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Breast Cancer: Performance of prognostic signatures

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Breast Cancer: Performance of prognostic signatures

Last Updated on February 17, 2018 by Joseph Gut – thasso

February 17, 2018 – In a new study, published in JAMA Oncology online on February 15, 2018, a comparison of the performance of 6 prognostic signatures for estrogen receptor (ER) –positive breast cancer was performed in a secondary analysis of a randomized clinical trial.

Almost all women with estrogen receptor (ER)–positive primary breast cancer are offered adjuvant endocrine therapy, and a highly relevant clinical question is who remains at high risk for distant recurrence despite completion of primary adjuvant therapy. Multigene expression profiles have significantly increased the ability to estimate distant recurrence in ER-positive breast cancer after surgery and endocrine treatment. These signatures are used in combination with different clinical characteristics to aid the selection of patients for whom chemotherapy may be appropriate based on prognosis. Several of these signatures are commercially available, including the Oncotype Dx recurrence score (RS) (Genomic Health), PAM50-based Prosigna risk of recurrence (ROR) (NanoString), Breast Cancer Index (BCI) (bioTheranostics), EndoPredict (EPclin) (Myriad Genetics), and MammaPrint Netherland Kanker Institute 70-gene signature (Agendia BV), are endorsed by several guidelines and are routinely used by clinicians.

In the present study, a within-patient comparison of the prognostic value of 6 multigene signatures in women with early ER-positive breast cancer who received endocrine therapy for 5 years was conducted. The retrospective biomarker analysis included 774 postmenopausal women with ER-positive ERBB2 (formerly HER2)–negative breast cancer. This analysis was performed as a preplanned secondary study of data from the Anastrozole or Tamoxifen Alone or Combined randomized clinical trial comparing 5-year treatment with anastrozole vs tamoxifen with 10-year follow-up data (see the study protocol and trial registration ISRCTN18233230). The analysed  signatures included the Oncotype Dx recurrence score, PAM50-based Prosigna risk of recurrence (ROR), Breast Cancer Index (BCI), EndoPredict (EPclin), Clinical Treatment Score, and 4-Marker Immunohistochemical Score. Data were collected from January 2009, through April 2015.

Overall, for women with node-negative disease, the ROR, BCI, and EPclin were significantly more prognostic for overall and late distant recurrence than any of the other signatures analyzed. For women with 1 to 3 positive nodes, limited independent information was available from any test. These data might help oncologists and patients to choose the most appropriate test when considering chemotherapy use and/or extended endocrine therapy. Still, there may be not one test, who may tell all about the future course of the disease, i.e. breast cancer, in each individual patient. There may still be room for validation or cross-validation of tests for prognostic power regarding long term outcomes in order to take reliable therapy decisions in real time.

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Ph.D.; Professor in Pharmacology and Toxicology. Senior expert in theragenomic and personalized medicine and individualized drug safety. Senior expert in pharmaco- and toxicogenetics. Senior expert in human safety of drugs, chemicals, environmental pollutants, and dietary ingredients.

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