Consensus Guidelines on Genetic` Testing for Hereditary Breast Cancer from the American Society of Breast Surgeons.

BACKGROUND: The purpose of this consensus guideline is to outline recommendations for genetic testing that medical professionals can use to assess hereditary risk for breast cancer. METHODS: Literature review included large datasets, basic and clinical science publications, and recent updated national guidelines. Genetic testing to assess hereditary risk of cancer is a complex, broad, and dynamic area of medical research. The dominant focus of this guideline is limited in scope to breast cancer. RESULTS: There is a lack of consensus among experts regarding which genes among many should be tested in different clinical scenarios. There is also variation in the degree of consensus regarding the understanding of risk and appropriate clinical management of mutations in many genes. CONCLUSIONS: Genetic testing should be made available to all patients with a personal history of breast cancer. Recent data are reviewed that support genetic testing being offered to each patient with breast cancer (newly diagnosed or with a personal history). If genetic testing is performed, such testing should include BRCA1/BRCA2 and PALB2, with other genes as appropriate for the clinical scenario and family history. For patients with newly diagnosed breast cancer, identification of a mutation may impact local treatment recommendations. Patients who had genetic testing previously may benefit from updated testing. Genetic testing should be made available to patients without a history of breast cancer who meet National Comprehensive Cancer Network guidelines. Finally, variants of uncertain significance are not clinically actionable and these patients should be managed based on their individual risk factors.

Germline Genetic Testing: What the Breast Surgeon Needs to Know.

PURPOSE: The American Society of Breast Surgeons (ASBrS) sought to provide educational guidelines for breast surgeons on how to incorporate genetic information and genomics into their practice. METHODS: A comprehensive nonsystematic review was performed of selected peer-reviewed literature. The Genetics Working Group of the ASBrS convened to develop guideline recommendations. RESULTS: Clinical and educational guidelines were prepared to outline the essential knowledge for breast surgeons to perform germline genetic testing and to incorporate the findings into their practice, which have been approved by the ASBrS Board of Directors. RECOMMENDATIONS: Thousands of women in the USA would potentially benefit from genetic testing for BRCA1, BRCA2, and other breast cancer genes that markedly increase their risk of developing breast cancer. As genetic testing is now becoming more widely available, women should be made aware of these tests and consider testing. Breast surgeons are well positioned to help facilitate this process. The areas where surgeons need to be knowledgeable include: (1) identification of patients for initial breast cancer-related genetic testing, (2) identification of patients who tested negative in the past but now need updated testing, (3) initial cancer genetic testing, (4) retesting of patients who need their genetic testing updated, (5) cancer genetic test interpretation, posttest counseling and management, (6) management of variants of uncertain significance, (7) cascade genetic testing, (8) interpretation of genetic tests other than clinical cancer panels and the counseling and management required, and (9) interpretation of somatic genetic tests and the counseling and management required.

Inconsistent Associations Between Risk Factor Profiles and Adjuvant Radiation Therapy (ART) Treatment in Patients with Cutaneous Squamous Cell Carcinoma and Utility of the 40-Gene Expression Profile to Refine ART Guidance.

INTRODUCTION: National Comprehensive Cancer Network (NCCN) recommendations for adjuvant radiation therapy (ART) use are similar for High Risk and Very High Risk cutaneous squamous cell carcinoma (cSCC) with negative post-surgical margins. Although studies report reductions in disease progression following ART treatment, ART use is likely inconsistent when guided by available risk factors. This study evaluated the association of ART with clinical risk factors in ART-treated and untreated patients and showed the clinical utility of the 40-gene expression profile (40-GEP) for guiding ART. METHODS: A multicenter study of 954 patients was conducted with institutional review board (IRB) approval. The 40-GEP test was performed using primary tumor tissue from patients with either a minimum of 3 years of follow-up or a documented regional or distant metastasis. Unsupervised hierarchical cluster analysis identified patterns of clinical risk factors for ART-treated patients, then identified untreated patients with matching risk factor profiles. Results were cross-referenced to 40-GEP test results to determine utility of the test to guide ART. RESULTS: Analysis demonstrated inconsistent implementation of ART for eligible patients. Cluster analysis identified four patient profiles based on clusters of risk factors and, notably, matching profiles in ART-treated and untreated patients. Further, the analysis identified patients who received but could have deferred ART on the basis of 40-GEP test result and biologically low risk of metastasis, and untreated patients who likely would have benefitted from ART on the basis of their 40-GEP test result. CONCLUSIONS: ART guidance is not determined by the presence of specific clinicopathologic factors, with treated and untreated patients sharing the same risk factor profiles. cSCC risk determination based on NCCN recommendations for clinical factor assessment results in inconsistent use of ART. Including tumor biology-based prognostic information from the 40-GEP refines risk and identifies patients who are most appropriate and likely to benefit from ART, and those that can consider deferring ART.