How and when to refer patients for oncogenetic counseling in the era of PARP inhibitors

Abstract

Poly(ADP-ribose)polymerase (PARP) inhibitors are targeted therapy for cancers with homologous repair deficiency (HRD). They were first approved for ovarian cancer and have changed current treatment strategies. They have also demonstrated efficacy in HER2-negative metastatic breast cancer and advanced prostate cancer with BRCA1/2 or ATM mutations. Patients with somatic and/or germline BRCA1/2 mutations benefit more from these treatments than other patients. Nowadays, the diagnosis of HRD is largely based on germline genetic testing, which is performed after an in-person genetic counseling session, even for patients without any family history of cancer. However, with the increasing number of PARP inhibitor indications across different tumor types, rapid access to oncogenetic consultations will become a challenge. To meet this demand, tumor genomic testing could be offered at initial diagnosis. Telephone counseling and other referral systems could replace in-person consultations for certain subgroups of patients deemed to have a low risk of harboring a germline mutation. This article reviews international guidelines for genetic counseling testing. We herein propose new care pathways for breast, prostate and ovarian cancers, including tumor genomic testing at initial diagnosis in order to help triage genetic counseling referrals.

Frontline Management of Epithelial Ovarian Cancer—Combining Clinical Expertise with Community Practice Collaboration and Cutting-Edge Research

“…Germline genetic testing should be considered both due to the relatively high percentage of hereditary ovarian cancer with some studies estimating that more than 20% is hereditary in etiology [ 71 , 72 , 73 ], and due to the potential for treatment implications [ 74 ]. Generally, it is preferable for an individual to undergo germline testing as soon as diagnosis occurs [ 75 , 76 ]. This allows ample time to obtain and disclose results, especially in the setting of a patient who may have a guarded prognosis.…”

Clinical practice guidelines for BRCA1 and BRCA2 genetic testing

“…The major benefit of PARPi therapy for newly diagnosed ovarian cancer combined with improved progression-free survival in advanced ovarian, breast, prostate and pancreatic cancers [6,7] has prompted the development of BRCAm detection for targeted therapies. In some situations, such as ovarian cancer or prostate cancer, detecting somatic mutations has been effective for identifying PARPi-sensitive patients [8].…”

“…More than 30 guidelines on BRCA testing are available worldwide [7,9,10]. In the United States, the US National Comprehensive Cancer Network [11], the American Society of Clinical Oncology [6,12] and the US Preventive Services Task Force [13] have published policy statements for genetic testing for BRCA-related cancer.…”

“…In the United States, the US National Comprehensive Cancer Network [11], the American Society of Clinical Oncology [6,12] and the US Preventive Services Task Force [13] have published policy statements for genetic testing for BRCA-related cancer. Sixteen different guidelines exist in Europe [7,9,10]. However, most guidelines do not represent international consensus, differ from each other in the lBRCAm threshold retained (10% [14,15] or 5% [11]) and may not integrate the recent need for BRCA genotyping for PARPi treatment and personalised breast cancer management.…”

Targeted therapy with Poly(ADP-ribose) polymerase (PARP) inhibitors for the treatment of solid tumours

“…Inhibition of PARP activity can lead to the death of cells with the BRCA1 /BRCA2 mutation. Patients with somatic and/or embryonic mutation BRCA1/2 benefit more from these treatments than other patients [5]. For the first time PARP inhibitors have been approved for the treatment of ovarian cancer and this has completely changed the treatment strategy.…”