Adjuvant trastuzumab in the treatment of her-2-positive early breast cancer: a meta-analysis of published randomized trials

Background  

Breast cancer is the most common cancer in women in the U.S. and Western Europe. Amplification of the her-2/neu gene occurs in approximately 25% of invasive ductal carcinomas of the breast. The first HER-2/neu-targeted approach to reach the clinic was trastuzumab, a humanized monoclonal antibody directed against the extracellular domain of the HER-2/neu protein. Trastuzumab therapy prolongs the survival of patients with metastático HER-2/neu-overexpressing breast cancer when combined with chemotherapy and has recently been demonstrated to lead to dramatic improvements in disease-free survival when used in the adjuvant therapy setting in combination with or following chemotherapy. Here, we performed a meta-analysis of completed clinical trials of adjuvant trastuzumab in the adjuvant setting. Survival, recurrence, brain metastases, cardiotoxicity and directions for future research are discussed.     

The use of HER2 modulation in the adjuvant setting

Amplification of the her-2/neu gene is associated with poor prognosis in patients with early-stage and metastatic breast cancer. Trastuzumab is a humanized monoclonal antibody directed against the HER2 protein, which is overexpressed in approximately 25% of patients with primary invasive breast cancer. Randomized phase III clinical trials showed that administration of trastuzumab in combination with chemotherapy or following chemotherapy significantly improves disease-free and overall survival rates in patients with early-stage HER2-positive breast cancer. The integration of trastuzumab in the adjuvant setting is changing the natural history of HER2-driven breast cancer from one of the worst subtypes to one that is highly curable with available therapy.     

HER-2/neu positive breast cancer: how to prescribe adjuvant trastuzumab (Herceptin)?

One of the most recent advances in the management of Her-2/neu positive breast cancer is the validation of a targeted therapy from bench to the clinic, particularly towards the adjuvant setting. The recommended dose of trastuzumab (Herceptin), a humanized monoclonal antibody targeting the HER-2 antigen, has been determined in phase I studies. In the metastatic patients two randomised trials have demonstrated its efficacy when associated to taxanes. In less than 10 years, trastuzumab became the standard of care in the adjuvant treatment of HER-2/neu positive breast cancer. In this setting, two combinations regimen with chemotherapy (concomitant or sequential) have been recently published. The concomitant schedule has been used in three studies (North American Group, BCIRG, FinHer), whereas in the Hera trial trastuzumab was started after the end of neo-adjuvant and adjuvant chemotherapy. In this article, the advantages and uncertainties on efficacy and toxicities of the trastuzumab administration modalities, associated or not to chemotherapy and radiation therapy, are discussed.     

The Her-2/neu gene and protein in breast cancer 2003: biomarker and target of therapy

The HER-2/neu oncogene encodes a transmembrane tyrosine kinase receptor with extensive homology to the epidermal growth factor receptor. In this review, the association of HER-2/neu gene and protein abnormalities with prognosis and response to therapy with trastuzumab and to other therapies in breast cancer is presented. By considering a series of 80 published studies encompassing more than 25,000 patients, the relative advantages and disadvantages of Southern blotting, polymerase chain reaction amplification, and fluorescence in situ hybridization assays designed to detect HER-2/neu gene amplification are compared with HER-2/neu protein overexpression assays performed by immunohistochemical techniques applied to frozen and paraffin-embedded tissues and enzyme immunoassays performed on tumor cytosols. The significance of HER-2/neu overexpression in ductal carcinoma in situ and the HER-2/neu status in uncommon female breast conditions and male breast cancer are also considered. The role of HER-2/neu testing for the prediction of response to trastuzumab therapy in breast cancer is presented as well as its potential impact on responses to standard and newer hormonal therapies, cytotoxic chemotherapy, and radiation. The review also evaluates the status of serum-based testing for circulating HER-2/neu receptor protein and its ability to predict disease outcome and therapy response.     

Change in HER-2/neu Status from Negative to Positive following Treatment in Breast Cancer: A Case Report

INTRODUCTION: Approximately 25-30% of breast cancers are assumed to be HER-2/neu positive. It is well known that HER-2/neu-positive cancers after treatment with trastuzumab can become HER-2/neu negative. Change in HER-2/neu status from negative to positive following treatment has not been well studied. We describe a patient with inflammatory breast cancer who was initially HER-2/neu negative but became positive after treatment. A 59-year-old postmenopausal white female saw her surgeon for violaceous discoloration of the left breast for 4 months. The surgeon palpated a mass measuring 6 cm in the patient's left breast. Additionally, there was violaceous discoloration involving two thirds of the breast. Biopsy of the breast mass and skin revealed inflammatory breast cancer. The tumor was estrogen receptor positive, progesterone receptor positive and HER-2/neu negative. The patient was given four cycles of chemotherapy with cyclophosphamide, doxorubicin and docetaxol. She subsequently underwent a mastectomy, excision of the skin over the chest wall and axillary node dissection. Of the axillary lymph nodes, 14/14 were involved. The tumor was still estrogen receptor positive and progesterone receptor positive, but HER-2/neu was 2+ by immunohistochemistry and amplified at 3.3 as detected by fluorescent in situ hybridization. The patient received trastuzumab along with chemotherapy followed by radiation therapy and letrozole. She is currently receiving trastuzumab and letrozole in the adjuvant setting and appears to be doing well. CONCLUSION: A breast cancer which was initially HER-2/neu negative can become positive following treatment. Therefore, re-biopsy may be necessary during the course of treatment of breast cancer to re-assess the HER-2/neu status. This gives the clinician the opportunity to include drugs like trastuzumab and lapatinib in the treatment of patients with a transformation to HER-2/neu-positive cancer.     

Amplification of HER-2 in gastric carcinoma: association with Topoisomerase IIalpha gene amplification, intestinal type, poor prognosis and sensitivity to trastuzumab.

BACKGROUND: HER-2/neu gene amplification has predictive value in breast cancer patients responding to trastuzumab. We wanted to investigate the frequency and clinical significance of HER-2/neu amplification in gastric carcinoma. PATIENTS AND METHODS: The frequency of HER-2/neu and Topoisomerase IIalpha gene amplification was studied in adenocarcinomas of the stomach (n=131) and the gastroesophageal junction (n=100) by chromogenic in situ hybridization (CISH). Sensitivity of a gastric cancer cell line N87 with HER-2/neu amplification to trastuzumab was studied by a cell viability assay and compared with that of a HER-2 amplified breast cancer cell line SKBR-3. Growth inhibition of N87 cells was also verified in vivo in N87 xenograft tumors. RESULTS: HER-2/neu amplification was present in 16 (12.2%) of the 131 gastric and in 24 (24.0%) of the 100 gastroesophageal adenocarcinomas. Co-amplification of Topoisomerase IIalpha was present in the majority of gastric (63%) and esophagogastric junction cancers (68%) with HER-2/neu amplification. HER-2/neu amplification was more common in the intestinal histologic type of gastric cancer (21.5%) than in the diffuse (2%) or the mixed/anaplastic type (5%, P=0.0051), but it was not associated with gender, age at diagnosis or clinical stage. Presence of HER-2/neu amplification was associated with poor carcinoma-specific survival (P=0.0089). HER-2/neu targeting antibody trastuzumab inhibited the growth of a p185(HER-2/neu) overexpressing gastric and breast carcinoma cell lines (N87 and SKBR-3) with equal efficacy. CONCLUSIONS: HER-2/neu amplification is common in the intestinal type of gastric carcinoma, and it is associated with a poor outcome. HER-2 might be a useful target in this disease, and this hypothesis deserves to be investigated in clinical trials.     

Perspective of trastuzumab treatment

Trastuzumab (Herceptin) has many benefits for metastatic breast cancer patients with HER2 overexpression/amplification. Trastuzumab alone or trastuzumab in combination with chemotherapy regimens are standard treatment worldwide as first line therapy for metastatic breast cancer patients with HER2 overexpression/amplification. Furthermore, an international collaboration for adjuvant trastuzumab trials showed last year that trastuzumab treatment improves disease-free and overall survival after or in combination with adjuvant chemotherapy. However, there are many uncertain issues concerning trastuzumab adjuvant and metastatic treatment, such as treatment beyond disease progression (PD), combination with hormone therapy, duration of adjuvant treatment, and cardiac safety of long term treatment.     

HER-2/neu amplification detected by fluorescence in situ hybridization in fine needle aspirates from primary breast cancer.

BACKGROUND: The HER-2/neu gene is amplified in 20-30% of human breast cancers and has been shown to have prognostic and predictive value for treatment with chemotherapy, hormone therapy and antibodies against the HER-2/neu domain (trastuzumab). The aim of our study was to evaluate the reliability of HER-2/neu determination by fluorescence in situ hybridization (FISH) on fine-needle aspirates (FNAs) from primary breast cancer patients by comparison with the results obtained by FISH and immunohistochemistry (IHC) on the corresponding histological sections. MATERIALS AND METHODS: HER-2/neu amplification was determined by FISH on 66 breast cancer FNAs. Twenty-three and 36 corresponding formalin-fixed, paraffin-embedded sections were assayed by FISH and by IHC, respectively, in order to detect HER-2/neu amplification and HER-2/neu protein expression. RESULTS: Twenty-seven per cent (18/66) of breast cancer FNAs showed amplification of HER-2/neu by FISH. Paired results by FISH cytology and FISH histology were available in 22 cases. Concordance was 91% (20/22). Paired results by FISH cytology and IHC were available in 36 cases. Concordance was 92% (33/36). Eighteen of 66 breast cancer FNAs were also submitted to flow cytometric DNA analysis. None of the diploid cases showed HER-2/neu amplification by FISH. Six out of the eight aneuploid cases were amplified and two were polysomic. CONCLUSIONS: HER-2/neu gene amplification can be reliably estimated by FISH on breast cancer FNAs and a good correlation has been found between FISH and IHC results from the corresponding histological sections.     

Use of trastuzumab for the treatment of early stage breast cancer

In 1985, a growth factor pathway that depends on the presence of a tyrosine kinase transmembrane receptor present on the surface of 20–25% of breast cancer cells was discovered. The receptor is called human epidermal growth factor receptor (HER)-2 and the prognosis of those patients whose tumors overexpress it is poor. In the 1980s, a monoclonal antibody against this receptor, trastuzumab, was developed and, in 1998, approved for the treatment of metastatic breast cancer. In 2005, the results of five trials evaluating trastuzumab in the adjuvant setting, involving more than 10,000 women, were presented. Despite differences in design and having a short follow-up (between 1 and 2 years), these studies show the same astonishing results that adjuvant trastuzumab therapy halves the recurrence rate and reduces mortality by 30% in those trials mature enough to show survival gains. This benefit is, on average, higher than that of adjuvant chemotherapy and similar to that seen with adjuvant hormonal therapy. The main setback of trastuzumab is its potential for cardiotoxicity, although benefits seem to outweigh risks and the ensuing congestive heart failure is generally reversible. Today, the evaluation of HER-2 expression should be mandatory in every early breast cancer patient, since without it, there is the risk that access to this highly effective drug will be denied for women belonging to this unfavorable subgroup of patients.     

Use of trastuzumab for the treatment of early stage breast cancer

In 1985, a growth factor pathway that depends on the presence of a tyrosine kinase transmembrane receptor present on the surface of 20-25% of breast cancer cells was discovered. The receptor is called human epidermal growth factor receptor (HER)-2 and the prognosis of those patients whose tumors overexpress it is poor. In the 1980s, a monoclonal antibody against this receptor, trastuzumab, was developed and, in 1998, approved for the treatment of metastatic breast cancer. In 2005, the results of five trials evaluating trastuzumab in the adjuvant setting, involving more than 10,000 women, were presented. Despite differences in design and having a short follow-up (between 1 and 2 years), these studies show the same astonishing results that adjuvant trastuzumab therapy halves the recurrence rate and reduces mortality by 30% in those trials mature enough to show survival gains. This benefit is, on average, higher than that of adjuvant chemotherapy and similar to that seen with adjuvant hormonal therapy. The main setback of trastuzumab is its potential for cardiotoxicity, although benefits seem to outweigh risks and the ensuing congestive heart failure is generally reversible. Today, the evaluation of HER-2 expression should be mandatory in every early breast cancer patient, since without it, there is the risk that access to this highly effective drug will be denied for women belonging to this unfavorable subgroup of patients.     

Her-2/neu overexpression and response to oophorectomy plus tamoxifen adjuvant therapy in estrogen receptor-positive premenopausal women with operable breast cancer.

PURPOSE: Studies evaluating the relationship of HER-2/neu breast tumor status and response to adjuvant endocrine therapy have reached conflicting conclusions about resistance of HER-2/neu-positive tumors to this treatment. We studied 282 patients participating in a randomized controlled trial of adjuvant oophorectomy and tamoxifen or observation who had estrogen receptor-positive tumors and whose tumors were evaluated for HER-2/neu overexpression by immunohistochemistry. PATIENTS AND METHODS: Univariate and multivariate Cox proportional hazards regression models and Kaplan-Meier disease-free and overall survival estimate methods were used. RESULTS: HER-2/neu overexpression was a negative prognostic factor for overall survival. In univariate analyses, in HER-2/neu-positive patients, the hazard ratio (HR) for disease-free survival (DFS) with adjuvant endocrine therapy was 0.37 (95% confidence interval [CI], 0.26 to 0.89); for HER-2/neu-negative patients, the corresponding HR for DFS was 0.48 (95% CI, 0.31 to 0.71). The overall survival (OS) data were HR=0.26 (95% CI, 0.07 to 0.92) and HR=0.68 (95% CI, 0.32 to 1.42) for HER-2/neu-positive and HER-2/neu-negative patients, respectively. In multivariate models, the P values for tests of interaction of HER-2/neu status and response to adjuvant endocrine therapy were 0.18 and 0.07 for DFS and OS, respectively. Kaplan-Meier DFS and OS curves and 3-year DFS estimates were consistent in showing greater benefit to the HER-2/neu-positive subgroup given adjuvant treatment. CONCLUSION: HER-2/neu overexpression does not adversely and may favorably influence response to adjuvant oophorectomy and tamoxifen treatment in patients with estrogen receptor-positive tumors.     

Overview of epirubicin-based adjuvant therapy in breast cancer

Clinical trial data indicate that epirubicin-based adjuvant treatment of breast cancer is associated with marked improvement in relapse-free and overall survival compared with traditional cyclophosphamide/methotrexate/5-fluorouracil. The outcomes are comparable to those achieved with sequential use of doxorubicin/cyclophosphamide and paclitaxel. Dose intensification of epirubicin is feasible, with tolerable side effects and no increased risk of cardiotoxicity beyond that expected. Clinical trial data coupled with pharmacokinetic evidence provide a strong foundation and rationale for current and future investigation of epirubicin in combination with the taxanes in the adjuvant setting. An ongoing German study is evaluating epirubicin/cyclophosphamide in combination with trastuzumab as first-line therapy of metastatic breast cancer in patients whose tumors overexpress HER2/neu protein. These results, particularly the tolerability of this regimen, will form the basis for future adjuvant and neoadjuvant studies of epirubicin/trastuzumab-based regimens.     

HER-2/neu in node-negative breast cancer: prognostic significance of overexpression influenced by the presence of in situ carcinoma.

PURPOSE: Amplification and/or overexpression of the HER-2/neu oncogene have been shown to correlate with poor clinical outcome in patients with axillary node-positive breast cancer. In contrast, the prognostic significance of HER-2/neu in node-negative disease is controversial. This study was undertaken to evaluate further the relationship between HER-2/neu and clinical outcome in node-negative disease. PATIENTS AND METHODS: Overexpression of HER-2/neu was evaluated by permanent-section immunohistochemistry in tumors from 613 patients with long-term clinical follow-up enrolled in the Intergroup Study 0011. Patients were stratified into low-risk (n = 307) and high-risk (n = 306) groups on the basis of tumor size and estrogen-receptor (ER) status. Low-risk patients were defined as having small (less than 3 cm), ER-positive tumors and were observed without additional treatment after initial surgery. High-risk patients had either ER-negative or large (greater than or equal to 3 cm), ER-positive tumors and were randomized to be observed (n = 146) or to receive adjuvant chemotherapy (n = 160) after surgery. RESULTS: The rate of HER-2/neu overexpression was 14.3% in all tumors combined and was higher in invasive carcinomas with (21.5%) than without (11.2%) a significant noninvasive or in situ histologic component (P less than .0001). There was no relationship between overexpression and clinical outcome in the natural history setting of combined low-risk and high-risk patients not receiving adjuvant therapy (n = 453). Based on the reasoning that the influence of HER-2/neu may have been obscured by high-risk features and/or the presence of noninvasive carcinoma, we also analyzed the subset of patients with low-risk lesions not containing a significant in situ component (n = 179). Patients of this group with HER-2/neu-positive tumors showed only 40% disease-free survival (DFS) at 5 years, compared with over 80% in patients with HER-2/neu-negative tumors (P less than .0001). A similar inverse correlation was observed between overexpression and overall survival in the same group of patients (P = .0001). In a separate analysis involving patients receiving adjuvant chemotherapy, those with HER-2/neu-negative tumors showed significantly improved DFS in response to therapy compared with patients with HER-2/neu-positive tumors. CONCLUSION: Overexpression of HER-2/neu is associated with poor clinical outcome in a subset of node-negative patients with small, ER-positive, predominantly invasive tumors and may play a role in resistance to adjuvant chemotherapy.     

HER-2/neu oncogene protein and prognosis in breast cancer

Amplification of the HER-2/neu oncogene was recently reported to predict poor clinical outcome in node-positive breast cancer patients. Since expression of the oncogene as its protein product might be even more closely related than gene amplification to disease progression, we have now examined levels of the HER-2/neu oncogene protein for its prognostic potential in both node-positive and node-negative breast cancer. Using Western blot analysis, levels of this protein were determined in 728 primary human breast tumor specimens. We examined relationships between this protein and other established markers of prognosis, as well as clinical outcome. In node-negative patients (n = 378), the HER-2/neu protein failed to predict disease outcome. However, in node-positive patients (n = 350), those patients with higher HER-2/neu protein had statistically shorter disease-free (P = .0014) and overall survival (P less than .0001) than patients with lower levels of the protein. Higher HER-2/neu protein was found in tumors without estrogen receptor (ER) (P = .02) or progesterone receptor (PgR) (P = .0003), and in patients with more than three positive lymph nodes (P = .04). A significant correlation between levels of the HER-2/neu gene protein and amplification of the gene itself was also found (n = 48, P less than .001). Multivariate analyses in these patients showed that the HER-2/neu protein is a significant independent predictor of both the disease-free and the overall survival in node-positive breast cancer, even when other prognostic factors are considered.     

Neu antigen-negative variants can be generated after neu-specific antibody therapy in neu transgenic mice

Prolonged administration of HER-2/neu-specific monoclonal antibody therapy is now widely used for the treatment of HER-2/neu-overexpressing tumors in advanced-stage breast cancer patients. Monoclonal antibody therapy has the potential to promote reduced tumor expression of HER-2/neu by receptor down-modulation and/or the generation of antigen-negative variants. Loss of antigen by either mechanism could potentially impact subsequent therapeutic strategies targeting HER-2/neu. In this study, the effects of chronic neu-specific monoclonal antibody therapy on tumor growth and neu protein expression were examined in a murine model of neu-overexpressing breast cancer. Treatment of neu-overexpressing tumors with neu-specific antibody, in vitro or in vivo, resulted in significant tumor growth inhibition. When neu antibody was used to treat neu-overexpressing tumor cells both in vitro and in vivo in tumor-bearing mice, neu receptor expression was not diminished after cessation of therapy. However, in the setting of clinically undetectable disease in a fraction of animals, antigen-negative variants were generated. An understanding of the effects of monoclonal antibodies on target antigen expression is critical for the future design and testing of novel HER-2/neu-targeted therapies administered in combination with or after HER-2/neu-specific monoclonal antibody therapy.     

Adjuvant/neoadjuvant trastuzumab therapy in women with HER-2/neu-overexpressing breast cancer: a systematic review

BACKGROUND: A systematic review was undertaken to evaluate the evidence for the use of trastuzumab as (neo)adjuvant therapy for women with HER-2/neu-positive breast cancer and to develop and support recommendations pertaining to its use across five domains: as a single-agent therapy, in combination with chemotherapy, methods to identify women who will benefit from it, adverse events associated with it, and optimal dose, schedule, and duration. METHODS: MEDLINE, EMBASE, the American Society of Clinical Oncology, the San Antonio Breast Cancer Symposia proceedings, and the Cochrane Library were searched through May 2007 for reports of randomized controlled trials that met the inclusion criteria. RESULTS: Eight randomized trials, described across 23 citations, were identified. All six trials of adjuvant trastuzumab reported significantly improved disease-free survival (DFS) while 4 of 6 adjuvant trials showed significant improvement in overall survival (OS) for patients treated with trastuzumab over those that were not. Two trials of trastuzumab in the neoadjuvant setting reported significantly better pathological complete response (pCR) in patients treated with trastuzumab although both studies were limited by small sample size, and longer follow-up is needed. CONCLUSION: Although the optimal duration, schedule, and timing of adjuvant trastuzumab remains undefined, the bulk of the available evidence supports that adjuvant trastuzumab be offered for 1 year to all patients with HER-2-positive and node-positive or high-risk node-negative (tumour 1cm in size) primary breast cancer who are receiving or have received (neo)adjuvant chemotherapy.     

HER-2/neu amplification and overexpression in primary human breast cancer is associated with early metastasis.

The etiology of human breast cancer is poorly understood and no specific marker of transformation has been identified. Amplification of HER-2/neu, as reported in a comprehensive study by Slamon et al, was found to be the most powerful predictor of disease-free and overall survival after the status of the axillary lymph nodes. Our study examines the HER-2/neu oncogene in 61 primary human breast cancers at both the DNA level (by Southern blotting) and the protein level (by immunohistochemical methods). Of the 61 tumors analyzed in our study, 17 (28%) had amplification of HER-2/neu. There was no significant correlation of HER-2/neu amplification with age, tumor diameter or hormone receptor status; however, amplification and overexpression of HER-2/neu was significantly correlated with the status of the axillary lymph nodes (P = 0.02). Of 16 patients with amplification of HER-2/neu, 14 (88%) had positive regional nodes. One of the two node negative cases with amplified HER-2/neu had bone marrow micrometastasis. Overall, 16 out of 17 (94%) tumors of the patients having amplified HER-2/neu had metastatic disease at the time of diagnosis. In summary, HER-2/neu amplification is associated with early tumor dissemination in primary human breast cancer and may be a marker of poor prognosis.     

Neo(adjuvant) trastuzumab treatment: current perspectives

International collaboration with adjuvant trastuzumab trials showed that trastuzumab treatment improves disease-free and overall survival after or in combination with adjuvant chemotherapy. Trastuzumab treatment is already regarded as the standard therapy for HER2-positive breast cancer patients by many guidelines around the world. However, there are many uncertain issues concerning trastuzumab adjuvant treatment, for example duration of therapy, eligibility of elderly women, usability for small tumors (1 cm or less in size), and molecular marker status for individualized treatment in HER2-positive breast cancer.     

Reproducible Immunohistochemical Criteria Based on Multiple Raters’ Judgments for Expression of Thymidine Phosphorylase in Breast Cancer Tissue

The role of HER-2/ neu in male breast cancer is not well defined. The purpose of the current study was to measure the frequency of HER-2/ neu expression in primary male breast cancer, to demonstrate HER-2/ neu gene amplification in cases found to be positive for protein overexpression, and to correlate HER-2/ neu positivity with clinicopathological variables. Formalin-fixed, paraffin-embedded archival material from 99 primary male breast carcinomas was evaluated by immunohistochemistry (IHC) using the HercepTest (DAKO Corp., Hamburg, Germany). Scoring was performed according to established guidelines. All cases demonstrating HER-2/ neu staining by IHC (1+/2+ and 3+) were analyzed for HER-2/ neu gene amplification by fluorescence in situ hybridization (FISH) utilizing the PathVysion assay (Vysis Corp., Downers Grove, Illinois) to assess HER-2/ neu amplification status. The immunohistochemical staining of the HER-2/ neu protein revealed HER-2/ neu positivity in 15/99 (15.1%) cases, eight tumors showed 2+ and 7 tumors 3+ staining. HER-2/ neu gene amplification was observed in 11/99 cases (11,1%), and all of the 3+ and 4/8 from the 2+ cases were amplified. HER-2/ neu gene amplification/protein overexpression did not correlate with tumor state, histological grade or estrogen/progesterone receptor status nor the axillary lymph node status. This is the first comprehensive study of HER-2/ neu gene amplification by FISH analysis in primary male breast cancer. Compared to female primary breast cancer the percentage of HER-2/ neu positivity in our study was lower. Our data provide first evidence for HER-2/ neu gene amplification in male breast cancer. Further studies should be addressed on the potential application of the monoclonal rhuMAB HER-2/ neu antibody for treatment of HER-2/ neu positive male breast cancer.     

Immunologische Therapie beim Mammakarzinom

Besides radio- and chemotherapy, antibodies are one of the most effective substances in breast cancer therapy. Trastuzumab is the first humanized monoclonal antibody that specifically targets human epidermal growth factor receptor-2 (Her-2/neu) breast cancer cells, which are overexpressed in about 20–25% of breast carcinomas. For tumors overexpressing Her-2/neu, trastuzumab is applied as monotherapy or in combination with chemotherapies. Its application is an established part of systemic therapy in metastastic breast cancer, and data on its use in the adjuvant setting show significantly better relapse-free survival. The vascular endothelial growth factor-specific antibody bevacizumab shows good results if applied in the metastatic situation. Further antibodies (cetuximab) and tyrosine kinase inhibitors (gefitinib, erlotinib, lapatinib) are currently under evaluation in studies.