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Study Evaluates Ability of Tests to Gauge Late Distant Breast Cancer Recurrence Risk

NEW YORK (GenomeWeb) – A comparison of commercially available multigene breast cancer recurrence signatures suggests that some tests may be better than others at assessing which patients are at risk for late distant recurrence, which could be impacting oncologists' ability to guide appropriate treatment decisions for patients. 

Researchers led by Ivana Sestak from Queen Mary University London compared  a score based on the clinical features of cancers with five molecular tests ― Genoptix's IHC4, Genomic Health's Oncotype DX, BioTheranostics' Breast Cancer Index (BCI), NanoString's Prosigna, and Myriad Genetics' EndoPredict ― for their ability to assess the risk of distant breast cancer recurrence in the 10 years after diagnosis and the risk of late distant recurrence during years five to 10.

An accurate estimate of the risk of distant recurrence helps discern whether a patient should receive chemotherapy on top of endocrine therapy, while an accurate estimate of the risk of late distant recurrence helps determine whether patients should receive extended adjuvant endocrine therapy. More than 50 percent of women with estrogen receptor-positive breast cancer experience recurrence after five years.

"This [study] gives clinicians and oncologists the opportunity to review all the results and decide upon the test they want to use for their breast cancer patients," Sestak said in a statement discussing the analysis published today in JAMA Oncology and previously presented at the 2016 San Antonio Breast Cancer Symposium. 

The study involved a retrospective analysis of samples from nearly 800 postmenopausal women with ER-positive, HER2-negative breast cancer using the six signatures. The samples came from patients enrolled in the Translational Study of Anastrozole or Tamoxifen Alone or Combined (TransATAC), 591 of whom were node-negative and 183 of whom had node-positive breast cancer.

According to the analysis, all six signatures provided statistically significant prognostic value 10 years out from diagnosis in node-negative patients, though Prosigna, BCI, and EndoPredict "proved to be statistically more prognostic than the other signatures," the authors wrote. The analysis found that these molecular signatures provided significantly more prognostic information than the score based only on clinical features of the tumor, Oncotype DX, and IHC-4.

For 507 node-negative women, results were available from Oncotype DX Recurrence Score Pathology-Clinical (RSPC), a tool developed a few years ago combining the 21-gene expression score of Oncotype DX with clinical and pathological features. RSPC was much better at gauging risk of distant recurrence than the molecular recurrence score, the authors found.

In the node-positive setting, the performance of the signatures was "weaker" in assessing distant recurrence than in the node-negative setting. Therefore, using the combination of clinical and genomic signatures may be the best approach in the node-positive setting, the authors wrote.

EndoPredict and Prosigna, which factor clinical variables along with molecular markers, identified a group of women with node-positive breast cancer who had a very low risk of distant recurrence at 10 years, which suggests that "chemotherapy would be of very limited benefit in these women," according to the paper.

Although none of the signatures were developed to specifically gauge late distant recurrence, the authors evaluated this capability by looking at data from 535 women who were alive and didn't experience recurrence after five years of follow-up. Prosigna, BCI, and EndoPredict "provided significant prognostic value" for assessing risk of late distant recurrence, beyond using the clinical features of the cancer. Comparatively, the authors found that IHC4 and Oncotype DX did not provide significant prognostic value for late distant recurrence beyond the clinical treatment score.

"The [Oncotype DX] RSPC score provided twice as much prognostic information for late distant recurrence compared with the Recurrence Score alone in the univariate analysis but no prognostic value for late distant recurrence additional to [clinical treatment score]," the authors wrote.

In the node-positive group, researchers evaluated data from 154 women who were alive without distant recurrence within the first five years of follow up, and reported that EndoPredict provided the most prognostic value for late distant recurrence, then Prosigna, and BCI. While EndoPredict and BCI provided independent prognostic information beyond the clinical treatment score, IHC4 and Oncotype DX did not provide prognostic information in univariate analysis or in addition to the clinical treatment score.

Sestak and colleagues concluded in their paper that while all the signatures performed similarly during the first five years of follow up, there were differences in prognostic ability from years five to 10, which is important because during this time frame test results are used to guide decisions about whether to extend endocrine treatment for patients.

The study's publication comes as the UK's National Institute for Health and Care Excellence (NICE) is considering reversing its favorable recommendation for Oncotype Dx as an option for guiding adjuvant chemotherapy decisions, after finding that none of the tests it evaluated ― Oncotype DX, EndoPredict, Agendia's MammaPrint, Prosigna, and IHC4 ― are cost effective. 

However, Sestak and colleagues noted in their paper that their study only evaluated the prognostic capabilities of these signatures, and did not evaluate their ability to actually predict whether breast cancer patients are likely to benefit from chemotherapy or extended endocrine treatment. The study findings are also only applicable to chemotherapy-free and postmenopausal women.