Correlation of hexokinase-2 expression with overall survival and potential as a therapeutic target in the treatment of breast cancer brain metastases

Abstract BACKGROUND Breast cancer brain metastases (BCBM) commonly develop in human epidermal growth factor 2-positive (HER2+) breast cancer, but BCBM patients are underrepresented in clinical trials, leading to a lack of knowledge on the efficacy of HER2-targeted therapy in this population. METHODS We analyzed clinical characteristics and outcomes of HER2+BCBM patients from the National Cancer Database 2010–2016, comprising 70% of newly-diagnosed cancers in the U.S, to assess overall survival (OS) associated with HER2-targeted monoclonal antibody therapy (HER2-mab; i.e. trastuzumab, pertuzumab, and trastuzumab emtansine; encoded as of 2013). Survival was estimated with Kaplan-Meier techniques and compared with landmark analysis and Cox regression. The landmark timepoint was selected at which 75% of HER2-mab patients received HER2-mab, which was within 58 days of diagnosis. RESULTS 1,059 HER2+BCBM patients were identified, 717 (67.7%) patients were estrogen receptor negative (ER-) and 342 (32.3%) were ER+. Median follow-up was 12.0 months, at the end of which 73.8% of patients were deceased. Median OS was 12.2 and 22.1 months for ER- and ER+ patients, respectively. Following FDA approvals of pertuzumab (2012) and ado-trastuzumab emtansine (2013), HER2-mab usage for HER2+BCBM patients rose from 53.6% in 2013 to 71.7% in 2016. 420 BCBM patients had complete data for landmark analyses: 70.0% (n=294) received HER2-mab and 30.0% (n=126) did not, in which HER2-mab was associated with significantly improved OS in both ER- (median 22.2 months, 95%CI: 18.2-25.4; vs. 9.5 mos, 95%CI: 6.3-10.7; p=0.0001) and ER+ (median 25.7 months, 95%CI: 21.4-not reached; vs. 19.6 months, 95%CI: 11.1-35.2; p=0.02) patients. In multivariable Cox landmark analysis adjusted for ER status, age at diagnosis, extracranial disease, chemotherapy, radiotherapy, and metastasectomy; HER2-mab demonstrated significantly improved OS (hazard ratio 0.59 vs. no HER2-mab, 95%CI: 0.44-0.77; p< 0.001). CONCLUSIONS In this large national study, HER2-mab was associated with substantially improved overall survival in HER2+ BCBM patients.

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PO-0644: Overall survival following stereotactic radiosurgery (SRS) for breast cancer brain metastases

Radiotherapy and Oncology ◽

10.1016/s0167-8140(17)31081-2 ◽

2017 ◽

Vol 123 ◽

pp. S336-S337

Author(s):

H. Patel ◽

S. All ◽

A. Keller ◽

B. Dumas ◽

C. Sherrill ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Breast Cancer Brain Metastases

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74. EFFICACY OF HER2-TARGETED THERAPY IN HER2-POSITIVE BREAST CANCER BRAIN METASTASES: A NATIONAL ANALYSIS

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa073.061 ◽

2020 ◽

Vol 2 (Supplement_2) ◽

pp. ii15-ii16

Author(s):

Alexander Hulsbergen ◽

Marike Broekman ◽

Timothy Smith ◽

Bryan Iorgulescu

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Targeted Therapy ◽

Brain Metastases ◽

Cox Regression ◽

National Study ◽

Landmark Analysis ◽

Her2 Breast Cancer ◽

Breast Cancer Brain Metastases ◽

National Analysis

Abstract BACKGROUND Breast cancer brain metastases (BCBM) commonly develop in human epidermal growth factor 2-positive (HER2+) breast cancer, but BCBM patients are underrepresented in clinical trials, leading to a lack of knowledge on the efficacy of HER2-targeted therapy in this population. METHODS We analyzed clinical characteristics and outcomes of HER2+ BCBM patients from the National Cancer Database 2010–2016, comprising 70% of newly-diagnosed cancers in the U.S, to assess overall survival (OS) associated with HER2-targeted monoclonal antibody therapy (HER2-mab; i.e. trastuzumab, pertuzumab, and trastuzumab emtansine; encoded as of 2013). Survival was estimated with Kaplan-Meier techniques and compared with landmark analysis and Cox regression. The landmark timepoint was selected at which 75% of HER2-mab patients received HER2-mab, which was within 58 days of diagnosis. RESULTS 1,059 HER2+ BCBM patients were identified, 717 (67.7%) patients were estrogen receptor negative (ER-) and 342 (32.3%) were ER+. Median follow-up was 12.0 months, at the end of which 73.8% of patients were deceased. Median OS was 12.2 and 22.1 months for ER- and ER+ patients, respectively. HER2-mab usage for BCBM patients rose from 53.6% in 2013 to 71.7% in 2016. 420 BCBM patients had complete data for landmark analyses: 70.0% (n=294) received HER2-mab and 30.0% (n=126) did not, in which HER2-mab was associated with significantly improved OS in both ER- (median 22.2 months, 95%CI: 18.2–25.4; vs. 9.5 mos, 95%CI: 6.3–10.7; p=0.0001) and ER+ (median 25.7 months, 95%CI: 21.4-not reached; vs. 19.6 months, 95%CI: 11.1–35.2; p=0.02) patients. In multivariable Cox landmark analysis adjusted for ER status, age at diagnosis, extracranial disease, chemotherapy, radiotherapy, and metastasectomy; HER2-mab demonstrated significantly improved OS (hazard ratio 0.59 vs. no HER2-mab, 95%CI: 0.44–0.77; p<0.001). CONCLUSIONS In this large, national study, HER2-mab was associated with substantially improved overall survival in BCBM patients.

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Overall survival and the response to radiotherapy among molecular subtypes of breast cancer brain metastases treated with targeted therapies

Cancer ◽

10.1002/cncr.30616 ◽

2017 ◽

Vol 123 (12) ◽

pp. 2283-2293 ◽

Cited By ~ 21

Author(s):

Jacob A. Miller ◽

Rupesh Kotecha ◽

Manmeet S. Ahluwalia ◽

Alireza M. Mohammadi ◽

Samuel T. Chao ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Brain Metastases ◽

Targeted Therapies ◽

Molecular Subtypes ◽

Breast Cancer Brain Metastases

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Abstract 2864: RET as a novel therapeutic target in breast cancer brain metastases

10.1158/1538-7445.am2021-2864 ◽

2021 ◽

Author(s):

Simeng Liu ◽

Geoffrey Pecar ◽

Jagmohan Hooda ◽

Jennifer M. Atkinson ◽

Fangyuan Chen ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Therapeutic Target ◽

Breast Cancer Brain Metastases ◽

Novel Therapeutic

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Neural Stem Cell Delivery of Therapeutic Antibodies to Treat Breast Cancer Brain Metastases

10.21236/ada541313 ◽

2009 ◽

Author(s):

Brunhilde Felding-Habermann

Keyword(s):

Breast Cancer ◽

Stem Cell ◽

Brain Metastases ◽

Neural Stem Cell ◽

Cell Delivery ◽

Therapeutic Antibodies ◽

Stem Cell Delivery ◽

Breast Cancer Brain Metastases ◽

Treat Breast Cancer

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LINAC-based stereotactic radiosurgery/radiotherapy for brain metastases in patients with breast cancer

Journal of Radiotherapy in Practice ◽

10.1017/s1460396921000029 ◽

2021 ◽

pp. 1-9

Author(s):

Ankita Gupta ◽

Budhi Singh Yadav ◽

Nagarjun Ballari ◽

Namrata Das ◽

Ngangom Robert

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Brain Metastases ◽

Stereotactic Radiosurgery ◽

Progression Free Survival ◽

Rank Test ◽

Karnofsky Performance Score ◽

Breast Cancer Patients ◽

Free Survival ◽

Prior Surgery

Abstract Background: Brain metastases (BM) are common in patients with HER2-positive and triple-negative breast cancer. In this study we aim to report clinical outcomes with LINAC-based stereotactic radiosurgery/radiotherapy (SRS/SRT) for BM in patients of breast cancer. Methods: Clinical and dosimetric records of breast cancer patients treated for BM at our institute between May, 2015 and December, 2019 were retrospectively reviewed. Patients of previously treated or newly diagnosed breast cancer with at least a radiological diagnosis of BM; 1–4 in number, ≤3·5 cm in maximum dimension, with a Karnofsky Performance Score of ≥60 were taken up for treatment with SRS. SRT was generally considered if a tumour was >3·5 cm in diameter, near a critical or eloquent structure, or if the proximity of moderately sized tumours would lead to dose bridging in a single-fraction SRS plan. The median prescribed SRS dose was 15 Gy (range 7–24 Gy) and SRT dose was 27 Gy in 3 fractions. Clinical assessment and MR imaging was done at 6 weeks post-SRS and then every 3 months thereafter. Intracranial progression-free survival (PFS) and overall survival (OS) were calculated using Kaplan–Meier method and subgroups were compared using log rank test. Results: Total, 40 tumours were treated in 31 patients. The median tumour diameter was 2·3 cm (range 1·0–4·6 cm). SRS and SRT were delivered in 27 and 4 patients, respectively. SRS/SRT was given as a boost to whole brain radiotherapy (WBRT) in four patients and as salvage for progression after WBRT in six patients. In general, nine patients underwent prior surgery. The median follow-up was 7·9 months (0·2–34 months). Twenty (64·5%) patients developed local recurrence, 10 (32·3%) patients developed distant intracranial relapse and 7 patients had both local and distant intracranial relapse. The estimated local control at 6 months and 1 year was 48 and 35%, respectively. Median intracranial progression free survival (PFS) was 3·73 months (range 0·2–25 months). Median intracranial PFS was 3·02 months in patients who received SRS alone or as boost after WBRT, while it was 4·27 months in those who received SRS as salvage after WBRT (p = 0·793). No difference in intracranial PFS was observed with or without prior surgery (p = 0·410). Median overall survival (OS) was 21·7 months (range 0·2–34 months) for the entire cohort. Patients who received prior WBRT had a poor OS (13·31 months) as compared to SRS alone (21·4 months; p = 0·699). Conclusion: In patients with BM after breast cancer SRS alone, WBRT + SRS and surgery + SRS had comparable PFS and OS.

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