Online citations, reference lists, and bibliographies.
← Back to Search

Human Epidermal Growth Factor Receptor 2-positive Breast Cancer And Central Nervous System Metastases.

B. Leyland-Jones
Published 2009 · Medicine

Cite This
Download PDF
Analyze on Scholarcy
Share
PURPOSE To determine the incidence, outcomes, and current strategies for management of brain metastases in patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer. METHODS A literature review was performed to obtain data on central nervous system metastases in patients with breast cancer. RESULTS HER2 amplification/overexpression is a prognostic and predictive factor for the development of CNS metastases. Autopsy data show that the incidence rate for CNS metastases in patients with breast cancer is approximately 30%; this may be higher (ie, 30% to 50%) in patients with HER2-positive disease. Treatment with trastuzumab is not associated with an increased incidence of CNS metastases. Data from three phase III adjuvant trials showed the incidence was similar between patients who received trastuzumab and those who did not. Furthermore, trastuzumab can significantly improve overall survival in HER2-positive patients who already have CNS metastases compared with patients who do not receive trastuzumab or those who have HER2-negative brain metastases. This survival advantage is conferred via systemic control of the disease. The current standard of care for patients with CNS metastases is whole-brain radiotherapy (WBRT), with or without surgery, or stereotactic radiosurgery. In the future, novel therapies or combinations of therapies may additionally improve survival in these patients. CONCLUSION The incidence of CNS metastases in trastuzumab-treated patients is similar to that in all patients with HER2-positive disease. Trastuzumab can improve survival in patients with HER2-positive disease with CNS metastases.
This paper references
10.1007/978-1-4615-1589-0_3
Staging and prognosis in lung cancer: making the complex accessible.
C. Langer (2001)
10.1002/cncr.20813
Increased risk of brain metastases in patients with HER‐2/neu‐positive breast carcinoma
R. Altaha (2005)
10.1200/JCO.1990.8.1.103
Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: prognostic significance of erbB-2 protein overexpression in primary breast cancer.
S. Paik (1990)
10.1002/1097-0142(19831215)52:12<2349::AID-CNCR2820521231>3.0.CO;2-B
Central nervous system metastasis from breast carcinoma autopsy study
Y. Tsukada (1983)
10.1002/cncr.23468
Survival in patients with brain metastases from breast cancer
A. Eichler (2008)
10.1016/S1526-8209(11)70419-0
Use of intrathecal trastuzumab in a patient with carcinomatous meningitis.
L. Laufman (2001)
10.1038/sj.bjc.6601970
Incidence of cerebral metastases in patients treated with trastuzumab for metastatic breast cancer
A. Clayton (2004)
10.3816/CBC.2004.N.011
HER2 amplification ratios by fluorescence in situ hybridization and correlation with immunohistochemistry in a cohort of 6556 breast cancer tissues.
M. A. Owens (2004)
10.1002/cncr.20530
Central nervous system metastases in patients with high‐risk breast carcinoma after multimodality treatment
A. González-Angulo (2004)
10.1212/WNL.54.10.1886
Practice parameter: Anticonvulsant prophylaxis in patients with newly diagnosed brain tumors
M. Glantz (2000)
10.1016/J.CRITREVONC.2006.06.012
Therapeutic management of metastatic brain tumors.
G. M. Richards (2007)
10.1200/JCO.2006.07.0250
Prognostic significance of human epidermal growth factor receptor positivity for the development of brain metastasis after newly diagnosed breast cancer.
Z. Gabos (2006)
10.1200/JCO.1998.16.2.462
Prognostic and predictive value of c-erbB-2 overexpression in primary breast cancer, alone and in combination with other prognostic markers.
S. Sjögren (1998)
10.1093/ANNONC/MDG300
Occult central nervous system involvement in patients with metastatic breast cancer: prevalence, predictive factors and impact on overall survival.
K. Miller (2003)
10.1043/1543-2165(2003)127<1451:NSIBCM>2.0.CO;2
Her-2/neu status in breast cancer metastases to the central nervous system.
Kelly C. Lear-Kaul (2003)
10.1097/00000421-199706000-00020
Activity of combination chemotherapy in brain metastases from breast and lung adenocarcinoma.
M. Colleoni (1997)
10.1186/bcr1516
Central nervous system relapse in patients with breast cancer is associated with advanced stages, with the presence of circulating occult tumor cells and with the HER2/neu status
J. Souglakos (2006)
10.1093/annonc/mdn539
Trastuzumab treatment beyond brain progression in HER2-positive metastatic breast cancer.
I. Park (2009)
10.1007/s10549-004-0999-3
Central nervous system metastases in women after multimodality therapy for high risk breast cancer
L. Carey (2004)
10.1002/(SICI)1097-0142(19990401)85:7<1599::AID-CNCR23>3.0.CO;2-#
Front‐line chemotherapy with cisplatin and etoposide for patients with brain metastases from breast carcinoma, nonsmall cell lung carcinoma, or malignant melanoma
V. Franciosi (1999)
10.1093/ANNONC/MDL064
Identifying breast cancer patients at risk for Central Nervous System (CNS) metastases in trials of the International Breast Cancer Study Group (IBCSG).
B. Pestalozzi (2006)
10.1002/IJC.2910490504
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)
10.1200/JCO.2004.12.149
Incidence proportions of brain metastases in patients diagnosed (1973 to 2001) in the Metropolitan Detroit Cancer Surveillance System.
J. Barnholtz-Sloan (2004)
10.1007/s10549-007-9663-z
Cardiotoxicity and incidence of brain metastases after adjuvant trastuzumab for early breast cancer: the dark side of the moon? A meta-analysis of the randomized trials
E. Bria (2007)
10.1073/PNAS.0604318103
Noninvasive localized delivery of Herceptin to the mouse brain by MRI-guided focused ultrasound-induced blood-brain barrier disruption.
M. Kinoshita (2006)
10.1002/cncr.10541
Incidence of brain metastases in a cohort of patients with carcinoma of the breast, colon, kidney, and lung and melanoma
L. Schouten (2002)
Efficacy of intracerebral microinfusion of trastuzumab in an athymic rat model of intracerebral metastatic breast cancer.
Peter M. Grossi (2003)
10.1016/S1470-2045(06)70864-6
Meningeal carcinomatosis from breast cancer treated with intrathecal trastuzumab.
C. Platini (2006)
10.1056/NEJMOA052122
Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer.
E. H. Romond (2005)
10.1097/COC.0b013e3180653c0d
Improved Survival, Quality of Life, and Quality-Adjusted Survival in Breast Cancer Patients Treated With Efaproxiral (Efaproxyn) Plus Whole-Brain Radiation Therapy for Brain Metastases
C. Scott (2007)
10.1007/s11060-007-9420-5
Trastuzumab prolongs overall survival in patients with brain metastases from Her2 positive breast cancer
R. Bartsch (2007)
10.1358/DNP.2003.16.4.829334
Immuno-viral therapy as a new approach for the treatment of brain tumors.
M. Toda (2003)
10.3816/CBC.2003.N.016
Increased rate of brain metastasis with trastuzumab therapy not associated with impaired survival.
E. Lower (2003)
10.1200/JCO.2008.26.15_SUPPL.2032
Multicenter phase II study of temozolomide therapy for brain metastases in patients with malignant melanoma, breast cancer, or non-small cell lung cancer: Final results
Marco Danova (2008)
10.1007/s11060-005-9044-6
Systemic high-dose intravenous methotrexate for central nervous system metastases
A. Lassman (2005)
10.1002/cncr.20418
The risk of central nervous system metastases after trastuzumab therapy in patients with breast carcinoma
R. Lai (2004)
10.1002/cncr.23859
Phase 2 trial of temozolomide using protracted low‐dose and whole‐brain radiotherapy for nonsmall cell lung cancer and breast cancer patients with brain metastases
R. Addeo (2008)
10.1200/JCO.2006.10.4976
Congestive heart failure in older women treated with adjuvant anthracycline chemotherapy for breast cancer.
M. Pinder (2007)
10.1159/000102557
Phase II Study of Temozolomide and Concomitant Whole-Brain Radiotherapy in Patients with Brain Metastases from Solid Tumors
J. Kouvaris (2007)
10.1111/j.1468-1331.2006.01506.x
EFNS Guidelines on diagnosis and treatment of brain metastases: report of an EFNS Task Force
R. Soffietti (2006)
10.1093/annonc/mdn036
Defining prognosis for women with breast cancer and CNS metastases by HER2 status.
S. Dawood (2008)
10.1200/JCO.2007.12.3588
Phase II trial of lapatinib for brain metastases in patients with human epidermal growth factor receptor 2-positive breast cancer.
N. Lin (2008)
10.1200/JCO.2005.04.6474
Flare in neuropathy following rituximab therapy for Waldenstrom's macroglobulinemia.
V. Noronha (2006)
10.1016/J.BREAST.2005.04.017
Characteristics of patients with brain metastases receiving trastuzumab for HER2 overexpressing metastatic breast cancer.
H. Stemmler (2006)
10.1002/cncr.22127
Phase I study of capecitabine in combination with temozolomide in the treatment of patients with brain metastases from breast carcinoma
E. Rivera (2006)
10.1097/01.CAD.0000236313.50833.EE
Ratio of trastuzumab levels in serum and cerebrospinal fluid is altered in HER2-positive breast cancer patients with brain metastases and impairment of blood–brain barrier
H. Stemmler (2007)
10.1002/cncr.11436
Central nervous system metastases in women who receive trastuzumab‐based therapy for metastatic breast carcinoma
J. Bendell (2003)
10.1002/1097-0142(19860815)58:4<832::AID-CNCR2820580404>3.0.CO;2-W
Chemotherapy induces regression of brain metastases in breast carcinoma
D. Rosner (1986)
10.1126/SCIENCE.2470152
Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer.
D. Slamon (1989)
10.1080/02841860500486630
Incidence, pattern and timing of brain metastases among patients with advanced breast cancer treated with trastuzumab
T. Yau (2006)
10.1124/dmd.107.018374
The Role of Efflux and Uptake Transporters in N-{3-Chloro-4-[(3-fluorobenzyl)oxy]phenyl}-6-[5-({[2-(methylsulfonyl)ethyl]amino}methyl)-2-furyl]-4-quinazolinamine (GW572016, Lapatinib) Disposition and Drug Interactions
J. Polli (2008)
10.1016/S0140-6736(07)60028-2
2-year follow-up of trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer: a randomised controlled trial
I. Smith (2007)
10.1634/THEONCOLOGIST.12-7-884
Multidisciplinary management of brain metastases.
A. Eichler (2007)
10.1007/s11060-008-9578-5
Brain metastases in breast cancer: clinical and pathologic characteristics associated with improvements in survival
M. Melisko (2008)
10.1016/J.IJROBP.2008.06.880
Results of the Phase III ENRICH (RT-016) Study of Efaproxiral Administered Concurrent with Whole Brain Radiation Therapy (WBRT) in Women with Brain Metastases from Breast Cancer
J. Suh (2008)
10.1002/1097-0142(19920215)69:4<972::AID-CNCR2820690423>3.0.CO;2-P
Response of brain metastases from breast cancer to systemic chemotherapy
W. Boogerd (1992)
10.1159/000055088
Topotecan Chemotherapy in Patients with Breast Cancer and Brain Metastases: Results of a Pilot Study
C. Oberhoff (2001)
10.3747/CO.2007.129
Management of single brain metastasis: a practice guideline
A. Mintz (2007)
10.1126/SCIENCE.3798106
Human breast cancer: correlation of relapse and survival with amplification of the HER-2/neu oncogene.
D. Slamon (1987)
10.1016/S0305-7372(03)00105-1
The management of brain metastases.
R. Patchell (2003)
10.1016/S0960-9776(07)70091-7
P26 HER-2 overexpressed breast cancer and brain metastases
M. Lichinitse (2007)
10.1007/s10549-007-9885-0
A phase III randomized comparison of lapatinib plus capecitabine versus capecitabine alone in women with advanced breast cancer that has progressed on trastuzumab: updated efficacy and biomarker analyses
D. Cameron (2007)
10.1016/J.EJCA.2003.09.018
Central nervous system progression among patients with metastatic breast cancer responding to trastuzumab treatment.
E. Shmueli (2004)
10.1007/s11060-007-9409-0
Capecitabine Therapy of Central Nervous System Metastases from Breast Cancer
M. Ekenel (2007)
10.1097/COC.0b013e31815a43c4
Extended Survival in Women With Brain Metastases From HER2 Overexpressing Breast Cancer
D. Church (2008)



This paper is referenced by
10.18632/oncotarget.25041
Genetic heterogeneity and actionable mutations in HER2-positive primary breast cancers and their brain metastases
L. De Mattos-Arruda (2018)
10.1007/978-3-319-22536-4_14
Bubble-Assisted Ultrasound: Application in Immunotherapy and Vaccination.
Jean-Michel Escoffre (2016)
10.1016/j.clbc.2011.03.012
Human epidermal growth factor receptor 2-positive breast cancer relapsing post-adjuvant trastuzumab: pattern of recurrence, treatment and outcome.
J. Krell (2011)
10.1158/1078-0432.CCR-18-2851
Combination of Trastuzumab Emtansine and Stereotactic Radiosurgery Results in High Rates of Clinically Significant Radionecrosis and Dysregulation of Aquaporin-4
P. Stumpf (2019)
10.3390/ijms21010022
How to Make Anticancer Drugs Cross the Blood–Brain Barrier to Treat Brain Metastases
Eurydice Angeli (2019)
10.1016/j.ejca.2015.10.066
Genetic variants in the HER2 gene: Influence on HER2 overexpression and loss of heterozygosity in breast cancer.
N. Cresti (2016)
10.18632/oncotarget.16953
Increased risk of brain metastases in women with breast cancer and p16 expression in metastatic lymph-nodes
E. Furet (2017)
10.1002/stem.2109
Neural Stem Cells Secreting Anti‐HER2 Antibody Improve Survival in a Preclinical Model of HER2 Overexpressing Breast Cancer Brain Metastases
Deepak Kanojia (2015)
Defining the Relationship between the Bioactivation of Lapatinib by CYP3A and Lapatinib-Induced Hepatotoxicity
Michelle D. Wahlin (2014)
10.1016/j.breast.2010.11.008
Rational use of trastuzumab in metastatic and locally advanced breast cancer: implications of recent research.
S. Goel (2011)
10.1007/s11060-011-0661-y
Revisiting the role of molecular targeted therapies in patients with brain metastases
D. Papadatos-Pastos (2011)
10.1186/bcr2904
Luminal-B breast cancer and novel therapeutic targets
B. Tran (2011)
10.1038/bjc.2014.174
Long-term survivor characteristics in HER2-positive metastatic breast cancer from registHER
D. Yardley (2014)
10.1093/jjco/hyu156
Brain metastases in breast cancer.
N. Niikura (2014)
10.1111/tbj.13426
Upfront brain radiotherapy may improve survival for unfavorable prognostic breast cancer brain metastasis patients with Breast‐GPA 0‐2.0
D. Ou (2019)
10.1093/neuonc/now197
Systemic therapy of brain metastases: non-small cell lung cancer, breast cancer, and melanoma.
M. Chamberlain (2017)
10.1186/bcr3625
A BRCA1 deficient-like signature is enriched in breast cancer brain metastases and predicts DNA damage-induced poly (ADP-ribose) polymerase inhibitor sensitivity
R. P. McMullin (2013)
10.1080/14656566.2017.1409206
New agents for the management of resistant metastatic breast cancer
Jesus D Anampa (2017)
10.1016/J.BREASTDIS.2010.10.035
Central Nervous System Metastases in Breast Cancer: Have We Changed the Incidence and Natural History?
Shaheenah Dawood (2010)
10.1093/annonc/mdt348
Circulating tumor cells and brain metastasis outcome in patients with HER2-positive breast cancer: the LANDSCAPE trial.
J.-Y. Pierga (2013)
10.3816/CBC.2010.s.006
Clinical updates on EGFR/HER targeted agents in early-stage breast cancer.
Valentina Macrinici (2010)
10.1038/nrclinonc.2011.58
The biology of brain metastases—translation to new therapies
A. Eichler (2011)
10.1007/s00432-013-1511-4
Receptor change-clinicopathologic analysis of matched pairs of primary and cerebral metastatic breast cancer
C. Bachmann (2013)
10.1007/978-94-007-1399-4_10
Central Nervous System Tumours in Women Who Received Capecitabine and Lapatinib Therapy for Metastatic Breast Cancer
S. Sutherland (2011)
Review Article Leptomeningeal metastases in breast cancer
B. J. Scott (2013)
10.1007/s11095-018-2455-9
Barriers to Effective Drug Treatment for Brain Metastases: A Multifactorial Problem in the Delivery of Precision Medicine
Minjee Kim (2018)
10.1634/theoncologist.2015-0020
Patterns of Care and Clinical Outcomes of First-Line Trastuzumab-Based Therapy in HER2-Positive Metastatic Breast Cancer Patients Relapsing After (Neo)Adjuvant Trastuzumab: An Italian Multicenter Retrospective Cohort Study.
M. Lambertini (2015)
10.3390/cancers8120108
Androgen Receptor: A Complex Therapeutic Target for Breast Cancer
R. Narayanan (2016)
10.1002/cncr.27434
Incidence of brain metastases as a first site of recurrence among women with triple receptor–negative breast cancer
S. Dawood (2012)
10.1007/s11060-016-2309-4
Beyond breast specific—Graded Prognostic Assessment in patients with brain metastases from breast cancer: treatment impact on outcome
G. Griguolo (2016)
10.1200/JCO.20.00775
Intracranial Efficacy and Survival With Tucatinib Plus Trastuzumab and Capecitabine for Previously Treated HER2-Positive Breast Cancer With Brain Metastases in the HER2CLIMB Trial.
N. Lin (2020)
10.1634/theoncologist.2014-0107
Breast cancer with brain metastases: clinicopathologic features, survival, and paired biomarker analysis.
Q. Shen (2015)
See more
Semantic Scholar Logo Some data provided by SemanticScholar