NatIonal survey on the kNowledge and insight of individuals with meTastatic brEast cancer (MBC) on doSe optimisation of systemic anti-cancer TherapY (INTENSITY)

Open to UK applicants only.

Supervisors: 

• Dr Olubukola Ayodele  oa229@leicester.ac.uk
• Professor Harriet Walter  hw191@leicester.ac.uk
• Dr Natalie Darko

Project Description:

Despite advances in breast cancer treatment, metastatic breast cancer remains incurable and requires long-term systemic anti-cancer therapy (SACT). A critical challenge in managing this condition is determining the optimal treatment dose that balances therapeutic efficacy with treatment-related toxicity. Increasing evidence suggests that patients from different ethnic backgrounds may experience varying tolerability to treatment, yet these differences remain poorly understood.

This PhD project, INTENSITY, aims to investigate the knowledge, perceptions and experiences of individuals living with metastatic breast cancer regarding dose optimisation of systemic anti-cancer therapy, with a particular focus on ethnic disparities. The project is embedded within a wider programme of work addressing inequalities in cancer care at the University of Leicester and University Hospitals of Leicester NHS Trust.

The study will adopt a mixed-methods design comprising four interlinked phases. First, a systematic review will be conducted to synthesise existing evidence on dose optimisation strategies in metastatic breast cancer. This will provide a robust evidence base and identify current gaps in knowledge and practice.

Second, a national cross-sectional survey will be conducted involving approximately 1,100 patients with metastatic breast cancer. Participants will complete a 35-item online questionnaire developed in collaboration with a patient advocate and piloted in a clinical setting. The survey will explore patient understanding of dose optimisation, experiences of treatment-related toxicity, communication with healthcare professionals, and perceptions of personalised care.

Third, qualitative focus groups will be conducted to explore patient perspectives in greater depth. Three focus groups will be convened, and discussions will be audio-recorded and analysed using thematic analysis. This phase will provide rich insights into patient experiences, including cultural, social and communication-related factors influencing treatment decisions.

The final phase will involve the development of training and educational interventions tailored to the needs of different patient groups, particularly those from under-represented ethnic backgrounds. These outputs will aim to improve patient-clinician communication and support more personalised approaches to treatment dosing.

This research is highly relevant to current clinical practice. Suboptimal dosing can lead to significant toxicities, treatment interruptions and discontinuation, potentially reducing treatment benefit. Conversely, more individualised dosing strategies may improve tolerability and enable patients to remain on effective therapies for longer.

The expected outcomes of this project include improved understanding of patient knowledge and preferences regarding dose optimisation, identification of ethnic disparities in treatment experiences, and the development of practical tools to support personalised care. The findings will inform clinical guidelines, enhance patient-centred communication, and contribute to reducing inequalities in breast cancer outcomes.

The PhD student will receive comprehensive training in systematic reviews, quantitative and qualitative research methods, and health inequalities research. This project offers a unique opportunity to contribute to impactful, practice-changing research in metastatic breast cancer.

References:

1. WHO: Breast cancer [Internet], 2021[cited 04 Oct 2023]
2. SEER Fast Stats, last accessed 10/2023; 
3. Sabiston D. Sabiston Textbook of Surgery. 20th ed. Philadelphia, PA: Elsevier; 2016
4. O’Shaughnessy J. Oncologist. 2005;10(S3 Suppl 3):20–9.
5. Miglietta F, Bottosso M, Griguolo G, Dieci MV, Guarneri V. Major advancements in metastatic breast cancer treatment: when expanding options means prolonging survival. ESMO Open. 2022 Apr;7(2):100409.
6. US FDA: Project Optimus: Reforming the dose optimization and dose selection paradigm in oncology [Internet], 2022[cited 04 Oct 2023]
7. Rogatko A, Babb JS, Tighiouart M, Khuri FR, Hudes G. New paradigm in dose-finding trials: patient-specific dosing and beyond phase I. Clin Cancer Res. 2005 Aug 1;11(15):5342-6.
8. Diéras V, Harbeck N, Joy AA, et al: Palbociclib with Letrozole in Postmenopausal Women with ER+/HER2- Advanced Breast Cancer: Hematologic Safety Analysis of the Randomized PALOMA-2 Trial. Oncologist 24:1514–1525, 2019
9. Jain RK, Lee JJ, Hong D, et al: Phase I Oncology Studies: Evidence That in the Era of Targeted Therapies Patients on Lower Doses Do Not Fare Worse. Clinical Cancer Research 16:1289–1297, 2010
10. Shah M, Rahman A, Theoret MR, et al: The Drug-Dosing Conundrum in Oncology — When Less Is More. N Engl J Med 385:1445–1447, 2021
11. Adjei AA: What Is the Right Dose? The Elusive Optimal Biologic Dose in Phase I Clinical Trials. JCO 24:4054–4055, 2006

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