HER2 expression and HER2:HER2 dimerization identifies subpopulations of metastatic breast cancer patients with different probabilities of long-term survival following trastuzumab treatment and with different requirements for concomitant chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 10557-10557 ◽  
Author(s):  
M. P. Bates ◽  
C. Desmedt ◽  
J. Sperinde ◽  
W. Huang ◽  
D. Larsimont ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Protein Expression ◽  
Metastatic Breast ◽  
Her2 Overexpression ◽  
Her2 Expression ◽  
Concomitant Chemotherapy ◽  
Term Survival ◽  
Her2 Protein ◽  
Trastuzumab Treatment

10557 Background: Selection of patients for treatment with trastuzumab is currently based on the semi-quantitative measurement of HER2 protein expression (IHC) or gene amplification (FISH). We made quantitative measurements of HER2 expression and homodimerization using a novel assay, eTag, and correlated them with overall survival (OS) and time-to-progression (TTP) following trastuzumab treatment in a cohort of patients with metastatic breast cancer (MBC). We also examined the benefit of concomitant chemotherapy (CT) depending on quantitative HER2 expression. Methods: The Jules Bordet cohort (Brussels, Belgium, N=71) had MBC and prior treatment with at least two CT regimens. Patients received trastuzumab alone or combined with predominantly paclitaxel. Independent medical data review and central confirmation of HER2 overexpression by FISH (N=64) or IHC (N=7) were mandatory. The eTag assay was used to quantitate HER2 protein expression and HER2:HER2 dimers in FFPE specimens. eTag measurements were correlated with OS and TTP using Kaplan-Meier and Cox Proportional Hazards regression analyses. Results: Cox analyses identified three independent correlates of OS and TTP: number of metastatic sites (HROS = 2.4/site, 95%CI 1.5–3.9, p = 0.00019), treatment with trastuzumab only (HROS = 2.8, 95%CI 1.1–7.3, p = 0.036), and HER2 expression level (HROS = 0.24/log10(HER2), 95%CI 0.09–0.7, p = 0.0058). Patients with high HER2 (above median expression) experienced better OS than those with low HER2 (HR 0.24, p = 0.0014). Patients with high HER2 expression did not benefit from added CT (HR = 0.95, 95%CI 0.24–3.8, p = 0.94), while patients with low HER2 expression did (trastuzumab alone HR 4.4, 95% CI 1.3–18, p = 0.018). Similar results were observed for HER2:HER2 dimerization. Conclusions: Within a population of patients selected by FISH or IHC to receive trastuzumab, higher HER2 expression or HER2:HER2 dimerization correlated with better outcomes. Patients with high HER2 expression derived no benefit from concomitant CT, while patients with low HER2 expression benefited significantly from the addition of CT to trastuzumab. No significant financial relationships to disclose.

Differential survival following trastuzumab treatment based on quantitative HER2 expression and HER2:HER2 dimerization in a clinic-based cohort of patients with metastatic breast cancer

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 1025-1025 ◽  
Author(s):  
M. Toi ◽  
J. Sperinde ◽  
W. Huang ◽  
S. Saji ◽  
S. Ohno ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Cox Proportional Hazards ◽  
Her2 Expression ◽  
Her2 Gene ◽  
Her2 Positive ◽  
Differential Survival ◽  
Term Survival ◽  
Trastuzumab Treatment

1025 Background: Women with metastatic breast cancer (MBC) that overexpress HER2 experience improved overall survival (OS) when treated with trastuzumab. Immunohistochemistry (IHC) for HER2 protein expression and fluorescence in situ hybridization (FISH) for HER2 gene amplification are the preferred methods of determining HER2 positivity. However, not all HER2 positive patients respond equally well to trastuzumab. We describe the identification of subgroups of HER2+ patients with distinct clinical outcomes based on their quantitative levels of HER2 expression and HER2:HER2 dimerization. Methods: 75 patients with MBC drawn from six oncology clinics in Japan were assayed for HER2 expression and HER2:HER2 dimerization using FFPE specimens by the eTag assay, a proximity-based assay designed to detect and quantify protein-protein dimers. All patients had MBC, were treated with at least one chemotherapy (CT) regimen prior to receiving trastuzumab, and had FFPE specimens available for testing. 33% had at least 3 metastatic sites. 88% were selected for treatment based on IHC and 12% based on FISH. 16% were treated with trastuzumab alone and 84% with trastuzumab plus CT. Median clinical follow-up was 26 months. Cox proportional hazards and Kaplan-Meier (KM) analyses were performed. Results: The most significant variables associated with OS were the presence of brain metastases and the total number of metastases. In the overall population, correcting for the confounding influence of number of metastases, KM analyses demonstrated that patients with higher HER2 expression survived significantly longer than patients with lower HER2 expression (HR for death = 0.36, p = 0.0036). This relationship was even more significant for HER2:HER2 dimers (HR = 0.29, p = 0.0003). Conclusions: In a clinic-based population of Japanese women with MBC treated with heterogeneous prior and concomitant (with trastuzumab) CT regimens, the quantitative levels of HER2 expression and HER2:HER2 dimerization identified subsets of patients within a population of pre-selected HER2+ patients with different probabilities of long-term survival following trastuzumab treatment. No significant financial relationships to disclose.

Comparison of ER, PR, HER2 in primary and paired relapsed/metastatic lesions of metastatic breast cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 1063-1063
Author(s):  
E. Sari ◽  
G. Guler ◽  
M. Hayran ◽  
K. Altundag ◽  
I. Gullu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Her2 Status ◽  
Her2 Overexpression ◽  
Her2 Expression ◽  
Metastatic Lesions ◽  
Er Positive ◽  
Her 2 ◽  
Er Expression

1063 Background: The assessment of ER, PR and HER2 is made routinely in every breast cancer patient to have information about prognosis and to select patients (pts) who are candidates for hormonal and anti-HER2 therapy. Recent studies have shown some degrees of discordance in ER, PR, and HER-2 expression between primary and recurrent/metastatic lesions (RML). In this study we compared the ER, PR, and HER2 status of the primary and paired RML in metastatic breast cancer pts. Methods: Analysis was made on 79 metastatic breast cancer pts whose ER, PR, and/or HER2 status were known both on the tissue samples of primary and RML. ER, PR, and HER2 status were determined by immunohistochemistry and/or fluorescence-in-situ hybridization. Results: Among the RML sites, 24% were locoregional, 76% were distant metastatic sites. Among 72 pts with known ER expression on both primary and RML, 36% showed discordance on ER expression. Most of the change occurred from negative to positive ER status (15 of 48 ER positive primaries had ER negative paired metastasis and 11 of 24 ER negative primaries had ER positive paired metastasis). Among 68 pts with known PR expression on both primary and RML, 51.5% showed discordance on PR expression. Change in PR status from positive to negative and negative to positive was similar (23 of 45 PR positive primaries had PR negative paired metastasis and 12 of 23 PR negative primaries had PR positive paired metastasis). Among 58 pts with known HER2 expression on both primary and RML, 15.5% showed discordance on HER2 expression. Six pts with HER-2 negative primaries, showed HER2 overexpression in their paired RML. Four pts who had HER2 overexpressing primary did not show HER2 expression in the paired RML. Conclusions: A proportion of pts show discordances in hormonal receptor and HER2 expression between the primary tumor and the paired RML. As these discordant results make changes in treatment decision, a biopsy of the metastatic lesion could be recommended in metastatic breast cancer pts when feasible. No significant financial relationships to disclose.

Correlation of trastuzumab treatment benefit with quantitative HER2 expression levels in HER2 positive metastatic breast cancer.

2015 ◽  
Vol 33 (15_suppl) ◽  
pp. 593-593
Author(s):  
Beatrice Bachmeier ◽  
Jeff Sperinde ◽  
Jodi Marie Weidler ◽  
Yolanda Lie ◽  
Ahmed Chenna ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Metastatic Breast ◽  
Her2 Expression ◽  
Her2 Positive ◽  
Treatment Benefit ◽  
Expression Levels ◽  
Trastuzumab Treatment

scholarly journals HER3, p95HER2, and HER2 protein expression levels define multiple subtypes of HER2-positive metastatic breast cancer

2013 ◽  
Vol 141 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Allan Lipton ◽  
Laurie Goodman ◽  
Kim Leitzel ◽  
Jennifer Cook ◽  
Jeff Sperinde ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Protein Expression ◽  
Metastatic Breast ◽  
Her2 Positive ◽  
Her2 Protein ◽  
Expression Levels

scholarly journals Post-surgical depressive symptoms and long-term survival in non-metastatic breast cancer patients at 11-year follow-up

2017 ◽  
Vol 44 ◽  
pp. 16-21 ◽  
Author(s):  
Michael H. Antoni ◽  
Jamie M. Jacobs ◽  
Laura C. Bouchard ◽  
Suzanne C. Lechner ◽  
Devika R. Jutagir ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Depressive Symptoms ◽  
Cancer Patients ◽  
Metastatic Breast ◽  
Breast Cancer Patients ◽  
Term Survival ◽  
Long Term Survival

scholarly journals Is There Any Rationale for Detecting Hormone Receptor/HER2 Status with Rebiopsy Without Progression Upfront Metastatic Breast Cancer? with 2 Cases

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Duman BB ◽  
Cil T
Keyword(s):  
Breast Cancer ◽  
Metastatic Breast Cancer ◽  
Maintenance Therapy ◽  
Hormone Receptor ◽  
Tumor Heterogeneity ◽  
Hormone Receptors ◽  
Triple Negative ◽  
Neoadjuvant Treatment ◽  
Metastatic Breast ◽  
Her2 Overexpression

Alteration of biomarkers is well-documented in breast cancer at locoregional recurrence or metastasis attributed to tumor heterogeneity and change in biology. There is some data about discordance between primary and metastatic sites. At the same time hormone, receptor status can change after neoadjuvant treatment and at the time of recurrence. Metastatic breast cancer without progression or recurrence after the targeted chemotherapy combination for planning maintenance therapy in Human epidermal growth factor receptor 2 (HER2) overexpression positive hormone receptors positive or triple-negative patient after chemotherapy. In guidelines, the time of rebiopsy has no exact time, if the time of biopsy is usually after the progression of the tumor. We presented cases in which we detected different hormone receptor statuses from the beginning without progression and before deciding on maintenance therapy. This subject is important for deciding therapy in the aspect of heterogeneous tumors like breast cancer. The important decision of rebiopsy time is debate. In this aspect, these two cases are important examples for these kinds of patients tumor heterogeneity in breast cancer is one of the most widely known entities. We found that two patients, one of whom was estrogen progesterone receptor negative HER2 3 (+++) at the time of diagnosis and the other who was triple negative at the time of diagnosis, had positive hormone receptors in the re-biopsies without progression. We aimed to discuss the tumor heterogeneity and timing of rebiopsy in breast cancer in the light of two cases.

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