Aki Morikawa1, Lilly Jordan1, Raquel Rozner1, Sujata Patil2, Adrienne Boire3, Elena Pentsova3, Andrew D Seidman4. 1. Breast Cancer Medicine Service, Memorial Sloan Kettering Cancer Center, New York, NY. 2. Department of Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY. 3. Department of Neurology, Memorial Sloan Kettering Cancer Center, New York, NY. 4. Breast Cancer Medicine Service, Memorial Sloan Kettering Cancer Center, New York, NY. Electronic address: seidmana@mskcc.org.
Abstract
BACKGROUND: Disease presentation, prognostic factors, and treatment patterns for patients with breast cancer with leptomeningeal metastasis are not well characterized. In this study, we examined patient characteristics and prognostic factors for survival after a diagnosis of leptomeningeal metastasis. PATIENTS AND METHODS: Three hundred eighteen consecutive patients with breast cancer diagnosed with leptomeningeal metastasis from January 1998 to December 2013 at Memorial Sloan Kettering Cancer Center were identified. Clinicopathologic and treatment information were obtained in a retrospective review. Associations with time from leptomeningeal diagnosis to death were evaluated according to Kaplan-Meier curves, log rank tests, and Cox proportional hazard models. RESULTS: Of the 318 patients, 44% were hormone receptor-positive (HR+) HER2-, 18% were HR+HER2+, 8.5% were HR-HER2+, 25.5% were triple-negative; and 4% had missing information. The median survival was 3.5 months (95% confidence interval, 3.0-4.0) with 63 patients (20%) surviving >1 year. Recent diagnosis (after 2006), HER2+ subtype, higher performance status, cranial-only involvement, and no evidence of noncentral nervous system disease were independently associated with improved survival in multivariate analysis. CONCLUSION: Despite the improvement noted with the more recent years of diagnosis, survival after a diagnosis of leptomeningeal metastasis remains poor. Similar to patients with parenchymal brain metastasis only, the survival differs among different receptor subtypes. A closer examination to identify factors, such as introduction of new systemic therapies that might contribute to longer-term survival might provide insight to improve management of these patients. In addition, factors we identified that are associated with survival might be considered as stratification variables in the design of future randomized clinical trials in this population.
BACKGROUND: Disease presentation, prognostic factors, and treatment patterns for patients with breast cancer with leptomeningeal metastasis are not well characterized. In this study, we examined patient characteristics and prognostic factors for survival after a diagnosis of leptomeningeal metastasis. PATIENTS AND METHODS: Three hundred eighteen consecutive patients with breast cancer diagnosed with leptomeningeal metastasis from January 1998 to December 2013 at Memorial Sloan Kettering Cancer Center were identified. Clinicopathologic and treatment information were obtained in a retrospective review. Associations with time from leptomeningeal diagnosis to death were evaluated according to Kaplan-Meier curves, log rank tests, and Cox proportional hazard models. RESULTS: Of the 318 patients, 44% were hormone receptor-positive (HR+) HER2-, 18% were HR+HER2+, 8.5% were HR-HER2+, 25.5% were triple-negative; and 4% had missing information. The median survival was 3.5 months (95% confidence interval, 3.0-4.0) with 63 patients (20%) surviving >1 year. Recent diagnosis (after 2006), HER2+ subtype, higher performance status, cranial-only involvement, and no evidence of noncentral nervous system disease were independently associated with improved survival in multivariate analysis. CONCLUSION: Despite the improvement noted with the more recent years of diagnosis, survival after a diagnosis of leptomeningeal metastasis remains poor. Similar to patients with parenchymal brain metastasis only, the survival differs among different receptor subtypes. A closer examination to identify factors, such as introduction of new systemic therapies that might contribute to longer-term survival might provide insight to improve management of these patients. In addition, factors we identified that are associated with survival might be considered as stratification variables in the design of future randomized clinical trials in this population.
Keywords:
Central nervous system metastasis; Leptomeningeal disease; Metastatic breast cancer; Prognosis; Survival in patients with leptomeningeal metastases
Authors: W Boogerd; M J van den Bent; P J Koehler; J J Heimans; J J van der Sande; N K Aaronson; A A M Hart; J Benraadt; Ch J Vecht Journal: Eur J Cancer Date: 2004-12 Impact factor: 9.162
Authors: Paul W Sperduto; Norbert Kased; David Roberge; Zhiyuan Xu; Ryan Shanley; Xianghua Luo; Penny K Sneed; Samuel T Chao; Robert J Weil; John Suh; Amit Bhatt; Ashley W Jensen; Paul D Brown; Helen A Shih; John Kirkpatrick; Laurie E Gaspar; John B Fiveash; Veronica Chiang; Jonathan P S Knisely; Christina Maria Sperduto; Nancy Lin; Minesh Mehta Journal: Int J Radiat Oncol Biol Phys Date: 2011-04-15 Impact factor: 7.038
Authors: Marc Chamberlain; Riccardo Soffietti; Jeffrey Raizer; Roberta Rudà; Dieta Brandsma; Willem Boogerd; Sophie Taillibert; Morris D Groves; Emilie Le Rhun; Larry Junck; Martin van den Bent; Patrick Y Wen; Kurt A Jaeckle Journal: Neuro Oncol Date: 2014-05-27 Impact factor: 12.300
Authors: Ishwaria M Subbiah; Xiudong Lei; Jeffrey S Weinberg; Erik P Sulman; Mariana Chavez-MacGregor; Debu Tripathy; Rohan Gupta; Ankur Varma; Jay Chouhan; Richard P Guevarra; Vicente Valero; Mark R Gilbert; Ana M Gonzalez-Angulo Journal: J Clin Oncol Date: 2015-05-18 Impact factor: 44.544
Authors: E Le Rhun; S Taillibert; F Zairi; N Kotecki; P Devos; A Mailliez; V Servent; L Vanlemmens; P Vennin; T Boulanger; M C Baranzelli; C André; G Marliot; J L Cazin; F Dubois; R Assaker; J Bonneterre; M C Chamberlain Journal: J Neurooncol Date: 2013-03-01 Impact factor: 4.130
Authors: Sausan Abouharb; Joe Ensor; Monica Elena Loghin; Ruth Katz; Stacy L Moulder; Francisco J Esteva; Benjamin Smith; Vicente Valero; Gabriel N Hortobagyi; Amal Melhem-Bertrandt Journal: Breast Cancer Res Treat Date: 2014-07-20 Impact factor: 4.872
Authors: Nancy U Lin; Lisa A Carey; Minetta C Liu; Jerry Younger; Steven E Come; Matthew Ewend; Gordon J Harris; Elizabeth Bullitt; Annick D Van den Abbeele; John W Henson; Xiaochun Li; Rebecca Gelman; Harold J Burstein; Elizabeth Kasparian; David G Kirsch; Ann Crawford; Fred Hochberg; Eric P Winer Journal: J Clin Oncol Date: 2008-04-20 Impact factor: 44.544
Authors: Nancy U Lin; Véronique Diéras; Devchand Paul; Dominique Lossignol; Christos Christodoulou; Hans-Joachim Stemmler; Henri Roché; Minetta C Liu; Richard Greil; Eva Ciruelos; Sibylle Loibl; Stefania Gori; Andrew Wardley; Denise Yardley; Adam Brufsky; Joanne L Blum; Stephen D Rubin; Bernie Dharan; Klaudia Steplewski; Denise Zembryki; Cristina Oliva; Debasish Roychowdhury; Paolo Paoletti; Eric P Winer Journal: Clin Cancer Res Date: 2009-02-15 Impact factor: 12.531
Authors: Paul W Sperduto; Norbert Kased; David Roberge; Samuel T Chao; Ryan Shanley; Xianghua Luo; Penny K Sneed; John Suh; Robert J Weil; Ashley W Jensen; Paul D Brown; Helen A Shih; John Kirkpatrick; Laurie E Gaspar; John B Fiveash; Veronica Chiang; Jonathan P S Knisely; Christina Maria Sperduto; Nancy Lin; Minesh Mehta Journal: J Neurooncol Date: 2013-03-06 Impact factor: 4.130
Authors: Anna Niwińska; Katarzyna Pogoda; Wojciech Michalski; Michał Kunkiel; Agnieszka Jagiełło-Gruszfeld Journal: J Neurooncol Date: 2018-02-12 Impact factor: 4.130
Authors: Emilie Le Rhun; Jennifer Wallet; Audrey Mailliez; Marie Cecile Le Deley; Isabelle Rodrigues; Thomas Boulanger; Veronique Lorgis; Jerome Barrière; Yves Marie Robin; Michael Weller; Jacques Bonneterre Journal: Neuro Oncol Date: 2020-04-15 Impact factor: 12.300
Authors: Aki Morikawa; Elisa de Stanchina; Elena Pentsova; Margaret M Kemeny; Bob T Li; Kendrick Tang; Sujata Patil; Martin Fleisher; Catherine Van Poznak; Larry Norton; Andrew D Seidman Journal: Clin Cancer Res Date: 2019-04-15 Impact factor: 12.531
Authors: Desmond A Brown; Victor M Lu; Benjamin T Himes; Terry C Burns; Alfredo Quiñones-Hinojosa; Kaisorn L Chaichana; Ian F Parney Journal: Clin Exp Metastasis Date: 2020-01-16 Impact factor: 5.150