Characteristics of patients with prolonged survival after breast cancer brain metastases (BCBM).

e20659 Background: BCBM development predicts short survival for majority of pts. However, 10%, of pts survive up to 2 yrs, and some of those pts has extended survival to more than 2 yrs after BM. Whether there are differences between pts in those arbitrary determined subgroups with prolonged survival is still unknown. The aim of this paper is to analyze and compare characteristics of BCBM pts with survival after BM (BMs) between ≥ 12 - 24 months and ≥ 25 month. Methods: A 193 consecutive BCBM pts have been registered during 5 yrs (January 2008-December 2012). All BM were confirmed by CT/MRI. All pts underwent BM treatment: WBRT 160 (83%); postoperative WBRT in 32 pts (17 %); gamma knife in 7 pts (3,6 %). BMs is known for 169 pts and was median 5,5 months (range 1-72+ months). Only pts with BMs ≥ 12 months were considered for this analysis. Results: 39/169 pts (23%) with median BMs 19 months (range 12-72+) were identified and divided in 2 groups (see Table). MBC in other organ sites, predominantly non visceral, was present in 45% pts (A) and in 40% (B), at the time of BM diagnose. There was no statistically significant difference between group A and B. Conclusions: Despite BM, a subgroup of pts still has indolent MBC course with median BMs of 19 months, and 6% has BMs of median 35 months. There were no statistically significant difference between standard clinical/pathological parameters Therefore, other characteristics, both patients and BC/BM must be considered. Better understanding of crucial characteristics of this subgroup of BCBM pts, is needed because these pts might potentially represents the best candidates for future BM preventive strategies. [Table: see text]

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Immune microenvironment profiling of breast cancer brain metastases using multiplex immunofluorescence.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.2526 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 2526-2526

Author(s):

Gaia Griguolo ◽

Anna Tosi ◽

Valentina Guarneri ◽

Maria Vittoria Dieci ◽

Susan Fineberg ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Spatial Information ◽

Immune Cell ◽

Total Sample ◽

Clinical Variable ◽

Immune Microenvironment ◽

Significant Difference ◽

Tumor Recognition ◽

Breast Cancer Brain Metastases

2526 Background: Despite clinical implications, the complexity of brain metastases (BM) immune microenvironment in breast cancer (BC) patients is poorly understood. Multiplex immunofluorescence (mIF), a novel imaging technique allowing simultaneous visualization and quantification of several IF labeled proteins while maintaining spatial information, holds promise to comprehensively describe BCBM immune microenvironment, potentially providing valuable information to improve treatment. Methods: Clinical data and archival BM samples were collected for 60 BC patients undergoing neurosurgery (2003-2018) at three institutions. BM immune contexture was characterized using a custom mIF panel, including cell subtyping (CD4, CD8, FOXP3, CD68), activation (Granzyme B) and localization (keratin for tumor recognition) markers. Mean immune cell density (cells/mm2) for each sample was determined by digital image analysis and classified in tumor and stroma areas. Associations between immune subpopulations, BC subtype and overall survival from BM diagnosis (OS) were studied. Results: Up to date, 30 BCBM samples have been analyzed; 33% HR+/HER2-, 20% HR-/HER2+, 10% HR+/HER2+, 37% HR-/HER2-. At a median follow-up of 46 months, BC subtype was the only clinical variable associated with OS (longest for HER2+ and shortest for HR-/HER2-, log-rank p = 0.002). In the total sample area, no significant difference in immune cell densities was observed according to BC subtype. In the tumor area, HR+/HER2- tumors showed higher densities of CD8+ and CD68+ cells compared to other subtypes (p = 0.036 and p = 0.016, respectively). In stroma, HR-/HER2- tumors presented numerically higher densities of CD4+ and FOXP3+ cells and higher ratio of CD4/CD8 and FOXP3/CD8 ratio (not statistically significant). Higher CD4/CD8 and FOXP3/CD8 ratio in the stroma was significantly associated with worse OS, even after correction by BC subtype (Table). Conclusions: In BCBM, immune infiltrate differs according to BC subtype. Preliminary results suggest that a more tolerogenic immune microenvironment is associated with worse OS and might represent a target for optimization of immunotherapy for these patients. Updated results for all 60 patients will be presented. [Table: see text]

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Genomic profiling of breast cancer brain metastases reveals targetable alterations.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.2525 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. 2525-2525

Author(s):

Sheheryar Kairas Kabraji ◽

Liam F. Spurr ◽

Melissa E Hughes ◽

Yvonne Y. Li ◽

Jose Pablo Leone ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Copy Number ◽

Enrichment Analysis ◽

Fisher Exact Test ◽

Copy Number Alterations ◽

Genomic Alterations ◽

Primary Tumors ◽

Significant Difference ◽

Breast Cancer Brain Metastases

2525 Background: Genomic characterization of breast cancer brain metastases (BCBMs) has thus far been limited. The objective of this study was to describe the landscape of genomic alterations in patients (pts) with BCBMs. Methods: Targeted next-generation DNA sequencing of > 300 cancer-related genes (OncoPanel) was prospectively performed on primary and metastatic (met) tumors in 321 pts with a diagnosis of BCBM between August 2016 and April 2019 at Dana-Farber Cancer Institute (table). Enrichment analysis of genomic alterations was performed using a two-sided Fisher exact test and differences in tumor mutation burden (TMB) between groups were assessed using two-sided Mann-Whitney U test. Multiple comparison correction was performed using the Benjamini-Hochberg procedure. Results: All subtypes were represented in BCBM (25 HR+/HER2-; 24 HR+/HER2+; 27 HR-/HER2+; 18 TNBC; 5 unknown; n = 99) and extracranial (EC) samples: (96 HR+/HER2-; 32 HR+/HER2+; 22 HR-/HER2+; 41 TNBC; 31 unknown; n = 222). BCBMs were found most commonly to have mutations or copy number alterations in TP53, ERBB2, PIK3CA, GATA3, PTEN, ESR1, CDH1, BRCA2, ARID1A, BRCA1 (>5% frequency, table). Two pts acquired ERBB2 amplification (amp) between the matched primary breast sample and brain met. In pair-wise comparisons of BCBMs to unmatched primaries or EC mets, only ERBB2 amp was significantly enriched (table, † = adjusted p < 0.05). There was no significant difference in TMB between BCBM and EC mets (median 9.12 vs 7.26, p = 0.15). In contrast, TMB was significantly higher in BCBMs compared to unmatched primaries (median 9.12 vs 7.26, p=0.005). Conclusions: BCBMs display similar mutations and copy number alterations compared to primary tumors and EC mets in pts with BCBM. These data suggest that BCBMs contain actionable genomic alterations that are most often also reflected in EC disease. Alterations in ERBB2, PIK3CA/PTEN, and BRCA1/2 represent potentially targetable alterations in pts with BCBM. [Table: see text]

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PO79 PROLONGED SURVIVAL AFTER BREAST CANCER BRAIN METASTASES (BCBM): WHO HAS A CHANCE?

The Breast ◽

10.1016/s0960-9776(13)70092-4 ◽

2013 ◽

Vol 22 ◽

pp. S46-S47

Author(s):

Zorica Tomasevic ◽

Zeljko Kovac ◽

Zoran Tomasevic ◽

Zorka Milovanovic

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Prolonged Survival ◽

Breast Cancer Brain Metastases

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Impact of Histological Subtype on the Outcome of Breast Cancer Brain Metastases Patients Treated With Gamma-knife Radiosurgery

International Journal of Radiation Oncology*Biology*Physics ◽

10.1016/j.ijrobp.2012.07.590 ◽

2012 ◽

Vol 84 (3) ◽

pp. S227

Author(s):

M.E. Hardee ◽

H. Hsu ◽

E.C. Parker ◽

A. Narayana ◽

J.G. Golfinos ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Gamma Knife ◽

Gamma Knife Radiosurgery ◽

Histological Subtype ◽

Breast Cancer Brain Metastases

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Her2-enriched breast cancer brain metastases exhibit resistance to Gamma Knife radiosurgery: findings from a single institutional series review

Journal of Radiation Oncology ◽

10.1007/s13566-012-0026-y ◽

2012 ◽

Vol 1 (3) ◽

pp. 283-290 ◽

Cited By ~ 1

Author(s):

Jeffrey D. Radawski ◽

Dongqing Zhang ◽

Alex Nelson ◽

John C. Grecula ◽

Nina A. Mayr ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Gamma Knife ◽

Gamma Knife Radiosurgery ◽

Breast Cancer Brain Metastases

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Gamma Knife surgery as sole treatment for multiple brain metastases: 2-center retrospective review of 1508 cases meeting the inclusion criteria of the JLGK0901 multi-institutional prospective study

Journal of Neurosurgery ◽

10.3171/2010.8.gks10838 ◽

2010 ◽

Vol 113 (Special_Supplement) ◽

pp. 48-52 ◽

Cited By ~ 37

Author(s):

Toru Serizawa ◽

Masaaki Yamamoto ◽

Yasunori Sato ◽

Yoshinori Higuchi ◽

Osamu Nagano ◽

...

Keyword(s):

Brain Metastases ◽

Gamma Knife ◽

Class Ii ◽

Hazard Ratio ◽

Gamma Knife Surgery ◽

Inclusion Criteria ◽

Primary Tumors ◽

Poor Prognostic Factor ◽

Group A ◽

Group B

Object The authors retrospectively reviewed the results of Gamma Knife surgery (GKS) used as the sole treatment for brain metastases in patients who met the eligibility criteria for the ongoing JLGK0901 multi-institutional prospective trial. They also discuss the anticipated results of the JLGK0901 study. Methods Data from 1508 consecutive cases were analyzed. All of the patients were treated at the Gamma Knife House of Chiba Cardiovascular Center or the Mito Gamma House of Katsuta Hospital between 1998 and 2007 and met the following JLGK0901 inclusion criteria: 1) newly diagnosed brain metastases, 2) 1–10 brain lesions, 3) less than 10 cm3 volume of the largest tumor, 4) no more than 15 cm3 total tumor volume, 5) no findings of CSF dissemination, and 6) no impairment of activities of daily living (Karnofsky Performance Scale score < 70) due to extracranial disease. At the initial treatment, all visible lesions were irradiated with GKS without upfront whole-brain radiation therapy. Thereafter, gadolinium-enhanced MR imaging was performed every 2–3 months, and new distant lesions were appropriately retreated with GKS. Patients were divided into groups according to numbers of tumors: Group A, single lesions (565 cases); Group B, 2–4 tumors (577 cases); and Group C, 5–10 tumors (366 cases). The differences in overall survival (OS) were compared between groups. Results The median age of the patients was 66 years (range 19–96 years). There were 963 men and 545 women. The primary tumors were in the lung in 1114 patients, gastrointestinal tract in 179, breast in 105, urinary tract in 66, and other sites in 44. The overall mean survival time was 0.78 years (0.99 years for Group A, 0.68 years for Group B, and 0.62 years for Group C). The differences between Groups A and B (p < 0.0001) and between Groups B and C (p = 0.0312) were statistically significant. Multivariate analysis revealed significant prognostic factors for OS to be sex (poor prognostic factor: male, p < 0.0001), recursive partitioning analysis class (Class I vs Class II and Class II vs III, both p < 0.0001), primary site (lung vs breast, p = 0.0047), and number of tumors (Group A vs Group B, p < 0.0001). However, no statistically difference was detected between Groups B and C (p = 0.1027, hazard ratio 1.124, 95% CI 0.999–1.265). Conclusions The results of this retrospective analysis revealed an upper CI of 1.265 for the hazard ratio, which was lower than the 1.3 initially set by the JLGK0901 study. The JLGK0901 study is anticipated to show noninferiority of GKS as sole treatment for patients with 5–10 brain metastases compared with those with 2–4 in terms of OS.

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Prolonged survival in a subgroup of patients with brain metastases treated by gamma knife surgery

Journal of Neurosurgery ◽

10.3171/sup.2005.102.s_supplement.0262 ◽

2005 ◽

Vol 102 (Special_Supplement) ◽

pp. 262-265

Author(s):

C. P. Yu ◽

Joel Y. C. Cheung ◽

Josie F. K. Chan ◽

Samuel C. L. Leung ◽

Robert T. K. Ho

Keyword(s):

Brain Metastases ◽

Gamma Knife ◽

Patient Survival ◽

Gamma Knife Surgery ◽

Prolonged Survival ◽

Organ Involvement ◽

Lesion Volume ◽

Content Type ◽

The Mean ◽

Fine Print

Object. The authors analyzed the factors involved in determining prolonged survival (≥ 24 months) in patients with brain metastases treated by gamma knife surgery (GKS). Methods. Between 1995 and 2003, a total of 116 patients underwent 167 GKS procedures for brain metastases. There was no special case selection. Smaller and larger lesions were treated with different protocols. The mean patient age was 56.9 years, the mean number of initial lesions was 3.15, and the mean lesion volume was 10.45 cm.3 The mean follow-up time was 9.2 months. The median patient survival was 8.68 months. One-, 2-, 3-, 4-, and 5-year actuarial survival rates were 31.8%, 19.8%, 14.6%, 7.7%, and 6.9%, respectively. Patient age, number of lesions at presentation, and lesion volume had no influence on patient survival. Twenty-three (19.8%) patients survived for 24 months or more. Certain factors were associated with increased survival time. These were stable primary disease (21 of 23 patients), a long latency between diagnosis of the primary tumor and the occurrence of brain metastases (mean 28.4 months, median 16 months), absence of third-organ involvement, and repeated local procedures. Ten patients underwent repeated GKS (mean 3.4 per patient). Seven patients required open surgery for local treatment failures (recurrence or radiation necrosis). Two patients had both. Fifteen patients underwent repeated procedures. Conclusions. Aggressive local therapy with GKS, repeated GKS, and GKS plus surgery can achieve increased survival in a subgroup of patients with stable primary disease, no third-organ involvement, and long primary-brain secondary intervals.

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