Miller, Devon

Abstract Rapid developments in cancer genetics and hereditary cancer risk assessments have enabled the identification of individuals at elevated risk for hereditary malignancies to guide enhanced cancer screening and prevention efforts. Multigene panel testing has emerged as the standard approach as emphasized in the National Comprehensive Cancer Network (NCCN) guidelines. The purpose of this study was to investigate the frequency of other pathogenic mutations identified through multigene panel testing in individuals who previously tested negative for germline BRCA1/2 and assess the clinical impact of panel testing. Patients either previously diagnosed with breast cancer or with a family history of breast or ovarian cancer that had also been seen by Oncology Genetics at a single institution and tested negative for BRCA1/2 genes but had not undergone prior multigene panel testing were invited via a letter to return for an additional genetic counseling visit to discuss multigene panel testing. Patients were also able to opt-in to a survey component of the study and received an email to fill out the Multidimensional Impact of Cancer Risk Assessment (MICRA) and Cancer Worry Scale (CWS). Surveys were completed prior to the initial genetic counseling appointment and repeated after discussion of the multigene panel test results. A total 24 women met with a genetic counselor of which 22 (92%) had a personal history of breast cancer, 1 (4%) had a family history of breast cancer, and 1 (4%) had a family history of ovarian cancer. The mean age was 52.6 years (range, 42-68) and 100% of women were Caucasian. Of the 24 women, 17 (71%) completed multigene panel testing. Of the women that underwent testing, 7 (41%) had negative results, 6 (35%) had variants of unknown significance (VUS), and 4 (24%) had a pathogenic mutation identified in another gene (CDKN2A, CHEK2, and CFTR). There was no significant change in MICRA or CWS scores after multigene panel results were reviewed in the 9 patients that completed both pre- and post-genetic testing surveys. The mean/median summary MICRA scores pre- and post-counselling were 30 (SD 12.4), median 26 (min 18, max 56), and 21.2 (SD 15.4), median 21 (min 3, max 43), respectively (p=0.19, Wilcoxon signed ranks test). The mean/median summary CWS scores pre- and post-counselling were 14.3 (SD 5), median 15 (min 7, max 24), and 13.6 (SD 2.59), median 14 (min 10, max 17), respectively (p=0.53, Wilcoxon signed ranks test). Of the 4 patients with newly identified pathogenic mutations, 2 started new screening protocols and 1 underwent a prophylactic mastectomy. In conclusion, multigene panel testing identified pathogenic mutations in a subset of individuals who previously tested negative for BRCA1/2 genes leading to changes in clinical management. The completion of multigene panel testing did not lead to a significant increase in MICRA or CWS scores. Key limitations of this study include a small sample size and an all Caucasian population. Citation Format: Devon Miller, Stephanie Pritzl, Angela Tess, Jessica Gooding, Lisa Barroilhet, Lori Dubenske, Kari Wisinski. Clinical Impact of Multigene Panel Testing in Patients with a Personal or Family History of Breast or Ovarian Cancer Previously Negative for BRCA1/2 Genes [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO1-09-03.

AbstractBackgroundSarcomas are rare diagnoses but are seen with relative frequency in adolescents and young adults and thus can present in pregnancy. We sought to study the administration of anthracyclines and/or ifosfamide in pregnancy‐associated sarcomas.Patients and MethodsWe conducted a multi‐institutional retrospective study, identifying sarcoma patients who received anthracyclines and/or ifosfamide during pregnancy. Chart review identified variables related to demographics, cancer diagnosis, therapies, and outcome of the patient and fetus. Wilcoxon rank‐sum test compared two independent samples.ResultsWe identified 13 patients at seven institutions with sarcoma who received anthracyclines and/or ifosfamide during pregnancy, including four bone sarcomas and nine soft tissue sarcomas diagnosed at a mean gestational age of 16.7 ± 5.9 weeks. Only nine patients had live births (9/13, 69.2%), with mean gestational age of 30.8 ± 3.8 weeks at delivery. The four patients with pregnancy loss all received both doxorubicin and ifosfamide, with chemotherapy initiated at 15.5 weeks as compared with 21.3 weeks for those patients with live births (p = 0.016).ConclusionIn this multi‐institutional study of sarcoma chemotherapy regimens administered during pregnancy, we found a high rate of fetal demise that was seen only in patients receiving both doxorubicin and ifosfamide and statistically more likely with chemotherapy initiation earlier in the second trimester. While limited by a small sample size, our study represents the largest study of sarcoma patients that received anthracyclines and/or ifosfamide in pregnancy thus far reported and supports development of an international registry to study concerns raised by our study.