Titles and Affiliations
Professor, Cancer Therapeutics
Head, Translational Breast Cancer Genomics and Therapeutics Lab
Peter MacCallum Cancer Centre
Research area
Building large datasets to help tailor more effective treatments for younger patients.
Impact
Women younger than 40 years old with breast cancer have poor outcomes, with increased rates of both local and distant recurrence compared with their older counterparts. Although younger women have higher rates of triple-negative breast cancer (TNBC), hormone receptor (HR) – positive breast cancer seems to be more aggressive in this population. To understand the biological reasons behind this observation, Dr. Loi and her team have been analyzing tumor samples in premenopausal women with breast cancer from the landmark Suppression of Ovarian Function Trial (SOFT) which demonstrated the benefit of the addition of ovarian function suppression to chemotherapy and endocrine therapy after surgery in women under 40.
Progress Thus Far
After analyzing thousands of HR-positive cases from the SOFT trial this year, the research team found that even a small increase in tumor infiltrating lymphocytes (TILs, above 1%) was indicative of a significantly lower risk of distant recurrence. TILs are immune cells that can serve as a prognostic biomarker in breast cancer and can be quantified from digitized tumor samples. This association was more evident in higher grade tumors. TILs predicted prognosis independent of the ovarian suppression therapy, indicating their levels reflect the intrinsic tumor biology rather than being related to any biological response from therapy. This highlights their value as a biomarker to personalize treatments in younger patients with HR-positive breast cancer.
In addition, the team analyzed genetic sequences in tumor samples to further understand targeted drug resistance in younger women with advanced HER2-positive disease. They found striking genetic differences between primary and metastatic tumors, including amplification of a gene that plays a critical role in cell growth and a decrease in expression of the HER2 gene, both of which may enable cancer survival. The team is investigating how exposure to drugs such as immunotherapy may drive these genetic changes.
What’s next
In the coming year, Dr. Loi and her team will continue to explore how the immune system influences breast cancer development, progression and response to therapy. They will increase the number of samples they are analyzing to include triple-negative breast cancer tumors and will study a type of immune-cell receptor at the single-cell level to uncover patterns that may predict who can benefit the most from immunotherapy.
A major new focus for the research team in the coming year is to understand how pregnancy and lactation can protect against aggressive breast cancer. Their recent findings in model systems indicate that protective immune cells increase after pregnancy and a complete lactation period. This increase in immune cells may help control tumor growth. The team will further test whether these immune changes lead to a greater response to immune-based therapies in their models and further validate their findings by analyzing publicly available datasets of single-cell profiles from normal breast tissue. These data will be used to inform future prevention strategies that aim to harness the immune system to reduce breast cancer risk.
Biography
Sherene Loi, MMBS (Hons), FRACP, PhD is a Professor of Medicine at the University of Melbourne and a fellow of the Australian Academy of Health and Medical Sciences. She is a medical oncologist and clinician scientist with expertise in genomics, immunology, and drug development in breast cancer. She has published over 295 peer-reviewed research articles and has ranked in the top 1% of highly cited researchers globally by Clarivate Analytics since 2018. She has won numerous international awards including, but not limited to: American Association for Cancer Research (AACR) Outstanding Investigator Award for Breast Cancer Research, European Society of Clinical Oncology’s Breast Cancer Award, and Prime Minister’s Frank Fenner Prize for Life Scientist of the Year (Australia).
Dr. Loi completed her medical oncology training in Melbourne and worked for a large clinical trial network in Brussels, Belgium for nearly a decade before returning to the Peter MacCallum Cancer Centre as an independent researcher in 2013. She is the Executive Director of Breast International Group (BIG), Chair of the Executive Committee of the Kathleen Cuningham Foundation Consortium for Research into Familial Aspects of Breast Cancer, and Board Director of the Scientific Advisory Committee of the Australia New Zealand Breast Cancer Trials Group, the largest breast cancer clinical trials cooperative group in Australia. She has co-chaired with Dr Roberto Salgado an internationally recognized pathology working group on immune biomarkers in breast cancer (www.tilsinbreastcancer.org) and is a scientific committee member of European Society of Medical Oncology, Molecular Analysis for Precision Oncology Congress, and Molecular Analysis for Precision Oncology Congress.
“BCRF support helped us uncover how pregnancy and immunity protect against breast cancer and enabled immune marker discovery to guide treatment and improve care for young women.”
