Breast Cancer Grand Round

Rethinking Immune Responsiveness in Breast Cancer

29 October 2025

From reproductive history to checkpoint blockade

Breast cancer is traditionally viewed as immunologically cold, particularly in hormone receptor-positive (HR+) subtypes. However, two recent advances challenge this paradigm.

First, data from the two phase III clinical trials demonstrate that adding PD-1 inhibitors to neoadjuvant chemotherapy in early-stage HR+ breast cancers can enhance pathological complete response, with biomarkers of immune enrichment seen in responders. This indicates that a subset of HR⁺ tumours may be highly immunogenic and responsive to checkpoint blockade.

Second, our discovery that pregnancy and lactation induce increases in durable CD8⁺ T cells in normal human breast tissue suggests that immune reprogramming through physiological events can confer long-term protection against breast cancer.

These findings reveal a previously unappreciated role for reproductive history in shaping local adaptive immunity which impacts both breast cancer risk and potentially treatment response.

Together this work opens new avenues for biomarker development, immunoprevention, and expanding the reach of immunotherapy beyond triple-negative breast cancer.

Speaker

Prof Sherene Loi
Consultant Medical Oncologist, Breast Unit, Peter MacCallum Cancer Centre
Research and Education Lead, Breast Cancer, VCCC Alliance
Professor Loi is a Medical Oncologist specialised in breast cancer treatment as well as a clinician scientist (Group Leader) at the Peter MacCallum Cancer Centre. She is recognised internationally as a leading clinician scientist whose work has led to new insights into the breast cancer immunology field as well as leading international clinical trials in breast cancer immunotherapy.

To date, she has published over 360 peer-reviewed research articles with a lifetime H-index of >123 with over 78,000 citations (Google Scholar). Her recent work has been highly influential: she has been ranked in the top 1% of highly cited researchers globally by the Web of Science since 2018. In 2023 she was named Australia’s top researcher in Oncology by The Australian newspaper.

She chairs the Scientific Committee of the International Breast Cancer Study Group (IBCSG) based in Bern, Switzerland, one of the largest global academic breast cancer trial cooperative groups, as well as the Kathleen Cunningham Familial Research Consortium.

She is hold the Inaugural National Breast Cancer Foundation (NBCF) of Australia Endowed Chair and in 2021 received one of the Prime Ministers’ Awards for Science.

Chair

Prof Sarah-Jane Dawson
Medical Oncologist, Breast Unit, Peter MacCallum Cancer Centre
Professor Dawson is a clinician-scientist at the Peter MacCallum Cancer Centre and Centre for Cancer Research University of Melbourne. She is the co-program head of the Cancer Biology and Therapeutics Program, Group leader of the Molecular Biomarkers and Translational Genomics Laboratory and Medical Oncologist in the Breast Unit. Her current research interests are focused on the development of noninvasive blood-based biomarkers ('liquid biopsies') for clinical application, including early detection, risk stratification and disease monitoring in cancer management.

Warning: The VCCC Alliance Breast Cancer Grand Round is targeted at a clinical audience and features open discussion about real cases and patients. While these cases are de-identified, the imagery, content and discussion can be graphic. It is not appropriate for consumer participants.