Impact of multidisciplinary team meetings on the management of patients with breast cancer in a large private healthcare facility.

AIMS: Multidisciplinary meetings (MDMs) play a crucial role in decision-making in breast cancer patient care. This study aimed to firstly assess the impact of breast cancer MDMs in decision-making for breast cancer patients and secondly to determine the concordance between MDM recommendations and implementation of clinical practice. METHODS: Patient cases to be presented at the weekly breast cancer MDMs were identified and prospectively enrolled. Management plans were predicted by the treating surgeon with the pre-MDM management plans then compared to MDM recommendations. Changes in decision-making were assessed in the following domains: further surgery, systemic therapy (endocrine, chemotherapy or targeted), radiotherapy, enrolment in a clinical trial, further investigations, and referral to other specialists or services. Patient records were subsequently reviewed at 3 months post-MDM to assess the rate of implementation of MDM recommendations and any reasons for discordance. RESULTS: Out of 50 cases, 66% (CI 53-79%; p < .005) experienced a change in management plan as a result of MDM discussion, with a total of 66 episodes of recorded change per decision-making domain affecting the following: further surgery (7.6%), endocrine therapy (4.5%), chemotherapy (19.7%), targeted therapy (4.5%), radiotherapy (18.2%), enrolment for a clinical trial (12.1%), additional investigations (22.7%), and further referrals (10.6%). MDM recommendations were implemented in 83.7% of cases. CONCLUSION: The breast cancer MDMs were found to substantially impact on the management plans for breast cancer patients, with 83.7% of MDM recommendations being implemented into clinical practice. This study reinforces the importance of MDMs in the management of these patients, as well as highlighting the need for further investigating and addressing the potential barriers to the implementation of MDM recommendations.

The role of depression and other psychological factors in work ability among breast cancer survivors in Australia.

OBJECTIVE: Identifying modifiable factors affecting work ability among cancer survivors is important. The primary aim of the present study was to examine the effects of depression and related psychological factors on work ability among breast cancer survivors in Australia. METHODS: In this cross-sectional electronic and postal survey, Australian breast cancer survivors were investigated. Work status and conditions before and after cancer treatment were analysed. Work ability was measured using the Work Limitation Questionnaire©-Short Form (WLQ-SF) with its four domains (time management, physical tasks, mental-interpersonal tasks, and output tasks). Three psychological factors were investigated: depression, fear of cancer recurrence, and demoralisation. Sociodemographic and clinical data were also collected. Multivariate regression analysis was used to identify the associations of psychological factors with WLQ-SF. RESULTS: Among eligible survivors, 310 (50%) responded to the survey and were analysed. Nearly one third reported their work conditions had changed after cancer treatment. The depressed group reported limited work ability in 35%-44% of the four domains of WLQ-SF, while the non-depressed group reported limited work ability in only 8%-13%. At-work productivity loss was approximately fourfold higher in the depressed group than in the non-depressed group. In multivariate analysis, at-work productivity loss was associated with depression, demoralisation, and past history of anxiety. CONCLUSIONS: After breast cancer treatment, work conditions changed toward lower wages and working hours. Depression, demoralisation, and past history of anxiety were associated with lower work ability. Further evaluations of work rehabilitation in breast cancer survivors are warranted.

Evaluation of FGFR targeting in breast cancer through interrogation of patient-derived models.

BACKGROUND: Particular breast cancer subtypes pose a clinical challenge due to limited targeted therapeutic options and/or poor responses to the existing targeted therapies. While cell lines provide useful pre-clinical models, patient-derived xenografts (PDX) and organoids (PDO) provide significant advantages, including maintenance of genetic and phenotypic heterogeneity, 3D architecture and for PDX, tumor-stroma interactions. In this study, we applied an integrated multi-omic approach across panels of breast cancer PDXs and PDOs in order to identify candidate therapeutic targets, with a major focus on specific FGFRs. METHODS: MS-based phosphoproteomics, RNAseq, WES and Western blotting were used to characterize aberrantly activated protein kinases and effects of specific FGFR inhibitors. PDX and PDO were treated with the selective tyrosine kinase inhibitors AZD4547 (FGFR1-3) and BLU9931 (FGFR4). FGFR4 expression in cancer tissue samples and PDOs was assessed by immunohistochemistry. METABRIC and TCGA datasets were interrogated to identify specific FGFR alterations and their association with breast cancer subtype and patient survival. RESULTS: Phosphoproteomic profiling across 18 triple-negative breast cancers (TNBC) and 1 luminal B PDX revealed considerable heterogeneity in kinase activation, but 1/3 of PDX exhibited enhanced phosphorylation of FGFR1, FGFR2 or FGFR4. One TNBC PDX with high FGFR2 activation was exquisitely sensitive to AZD4547. Integrated 'omic analysis revealed a novel FGFR2-SKI fusion that comprised the majority of FGFR2 joined to the C-terminal region of SKI containing the coiled-coil domains. High FGFR4 phosphorylation characterized a luminal B PDX model and treatment with BLU9931 significantly decreased tumor growth. Phosphoproteomic and transcriptomic analyses confirmed on-target action of the two anti-FGFR drugs and also revealed novel effects on the spliceosome, metabolism and extracellular matrix (AZD4547) and RIG-I-like and NOD-like receptor signaling (BLU9931). Interrogation of public datasets revealed FGFR2 amplification, fusion or mutation in TNBC and other breast cancer subtypes, while FGFR4 overexpression and amplification occurred in all breast cancer subtypes and were associated with poor prognosis. Characterization of a PDO panel identified a luminal A PDO with high FGFR4 expression that was sensitive to BLU9931 treatment, further highlighting FGFR4 as a potential therapeutic target. CONCLUSIONS: This work highlights how patient-derived models of human breast cancer provide powerful platforms for therapeutic target identification and analysis of drug action, and also the potential of specific FGFRs, including FGFR4, as targets for precision treatment.