clinical, histological, and genomic features, which guide prognosis and selection of adjuvant therapy. This review focuses on recent and emerging adjuvant therapies, specifically for high-risk patients across breast cancer subtypes: hormone receptor‑positive (HR‑positive), human epidermal growth factor receptor 2-positive (HER2-positive), and triple‑negative breast cancer (TNBC).