Introduction: Biomarkers in Breast Cancer

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There has been tremendous growth in the evaluation of breast cancer biomarkers, states Edith A. Perez, MD. Markers may include germline mutations that indicate a predisposition for developing breast cancer, as well as prognostic and predictive markers in tumors to enable clinicians to better understand the benefits of therapy.

Individuals with mutations in the partner and localizer of the BRCA2 gene, PALB2, have an increased predisposition for developing breast cancer, where the ultimate risk of disease may be as high as 33%, explains Perez. Gathering more data about a gene and its families allows for more precision regarding whether a particular aberration is deleterious, says Debu Tripathy, MD. The variant of unknown significance rate for PALB2 and other genes is higher than in the BRCA1/2 families, making it challenging to counsel patients on how to proceed with therapy, he observes.

Breast cancer 3 (BRCA3) is an early onset gene on chromosome 13 that was found to be associated with BRCA2 but has not been associated with increased risk of breast cancer development, says Carlos L. Arteaga, MD. More research must first be completed before BRCA3 is ready for clinical use, comments Arteaga.

High-risk patients who have strong family histories and develop breast cancer in their 20s should be tested for biomarkers beyond BRCA1/2, shares Tripathy. It is important for genetic counselors to collaborate with biomedical geneticists in making decisions regarding which individuals should undergo multipanel testing, he says. More genetic counselors are needed throughout the nation, adds Perez, stating that individuals diagnosed with triple-negative breast cancer should also receive testing.

There is a distinction between germline DNA sequencing and tumor genome sequencing, says Arteaga. In general, germline DNA must be sequence in order to accurately interpret the tumor genome. Germline DNA sequencing may result in a fortuitous finding of germline mutations that marks patients and their families for a risk that they were not anticipating, he states.

There has been opposition from genetic experts concerning the current practice of multipanel testing, says Joyce O’Shaughnessy, MD. Opponents suggest that the current technology is beyond the ability of most healthcare providers, including genetic counselors, to interpret and apply results. Therefore, they caution against conducting these panels until better cancer risk estimates can be achieved.