Sabine Grill1, Evelyn Klein1. 1. Department of Gynecology and Obstetrics, Klinikum Rechts der Isar, Technical University Munich (TUM), Munich, Germany.
Abstract
BACKGROUND: Treatment of patients with luminal metastatic breast cancer (MBC) has become even more complex over the last few years as molecular profiling has begun to alter disease management. It is well accepted that MBC is not curable but is treatable. Today we are able to prolong progression-free survival and partly overall survival with targeted and more individual treatment strategies adjusted according to the molecular subtype. SUMMARY: Genetic and genomic testing has become therapeutically relevant in luminal MBC and is therefore an integral component within the treatment spectrum. By now, germline testing of BRCA1 and BRCA2 and somatic testing for PIK3CA mutations are inevitable elements in disease management and the current state of the art in luminal MBC patients. Furthermore, testing of ESR1 resistance mutation, ERBB2 mutation, microsatellite instability, and neurotrophic tyrosine receptor kinase (NTRK) gene fusion (mainly in secretory breast cancer) has recently gained increasing attention. However, based on the expanding role of personalized medicine, clinicians are now faced with substantial new challenges and possibly unsuspected possibilities. The following review summarizes current developments in genetic and genomic testing in luminal MBC. KEY MESSAGES: In luminal MBC genomics have become an integral component within the spectrum of oncological treatment establishing novel therapeutic facilities. Further developments in treatment personalization adjusted according to the molecular subtype should become increasingly important in order to enhance the progress of de-escalation of chemotherapy in luminal MBC. However, based on the expanding role of personalized medicine, clinicians are now faced with substantial new challenges and possibly unsuspected possibilities.
BACKGROUND: Treatment of patients with luminal metastatic breast cancer (MBC) has become even more complex over the last few years as molecular profiling has begun to alter disease management. It is well accepted that MBC is not curable but is treatable. Today we are able to prolong progression-free survival and partly overall survival with targeted and more individual treatment strategies adjusted according to the molecular subtype. SUMMARY: Genetic and genomic testing has become therapeutically relevant in luminal MBC and is therefore an integral component within the treatment spectrum. By now, germline testing of BRCA1 and BRCA2 and somatic testing for PIK3CA mutations are inevitable elements in disease management and the current state of the art in luminal MBC patients. Furthermore, testing of ESR1 resistance mutation, ERBB2 mutation, microsatellite instability, and neurotrophic tyrosine receptor kinase (NTRK) gene fusion (mainly in secretory breast cancer) has recently gained increasing attention. However, based on the expanding role of personalized medicine, clinicians are now faced with substantial new challenges and possibly unsuspected possibilities. The following review summarizes current developments in genetic and genomic testing in luminal MBC. KEY MESSAGES: In luminal MBC genomics have become an integral component within the spectrum of oncological treatment establishing novel therapeutic facilities. Further developments in treatment personalization adjusted according to the molecular subtype should become increasingly important in order to enhance the progress of de-escalation of chemotherapy in luminal MBC. However, based on the expanding role of personalized medicine, clinicians are now faced with substantial new challenges and possibly unsuspected possibilities.
Authors: J Mateo; D Chakravarty; R Dienstmann; S Jezdic; A Gonzalez-Perez; N Lopez-Bigas; C K Y Ng; P L Bedard; G Tortora; J-Y Douillard; E M Van Allen; N Schultz; C Swanton; F André; L Pusztai Journal: Ann Oncol Date: 2018-09-01 Impact factor: 32.976
Authors: Alexander Drilon; Theodore W Laetsch; Shivaani Kummar; Steven G DuBois; Ulrik N Lassen; George D Demetri; Michael Nathenson; Robert C Doebele; Anna F Farago; Alberto S Pappo; Brian Turpin; Afshin Dowlati; Marcia S Brose; Leo Mascarenhas; Noah Federman; Jordan Berlin; Wafik S El-Deiry; Christina Baik; John Deeken; Valentina Boni; Ramamoorthy Nagasubramanian; Matthew Taylor; Erin R Rudzinski; Funda Meric-Bernstam; Davendra P S Sohal; Patrick C Ma; Luis E Raez; Jaclyn F Hechtman; Ryma Benayed; Marc Ladanyi; Brian B Tuch; Kevin Ebata; Scott Cruickshank; Nora C Ku; Michael C Cox; Douglas S Hawkins; David S Hong; David M Hyman Journal: N Engl J Med Date: 2018-02-22 Impact factor: 91.245
Authors: Aurelien Marabelle; Dung T Le; Paolo A Ascierto; Anna Maria Di Giacomo; Ana De Jesus-Acosta; Jean-Pierre Delord; Ravit Geva; Maya Gottfried; Nicolas Penel; Aaron R Hansen; Sarina A Piha-Paul; Toshihiko Doi; Bo Gao; Hyun Cheol Chung; Jose Lopez-Martin; Yung-Jue Bang; Ronnie Shapira Frommer; Manisha Shah; Razi Ghori; Andrew K Joe; Scott K Pruitt; Luis A Diaz Journal: J Clin Oncol Date: 2019-11-04 Impact factor: 44.544
Authors: Karoline B Kuchenbaecker; John L Hopper; Daniel R Barnes; Kelly-Anne Phillips; Thea M Mooij; Marie-José Roos-Blom; Sarah Jervis; Flora E van Leeuwen; Roger L Milne; Nadine Andrieu; David E Goldgar; Mary Beth Terry; Matti A Rookus; Douglas F Easton; Antonis C Antoniou; Lesley McGuffog; D Gareth Evans; Daniel Barrowdale; Debra Frost; Julian Adlard; Kai-Ren Ong; Louise Izatt; Marc Tischkowitz; Ros Eeles; Rosemarie Davidson; Shirley Hodgson; Steve Ellis; Catherine Nogues; Christine Lasset; Dominique Stoppa-Lyonnet; Jean-Pierre Fricker; Laurence Faivre; Pascaline Berthet; Maartje J Hooning; Lizet E van der Kolk; Carolien M Kets; Muriel A Adank; Esther M John; Wendy K Chung; Irene L Andrulis; Melissa Southey; Mary B Daly; Saundra S Buys; Ana Osorio; Christoph Engel; Karin Kast; Rita K Schmutzler; Trinidad Caldes; Anna Jakubowska; Jacques Simard; Michael L Friedlander; Sue-Anne McLachlan; Eva Machackova; Lenka Foretova; Yen Y Tan; Christian F Singer; Edith Olah; Anne-Marie Gerdes; Brita Arver; Håkan Olsson Journal: JAMA Date: 2017-06-20 Impact factor: 56.272
Authors: Charlotte Fribbens; Ben O'Leary; Lucy Kilburn; Sarah Hrebien; Isaac Garcia-Murillas; Matthew Beaney; Massimo Cristofanilli; Fabrice Andre; Sherene Loi; Sibylle Loibl; John Jiang; Cynthia Huang Bartlett; Maria Koehler; Mitch Dowsett; Judith M Bliss; Stephen R D Johnston; Nicholas C Turner Journal: J Clin Oncol Date: 2016-06-06 Impact factor: 44.544