← Back to Search
Prognostic Significance Of Human Epidermal Growth Factor Receptor Positivity For The Development Of Brain Metastasis After Newly Diagnosed Breast Cancer.
Z. Gabos, R. Sinha, J. Hanson, N. Chauhan, J. Hugh, J. Mackey, B. Abdulkarim
Published 2006 · Medicine
Download PDFAnalyze on Scholarcy
PURPOSE As survival in breast cancer patients is improving, brain metastases are becoming increasingly prevalent. The risk of brain metastases in newly diagnosed human epidermal growth factor receptor 2 (HER-2) -overexpressing breast cancer patients is not yet fully defined. We aimed to analyze the risk of brain metastasis in newly diagnosed HER-2-positive breast cancer patients in comparison with HER-2-negative patients. PATIENTS AND METHODS To determine the incidence of brain metastases in HER-2-overexpressing patients, we analyzed a cohort of newly diagnosed 301 HER-2-positive and 363 HER-2-negative patients identified between January 1998 and December 2003. The association between histologic features and the occurrence of brain metastases was evaluated with univariate and multivariate Cox regression analysis. RESULTS Median follow-up was 3.9 years. Brain metastases were identified in 9% (27 patients) with HER-2-overexpressing breast cancer compared with only 1.9% (7 patients) in the HER-2 negative patients (hazard ratio 4.23 [1.84-9.74], P = .0007). HER-2 overexpression, tumor size larger than 2 cm, at least one positive node, and grade 2/3 disease were predictors of brain metastases in univariate analysis. In multivariate analysis, HER-2 overexpression, tumor size larger than 2 cm, and hormone-receptor negativity were independent prognostic factors for the development of brain metastases, whereas hormone-receptor expression was protective. CONCLUSION Our study shows that newly diagnosed HER-2-overexpressing breast cancer patients are at increased risk for brain metastases. Because most brain metastases occur after the development of systemic disease, these findings prompt consideration of brain prophylaxis strategies with HER-2-inhibiting small molecules able to cross the blood-brain barrier and/or radiologic screening to detect asymptomatic brain metastases.
This paper references
Clinical practice guidelines for the care and treatment of breast cancer: 16. Locoregional post-mastectomy radiotherapy
P. Truong (2004)
Survival of patients with metastatic breast carcinoma
J. Chang (2003)
Involvement of chemokine receptors in breast cancer metastasis
A. Müller (2001)
The natural history of breast cancer patients with brain metastases
A. Distefano (1979)
Structure of the extracellular region of HER2 alone and in complex with the Herceptin Fab
Hyun-Soo Cho (2003)
Risk factors for brain relapse in patients with metastatic breast cancer.
K. Slimane (2004)
Brain metastases in breast cancer; natural history, prognostic factors and outcome
W. Boogerd (2005)
Consensus conference on second opinions in diagnostic anatomic pathology. Who, What, and When.
J. Tomaszewski (2000)
The role of CXCR4 receptor expression in breast cancer: a large tissue microarray study
O. Salvucci (2005)
Clinical practice guidelines for the care and treatment of breast cancer: adjuvant systemic therapy for node-negative breast cancer (summary of the 2001 update).
M. Levine (2001)
Determinants and prognoses of locoregional and distant progression in breast cancer.
J. Engel (2003)
Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer.
E. H. Romond (2005)
neu/erbB-2 amplification identifies a poor-prognosis group of women with node-negative breast cancer. Toronto Breast Cancer Study Group.
I. Andrulis (1998)
HER-2/neu oncogene protein and prognosis in breast cancer.
A. K. Tandon (1989)
Adjuvant docetaxel for node-positive breast cancer.
M. Martín (2005)
Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer
A. Clayton (2004)
Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer.
M. Piccart-Gebhart (2005)
Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer.
D. Slamon (1989)
Upregulation of CXCR4 is essential for HER2-mediated tumor metastasis.
Y. Li (2004)
ErbB‐2 is a common auxiliary subunit of NDF and EGF receptors: implications for breast cancer.
D. Karunagaran (1996)
CXCL-12/stromal cell-derived factor-1alpha transactivates HER2-neu in breast cancer cells by a novel pathway involving Src kinase activation.
N. Cabioğlu (2005)
Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.
D. Slamon (1987)
Association of C‐erbB‐2 protein over‐expression with high rate of cell proliferation, increased risk of visceral metastasis and poor long‐term survival in breast cancer
O. Kallioniemi (1991)
CNS metastases in breast cancer.
N. Lin (2004)
Occult central nervous system involvement in patients with metastatic breast cancer: prevalence, predictive factors and impact on overall survival.
K. Miller (2003)
Involvement of the chemokine receptor CXCR4 and its ligand stromal cell-derived factor 1alpha in breast cancer cell migration through human brain microvascular endothelial cells.
Byeong-Chel Lee (2004)
Do we need HER‐2/neu testing for all patients with primary breast carcinoma?
S. Taucher (2003)
The ErbB-2/HER2 oncoprotein of human carcinomas may function solely as a shared coreceptor for multiple stroma-derived growth factors.
L. Klapper (1999)
MCF-7 breast cancer cells overexpressing transfectedc-erbB-2 have anin vitro growth advantage in estrogen-depleted conditions and reduced estrogen-dependence and tamoxifen-sensitivityin vivo
Y. Liu (2004)
Randomized phase II trial of the efficacy and safety of trastuzumab combined with docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer administered as first-line treatment: the M77001 study group.
M. Marty (2005)
HER-2 tyrosine kinase pathway targets estrogen receptor and promotes hormone-independent growth in human breast cancer cells.
R. Pietras (1995)
Clinical practice guidelines for the care and treatment of breast cancer: breast radiotherapy after breast-conserving surgery (summary of the 2003 update).
T. Whelan (2003)
High incidence of central nervous system involvement in patients with metastatic or locally advanced breast cancer treated with epirubicin and docetaxel.
D. Crivellari (2001)
Amplification of a novel v-erbB-related gene in a human mammary carcinoma.
C. R. King (1985)
Central nervous system metastases in women who receive trastuzumab‐based therapy for metastatic breast carcinoma
J. Bendell (2003)
Estrogen-dependent, tamoxifen-resistant tumorigenic growth of MCF-7 cells transfected with HER2/neu
C. Benz (2005)
Recursive partitioning analysis (RPA) of prognostic factors in three Radiation Therapy Oncology Group (RTOG) brain metastases trials.
L. Gaspar (1997)
Clinical practice guidelines for the care and treatment of breast cancer: 15. Treatment for women with stage III or locally advanced breast cancer
T. Shenkier (2004)
This paper is referenced by
Human epidermal growth factor receptor 2-positive breast cancer and central nervous system metastases.
B. Leyland-Jones (2009)
The effect of early detection of occult brain metastases in HER2-positive breast cancer patients on survival and cause of death.
A. Niwińska (2010)
Structure-based Design of Peptides with High Affinity and Specificity to HER2 Positive Tumors
Lingling Geng (2015)
Anticancer therapies and CNS relapse: overcoming blood–brain and blood–cerebrospinal fluid barrier impermeability
M. Chamberlain (2010)
Peptide-based B-cell epitope vaccines targeting HER-2/neu
Joan T. Garrett (2007)
Gamma Knife Radiosurgery for Breast Cancer Metastases to the Brain: Outcomes and Prognostic Factors from a Large Prospectively Collected Database
A. Wolf (2012)
Immunohistochemical profiles of brain metastases from breast cancer
K. Yonemori (2008)
When Standard Therapy Fails in Breast Cancer: Current and Future Options for HER2-Positive Disease
Erin E. Olson (2013)
Brain Metastasis of Patients with Lung Adenocarcinoma: Epidermal Growth Factor Receptor Mutations and Response to Whole-Brain Radiation Therapy
Shang-Gin Wu (2014)
Time to tackle the blood‐brain barrier in HER2‐mutant lung cancer
J. Lin (2019)
Relationship between HER-2 overexpression and brain metastasis in esophageal cancer patients.
T. Abu Hejleh (2012)
Time for more optimism in metastatic breast cancer?
E. Senkus (2014)
Malignant gliomas: current perspectives in diagnosis, treatment, and early response assessment using advanced quantitative imaging methods
R. Ahmed (2014)
Trastuzumab Emtansine: A Unique Antibody-Drug Conjugate in Development for Human Epidermal Growth Factor Receptor 2–Positive Cancer
P. LoRusso (2011)
Apparent diffusion coefficient histogram in breast cancer brain metastases may predict their biological subtype and progression
Sung Jun Ahn (2018)
Pathology of Breast Cancer: from Classic Concepts to Molecular Pathology and Pathogenesis
Ilze Štrumfa (2012)
CNS metastases in breast cancer patients: prognostic implications of tumor subtype
C. Bachmann (2014)
Predominance of the basal type and HER-2/neu type in brain metastasis from breast cancer
M. Melisko (2008)
Biological subtypes of breast cancer: Prognostic and therapeutic implications.
O. Yersal (2014)
Breast Cancers in Young Women : A Retrospective Study at King Hussein Medical Center
Luma Fayyad (2015)
Breast cancer brain metastases
X. Cheng (2007)
Chemotherapy and biological treatment options in breast cancer patients with brain metastasis: an update
C. Arslan (2014)
Metastases to the central nervous system: Molecular basis and clinical considerations
Pitchaya Wanleenuwat (2020)
Prognostic factors for patients with newly diagnosed brain metastasis from breast cancer.
C. Castaneda (2015)
Research progress in the use of drugs for breast cancer targeted therapy
Shun’e Yang (2008)
Profile of Patients with Breast Cancer Brain Metastasis in Abidjan
Kouamé Konan Yvon Kouassi (2018)
Brain metastasis in patients with metastatic breast cancer in the real world: a single-institution, retrospective review of 12-year follow-up
S. Matsuo (2017)
Brain metastases in HER2-positive breast cancer: challenges and opportunities.
Davis Yuri Torrejon (2012)
Ado-trastuzamab emtansine associated hyponatremia and intracranial hemorrhage
A. Kolarich (2014)
Occurrence and outcome of de novo metastatic breast cancer by subtype in a large, diverse population
Li Tao (2016)
Human Epidermal Growth Factor Receptor 2 ( HER 2 ) in Cancers : Overexpression and Therapeutic Implications
N. Iqbal (2015)
Multifactorial Central Nervous System Recurrence Susceptibility in Patients With HER 2-Positive Breast Cancer Epidemiological and Clinical Data From a Population-Based Cancer Registry Study
Antonino Musolino (2011)See more