Stroma genomic signature predicts resistance to anthracyclin-based chemotherapy in breast cancer

February 3, 2009

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.

To achieve this task, Drs Farmer, Mauro Delorenzi, and Pratyaksha Wirapati from the Swiss Institute of Bioinformatics developed new computational methods to extract relevant gene patterns from the vast quantity of data generated by the microarray experiment. "In this study, we have mined the gene expression data in order to find a particular gene activity pattern, or gene signature, that would be associated with how patients respond to chemotherapy," Dr Farmer said.

Results showed that a signature measuring the biological activity of tumor's microenvironment, also known as reactive stroma, predicted how patients would respond to the treatment.

Researchers found that it is precisely the magnitude of this stroma reaction that was predictive of a response to chemotherapy. "It was a surprise to us to find that it was not the tumor itself but rather how surrounding non-tumorous tissue reacts to the presence of the tumor that was our best clue in predicting resistance to treatment," Dr Farmer continued. "Patients who had a strong stroma reaction characterized by an increased quantity of fibroblasts surrounding the tumor were more likely to have a bad response to this particular chemotherapy."

"What this means is that success in treatment, having tumors shrink or disappear altogether, is in part due to molecular differences in tumors and their immediate surroundings," Dr Farmer continued.

Researchers hope that one day this discovery will contribute to changing how breast cancer patients are treated. Indeed, in the future, if a clinician learns with a simplified test that a particular woman has a high probability of not responding to an anthracyclin-based therapy, this clinician may consider prescribing an alternative chemotherapeutic regimen. Moreover, this study suggests that predicting how individual patients might respond to chemotherapy could be possible, which raises hopes that one day, personalized medicine in the treatment of breast cancer may become a reality.

Source: Swiss Institute of Bioinoformatics

Explore further: Adult leukaemia can be caused by gene implicated in breast cancer and obesity

Related Stories

Adult leukaemia can be caused by gene implicated in breast cancer and obesity

January 16, 2018
When people think of leukaemia, they usually think of blood cancers that affect children. These mostly come under the category of acute lymphoblastic leukaemia – or ALL – and are different to the group of blood cancers ...

Breast cancer treatment link to chronic disease

January 16, 2018
Women who have undergone hormonal therapy for breast cancer are at increased risk of developing chronic conditions later in life, according to new research.

FDA approves first drug for tumors tied to breast cancer genes

January 12, 2018
(HealthDay)—The U.S. Food and Drug Administration on Friday approved the first drug aimed at treating metastatic breast cancers linked to the BRCA gene mutation.

Breast cancer gene does not boost risk of death: study

January 12, 2018
Young women with the BRCA gene mutation that prompted actress Angelina Jolie's pre-emptive and much-publicised double mastectomy are not more likely to die after a breast cancer diagnosis, scientists said Friday.

New treatments, screening methods dramatically reduce breast cancer deaths, study finds

January 9, 2018
In the last few decades, dozens of new breast cancer drugs—from chemotherapies to targeted compounds—have become available for clinical use, and mammogram technology has gone from film to digital. But are the changes ...

Scientists identify breast cancer patients who may develop incurable secondary cancers

January 9, 2018
Scientists from King's College London, funded by Breast Cancer Now, believe they have found a way to identify lymph-node positive breast cancer patients who are most likely to develop incurable secondary tumours (metastases) ...

Recommended for you

Presurgical targeted therapy delays relapse of high-risk stage 3 melanoma

January 17, 2018
A pair of targeted therapies given before and after surgery for melanoma produced at least a six-fold increase in time to progression compared to standard-of-care surgery for patients with stage 3 disease, researchers at ...

Dulling cancer therapy's double-edged sword

January 17, 2018
Researchers have discovered that killing cancer cells can actually have the unintended effect of fueling the proliferation of residual, living cancer cells, ultimately leading to aggressive tumor progression.

Researchers develop swallowable test to detect pre-cancerous Barrett's esophagus

January 17, 2018
Investigators at Case Western Reserve University School of Medicine and University Hospitals Cleveland Medical Center have developed a simple, swallowable test for early detection of Barrett's esophagus that offers promise ...

Scientists zoom in to watch DNA code being read

January 17, 2018
Scientists have unveiled incredible images of how the DNA code is read and interpreted—revealing new detail about one of the fundamental processes of life.

T-cells engineered to outsmart tumors induce clinical responses in relapsed Hodgkin lymphoma

January 16, 2018
WASHINGTON-(Jan. 16, 2018)-Tumors have come up with ingenious strategies that enable them to evade detection and destruction by the immune system. So, a research team that includes Children's National Health System clinician-researchers ...

Researchers identify new treatment target for melanoma

January 16, 2018
Researchers in the Perelman School of Medicine at the University of Pennsylvania have identified a new therapeutic target for the treatment of melanoma. For decades, research has associated female sex and a history of previous ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.