Patients who paused their endocrine therapy experienced short-term rates of breast cancer recurrence similar to women who did not pause therapy for pregnancy, and many went on to conceive and deliver healthy babies, according to results from the POSITIVE clinical trial presented at the 2022 San Antonio Breast Cancer Symposium.

Professor Christobel Saunders, consultant surgeon at Peter Mac and the James Stewart Chair of Surgery at the University of Melbourne was the lead investigator in Australia for the study which enrolled patients from 116 hospitals across 20 countries. 

Forty to 60 percent of patients who are diagnosed with breast cancer at age 40 or younger are concerned about their future fertility, especially if the disease occurs before they could decide whether to become a mother or not.

Young women with early-stage hormone receptor (HR)-positive breast cancer are often treated with endocrine therapy, such as ovarian function suppression, aromatase inhibitors, or selective estrogen receptor modulators.

“This study confirms breast cancer patients who stop hormone therapy to become pregnant did not experience worse short-term recurrence rates,” Professor Saunders said.

“Women now know there is hope if they want a family.”

To examine the impact of pausing endocrine therapy to pursue pregnancy, researchers designed the single-arm POSITIVE clinical trial (Pregnancy Outcome and Safety of Interrupting Therapy for Women with Endocrine Responsive Breast Cancer).

From December 2014 through December 2019, 518 women aged 42 or younger who desired to become pregnant enrolled in the study, opting to pause endocrine therapy for approximately two years to try to get pregnant. Before pausing their treatment, women had completed between 18 and 30 months of adjuvant endocrine therapy.

Researchers found that the percentage of women whose breast cancer came back (8.9%) was comparable to what occurred in patients enrolled in other studies (9.2%).

In addition, with a total of 365 babies born to women in the study, the rates of conception and childbirth were similar to, or higher, than rates in the general population.

The study is sponsored and conducted by the International Breast Cancer Study Group (IBCSG), a division of ETOP-IBCSG Partners Foundation, and by the Alliance for Clinical Trials in Oncology in North America, in collaboration with the Breast International Group (BIG). The study concept was initiated within the BIG-NCTN (National Clinical Trials Network) Endocrine Working Group, then developed, and coordinated globally by the IBCSG to address this important, patient-oriented, unmet medical need.

The NHMRC ideas grants are designed to support researchers at all stages of their career with innovative and creative medical research ideas.  The research can span discovery to implementation and the grants are highly competitive.

Peter Mac is very pleased to announce six of our staff were successful applicants for 2023. 

Congratulations to Dr Dineika Chandrananda, Associate Professor Nick Clemons, Dr Luc Furic, Dr Ali Motazedian, Associate Professor Karen Sheppard, and Dr Anna Trigos. 

A brief description of their innovative research ideas are listed below:

Dr Dineika Chandrananda - “Tracking transcriptional evolution using circulating tumour DNA”

Tumours shed small amounts of DNA into the patient’s bloodstream known as circulating tumour DNA (ctDNA). Because of this a simple blood test allows us to study the cancer, and can offer a non-invasive alternative to tissue biopsies. Dr Chandrananda will use ctDNA in the blood to study how cancer evolves and becomes resistant to treatment in advanced breast cancer. This method is generalisable across tumour types and has the potential to transform real-time cancer monitoring.

Associate Professor Nick Clemons - “Overcoming ferroptosis resistance to improve outcomes in oesophageal cancer”

Compared to normal tissues, oesophageal cancers increase their consumption of nutrients from the surrounding environment.  Oesophageal cancers also change the way they use these nutrients in order to survive, grow, spread to other organs and become resistant to treatments. This research project will identify which nutrients oesophageal cancers depend on to survive. Dr Clemons will develop strategies to exploit these dependencies and improve the efficacy of treatments used to combat oesophageal cancer.

Dr Luc Furic - “​Codon bias and the role of tRNA modifications in cancer”

Cancer is characterised by a high rate of cell growth and proliferation. Cancer cells need to increase their biomass to divide and this is dependent on the synthesis of proteins. Small molecules that carry the building blocks needed for protein synthesis are called transfer RNA (tRNA) ​and they are responsible for decoding the information contained in messenger RNA (mRNAs). Recently it was discovered that tRNA are chemically modified ​in a dynamic manner and that these modifications could be targeted as a way to strongly inhibit tumour growth and progression.  This research project will try to determine the impact of changes to tRNA and how best to target the tRNA to stop cancer growing. This pathway could be applicable to a wide range of cancers.

Dr Ali Motazedian - “Understanding clonal hierarchy and tissue reconstruction post injury”

Millions of blood cells are made by the body every day in specialised organ compartments. T-cells are white blood cells and make up an important part of the immune system that fights infections and cancer. In this study, we aim to find out how blood stem cells turn into T-cells as they move through different organ compartments. We are trying to understand how the blood system is regenerated after damage from cancer therapies by stem cell transplants to improve patient outcomes.

Associate Professor Karen Sheppard - “A fat chance for melanoma”

Recently a study in melanoma patients showed that overweight patients did much better on treatment than normal weight patients. This project aims to understand how body fat makes melanoma patients more responsive to therapy. By understanding the biological basis for this association, we can design new therapeutic strategies that will improve the outcomes for melanoma patients and not lead to adverse health effects associated with being overweight.

Dr Anna Trigos - “Spatial analysis to investigate cancer evolution as a complex ecosystem of interacting tumour populations ”

Cancer is a disease where cells grow rapidly, creating tumours. However, all tumour cells are not the same. There can be multiple cell types within a single tumour that most likely interact to help each other grow. This research project will analyse tissue samples from metastatic prostate cancer to understand which tumour cells are cooperating with each other to grow. With this knowledge, we will be able to develop a new type of treatment that kills tumours by disrupting how cells talk with each other, providing new treatment options for prostate cancer patients in the future.

The program, which had its inaugural intake this year, is delivered by The Centre for Digital Transformation of Health at The University of Melbourne.

The Fellows will be supported to deliver projects that advance digital health initiatives at Peter Mac, with a view to improving patient outcomes across both Peter Mac and the wider community.

Renae McDougall is a medical health consultation liaison nurse, aiming to lead projects centred on service improvement for consumers. Her project will develop an EMR based solution to help nurses identify patients at risk of clinical aggression and support appropriate, compassionate, and evidence-based interventions and escalation pathways. Renee is working toward her ultimate passion of maintaining high levels of job satisfaction across the nursing workforce and increased efficiency and effectiveness of nursing care throughout the community, using technology and digital health solutions to achieve this.

Elizabeth Crone is a cancer nurse researcher with the Academic Nursing Unit and the Department of Anaesthetics and Pain Management. Her project will implement routine, standardised collection of social determinants of health data for patients with cancer, using a digitally enabled solution. Elizabeth believes in the critical importance of health services research and implementation science as vehicles to examine and innovate health systems and health outcomes.

Belinda Lambros is a nurse practitioner with the Department of Infectious Diseases. She is co-leading the implementation of the precinct-wide adult sepsis pathway in the Electronic Medical Record EPIC, and has a key role monitoring all patients with sepsis at Peter Mac. Belinda’s project will establish a learning health systems framework to implement the clinical care standard, and optimise the implementation and uptake of the sepsis workflows at Peter Mac.

Associate Director of Health Services Research and Implementation Science at Peter Mac, Professor Karin Thursky, congratulates the new Fellows, "This fellowship program is a wonderful way to build a workforce that is skilled in introducing improved models of care using digital health that are evidence based, successful and sustainable."

"We look forward to supporting them and building our community of practice.'