The field of oncologic genomics is rapidly expanding, and this is evident by guideline-recommended therapies that incorporate genomic testing into administration recommendations. However, there is also confusion, as availability of data from genomic testing has outpaced the understanding of the clinical implications of the germline findings. To help address these concerns, the American Society of Clinical Oncology (ASCO) published guidelines on germline testing in patients with breast cancer (BC).
The purpose of the guidelines is to provide clinicians and other healthcare practitioners and patients and caregivers with formal guideline-based recommendations regarding the role of germline mutation testing in patients with BC based on the best available evidence. The systematic-review based guidelines were developed using a combination of a PubMed literature reviews from between September 20, 2012, and February 7, 2023, and an ASCO-modified Delphi formal consensus methodology due to a paucity of high-quality published evidence.
The recommendations are divided into two main themes: 1) germline mutation testing–related recommendations (which incorporated information from 47 articles) and 2) patient genetic counseling recommendations (which included information from eight articles).
The clinical practice guidelines address five questions and offer 14 recommendations, including 10 that address germline mutation testing and four that address patient counseling.
The first question asked which BC patients should receive BRCA1/2 testing. The recommendations state that BRCA1/2 testing should be offered to all patients with newly diagnosed BC stage I to III or de novo stage IV/metastatic disease who are aged <65 years and to those aged >65 years who are candidates for poly(ADP-ribose) polymerase (PARP) inhibitor therapy for early stage or metastatic disease and who have the following four age-specific qualifiers: presence of triple-negative BC, personal or family history suggestive of the presence of a pathogenic variant, assigned male at birth, and if the older adult is of Ashkenazi Jewish ancestry or is a member of a population with an increased prevalence of founder mutations. The guidelines also advised that for patients undergoing BRCA1/2 testing, testing for other cancer predisposition genes should be offered based on personal or family history.
Question 2 inquired as to whether all people with recurrent disease, local or metastatic BC, or those with a second primary BC should be offered BRCA1/2 testing. The guidelines recommend that based on limited data, all patients with recurrent BC who are candidates for PARP inhibitor therapy should be offered testing regardless of family history, as should those patients with a second primary BC in either the contralateral or ipsilateral breast.
Question 3 focused on whether patients with a personal history of BC but no active disease should receive BRCA1/2 testing. The guidelines suggest that for those aged <65 years, testing is recommended if the result will inform personal risk management or family risk assessment, and in those aged >65 years, it is advised if the four age-specific qualifiers are present.
Question 4 centers on whether BC patients should be tested for other predisposition genes other than BRCA1/2 as well. The guidelines offer three recommendations, including that testing for high penetrance genes, including PALB2, TP53, PTEN, STK11, and CDH1, could be helpful in informing medical therapy, influencing surgical decision making, determining risk of secondary primary cancers, and informing family risk assessment. However, such testing offers no benefit for treatment of the index BC but may be useful to inform risk of second primary cancer or family risk assessment. If a multigene panel of genetic testing is utilized, it should take into consideration the patient’s personal and family history.
The fifth and last question that the guidelines address pertains to how BC patients considering genetic testing should be counseled. Four recommendations are offered, which include the following: patients should be given sufficient information prior to testing to be able to provide informed consent; patients with pathogenic variants should receive individualized post-test genetic counseling and appropriate referrals should be made as needed; explanations should be provided to patients that variants of uncertain significance will not be used to alter their therapeutic plan but that periodic reevaluation of the significance of these variants will occur as more evidence becomes available; and even if pathogenic variants are not present, counseling should still be encouraged if there is a significant family history of cancer and referral to a provider experienced in clinical cancer genetics is warranted.
As pharmacists are routinely embedded in oncology teams and are often responsible for ordering and/or interpreting genomic testing, these guidelines are essential for defining the appropriate use of BC germline testing to optimize patient care and reduce healthcare expenditures.
The content contained in this article is for informational purposes only. The content is not intended to be a substitute for professional advice. Reliance on any information provided in this article is solely at your own risk.
