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Interview with Dr. Dimitrios Zardavas, Associate Scientific Director at BIG

Intro text: 

Regarding his analysis of PIK3CA mutations’ prognostic relevance in early breast cancer

Congratulations for presenting the results of this analysis at the recent ASCO annual meeting, and could you please describe the award you received for this work?

I received the ASCO Merit Award. It is an award given by the American Society of Clinical Oncology (ASCO) to young cancer investigators, based on the scientific merit of their work presented at the annual meeting.

Could you tell us a little bit about the work you did for which you were recognized with this award?

In breast cancer there is genomic aberration called PIK3CA mutation, which is one of the most common aberrations seen in early-stage breast cancer. During the last 10 years, many different investigators around the world have wanted to know if this common aberration was useful in determining breast cancer prognosis.

Over 20 studies have been conducted around the world, trying to determine the impact of this aberration on the progression of early-stage breast cancer. However, the studies were focused on different sub-sets of patients, including age, disease characteristics, etc. Of note, these studies reported inconsistent results concerning the prognostic relevance of PIK3CA mutations. Some identified this mutation as a positive prognosticator (meaning it led to better patient outcomes); others found it to be a negative prognosticator; still others found it was not significant.

As a result, we did not know the prognosis for the patients with this common mutation. That fueled our motivation, together with Dr. Sherene Loi from the Peter MacCallum Cancer Center, Melbourne, Australia, to conduct a pooled analysis of all the studies that assessed the potential prognostic relevance of this mutation. We wrote a protocol about the research questions we would like to address, then reached out to all the investigators who conducted these studies and asked if they would provide their patient data. Most of them accepted, but this process took over a year.

The investigators sent us their data sets with individual patient data. We pooled the data together for more than 4.500 patients with early stage breast cancer, including information about the mutational status of the PIK3CA gene, characteristics of the disease, the treatments received and the clinical outcome. We were able to achieve a much higher statistical power by pooling the data.

We found some interesting results, with some of them not seen before: PIK3CA mutations were overall associated with positive prognostication (better patient outcomes) – seen mostly during the first 3 years after the primary diagnosis; after that the positive impact fades. This indicates that the mutation could potentially protect patients from early relapses.

Additionally, this positive prognostication derives from the subset of young women (age 50 and below). For young women below 50 with hormone-sensitive disease, this finding could have important clinical consequences, because it could spare them chemotherapy; they could simply be treated with a PI3K blocking agent and endocrine treatment.

What we did not assess was what the predictive value of these mutations is, meaning whether they would help us identify which patients would respond best to treatment. BIG is currently conducting some clinical trials trying to assess if PIK3CA mutations have predictive value for identifying patients whose breast cancer disease will be sensitive to PI3K blocking agents. There are 2 trials currently ongoing under the BIG umbrella, both conducted in the neo-adjuvant (i.e. pre-surgical) setting: NeoPHOEBE , the results of which will be presented at the San Antonio Breast Cancer Symposium in December 2015, and the ongoing LORELEI trial, which focuses on older women with early stage ER+ breast cancer. This study looks at providing endocrine treatment in the neo-adjuvant setting with or without an agent that targets this mutation.

 

How will this recognition help bring attention and/or help you make more progress in this area of research?

The publication of this work in the form of a full report, after review by the collaborators, will bring attention to the results of our study, and should attract the attention of other breast cancer research groups, many of whom already do research on this mutation.

 

Do you have any final remarks on how you felt about receiving the award?

I would like to thank the Co-Principal Investigator of this project, Dr. Sherene Loi. I would also like to thank the numerous investigators who agreed to collaborate for this study.

I am very happy about the work itself, and the results. I feel very honored to have the trust of the investigators who accepted to collaborate and provide their data sets for this study.