HER-2/neu Assessment in Primary Chemotherapy Treated Breast Carcinoma: No Evidence of Gene Profile Changing

Dagrada, Gian Paolo; Mezzelani, Alessandra; Alasio, L.; Ruggeri, Mario; Romanò, Roberta; Pilotti, Silvana

doi:10.1023/a:1024579206250

Cited by 22 publications

(18 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consequently, it is often assumed that the biomarker status in the primary reflects the metastatic lesion (30 -32). This is shown by Her2, where treatment options are discussed almost always on the basis of the Her2 status in the primary tumors and only few studies have addressed the presence of biomarkers in primary tumors and corresponding axillary lymph node metastases (31). The present data indicate that NY-BR-1 expression in the primary tumors is concordant with its metastatic expression pattern.…”

Section: Discussionmentioning

confidence: 50%

Preferential Nuclear and Cytoplasmic NY-BR-1 Protein Expression in Primary Breast Cancer and Lymph Node Metastases

Varga

Theurillat

Filonenko

et al. 2006

Clinical Cancer Research

View full text Add to dashboard Cite

Purpose: NY-BR-1 is a recently isolated differentiation antigen, which is expressed in normal mammary tissue and in breast cancer. However, current data are based on RT-PCR analysis and nothing is known about the presence of NY-BR-1 on a protein level. We previously generated a monoclonal antibody to NY-BR-1to study the protein expression of NY-BR-1. Methods: In our immunohistochemical study, NY-BR-1was analyzed in normal tissues, various tumor types, 124 primary breast cancers, and 37 paired lymph node metastases. Results: Among normal tissues, NY-BR-1was present solely in ductal epithelium of the breast. In tumors, carcinoma in situ and invasive carcinoma of the breast were NY-BR-1 positive whereas other tumors and normal tissues were negative. Sixty percent of invasive breast carcinomas were NY-BR-1positive, displaying cytoplasmic and/or nuclear immunoreactivity.This coexpression was verified by confocal microscopy. Although the monoclonal antibody identified intratumoral heterogeneity, a majority (72%) of NY-BR-1-positive carcinomas revealed immunoreactivity in >50% of the tumor cells. NY-BR-1 expression was more frequent in estrogen receptor^positive and lymph node^negative primary carcinomas (P < 0.05 each) and was more common in grade 1 (77%) than in grade 2 (63%) or grade 3 (50%) carcinomas (P < 0.05). This suggests that NY-BR-1expression is lost with tumor progression. Forty-nine percent of lymph node metastases were NY-BR-1positive. Conclusion:This study supports the notion that NY-BR-1is a differentiation antigen of the breast, which is present in normal and tumorous mammary epithelium. The organ-specific expression of NY-BR-1and its high prevalence in metastases indicate that it could be a valuable target for cancer immunotherapy.

show abstract

Section: Discussionmentioning

confidence: 50%

Preferential Nuclear and Cytoplasmic NY-BR-1 Protein Expression in Primary Breast Cancer and Lymph Node Metastases

Varga

Theurillat

Filonenko

et al. 2006

Clinical Cancer Research

View full text Add to dashboard Cite

show abstract

“…Similar findings with FISH were reported in one study. 34 The current study included 32 tumor metastases in which HER-2 status was determined after chemotherapy (either neoadjuvant or adjuvant) and showed no changes in HER-2 status compared with the paired primary tumors that were sampled prior to therapy. These findings indicate that the HER-2 status not only is stable during disease progression but also is not affected by chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

Comparison of HER‐2 status determined by fluorescence in situ hybridization in primary and metastatic breast carcinoma

Gong

Booser

Sneige

2005

Cancer

144

View full text Add to dashboard Cite

BACKGROUNDAccurate assessment of HER‐2 status is necessary prior to anti‐HER‐2 antibody (trastuzumab) therapy for metastatic breast carcinoma. However, controversy exists regarding whether to assess HER‐2 status in the primary tumor or in metastatic lesions. It is also unclear whether HER‐2 status can change during disease progression or after chemotherapy.METHODSBreast carcinoma samples from 60 women with known HER‐2 status in both primary tumors and paired metastases (locoregional disease, n = 43 patients; distant disease, n = 17 patients) were reviewed retrospectively. Thirty‐two patients underwent chemotherapy before their metastatic lesions were sampled, including 18 patients who received neoadjuvant chemotherapy and 14 patients who received adjuvant chemotherapy. The HER‐2 gene was examined by fluorescence in situ hybridization either in paraffin‐embedded tissue samples (48 primary tumors and 9 metastatic tumors) or in fine‐needle aspirates (12 primary tumors and 51 metastatic tumors). HER‐2 gene amplification was defined as a HER‐2:chromosome 17 signal ratio ≥ 2.0.RESULTSThe HER‐2 status of primary and metastatic tumors agreed in 58 of 60 patients (97%), including 18 (30%) amplified tumors and 40 (67%) nonamplified tumors. A discrepancy in HER‐2 status was observed in specimens from two patients in which HER‐2 amplification was detected in the primary tumor but not the metastatic tumors. In one patient, three foci of tumor nodules were found in the same breast; the HER‐2 status was assessed in only one of them, which showed amplification; however, HER‐2 amplification was not detected in the axillary lymph node metastasis. In another patient, the HER‐2 gene was amplified in the primary tumor but not in the liver metastasis. No metastases showed HER‐2 amplification without amplification in the primary tumor. Locoregional and distant metastases demonstrated similar concordance rates with their corresponding primary tumors (98% and 94%, respectively). Complete concordance of HER‐2 status was found between primary tumors prior to chemotherapy and metastases that were sampled after chemotherapy.CONCLUSIONSThe HER‐2 status in breast carcinoma generally was stable during metastasis, whether to locoregional or distant sites. Chemotherapy did not modify the HER‐2 status in metastatic lesions. Therefore, HER‐2 amplification can be evaluated reliably in material from either primary or metastatic tumors in most patients. Further study with larger series is warranted to elucidate the significance of discordant results. Cancer 2005. © 2005 American Cancer Society.

show abstract

“…Comparison of expression profile on both DNA and protein level before and after chemotherapy for breast cancer has not been investigated extensively [7,11,22]. We are aware of two previous papers determining Her2 gene characteristics on pre-treatment smears or cores and post-treatment sections by neoadjuvant treatment modality using a quantitative and an in situ hybridization (FISH) methodology, respectively [7,22].…”

Section: Discussionmentioning

confidence: 99%

“…We are aware of two previous papers determining Her2 gene characteristics on pre-treatment smears or cores and post-treatment sections by neoadjuvant treatment modality using a quantitative and an in situ hybridization (FISH) methodology, respectively [7,22].…”

Section: Discussionmentioning

confidence: 99%

“…Preferential and comparative detection methods of Her2 testing have been the subject of several investigations as well [2,15,17,26]. Nevertheless, stability of the Her2 gene and protein after chemotherapy has not been thoroughly studied [7,10,22]. In routine practice, it is not common to determine Her2 status on breast cancer more than once during the disease course, postulating gene stability.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Stability of the HER2 gene after primary chemotherapy in advanced breast cancer

2005

View full text Add to dashboard Cite

We investigated whether alterations of the Her2 gene could be detected in breast cancer samples following primary chemotherapy in advanced breast cancer. The prospective study involved 23 patients with stage-II, -III or -IV breast cancer. All patients were treated with two to six cycles of fluorouracil-epirubicin and/or cyclophosphamid/epi-docetaxel. The Her2 protein and gene were assessed both on core needle biopsies prior to and on surgical specimens after completing chemotherapy using immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH) methods. Estrogen and progesterone receptors (ER/PR) were also determined on both samples using IHC. Her2 status was modified in eight patients using IHC (35%) and in three patients using FISH (13%). Changes in ER/PR expression were detected in seven patients (30%). Our data suggest that alterations of the Her2 gene can occur, although not usually after primary or neoadjuvant chemotherapy. However, changes in ER/PR status seem to be a more common event; thus, both can lead to different therapeutic options. Intratumoral heterogeneity as well as sampling variations can contribute to modification of the Her2 status after primary chemotherapy.

show abstract

HER-2/neu Assessment in Primary Chemotherapy Treated Breast Carcinoma: No Evidence of Gene Profile Changing

Cited by 22 publications

References 27 publications

Preferential Nuclear and Cytoplasmic NY-BR-1 Protein Expression in Primary Breast Cancer and Lymph Node Metastases

Preferential Nuclear and Cytoplasmic NY-BR-1 Protein Expression in Primary Breast Cancer and Lymph Node Metastases

Comparison of HER‐2 status determined by fluorescence in situ hybridization in primary and metastatic breast carcinoma

Stability of the HER2 gene after primary chemotherapy in advanced breast cancer

Contact Info

Product

Resources

About