Nicole Casasanta1, Sarit T Kipnis2, Laura Linville2, Shawn Lipinski3, Alice Knoedler4, Amy Marino5, Allision McHenry6, Tara Biagi6, Elizabeth Stark6, Richard Amdur7, Neelima Denduluri3, Patricia Rodriguez3, Claudine Isaacs4, Rebecca Kaltman6. 1. George Washington University School of Medicine and Health Sciences, MD Program, Washington, DC. Electronic address: ncasasanta@gwmail.gwu.edu. 2. George Washington University School of Medicine and Health Sciences, MD Program, Washington, DC. 3. Virginia Cancer Specialists, Arlington, VA. 4. Georgetown Lombardi Comprehensive Cancer Center, Washington, DC. 5. University of Pittsburg Medical Center Hillman Cancer Center, Pittsburgh, PA. 6. Medical Faculty Associates, GW Cancer Center, Ruth Paul Cancer Genetics and Prevention Service, The George Washington University, Washington, DC. 7. Medical Faculty Associates, The George Washington University, Washington, DC.
Abstract
BACKGROUND: Oncotype DX (ODX) is a genomic assay of tumor tissue that is utilized to predict the likelihood of recurrence and benefit of chemotherapy in breast cancer patients. Five to 10% of breast cancers are hereditary, and hereditary syndromes may not be uncovered through family history alone. We hypothesized that high ODX recurrence score (RS) may signal a potential hereditary cancer risk. PATIENTS AND METHODS: We performed a retrospective analysis of data from hormone receptor-positive breast cancer patients who had undergone ODX and germline genetic testing. The chi-square test and Fisher exact test were used to examine univariable association between RS and germline mutation status. Multivariable logistic regression was utilized to examine if there was an association of RS with germline mutation status. RESULTS: In univariable analysis, the association of RS with germline mutation status was significant (P < .0001). In the multivariable logistic regression model predicting germline mutation status, RS level remained significantly associated with germline mutation, in particular BRCA1 or BRCA2. The mean RS for those with non-BRCA1/2 germline mutations versus those without germline mutations was not significant (P = .38). CONCLUSION: High RS is associated with germline mutation status. Breast cancer patients with high RS are more likely to harbor a mutation in the BRCA1 or BRCA2 genes. If confirmed prospectively, oncologists may consider referring patients with high RS for genetic risk assessment and counseling to inform management plans, as well as counseling of family members.
BACKGROUND: Oncotype DX (ODX) is a genomic assay of tumor tissue that is utilized to predict the likelihood of recurrence and benefit of chemotherapy in breast cancerpatients. Five to 10% of breast cancers are hereditary, and hereditary syndromes may not be uncovered through family history alone. We hypothesized that high ODX recurrence score (RS) may signal a potential hereditary cancer risk. PATIENTS AND METHODS: We performed a retrospective analysis of data from hormone receptor-positive breast cancerpatients who had undergone ODX and germline genetic testing. The chi-square test and Fisher exact test were used to examine univariable association between RS and germline mutation status. Multivariable logistic regression was utilized to examine if there was an association of RS with germline mutation status. RESULTS: In univariable analysis, the association of RS with germline mutation status was significant (P < .0001). In the multivariable logistic regression model predicting germline mutation status, RS level remained significantly associated with germline mutation, in particular BRCA1 or BRCA2. The mean RS for those with non-BRCA1/2 germline mutations versus those without germline mutations was not significant (P = .38). CONCLUSION: High RS is associated with germline mutation status. Breast cancerpatients with high RS are more likely to harbor a mutation in the BRCA1 or BRCA2 genes. If confirmed prospectively, oncologists may consider referring patients with high RS for genetic risk assessment and counseling to inform management plans, as well as counseling of family members.