Dr. Martin Sjöström Discusses an Important Study for Women with Early-Stage Breast Cancer

Researchers with PFS Genomics identified a gene expression signature, named Profile for the Omission of Local Adjuvant Radiation (POLAR), to predict whether women with early-stage invasive breast cancer, treated with breast conserving surgery, are likely to benefit from radiotherapy. Early results suggest that POLAR may effectively discern patients with a low risk of locoregional recurrence without adjuvant therapy following breast conserving surgery, and these women can safely be spared radiotherapy.

DocWire News sat down Dr. Martin Sjöström, lead study author and associate researcher at Lund University, to speak about the findings and their clinical implications.

DocWire News: Can you talk to us about this study and its importance?

Dr. Martin Sjöström: Absolutely. So, first of all, the reason we undertook this study is that the standard of care for early stage breast cancer is breast-conserving surgery, which is done in about 60 to 70% of patients, with additional adjuvant radiotherapy, and primarily to prevent local regional recurrences.

However, we know that only three out of 10 patients get the optimal therapy this way, and that is because six out of 10 patients will be recurrence free without any radiotherapy, and about one out of 10 will develop recurrence even with radiotherapy. And the challenge is, of course, to know beforehand who will benefit or not from the therapy.

The overall hypothesis was that gene expression analysis of the tumor could help determine this, and the aim of this particular study is to use gene expression analysis of the tumor to identify patients with such low risk of locoregional recurrence that they can safely be omitted radiotherapy. And, to do this, we analyzed data from the [inaudible] RT randomized clinical trial, which randomized patients operated in breast-conserving surgery to receive either adjuvant radiotherapy or no radiotherapy. And so, which 706 before tumors having profiled for gene expression therapies. And we restricted the analysis to ER positive and HER2 negative patients, as they would be the most likely candidates for therapy admission.

We also restricted the analysis to patients without systemic adjuvant therapy in order to assess the pure prognostic information, and to grade the therapy’s specific treatment effect without confounding from other therapies. And, to develop the actual gene expression signature, we split the patients into training and a validation cohort, and we developed a 16-gene signature that was based on low grade of recurrence risk and biology associated with low grade of recurrence in the training cohort. The signature was done, locked, and tested in the validation cohort, and we named the signature the Profile for the Mission of Adjuvant Radiation, or POLAR for short.

In the validation cohort, POLAR low-risk patients had a 10 year local regional recurrence rate of 7%, and POLAR was prognostic also after adjusting for patient age, [inaudible], tumor size, and molecular subtype, showing that it provides additional prognostic information. And importantly, the POLAR low-risk patients have no benefits from adjuvant radiotherapy, while the POLAR high-risk patients had a substantial benefit from radiotherapy. In conclusion, POLAR may identify patients with early-stage breast cancer with such low risk of locoregional recurrence that omission of adjuvant radiotherapy could be considered.

Did the study have any limitations?

That is a very good question. One of the limitations of this study is that patients were not treated with systemic adjuvant therapy, and this provides an opportunity to analyze the pure prognostic effect and a specific effect of radiotherapy, but it makes it a bit more challenging to interpret the absolute recurrence rates with modern systemic therapy. However, the locoregional recurrence across rate will most likely be lower with adjuvant systemic therapy, meaning that the rates in the [inaudible] trial are probably conservative estimates of recurrence rates.

What are the clinical implications of these findings?

The clinical implications of this study are that, if further validated, POLAR could provide a tool for clinicians to personalize radiotherapy for early-stage breast cancer patients operated with breast-conserving surgery. That would mean that the only patients that really benefit from therapy will receive it, and those without benefit would be spared unnecessary therapy with potential side-effects.

Any closing thoughts?

Gene expression analysis of breast cancer has already changed the way we administer adjuvant systemic therapy to breast cancer patients, and that means personalized treatment decisions to increase benefit and reduce toxicity for the patients, and our hope is really that this study will help moving the field towards personalizing, also, radiotherapy for every patient.