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Luca Gianni, MD

Director, Medical Oncology,
Head of the New Drug Development
Laboratory of Clinical Pharmacology
Ospedale San Raffaele
Milan, Italy

Current Research

  • Seeking to improve response to immunotherapy in triple negative breast cancer. 
  • An immune-related gene signature is used to identify patients most likely to benefit from immunotherapy.
  • These efforts will inform future clinical trials to improve outcomes in triple negative breast cancer.

Immunotherapy has had some success, though limited, in clinical trials in breast cancer. One type of breast cancer that has shown some response is triple negative breast cancer, but the response rate is still under 20 percent. Part of this may be due to a lack of a biomarker to predict response to these therapies. Dr. Gianni has developed an immune-based gene score that he believes will distinguish patients most likely to benefit from immunotherapy from those who will not. 

Full Research Summary

Immune-checkpoints inhibitors are a class of immune-targeting drugs that have shown promising results in some patients with triple negative breast cancer (TNBC). There are currently 11 phase III trials ongoing for this indication. However, the selection of patients for these trials is empirical rather than biomarker-based, which helps to explain why benefit is seen in a small fraction of clinical trial participants. 

In his BCRF research, Dr. Gianni is testing an immune-related gene signature (IRS) developed by his team to identify TNBC patients most likely to benefit from checkpoint inhibitor therapy and those who will do well with chemotherapy alone. 

The goal is to use the IRS to differentiate those patients with very good prognosis from those with poor prognosis. Patients with good prognosis would be less likely to need the immune checkpoint therapy while those with poor prognosis would likely benefit from the therapy. The net result would be to select patients for immunotherapy based on the IRS and limit the use of immune-checkpoints inhibitors for those less likely to benefit, thus decreasing clinical and financial toxicity.

In the process of validating the immune-related gene signature, Dr. Gianni’s team will characterize other tumor-associated immune factors linked to the risk of recurrence by also measuring serum biomarkers before, during and after neoadjuvant therapy. These studies will add to our understanding the role of the tumor-immune cell interaction and inform the design of a new generation of trials tailoring immune-combination to triple-negative breast cancer.


Dr. Gianni is the Director of the Department of Medical Oncology and the head of the Project of Development of New Drugs and Innovative Therapies in Solid Tumours at the San Raffaele Scientific Institute in Milan, Italy. He also is the Cofounder and President of the Michelangelo Foundation, a non-profit organisation designed to advance research in oncology, and chairman of the Michelangelo Breast Cancer Study Group. Recently Dr. Gianni also became 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. 

Dr. Gianni has conducted and contributed key research with anthracyclines, and performed studies of drug disposition of several new anticancer agents. He founded the first Phase I Unit in Italy in 1983 upon return to work with Dr. Bonadonna at the Istituto Nazionale Tumori, and led the phase I project there until he moved to San Raffaele in 2011. Since 1995 he has been in charge of the clinical and research activity related to breast cancer at the Istituto Nazionale and at the Fondazione Michelangelo.  

Specifically related to breast cancer, Dr. Gianni has been involved in the development of paclitaxel. Dr. Gianni also served in the Executive Committee of the HERA trial, one of the first testing trastuzumab as adjuvant therapy. He launched and conducted the NOAH neo-adjuvant trial of chemotherapy and trastuzumab in women with locally advanced/inflammatory HER2-positive breast cancer, which proved the benefit of adding the monoclonal antibody in terms of eradication of local disease, event free survival and overall survival. The results were the basis for trastuzumab becoming the first approved neoadjuvant therapy in women with HER2-positive breast cancer in Europe. 

More recently Dr. Gianni contributed to the design of the development of Pertuzumab in metastatic breast cancer, and designed and chaired the neoadjuvant trial known as NeoSphere, a collaboration of the Michelangelo Breast Cancer study group with Roche/Genentech, that 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 have documented the ability of obtaining major antitumor effects including several pathologic complete responses with a chemotherapy-free approach in women with HER2+/ER+ operable breast cancer by combining trastuzumab and pertuzumab plus fulvestrant plus the cdk4/6 inhibitor palbociclib. 

Dr. Gianni is recipient of several grants and research support, and was awarded the “Gianni Bonadonna Award and Fellowship” by the American Society of Clinical Oncology in 2011. 

Grid Reasercher Headshot - Lucca Gianni

BCRF Investigator Since


Donor Recognition

The Blizzard Entertainment Award

Area(s) of Focus