With the recent Health Canada approval of olaparib for high-risk, HER2-negative early breast cancer, physicians are now facing the practical challenges of integrating olaparib into current management of triple-negative breast cancer (TNBC) and HR-positive, HER2-negative (HR+/HER2−) early breast cancer. This review provides perspectives on some of the challenges related to identification of olaparib candidates, with a focus on the latest guidance for germline BRCA testing and considerations regarding high-risk disease definitions. Updated treatment pathways are explored for both disease states, including other adjuvant treatment options such as pembrolizumab, capecitabine, and abemaciclib. Gaps in the current literature regarding the sequential or combined use of these adjuvant therapies are noted and future, potentially informative, studies are briefly examined.

Knowledge of critical care nurses' intravenous fluid bolus therapy (FBT) practice remains underexplored. Using a multi-choice online survey conducted between September and October 2014, we sought to describe the self-reported practice of critical care nurses located in Australia and New Zealand. Two hundred and ninety-five critical care nurses responded to the survey with most practising in adult ICUs. Overall, 0.9% saline solution was the preferred solution for FBT. However, more Australian than New Zealand respondents preferred ‘albumin 4%’ (31% versus 3.6%, P <0.01) for FBT. In contrast, more New Zealand respondents preferred ‘Plasma-Lyte ^® ’; (33.3% versus 6.4%, P 1000 ml and administration duration from as quickly as possible to 60 minutes. In response to FBT, almost half of the respondents expected an increase in mean arterial pressure of between 11 to 20 mmHg. Similarly, >40% expected a central venous pressure increase >3 mmHg, >70% expected a urinary output increase of 0.5 to 1.0 ml/kg/hr, and >60% expected a decrease in heart rate of >11/min. Overall, 0.9% saline remains the most common solution for FBT, but there are significant national differences in the preference for albumin and Plasma-Lyte. A volume of 250 ml defines a fluid bolus, with a range from 100 ml to >1000 ml, and speed of delivery from stat to 60 minutes. Most nurses expect substantial physiological effects with FBT.

Background: Integrating germline genetic testing (GGT) recommendations from tumor testing into hereditary cancer clinics and precision oncology trials presents challenges that require multidisciplinary expertise and infrastructure. While there have been advancements in standardizing molecular tumor boards, the implementation of tumor profiling for germline-focused assessments has only recently gained momentum. However, this progress remains inconsistent across institutions, largely owing to a lack of systematic approaches for managing these findings. This study outlines the development of a clinical pathway for identifying potential germline variants from an institutional tumor-sequencing research program at Princess Margaret Cancer Centre. Methods: Between August 2022 and August 2023, a clinical pathway led by a germline Molecular Tumor Board (gMTB) was established to review tumor genetic variants (TGVs) flagged as potential germline findings in patients with advanced cancer via a multigene panel. Eligibility for hereditary cancer syndrome investigation (‘germline criteria’) followed Cancer Care Ontario’s Hereditary Cancer Testing Criteria and clinical judgment. Germline-focused analysis of TGVs followed the European Society of Medical Oncology guidelines and similar published criteria (‘tumor-only criteria’). Results: Of 243 tumor profiles, 83 (34.2%) had at least one TGV flagged by the genetic laboratory as potentially germline and were therefore referred to the gMTB for further review. Among these 83 cases, 47 (56.6%) met ‘germline criteria’ for GGT, regardless of the TGV assessment. A total of 127 TGVs were assessed in these 83 cases, of which 44 (34.6%) were considered germline relevant. Tier I TGVs, interpreted as pathogenic/likely pathogenic (P/LP) and found in most- or standard-actionable genes with high germline conversion rates (GCRs) in any context, were more likely to be considered germline relevant (p-value < 0.05). One confirmed germline variant was identified in nine patients meeting solely ‘tumor-only criteria’. Overall, 27/44 germline relevant TGVs underwent germline testing. We found a germline P/LP variant in 9 cases of the entire cohort, with a GCR of 33% (9/27). Conclusions: Incorporating genetic counselors into gMTBs enhanced the integration of research findings into clinical care and improved the detection of disease-causing variants in patients outside traditional testing criteria.

Genetic testing in hereditary cancer is evolving from single-gene-focused approaches in affected individuals to multi-gene panel testing for affected individuals and unaffected relatives. The widespread use of multi-gene panel testing has led to the identification of individuals with two or more pathogenic or likely pathogenic variants in hereditary cancer susceptibility genes (CSGs), termed Multilocus Inherited Neoplasia Allele Syndrome (MINAS) carriers. It remains unclear whether MINAS carriers are at increased risk of multiple, atypical, or more severe cancer phenotypes, and currently, there is no consensus on how best to identify and manage cancer risk. In this retrospective study, we identified 54 MINAS carriers at Princess Margaret Cancer Center in Toronto, Canada. Demographic, clinical, and genetic data were extracted from medical records. Group comparisons were performed using Fisher’s exact or chi-square tests for categorical variables and independent t tests for age at cancer diagnosis. Statistical significance was set at p ≤ 0.05. The majority of affected MINAS carriers had a cancer consistent with the expression of at least one pathogenic variant. Approximately 28% of MINAS carriers were diagnosed with one atypical cancer. The most frequent gene pair combinations included hereditary breast cancer genes, with some carriers exhibiting earlier age of breast cancer onset than single CSG variants reported in the literature. Our study indicates that the cancer spectrum associated with CSGs is expanding and suggests that more intensive cancer surveillance for subgroups of MINAS carriers with hereditary breast cancer CSGs may be warranted.

Genetic testing for solid tumor syndromes typically uses peripheral blood leukocytes (PBL) as the source of germline DNA. This approach has shortcomings in certain situations, such as somatic mosaicism and hematologic malignancies. Here we describe a case where germline genetic testing on PBL revealed an unsuspected diagnosis of myelodysplastic syndrome (MDS). A 68-year-old male with a history of three solid tumors and a significant family history of cancer underwent germline genetic testing with a 76-gene hereditary cancer panel. Initial testing using PBL revealed deletions of the entire APC and CTNNA1 genes, suggestive of a contiguous deletion of chromosome 5 (del(5q)). Subsequent testing on cultured fibroblasts was negative, indicating the deletions were somatic. Bone marrow analysis confirmed the presence of del(5q) and a diagnosis of MDS. This case demonstrates the potential to uncover hematologic disorders through hereditary cancer genetic testing, emphasizing the importance of careful results interpretation, multidisciplinary follow-up, and DNA source selection.