IMPAKT 2013 Press Release: Genetic and clinical factors best for predicting late recurrence in oestrogen receptor positive breast cancer

Lugano-CH, Brussels-BE, 2 May 2013

A new analysis has provided a comprehensive comparison of scores designed to predict which women with oestrogen-receptor positive breast cancer are at high risk of recurrence beyond five years after diagnosis, and may benefit from prolonged endocrine treatment.

The promising new findings will likely benefit the many women with oestrogen-receptor positive breast cancer whose cancer recurs more than five years after diagnosis, researchers told 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 oestrogen-receptor positive women, half of all recurrences of breast cancer will occur after the women finish the standard 5 years of hormonal treatment, explains lead author Dr Ivana Sestak from the Wolfson Institute of Preventive Medicine in London, UK.

“There is great interest in establishing which women are at adequate high risk of late recurrence after the initial hormonal treatment period, which is currently 5 years,” Dr Sestak says.

At the meeting, researchers reported the findings of a comparison of five different scores designed to predict which women may be at increased risk of developing a late recurrence of their cancer. This is the first time that all five scores have been compared within one dataset.

Knowing which women may be at increased risk of developing a late recurrence would enable doctors to identify those women who may be good candidates for extended hormonal therapy, she says.

The ATAC trial included nearly 10,000 women who were treated with surgery followed by five years of treatment with the drugs anastrozole, tamoxifen or a combination of both. Of these 1,125 from the monotherapy arms (tamoxifen, anastrozole) were included in the transATAC study.

The five scores being compared were the:

  • Clinical Treatment Score, which includes information on the patient’s disease and treatments so far;
  • IHC4 score, which characterises the presence of cell surface markers on cancer cells;
  • Three different gene expression scores -- the Oncotype Dx Recurrence Score; the PAM50 Risk of Recurrence Score; and the Breast Cancer Index score.

The results showed that the clinical treatment score alone was the best for predicting late recurrence, the researchers report. The components of this score include some that are already widely used by doctors, such as whether the cancer has spread to sentinel lymph nodes, the tumour size and grade.

Among the other tests, the PAM50 risk of recurrence score and the Breast Cancer Index score added the most significant prognostic value between years 5 and 10 after diagnosis.

“The most promising new scores from this study are the PAM50 Risk of Recurrence score and the Breast Cancer Index score, both containing different genetic information that are not included in the clinical treatment score and at the moment not routinely measured in clinics,” Dr Sestak says.

“Our further interest now lies in the investigation of which individual components of these scores attribute specifically to the prediction of late recurrence, since the Risk of Recurrence and Breast Cancer Index scores consist of several genes and other components. We are now undertaking these analyses and the results will hopefully tell us which genes specifically predict late recurrence. However, at this stage it is not possible to predict response to treatment.”

Commenting on the results, Dr Peter Dubsky from the Medical University of Vienna, Austria, noted that oestrogen-receptor positive and Her2 negative breast cancers are prone to late recurrences.

“About half of all recurrences observed within 15 years of follow-up occur five years after diagnosis. Although there is a sustained benefit of adjuvant endocrine therapy beyond five years, we still see two-thirds of breast cancer deaths occurring after this time. Clearly, the identification of women that are at risk for these late types of recurrences is an important clinical research goal,” said Dr Dubsky, who was not involved in the study.

“Sestak and colleagues provide highly relevant new data to meet this end: they have compared five different prognostic scores in order to predict outcome beyond the first five years of follow-up. Of note, none of these scores were primarily trained to specifically predict late recurrence. They show that a Clinical Treatment score (CTS) contained most of the prognostic information relevant to late distant metastases. Interestingly, only the Risk of Recurrence (ROR) score (PAM50) and the Breast Cancer Index (BCI) score provided additional information to the CTS. This data will need further validation before actually being incorporated into clinical decision-making concerning adjuvant endocrine therapy beyond five years.”

These findings are similar to those proposed by the Austrian Breast and Colorectal Cancer Study Group recently, Dr Dubsky said. “The Endopredict Score was able to add additional prognostic information to clinical variables concerning distant metastases occurring later than five years after diagnosis. Future research should further address which are the biologic motifs behind late recurrences. Furthermore, molecular tools specifically designed to predict late metastasis should be developed.”

Notes to Editors

Session info: Best Abstract Session

Friday, 3 May 2013, 10:45 AM – 12:15 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 54O_PR 

COMPARISON OF FIVE DIFFERENT SCORES FOR THE PREDICTION OF LATE RECURRENCE FOR OESTROGEN RECEPTOR POSITIVE BREAST CANCER

I. Sestak1, M. Dowsett2, J.W. Cowens3, S. Ferree3, J. Cuzick1 1Wolfson Institute Of Preventive Medicine, Centre for Cancer Prevention, London/UNITED KINGDOM, 2Breast Cancer Research, Institute of Cancer Research, London/UNITED KINGDOM, 3Suite 2000, NanoString Technologies 530 Fairview Avenue N, Seattle/UNITED STATES OF AMERICA

Background: Adjuvant endocrine therapy beyond 5 years is may be of benefit to some oestrogen receptor positive (ER+) patients, but it is unclear which patients have sufficient residual risk to merit this and prognostic factors for late recurrence is an unmet need. We have previously shown that 4 immunohistochemical (IHC) markers (ER, PgR, Ki67, HER-2) and specifically clinical variables are significantly correlated with time to distant recurrence. Here, we assess and compare the value five different scores for predicting outcome beyond 5 years.

Material and Methods: We used univariate and multivariate models to determine the prognostic value of the Clinical Treatment Score (CTS), IHC4 score, the Oncotype Dx Recurrence Score (RS), the Risk of Recurrence (ROR) score (PAM50) and the Breast Cancer Index (BCI) score (molecular index, H/I) for distant recurrence, separately in years 0-5 and 5-10 for all patients in the Arimidex, Tamoxifen, Alone or in Combination (ATAC) trial.

Results: All scores added significant and similar prognostic information in years 0-5, with the Clinical Treatment Score (CTS) being the strongest in the univariate analysis. When CTS was added to the model, IHC4 added most information on distant recurrences in years 0-5. In years 5-10, CTS added most prognostic information compared to any other score, followed by ROR and BCI, which both added significant prognostic information in this late time period. In the multivariate model (with CTS), ROR was the strongest additional prognostic factor in this time period, followed by BCI. IHC4 and RS added only little prognostic information in the late follow-up phase. Similar results were seen for the node-negative population.

Conclusions: CTS was the strongest prognostic factor in years 0-5, but also in the late follow-up period. ROR and BCI were the only molecular scores that added substantial prognostic information in years 5-10. These results may be used to select patients who could benefit from hormonal therapy beyond 5 years of treatment.

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.