Central nervous system metastases in breast cancer patients with germline BRCA pathogenic variants compared to non-carriers: a matched-pair analysis.
BRCA mutation
Breast cancer
Central nervous system (CNS) metastasis
Leptomeningeal metastasis
Journal
BMC cancer
ISSN: 1471-2407
Titre abrégé: BMC Cancer
Pays: England
ID NLM: 100967800
Informations de publication
Date de publication:
16 Feb 2024
16 Feb 2024
Historique:
received:
07
11
2023
accepted:
06
02
2024
medline:
17
2
2024
pubmed:
17
2
2024
entrez:
16
2
2024
Statut:
epublish
Résumé
Breast cancer is a common cause for central nervous system (CNS) metastasis, resulting in a significant reduction in overall survival. Germline pathogenic variants (PVs) in BRCA1/2 are the most common genetic risk factor for breast cancer, associated with poor prognostic factors. This study sought to explore the patterns and outcome of CNS metastases in breast cancer patients with germline PVs in BRCA1/2 genes. A retrospective cohort of 75 breast cancer patients with known BRCA1/2 mutation status, who were diagnosed with CNS metastases in 2006-2021. Histopathology, characteristics of CNS disease, treatments, and survival were compared between BRCA1/2 carriers (n = 25) and non-carriers (n = 50), using propensity score matching (1:2 ratio) to control for the possible influence of tumor receptor status (ER, PR, HER2) and patient age. Pearson chi-square or Fisher exact test and Kaplan-Meier survival curves with log-rank test were used for statistical analyses. Patients with PVs in BRCA1/2 had more high-grade tumors (88% vs. 68%, P = 0.060), were younger at CNS disease diagnosis (median 46.69 vs. 55.02 years, P = 0.003) and had better ECOG performance status (ECOG PS 0 in 20% vs. 2%, P = 0.033), but without significant differences in systemic or CNS-directed treatment approaches. BRCA1/2 mutation was associated with a higher rate of temporal lobe involvement (52% vs. 26%, P = 0.026) and leptomeningeal spread (40% vs. 20%, P = 0.020). Survival after diagnosis of CNS disease was shorter (median 8.03 vs. 28.36 months, P < 0.0001), with no significant differences in time to development of CNS metastases or overall-survival. Patients with CNS metastatic breast cancer and PVs in BRCA1/2 showed a higher rate of leptomeningeal and temporal lobe involvement, and a shorter survival with CNS disease. To the best of our knowledge, this is the first study suggesting an exclusive impact of germline BRCA1/2 mutations in CNS metastatic breast cancer.
Sections du résumé
BACKGROUND
BACKGROUND
Breast cancer is a common cause for central nervous system (CNS) metastasis, resulting in a significant reduction in overall survival. Germline pathogenic variants (PVs) in BRCA1/2 are the most common genetic risk factor for breast cancer, associated with poor prognostic factors. This study sought to explore the patterns and outcome of CNS metastases in breast cancer patients with germline PVs in BRCA1/2 genes.
METHODS
METHODS
A retrospective cohort of 75 breast cancer patients with known BRCA1/2 mutation status, who were diagnosed with CNS metastases in 2006-2021. Histopathology, characteristics of CNS disease, treatments, and survival were compared between BRCA1/2 carriers (n = 25) and non-carriers (n = 50), using propensity score matching (1:2 ratio) to control for the possible influence of tumor receptor status (ER, PR, HER2) and patient age. Pearson chi-square or Fisher exact test and Kaplan-Meier survival curves with log-rank test were used for statistical analyses.
RESULTS
RESULTS
Patients with PVs in BRCA1/2 had more high-grade tumors (88% vs. 68%, P = 0.060), were younger at CNS disease diagnosis (median 46.69 vs. 55.02 years, P = 0.003) and had better ECOG performance status (ECOG PS 0 in 20% vs. 2%, P = 0.033), but without significant differences in systemic or CNS-directed treatment approaches. BRCA1/2 mutation was associated with a higher rate of temporal lobe involvement (52% vs. 26%, P = 0.026) and leptomeningeal spread (40% vs. 20%, P = 0.020). Survival after diagnosis of CNS disease was shorter (median 8.03 vs. 28.36 months, P < 0.0001), with no significant differences in time to development of CNS metastases or overall-survival.
CONCLUSION
CONCLUSIONS
Patients with CNS metastatic breast cancer and PVs in BRCA1/2 showed a higher rate of leptomeningeal and temporal lobe involvement, and a shorter survival with CNS disease. To the best of our knowledge, this is the first study suggesting an exclusive impact of germline BRCA1/2 mutations in CNS metastatic breast cancer.
Identifiants
pubmed: 38365640
doi: 10.1186/s12885-024-11975-7
pii: 10.1186/s12885-024-11975-7
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
219Informations de copyright
© 2024. The Author(s).
Références
Lin NU, Bellon JR, Winer EP. CNS metastases in breast cancer. J Clin Oncol. 2004;22(17):3608–17. https://doi.org/10.1200/JCO.2004.01.175 .
doi: 10.1200/JCO.2004.01.175
pubmed: 15337811
Leyland JB. Human epidermal growth factor receptor 2-positive breast cancer and central nervous system metastases. J Clin Oncol. 2009;27(31):5278–86. https://doi.org/10.1200/JCO.2008.19.8481 .
doi: 10.1200/JCO.2008.19.8481
Jia J, Yu G, Jian Z, Leiping W, Biyun W, Jun C, et al. Incidence, pattern and prognosis of brain metastases in patients with metastatic triple negative breast cancer. BMC Cancer. 2018;18:446. https://doi.org/10.1186/s12885-018-4371-0 .
doi: 10.1186/s12885-018-4371-0
Graesslin O, Abdulkarim BS, Coutant C, Huguet F, Gabos Z, Hsu L, et al. Nomogram to predict subsequent brain metastasis in patients with metastatic breast cancer. J Clin Oncol. 2010;28(12):2032–7. https://doi.org/10.1200/JCO.2009.24.6314 .
doi: 10.1200/JCO.2009.24.6314
pubmed: 20308667
Evans AJ, James JJ, Cornford EJ, Chan SY, Burrell HC, Pinder SE, et al. Brain metastases from breast cancer: identification of a high-risk group. Clin Oncol. 2004;16(5):345–9.
doi: 10.1016/j.clon.2004.03.012
Pestalozzi B, Zahrieh D, Price K, Holmberg S, et al. Identifying breast cancer patients at risk for central nervous system (CNS) metastases in trials of the international breast Cancer study group (IBCSG). Ann Oncol. 2006;17:935–44. https://doi.org/10.1093/annonc/mdl064 .
doi: 10.1093/annonc/mdl064
pubmed: 16603601
Leone JP, Lee AV, Brufsky AM. Prognostic factors and survival of patients with brain metastasis from breast cancer who underwent craniotomy. Cancer Med. 2015;4(7):989–94. https://doi.org/10.1002/cam4.439 .
doi: 10.1002/cam4.439
pubmed: 25756607
pmcid: 4529337
Lee SS, Ahn J, Kim MK, et al. Brain metastases in breast cancer: prognostic factors and management. Breast Cancer Res Treat. 2008;111:523–30. https://doi.org/10.1007/s10549-007-9806-2 .
doi: 10.1007/s10549-007-9806-2
pubmed: 17990100
Sperduto PW, Kased N, Roberge D, et al. The effect of tumor subtype on the time from primary diagnosis to development of brain metastases and survival in patients with breast cancer. J Neuro-Oncol. 2013;112:467–72. https://doi.org/10.1007/s11060-013-1083-9 .
doi: 10.1007/s11060-013-1083-9
Nam B, Kim SY, Han H, Kwon Y, Lee KS, Kim TH, et al. Breast cancer subtypes and survival in patients with brain metastases. Breast Cancer Res. 2008;10(R20) https://doi.org/10.1186/bcr1870 .
Balendran S, Liebmann-Reindl S, Berghoff AS, Reischer T, Popitsch N, Geier CB, et al. Next-generation sequencing-based genomic profiling of brain metastases of primary ovarian cancer identifies high number of BRCA-mutations. J Neuro-Oncol. 2017;133(3):469–76. https://doi.org/10.1007/s11060-017-2459-z .
doi: 10.1007/s11060-017-2459-z
Sekine M, Yoshihara K, Komata D, Haino K, Nishino K, Tanaka K. Increased incidence of brain metastases in BRCA1-related ovarian cancers. J Obstetr Gynecol Res. 2013;39(1):292–6. https://doi.org/10.1111/j.1447-0756.2012.01961.x .
doi: 10.1111/j.1447-0756.2012.01961.x
Ratner E, Bala M, Louie-Gao M, Aydin E, Hazard S, Brastianos P. Increased risk of brain metastases in ovarian cancer patients with BRCA mutations. Gynecol Oncol. 2019;153(3):568–73. https://doi.org/10.1016/j.ygyno.2019.03.004 .
doi: 10.1016/j.ygyno.2019.03.004
pubmed: 30876674
Chen S, Parmigiani G. Meta-analysis of BRCA1 and BRCA2 penetrance. J Clinical Oncol. 2007;25(11):1329–33. https://doi.org/10.1200/JCO.2006.09.1066 .
doi: 10.1200/JCO.2006.09.1066
Anglian Breast Cancer Study Group. Prevalence and penetrance of BRCA1 and BRCA2 mutations in a population-based series of breast cancer cases. Br J Cancer. 2000;83(10):1301–8. https://doi.org/10.1054/bjoc.2000.1407 .
doi: 10.1054/bjoc.2000.1407
pmcid: 2408797
Song Y, Barry WT, Seah DS, Tung NM, Garber JE, Lin NU. Patterns of recurrence and metastasis in BRCA1/BRCA2-associated breast cancers. Cancer. 2020;126(2):271–80. https://doi.org/10.1002/cncr.32540 .
doi: 10.1002/cncr.32540
pubmed: 31581314
Zavitsanos PJ, Wazer DE, Hepel JT, Wang Y, Singh K, Leonard KL. BRCA1 mutations associated with increased risk of brain metastases in breast Cancer: a 1:2 matched-pair analysis. Am J Clin Oncol. 2018;41(12):1252–6. https://doi.org/10.1097/COC.0000000000000466 .
doi: 10.1097/COC.0000000000000466
pubmed: 29782359
Ben-Zion Berliner M, Yerushalmi R, et al. Central nervous system metastases in breast cancer: the impact of age on patterns of development and outcome. Breast Cancer Res Treat. 2020;185(2):423–32. https://doi.org/10.1007/s10549-020-05959-x .
doi: 10.1007/s10549-020-05959-x
pubmed: 33037977
Corbin ZA, Nagpal S. Leptomeningeal metastases. JAMA Oncol. 2016;2(6):839. https://doi.org/10.1001/jamaoncol.2015.3502 .
doi: 10.1001/jamaoncol.2015.3502
pubmed: 27100632
Atalar B, Modlin LA, Choi CY, Adler JR, Gibbs IC, Chang SD, et al. Risk of leptomeningeal disease in patients treated with stereotactic radiosurgery targeting the postoperative resection cavity for brain metastases. Int J Radiat Oncol Biol Phys. 2013;87(4):713–8. https://doi.org/10.1016/j.ijrobp.2013.07.034 .
doi: 10.1016/j.ijrobp.2013.07.034
pubmed: 24054875
Meattini I, Livi L, Saieva C, Franceschini D, Marrazzo L, Greto D, et al. Prognostic factors and clinical features in patients with leptominengeal metastases from breast cancer: a single center experience. J Chemother. 2012;24:279–84. https://doi.org/10.1179/1973947812Y.0000000034 .
doi: 10.1179/1973947812Y.0000000034
pubmed: 23182047
Lekanidi K, Evans AL, Shah J, Jaspan T, Baker L, Evans AJ. Pattern of brain metastatic disease according to HER-2 and ER receptor status in breast cancer patients. Clin Radiol. 2013;68(10):1070–3. https://doi.org/10.1016/j.crad.2013.05.091 .
doi: 10.1016/j.crad.2013.05.091
pubmed: 23827085
Fouad H, Nucifora P, Masterova K, Melian E, NIMG-31. Breast cancer subtype as a determinant of the intracranial metastases locartion. Neuro-Oncol. 2018;20(Suppl 6):vi182. https://doi.org/10.1093/neuonc/noy148.757 .
doi: 10.1093/neuonc/noy148.757
pmcid: 6217374
Kyeong S, Cha YJ, Ahn SG, Suh SH, Son EJ, Ahn SJ. Subtypes of breast cancer show different spatial distributions of brain metastases. PLoS One. 2017;12(11):e0188542. https://doi.org/10.1371/journal.pone.0188542 .
doi: 10.1371/journal.pone.0188542
pubmed: 29155879
pmcid: 5695816
Liede A, Sebby W, Miriyala A.K.R. et al. Risk of seizures in a population of women with BRCA-positive metastatic breast cancer from an electronic health record database in the United States. BMC Cancer. 23, 78 (2023) https://doi.org/10.1186/s12885-023-10554-6 .
Ishizuka Y, Horimoto Y, Eguchi H, Murakami F, Nakai K, Onagi H, et al. BRCAness of brain lesions reflects a worse outcome for patients with metastatic breast cancer. Breast Cancer Res Treat. 2024;203(1):49–55. https://doi.org/10.1007/s10549-023-07115-7 .
doi: 10.1007/s10549-023-07115-7
pubmed: 37728693