2023 CLINICAL FELLOWSHIPS & INTERNATIONAL FELLOWSHIP SUPPORT

Patients with axillary node positive breast cancer are often treated with neoadjuvant chemotherapy (treatment before surgery) and conventional axillary dissection. However, many patients experience arm morbidity and reduced quality of life with this approach and new research suggests that less radical surgical strategies may improve patient outcomes. This study will ascertain the safety and efficacy of targeted axillary dissection (TAD) as an alternative to conventional axillary dissection, in patients who undergo neoadjuvant chemotherapy. It will also collect data on breast cancer patients to help establish a new registry specifically focused on TAD treatment.

The development of biologic signatures to assess recurrence risk for invasive breast cancer initially and later DCIS have been developed over time. A new combined clinical and genomic risk assessment test recently available in Australia is DCISionRT. This test prognosticates the 10‐year risk of DCIS recurrence or invasive breast cancer (IBC) developing, with or without radiation therapy. If we confirm the efficacy and impact of DCISionRT in tailored patient care, we could identify those that can avoid unnecessary radiotherapy, whilst identifying those at higher risk than initially presumed and provide beneficial RT. There have been multiple validation studies for DCISionRT, including a Melbourne based study, all showing impressive outcome prediction even when counter intuitive based on standard van Nuys type criteria [8, 9]. Currently, DCISionRT is only available for patients receiving therapy at one private RT company. In the Australian environment for the test to become widely available and funded, following on from the lack of success in Oncotype DX being MBS funded, a randomised trial (RCT) showing improvements in outcome for test users is likely to be necessary. The proposed outcome is development of a BCT‐led randomised control trial study protocol to evaluate the safety and efficacy of using DCISionRT in patient management decision making.

This project will continue work on the existing clinical trial called the Breast MRI Evaluation Study, which aims to establish when MRI’s improve patient outcomes and when it does not. The main focus of this Clinical Fellowship will be assessing the participant experience of undergoing MRI using patient reported outcome measures (PROMs). The hypothesis is that having a breast MRI will influence patient preferences for surgery, satisfaction with decision making and confidence in treatment. Whilst patient experience of MRI will be the key focus, we anticipate this fellowship would also provide the opportunity and time to report on other study objectives.

The BRCA-P clinical trial is a world-first study that aims to prevent breast cancer in women who carry the BRCA1 gene mutation. Dr Muttiah will assist in the clinical conduct of this study, to enable sites to develop and establish recruitment pathways through familial cancer and risk management clinics. The project will also provide preliminary interpretation/report on results from translational research sub-studies.

Approximately 70% of women experience moderate to high levels of fear of cancer recurrence (FCR) and up to 15% experience severe, disabling FCR characterised by constant, intrusive thoughts about cancer; interpretation of mild, unrelated symptoms as a sign of recurrence; a belief that cancer will return regardless of actual prognosis; and an inability to plan for the future due to cancer worry. FCR is a routine reason for seeking professional clinical support and is associated with psychological distress, poorer social and occupational functioning, and increased health care costs.

This study will provide useful exploratory data from the PROSPECT clinical trial, about the association between therapy de-escalation by omitting radiation therapy and FCR. It will also examine FCR and quality of life in women with DCIS.

The fellowship is primarily a research fellowship, with the opportunity to attend Breast Cancer and Early Drug Development trial clinics on a weekly basis. The aim of this research is to investigate the impact of novel breast cancer treatments on tumour biology, the tumour microenvironment and peripheral immunity, with the ultimate aim of uncovering new biomarkers of response and resistance to identify strategies to optimise response to novel therapies.

In recent years, multiple novel therapies including immune checkpoint inhibitors, antibody drug conjugates and oral small molecule inhibitors have been approved for the treatment of breast cancer. An improved understanding of which patients will derive the greatest benefit from these treatments, and in what sequence or combinations they should be used, is required to implement novel therapies in the clinic without unnecessary increase in toxicity or financial burden. Samples from patients treated with novel therapies on large clinical trials at IGR provide an invaluable repository for addressing these questions through translational research. This research will be supported by technical expertise from Prof André and his team, who have a track record of biomarker discovery.

Ultimately, the findings from such research will be applied to refine future clinical trial design, both in terms of patient selection and identification of more effective combinations or sequencing of therapies. In this way, both translational research and international collaboration are essential for successful and efficient clinical trial design, making this an important opportunity for a BCT member, particularly with respect to future BCT trials.