IMPAKT 2013 Press Release: Breast cancer heterogeneity no barrier to predictive testing, study shows

Lugano-CH, Brussels-BE, 2 May 2013

Breast cancers contain many different cell types with different patterns of gene expression, but a new study provides reassurance that this variability should not be a barrier to using gene expression tests to help tailor cancer treatments to individual patients.

The findings were reported at the 5th IMPAKT Breast Cancer Conference in Brussels, Belgium. The IMPAKT meeting presents cutting edge, ‘translational’ breast cancer research that is beginning to have an impact for patients.

In recent years it has become clear that breast cancers contain a variety of different cell types. An important result of this heterogeneity is that different biopsy specimens from a single breast cancer tumour can exhibit significant variability in genes expression.

This is a major concern for doctors seeking to understand which patients are likely to benefit from drugs designed to be effective against tumour cells with particular genetic characteristics. A number of studies at this year’s IMPAKT conference consider this issue.

In one study, Dr Michał Jarząb and colleagues from the Maria Skłodowska-Curie Memorial Cancer Center and Institute of Oncology, Poland took a total of 78 different biopsies from 26 individual tumours to assess the degree of genomic variation, and its impact on a set of 32 different prognostic and predictive multi-gene signatures.

“Some genomic tests have proven very useful in breast cancer, but in other important areas we have not achieved optimal results,” Dr Jarząb explains. “One of these areas where we haven’t done so well is in deciding whether a particular patient would benefit from certain type of chemotherapy or not, based on the material from pre-surgical needle biopsies. We hypothesized that some genomic tests may be prone to the heterogeneity of starting material and provide not reliable results.”

The researchers performed gene expression profiling on their 78 samples using oligonucleotide microarrays. Overall, they found that the gene expression profiles of the cores were variable, and in at least 5 patients this heterogeneity was substantial.

However, when they analysed a number of multi-gene signatures selected from previous studies, this heterogeneity was considerably less significant.

The gene sets differed in their variance between biopsies, the authors found. The most pronounced heterogeneity was observed in immune response-related genes, while the least heterogeneous were the classifiers based on genes selected by advanced bioinformatical methods from both cell culture experiments and patient tissues.

“Overall, the heterogeneity among the potentially predictive genes was small enough and we conclude that this factor should not prohibit their effective use in clinical practice,” Dr Jarząb says.

“Our study confirms that it is possible to address tumour heterogeneity when carrying out routine diagnostic procedures in patients. Our results may help to introduce the better tailoring of preoperative treatment.”

Commenting on the results, Dr. Angelo Di Leo, Head of the Sandro Pitigliani Medical Oncology Unit and Chair of the Oncology Department at the Hospital of Prato, Istituto Toscano Tumori, Italy, said: “If other studies report similar results to this one, then it could become common practice to evaluate prognostic or predictive breast cancer markers from more than one primary tumour area.”

"The study is innovative because it is one of the first to address the question of intratumour heterogeneity. It means that not all the cells from the same tumour have the same characteristics, and if we want to have a clear picture of the tumour biology we should not limit the evaluation of tumour markers to one area of the tumour itself," Dr. Di Leo said.

Notes to Editors

Session info: Heterogeneity of breast cancer: How much is there at the start and how much happens over time?

Thursday, 2 May 2013, 3:30 PM – 5:10 PM (CEST). Place: Gold Hall

Please contact the IMPAKT Press Office at media@esmo.org to schedule remote interviews or for any inquiry.

About the Breast International Group (BIG)

The Breast International Group (BIG) is a non-profit organisation for academic breast cancer research groups from around the world, based in Brussels, Belgium.

Founded by leading European opinion leaders in 1996, BIG now constitutes a network of 50 groups based in Europe, Canada, Latin America, Asia and Australasia. These research entities are tied to several thousand specialised hospitals and research centres worldwide. More than 30 clinical trials are run or are under development under the BIG umbrella. BIG also works closely with the US National Cancer Institute (NCI) and the North American Breast Cancer Groups (NABCG), so that together they act as a strong integrating force in the breast cancer research arena.

To make significant scientific advances in breast cancer research, reduce unnecessary duplication of effort, and optimally serve those affected by the disease, large-scale cooperation is crucial. Therefore BIG facilitates breast cancer research at international level, by stimulating cooperation between its members and other academic networks, and collaborating with, but working independently from, the pharmaceutical industry. To find out more about BIG, please visit: www.breastinternationalgroup.org

About the European Society for Medical Oncology (ESMO)

The European Society for Medical Oncology (ESMO) is the leading European professional organization committed to advancing the specialty of medical oncology and promoting a multidisciplinary approach to cancer treatment and care.

ESMO’s mission is to advance cancer care and cure through fostering and disseminating good science that leads to better medicine and determines best practice.

As a trusted organization with 35 years of experience, ESMO serves its members and the oncology community through: a brand of excellence in post-graduate oncology education and training; leadership in transforming evidence-based research into standards of cancer care in Europe; dedicated efforts to foster a more favorable environment for scientific research; innovative international platforms to share expertise, best practices and disseminate the most up-to-date scientific research to as wide an audience as possible.

ESMO’s scientific journal,Annals of Oncology, ranks among the top clinical oncology journals worldwide. ESMO events are the meeting place in Europe for medical oncologists to update their knowledge, to network and to exchange ideas. To find out more about ESMO, please visit: www.esmo.org

Abstract 41_O

HETEROGENEITY OF GENOMIC SIGNATURES IN BREAST CANCER CORE BIOPSY

M. Jarzab1, W. Bal1, M. Kowalska2, M. Kowal2, J. Rembak-Szynkiewicz3, K. Steinhof-Radwanska3, E. Stobiecka4, E. Chmielik4, B. Bobek-Billewicz3, R. Tarnawski1

1Iiird Dept. Of Radiation Therapy And Chemotherapy, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice/POLAND, 2Dept. Of Nuclear Medicine And Endocrine Oncology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice/POLAND, 3Dept. Of Radiology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice/POLAND, 4Dept. Of Tumor Pathology, Maria Sklodowska-Curie Memorial Cancer Center and Institute of Oncology, Gliwice/POLAND

Introduction: Genomic signatures were shown to efficiently define the tumor characteristics. However, when small specimens like core biopsy samples are considered, the small size of the collected material makes it difficult to obtain high tumor percentage in the specimen. In the study we test the strategy of obtaining three independent cores for molecular analysis and assess the influence of the stability of different prognostic and predictive signatures.

Methods: We analyzed breast core biopsies from 105 consecutive patients treated by pre-operative chemotherapy. In each patient, three cores from different tumor areas were sampled for molecular testing, independent of the cores collected for histopathological analysis. RNA was isolated by QIAGEN RNeasy kits, quantitative real-time PCR analysis and gene expression profiling (Affymetrix HG-U133 Plus 2.0 microarrays) were carried out in the subset of samples.

Results: In 40 patients, three independent specimens were analyzed by microarray gene expression profiling (in total 120 samples). When we assessed the set of chosen 32 prognostic and predictive signatures, we confirmed that the homogeneity of gene expression within the signatures is significantly better than for random sets of genes, but we observed the notable differences between the signatures. The heterogeneity decreased when genes with low between-patient variance were excluded; they also showed a higher intra-patient variability of gene expression. We also assessed the heterogeneity of single expression markers and furher validated our findings on an independent set of patients.Conclusions:The application of three independent cores for genomic analysis in breast cancer may be a successful strategy to overcome tumor heterogeneity and sampling error and result in more stable results of prognostic and/or predictive signatures.

Supported by Polish National Science Center grant N402 6861 40

Keywords: gene expression signatures, cancer genomics, intratumor heterogeneity, oligonucleotide microarray chip

Disclaimer: Information contained in this press release was provided by the abstracts’ authors and reflects the content of the studies. It does not necessarily express ESMO's or BIG’s point of view.