Titles and Affiliations
President, Gianni Bonadonna Foundation
Research area
Identifying biomarkers to improve the effectiveness of immunotherapy in breast cancer.
Impact
Immunotherapies are a promising class of cancer drugs designed to amplify the immune system to attack cancer cells. Triple-negative breast cancer, for example, has shown some response to immunotherapy when combined with chemotherapy, but the proportion of patients who benefit remains low. Consequently, some patients experience the side effects associated with immunotherapies, without clinical benefit. Dr. Gianni and his team are investigating potential biomarkers for response to immunotherapy, to better predict which patients should receive these treatments.
Progress Thus Far
By analyzing tumors at the single-cell level and studying changes in immune markers before and during treatment, Dr. Gianni and his team have found promising clues, like the expression level of the Ki67 gene, and the spatial patterns of immune cells within the tumor, that help explain who responds best to immunotherapy. Using advanced imaging, the team also mapped the immune cells present inside patient tumor samples and found that tumors surrounded by immune cells that suppress the body’s natural defenses tend to respond poorly to immunotherapy, while tumors rich in a specific immune cell called a B-cell tend to respond particularly well. These findings were initially made in triple-negative breast cancer, but similar patterns were observed in a separate, large study of HER2-positive breast cancer, suggesting they may apply broadly across breast cancer types. The team also found that tracking how quickly a tumor is growing, both before and especially during treatment, helps more accurately predict how a patient will respond to therapy.
What’s next
The team will use artificial intelligence to analyze standard tissue images routinely collected during diagnosis, building a large-scale digital imaging platform that could help predict treatment response, across both triple-negative and HER2-positive breast cancer. They will also add a new type of blood test that can detect tiny fragments of tumor DNA circulating in the bloodstream, combining this with existing tumor data to better predict outcomes and understand why some tumors respond to treatment while others do not. Together, these efforts aim to support less invasive, more personalized treatment approaches for patients with breast cancer.
“This is not just science; it is the promise of better outcomes, fewer unnecessary treatments, and real hope for every woman facing this diagnosis. BCRF makes it possible for us to turn that promise into reality, one patient at a time.”
Biography
Luca Gianni, MD is Co-founder of the Michelangelo Foundation, a non-profit organization designed to advance research in oncology, and chairman of the Breast Cancer Research Committee of Michelangelo. Recently, he was appointed the first President of the “Gianni Bonadonna Foundation” for innovative therapies for cancer.
During his career Dr. Gianni has worked on new drug development in the field of oncology and on the definition of innovative drug therapies in Medical Oncology. Since 1995, he focused on clinical and translational research in women with breast cancer and has overseen clinical and research activity related to breast cancer. Dr. Gianni has conducted and contributed key research on anthracyclines and performed studies of drug disposition of several new anticancer agents. He returned to Italy after his work at the National Cancer Institute in Bethesda, USA to work with Dr. Bonadonna at the Istituto Nazionale Tumori. In 1983, he launched the first Phase I Unit in Italy and led the phase I projects there until he moved to San Raffaele in 2011 where he was Director of the Department of Medical Oncology until November 2019.
Dr. Gianni has been involved in the development of paclitaxel, and later in that of the HER2-directed antibody trastuzumab as adjuvant therapy. He conducted the NOAH neo-adjuvant trial of chemotherapy and trastuzumab in women with locally advanced/inflammatory HER2-positive breast cancer, that led trastuzumab to become the first approved neoadjuvant therapy in women with HER2-positive breast cancer in Europe.
Dr. Gianni also contributed to the clinical development of pertuzumab to obtain dual block of the HER2 receptor leading to synergistic activity with trastuzumab in HER2+ early and metastatic breast cancer. The studies he chaired brought to the approval of dual block of HER2 as neoadjuvant approach and to the design of the Aphinity adjuvant trial in women with HER2+ early breast cancer. After establishing the profound differences of HER2+ breast cancer depending on the status of the estrogen receptor in the HER2+ tumor, Dr. Gianni and collaborators documented in the NA-PHER2 study the ability of obtaining major antitumor effects with a chemotherapy-free approach in women with HER2+/ER+ operable breast cancer.
In more recent years, under the leadership of Dr. Gianni, the Michelangelo Foundation has launched two major neoadjuvant trials in women with breast cancer with use of the PD-L1 directed immune check point inhibitor atezolizumab in combination with chemotherapy in triple-negative breast cancer (neoTRIP trial) and in combination with trastuzumab/pertuzumab in HER2+ early breast cancer (APTneo trial).
Dr. Gianni is recipient of several grants and research support, and of several awards, among which he was recipient of the “Gianni Bonadonna Award and Fellowship” by the American Society of Clinical Oncology in 2011.
