BACKGROUND: Genetic testing for cancer predisposition is recommended to women with breast cancer who meet the criteria for such testing. After the FDA approvals of the poly ADP ribose polymerase (PARP) inhibitors, olaparib and talazoparib, for treatment of metastatic breast cancer, carrying germline mutations in BRCA1 and BRCA2 genes, the genetic testing result has become critical in their care. With the recent FDA approval of alpelisib for the treatment of PIK3CA-mutated hormone-receptor positive metastatic breast cancer, tumor molecular profiling to identify somatic mutations and potential molecularly targeted agents is increasingly utilized in the treatment of advanced breast cancer. AIM: Combining germline and somatic sequencing (paired testing) offers an advantage over a single technique approach. Our study evaluates the role of paired testing on the management of breast cancer patients. METHODS AND RESULTS: Forty-three breast cancer patients treated at Rush University Medical Center underwent paired germline and somatic variant testing in 2015 to 2017. A retrospective chart review was conducted with the analysis of demographic, clinical, and genomic data. Three actionable germline variants were found in the CHEK2 (2) and ATM (1) genes. 95% of tumors had somatic mutations. Seventy-seven percent of tumors had genomic alterations targetable with agents approved for breast cancer and 88% had molecular targets for agents approved for other cancers. Clinical examples of such use are described and potential future directions of tumor and paired testing are discussed. CONCLUSIONS: Germline variants were present in a relatively small patient group not routinely tested for inherited alterations. Potentially targetable somatic alterations were identified in the majority of breast cancers. Paired testing is a feasible and efficient approach that delivers valuable information for the care of breast cancer patients and eliminates serial testing.
BACKGROUND: Genetic testing for cancer predisposition is recommended to women with breast cancer who meet the criteria for such testing. After the FDA approvals of the poly ADP ribose polymerase (PARP) inhibitors, olaparib and talazoparib, for treatment of metastatic breast cancer, carrying germline mutations in BRCA1 and BRCA2 genes, the genetic testing result has become critical in their care. With the recent FDA approval of alpelisib for the treatment of PIK3CA-mutated hormone-receptor positive metastatic breast cancer, tumor molecular profiling to identify somatic mutations and potential molecularly targeted agents is increasingly utilized in the treatment of advanced breast cancer. AIM: Combining germline and somatic sequencing (paired testing) offers an advantage over a single technique approach. Our study evaluates the role of paired testing on the management of breast cancerpatients. METHODS AND RESULTS: Forty-three breast cancerpatients treated at Rush University Medical Center underwent paired germline and somatic variant testing in 2015 to 2017. A retrospective chart review was conducted with the analysis of demographic, clinical, and genomic data. Three actionable germline variants were found in the CHEK2 (2) and ATM (1) genes. 95% of tumors had somatic mutations. Seventy-seven percent of tumors had genomic alterations targetable with agents approved for breast cancer and 88% had molecular targets for agents approved for other cancers. Clinical examples of such use are described and potential future directions of tumor and paired testing are discussed. CONCLUSIONS: Germline variants were present in a relatively small patient group not routinely tested for inherited alterations. Potentially targetable somatic alterations were identified in the majority of breast cancers. Paired testing is a feasible and efficient approach that delivers valuable information for the care of breast cancerpatients and eliminates serial testing.
Authors: Andreas Hochhaus; Richard A Larson; François Guilhot; Jerald P Radich; Susan Branford; Timothy P Hughes; Michele Baccarani; Michael W Deininger; Francisco Cervantes; Satoko Fujihara; Christine-Elke Ortmann; Hans D Menssen; Hagop Kantarjian; Stephen G O'Brien; Brian J Druker Journal: N Engl J Med Date: 2017-03-09 Impact factor: 91.245
Authors: Diana Mandelker; Liying Zhang; Yelena Kemel; Zsofia K Stadler; Vijai Joseph; Ahmet Zehir; Nisha Pradhan; Angela Arnold; Michael F Walsh; Yirong Li; Anoop R Balakrishnan; Aijazuddin Syed; Meera Prasad; Khedoudja Nafa; Maria I Carlo; Karen A Cadoo; Meg Sheehan; Megan H Fleischut; Erin Salo-Mullen; Magan Trottier; Steven M Lipkin; Anne Lincoln; Semanti Mukherjee; Vignesh Ravichandran; Roy Cambria; Jesse Galle; Wassim Abida; Marcia E Arcila; Ryma Benayed; Ronak Shah; Kenneth Yu; Dean F Bajorin; Jonathan A Coleman; Steven D Leach; Maeve A Lowery; Julio Garcia-Aguilar; Philip W Kantoff; Charles L Sawyers; Maura N Dickler; Leonard Saltz; Robert J Motzer; Eileen M O'Reilly; Howard I Scher; Jose Baselga; David S Klimstra; David B Solit; David M Hyman; Michael F Berger; Marc Ladanyi; Mark E Robson; Kenneth Offit Journal: JAMA Date: 2017-09-05 Impact factor: 56.272
Authors: Nadia Howlader; Sean F Altekruse; Christopher I Li; Vivien W Chen; Christina A Clarke; Lynn A G Ries; Kathleen A Cronin Journal: J Natl Cancer Inst Date: 2014-04-28 Impact factor: 13.506
Authors: Melinda L Telli; Kirsten M Timms; Julia Reid; Bryan Hennessy; Gordon B Mills; Kristin C Jensen; Zoltan Szallasi; William T Barry; Eric P Winer; Nadine M Tung; Steven J Isakoff; Paula D Ryan; April Greene-Colozzi; Alexander Gutin; Zaina Sangale; Diana Iliev; Chris Neff; Victor Abkevich; Joshua T Jones; Jerry S Lanchbury; Anne-Renee Hartman; Judy E Garber; James M Ford; Daniel P Silver; Andrea L Richardson Journal: Clin Cancer Res Date: 2016-03-08 Impact factor: 12.531
Authors: Sue Richards; Nazneen Aziz; Sherri Bale; David Bick; Soma Das; Julie Gastier-Foster; Wayne W Grody; Madhuri Hegde; Elaine Lyon; Elaine Spector; Karl Voelkerding; Heidi L Rehm Journal: Genet Med Date: 2015-03-05 Impact factor: 8.822
Authors: Ana M Mendes-Pereira; Sarah A Martin; Rachel Brough; Afshan McCarthy; Jessica R Taylor; Jung-Sik Kim; Todd Waldman; Christopher J Lord; Alan Ashworth Journal: EMBO Mol Med Date: 2009-09 Impact factor: 12.137
Authors: Elizabeth Elliott; Virginia Speare; James Coggan; Carin Espenschied; Holly LaDuca; Amal F Yussuf; Kelly Burgess; Phillip Gray; Melody Cobleigh; Ruta Rao; Jeremy Patel; Timothy Kuzel; Lela E Buckingham; Lydia Usha Journal: Cancer Rep (Hoboken) Date: 2020-09-03