Second-generation Prognostic Signatures

The second-generation signatures, also microarray- or qRT PCR-based, improved upon the first-generation signatures by boosting accuracy of determine risk for long-term recurrence.

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These scores include PAM 50 (Prosigna), the Breast Cancer Index (BCI), and EndoPredict. Of these, Prosigna is FDA-approved to assign patients into 1 of 3 risk groups for recurrence between 5 to 15 years after the primary diagnosis.13

BCI is based on the expression of the HOXB13 and IL17BR genes and is for use for patients with estrogen receptor–positive disease and classifies patients into 1 of 3 risk groups for early and late distant recurrence.

EndoPredict is the newest prognostic signature and has been validated in patients with estrogen receptor positive or negative disease, as well as HER2-negative tumors. The EndoPredict score can be combined with tumor size and nodal status, called the EndoPredictClin, to provide an even better long-term prognosis of distant recurrence.

Concordance Among Prognostic Signatures

With so many first- and second-generation prognostic signatures available, it can be difficult to decide which tools to incorporate into practice. “They are not recommended as part of the standard of care in expert guidelines, including National Comprehensive Cancer Network and ASCO,” Joseph A. Sparano, MD, of the Albert Einstein College of Medicine in New York, New York, who is not affiliated with the ASCO Educational Book article, told Cancer Therapy Advisor.

Dr Sparano uses prognostic signatures “routinely in ER-positive, HER2-negative breast cancer with 0 to 3 positive nodes, where the information may be useful in making a treatment decision.” He told Cancer Therapy Advisor that the “level of evidence supporting their use,” is an important feature when selecting a specific prognostic signature.

Various first- and second-generation prognostic signatures provide a similar prediction, despite the use of different genes and algorithms. The exception to this is the 2-gene BCI signature. In a study of 295 tumor samples, MammaPrint, Oncotype DX, intrinsic subtypes, and the wound response provided a similar prediction for risk, though the BCI signature did not.14

The ability of the BCI signature to determine outcomes was positive in another study, but negative in another.15,16 Drs Ribnikar and Cardoso suggested that “a model based on the analysis of only 2 genes is much more likely to be sensitive to technical differences in analysis platforms than 1 based on many genes.”

RELATED: Some Patients With Endocrine-responsive Early-stage Breast Cancer May Avoid Chemotherapy

Gene expression prognostic signatures continue to evolve to provide greater accuracy for both short- and long-term risk of recurrence, and currently provide value in terms of aiding treatment decisions.

They should, however, be used together with clinicopathologic factors. “Adjuvant treatment decision making in breast cancer involves an integration of the available clinicopathologic factors and new genomic tools, whenever appropriate, as well as a detailed and comprehensible discussion with each individual patient,” wrote Drs Ribnikar and Cardoso.


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