Is HER-2 over expression associated with brain metastases in Chinese breast cancer patients?

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.

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Prognostic significance of HER-2/neu over-expression on the incidence of brain metastasis in newly diagnosed breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.649 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 649-649 ◽

Cited By ~ 1

Author(s):

B. S. Abdulkarim ◽

Z. Gabos ◽

R. Sinha ◽

J. Hanson ◽

N. Chauhan ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Tumor Size ◽

Univariate Analysis ◽

Prognostic Significance ◽

Newly Diagnosed ◽

Breast Cancer Patients ◽

Over Expression ◽

Increased Risk ◽

Her 2

649 Background: As systemic therapy improves, brain metastases (BM) from breast cancer are becoming increasingly evident. An increased risk of BM in HER-2/neu over-expressing metastatic breast cancer patients has been suggested. However, the relationship between HER-2/neu over-expression and the risk of BM in newly diagnosed breast cancer patients is unknown. Methods: To determine incidence of BM in HER-2/neu over-expressing breast cancer patients, a cohort of patients between 01/1998 and 12/2003 with uniform HER-2/neu testing were identified from a cancer registry. A total of 460 patients with HER-2/neu over-expression and 500 patients with HER-2/neu negative disease were reviewed. Patients were excluded if there was breast cancer diagnosed before 01/1998 or others cancer. A total of 301 HER-2/neu over-expressing and 363 HER-2/neu negative patients were included for this analysis. The association between histological features and the occurrence of BM were evaluated with univariate and multivariate analyses. Results: BM were identified in 8% (24 patients) of HER-2/neu over-expressing breast cancer patients compared to only 1.7% (6 patients) in the HER-2/neu negative patients (hazard ratio 5.15 [2.079–12.78], p=0.0001). In patients with recurrent disease, the proportion of BM for HER-2/neu over-expressing patients was 24% compared to 10% in HER-2/neu negative patients. HER-2/neu over-expression, tumor size >2cm, ≥ 4 nodes positive and grade 2/3 were predictors of BM in univariate analysis. In multivariate analysis, HER-2/neu over-expression and tumor size>2cm were an independent prognostic factors for the development of BM, while hormone receptors expressions was protective (p=0.02). Conclusions: Our population based study show that newly diagnosed HER-2/neu over-expressing breast cancer patients are at significantly increased risk for BM. As most BM occur in HER-2/neu over-expressing patients with systemic metastatic disease, these findings could prompt consideration of brain prophylaxis strategies and/or serial radiologic screening to detect asymptomatic BM. No significant financial relationships to disclose.

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HER-2 overexpression does not decrease survival of breast cancer patients with brain metastases

European Journal of Cancer Supplements ◽

10.1016/s1359-6349(08)70764-x ◽

2008 ◽

Vol 6 (7) ◽

pp. 183

Author(s):

K. Krzemieniecki ◽

E. Pluta

Keyword(s):

Breast Cancer ◽

Brain Metastases ◽

Cancer Patients ◽

Breast Cancer Patients ◽

Her 2

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Prognostic value of HER-2/neu overexpression for the development of brain metastasis after treatment of early breast cancer

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.21044 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 21044-21044

Author(s):

J. Ahn ◽

S. Kim ◽

W. Kim ◽

G. Gong ◽

M. Kim ◽

...

Keyword(s):

Breast Cancer ◽

Brain Metastasis ◽

Brain Metastases ◽

Cancer Patients ◽

Early Breast Cancer ◽

Metastatic Breast ◽

Breast Cancer Patients ◽

Increased Risk ◽

Her 2 ◽

Independent Risk Factors

21044 Background: Several studies have addressed the incidence of brain metastasis in HER-2/neu-overexpressing metastatic breast cancer. However, the relevance of HER-2/neu overexpression as a risk factor for brain metastases in breast cancer has not yet been clearly defined. The aim of this study is to analyze the risk of brain metastasis in HER-2/neu-positive early breast cancer patients in comparison with HER-2/neu-negative patients. Methods: We used tissue microarray to examine HER- 2/neu overexpression by immunohistochemistry (IHC) in 773 consecutive patients diagnosed with breast carcinoma who underwent surgery between January 1993 and December 1998. Patients were considered HER-2/neu-positive if they were 3+ on IHC testing. A total of 194 (25.1%) patients with HER-2/neu-overexpressing newly diagnosed breast cancer were identified in our study. The medical records and pathologic data of all 773 patients were reviewed retrospectively. Results: During a median follow-up period of 8.1 years, brain metastasis were identified in 7.2% (14 patients) with 194 HER-2/neu-overexpressing breast cancer compared with 2.6% (15 patients) in 597 HER-2/neu-negative patients (hazard ratio 2.924 [1.385–6.175], P=0.005). More HER-2/neu-overexpressing patients developed distant metastasis (33.5% vs. 18.8%, P=0.0001). The 8-year overall survival was 76.1% for HER-2/neu-negative patients versus 56.4% for HER-2/neu-positive patients (P<0.00001). By multivariate analysis, HER-2/neu overexpression, tumor size larger than 2 cm, at least one positive node, and progesterone receptor (PR)-negativity were independent risk factors for the development of brain metastases. Conclusions: Our data show that HER-2/neu overexpressing early breast cancer patients are at significantly increased risk for brain metastases. Also, our results demonstrate that HER-2/neu overexpression is an important independent prognostic factor of early breast cancer, and suggest that more aggressive adjuvant chemotherapy and radiologic screening to detect brain metastases should be considered in this population. No significant financial relationships to disclose.

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