Researchers at the Swiss Institute of Bioinformatics and the Swiss National Center of Competence in Research in Molecular Oncology in Lausanne have developed a new test to predict how breast cancer patients respond to chemotherapy, which could help change how treatment is delivered in the future.
In an article, 'A stroma-related gene signature predicts resistance to neoadjuvant chemotherapy in breast cancer' i, published in Nature Medicine , Dr Pierre Farmer and colleagues showed the potential of the reactive stroma to modulate tumor phenotype and the clinical response to treatment. This is a major step forward in the field as identifying factors that influence response to cancer chemotherapy is crucial for improving its efficacy.
The study first started when a team of clinicians, cancer biologists and computational biologists combined their effort to address a very puzzling question: Why breast tumors that have very similar conditions in terms of aggressiveness (grade), invasiveness (node status) and hormone dependency (ER status), respond differently to the same kind of chemotherapy treatment.
"Two breast cancer patients might respond very differently to the same type of chemotherapy although their respective tumors are very similar from a clinical point of view," said Dr Pierre Farmer. "The reasons for these different responses are unknown."
To help find an answer to this question, a collaborative study was set-up within the framework of a large randomized clinical trial that involved more than 40 different hospitals throughout Europe, including those in the UK, France, Belgium, Netherlands, Poland, Sweden and Switzerland. It was led by Professor Hervé Bonnefoi of the European Organization for Research and Treatment of Cancer (EORTC) in collaboration with the Swedish Breast Cancer Group (SBCG), the Swiss Cancer Group (SAKK) and the Angloceltic group (ACOG).
In this trial, biopsies were taken from each patient and sent to Professor Richard Iggo's laboratory which was at the Swiss Institute for Experimental Cancer Research (ISREC) in Lausanne at the time of the study, which was to a large part sponsored by the National Center of Competence in Research (NCCR) in Molecular Oncology. In Lausanne, the genomic material (mRNA) of tumor samples were extracted and profiled on microarrays in order to measure the expression activity pattern of thousands of individual genes.
Meanwhile, all patients included in the said study had a tumor biopsy prior to receiving an anthracyclin-based chemotherapy followed by surgical excision of the tumour – a protocol that clinicians call neo-adjuvant chemotherapy. After the surgical intervention, pathologists analysed the surgical specimen and determined if tumor cells were still present. This is a way to measure the efficacy of the chemotherapy.
If no tumor cells were found, the patient was considered to be fully responsive to the treatment (defined as "complete pathological response"). The aim of the study was to test if genomic analysis of the tumor taken before chemotherapy treatment could allow the identification a signature which permits the prediction of the patients who would respond to the chemotherapy.