A step forward in personalised medicine in breast cancer

Two studies in yesterday’s proffered papers session explored use of DNA microarrays and surgery in breast cancer

Professor Jean-Yves Pierga from the Institute Curie, Paris, France, presented the first results of the REMAGUS04 trial using DNA arrays to select treatment.

“There is a need to determine robust and high throughput biotechnologies for biomarker determination for clinical use. DNA arrays allow quantifying gene expression at the whole genome level and could improve prediction of the benefit from specific immunotherapy,” said Professor Pierga.

The Diagonal Linear Discriminant Analysis-30 (DLDA30) probe has been developed to predict resistance to neoadjuvant chemotherapies with a better sensitivity than standard parameters.
The phase 3 REMAGUS04 trial set out to evaluate whether the expression of of DLD30 and with TOP2A could improve neoadjuvant chemotherapy efficacy.

In the study after under going biopsy, 142 patients with adenocarcinoma of the breast who were not eligible for breast conserving surgery were randomised to a standard treatment arm or a ‘genomic-driven’ arm where they received treatments according to their DLD30/TOP2A expression.

Results show that the pathological complete response (pCR) was 35% in the standard arm versus 38% in the genomic arm. The results also showed that a DLD30 positive score was associated with an increased likelihood of pCR, which occurred in 36% of DLD30 positive patients versus 3% of DLD30 negative patients.

“This is the first prospective trial showing that whole genome array is feasible in the context of daily practice within 15 days,” said Professor Pierga. “Gene expression arrays could be a solution in the future to propose an all-in one assay for personalised medicine.”

Dr Carmen Criscitiello, from the European School of Oncology, Milan, Italy, followed up with a thoughtful and patient-centric analysis of the NeoALTTO trial, looking to investigate the different factors affecting choice of surgery in patients enrolled in the NeoALTTO trial.

In the NeoALTTO trial, patients with HER2 positive breast cancer were randomised to either trastuzumab, lapatinib or their combination concomitantly with paclitaxel prior to surgery. Results showed that the pCR was 24.7% in patients receiving lapatinib plus paclitaxel versus 29.5% for patients receiving trastuzumab plus paclitaxel versus 51.3% for patients receiving all three drug."But despite the combination producing nearly double the pCR, breast conservation was similar in each arm,” said Dr Criscitiello. Breast conservation was achieved in 42.9% of patients in the lapatinib plus paclitaxel arm, 38.9% of patients in the trastuzumab plus paclitaxel arm and 41.3% in the lapatinib, trastuzumab and paclitaxel arm.
The factors found to be independently associated with the type of planned surgery at diagnosis were geographic region (with surgery occurring less frequently in developed countries) and tumour size.

“These results call for a clear consensus on the role of breast cancer surgery in patients responding to neoadjuvant therapies. This will translate the progress in neoadjuvant therapies into improved breast conservation rates,” said Dr Criscitiello.