Exploring the use and impact of adjuvant Trastuzumab for HER2-positive breast cancer patients in a large UK cancer network
Do the results of international clinical trials translate into a similar benefit for patients in South East Wales?

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Abstract

Background:

Trastuzumab was approved in the United Kingdom for adjuvant treatment of human epidermal growth factor receptor 2 (HER2)+ breast cancer in 2006 at significant economic cost and with limited evidence in smaller T1N0 tumours. The South East Wales Cancer Network covers a population of 1 420 000 and maintains a database of treatments used. We examined this database to ensure the outcome of Trastuzumab use is as expected, especially in patients with T1N0 cancers.

Ethods:

M Case notes of patients with HER2+ disease eligible for adjuvant Trastuzumab over 2005–2008 were reviewed. Disease-free survival (DFS) and overall survival (OS) were calculated with the Kaplan–Meier method using SPSS (version 16.0.01 for Windows, SPSS, Chicago, IL, USA).

Results:

A total of 239 of 338 (70.7%) eligible HER2+ patients received treatment. At 3 years, the DFS of the treated group was 90.3% vs 73.3% and the OS was 98.5% vs 87.6%. In all, 47 of 92 stage I patients received Trastuzumab. Despite a trend towards worse prognostic factors in the treated group the DFS was 100% vs 84.1% and the OS was 100% vs 93.3%.

Conclusion:

Our results are comparable to those from landmark Trastuzumab trials. As evidence continues to emerge that smaller HER2+ cancers may behave aggressively our analysis of stage I tumours adds further support to the use of Trastuzumab in these patients.

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Most cited references 10

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High risk of recurrence for patients with breast cancer who have human epidermal growth factor receptor 2-positive, node-negative tumors 1 cm or smaller.

Richard Theriault, Aysegul Sahin, Martine Piccart-Gebhart … (2009)

To evaluate the risk of recurrence in women diagnosed with T1a and T1b, node-negative, human epidermal growth factor receptor 2 (HER2) -positive breast cancer. We reviewed 965 T1a,bN0M0 breast cancers diagnosed at our institution between 1990 and 2002. Dedicated breast pathologists confirmed HER2 positivity if 3+ by immunohistochemistry or if it had a ratio of 2.0 or greater by fluorescence in situ hybridization (FISH). Patients who received adjuvant chemotherapy or trastuzumab were excluded. Kaplan-Meier product was used to calculate recurrence-free survival (RFS) and distant recurrence-free survival (DRFS). Cox proportional hazard models were fit to determine associations between HER2 status and survival after adjustment for patient and disease characteristics. Additionally, 350 breast cancers from two other institutions were used for validation. Ten percent of patients had HER2-positive tumors. At a median follow-up of 74 months, there were 72 recurrences. The 5-year RFS rates were 77.1% and 93.7% in patients with HER2-positive and HER2-negative tumors, respectively (P < .001). The 5-year DRFS rates were 86.4% and 97.2% in patients with HER2-positive and HER2-negative tumors, respectively (P < .001). In multivariate analysis, patients with HER2-positive tumors had higher risks of recurrence (hazard ratio [HR], 2.68; 95% CI, 1.44 to 5.0; P = .002) and distant recurrence (HR, 5.3; 95% CI, 2.23 to 12.62; P < .001) than those with HER2-negative tumors. Patients with HER2-positive tumors had 5.09 times (95% CI, 2.56 to 10.14; P < .0001) the rate of recurrences and 7.81 times (95% CI, 3.17 to 19.22; P < .0001) the rate of distant recurrences at 5 years compared with patients who had hormone receptor-positive tumors. Patients with HER2-positive T1abN0M0 tumors have a significant risk of relapse and should be considered for systemic, anti-HER2, adjuvant therapy.

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

Gustavo Viani, Sergio Afonso, Eduardo Stefano … (2007)

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. Methods A meta-analysis of randomized controlled trials (RCT) was performed comparing adjuvant trastuzumab treatment for HER2-positive early breast cancer (EBC) to observation. The MEDLINE, EMBASE, CANCERLIT and Cochrane Library databases, and abstracts published in the annual proceedings were systematically searched for evidence. Relevant reports were reviewed by two reviewers independently and the references from these reports were searched for additional trials, using guidelines set by QUOROM statement criteria. Results Pooled results from that five randomized trials of adjuvant Trastuzumab showed a significant reduction of mortality (p < 0.00001), recurrence (p < 0.00001), metastases rates (p < 0.00001) and second tumors other than breast cancer (p = 0.007) as compared to no adjuvant Trastuzumab patients. There were more grade III or IV cardiac toxicity after trastuzumab (203/4555 = 4.5%) versus no trastuzumab (86/4562 = 1.8%). The likelihood of cardiac toxicity was 2.45-fold higher (95% CI 1.89 – 3.16) in trastuzumab arms, however that result was associated with heterogeneity. The likelihood of brain metastases was 1.82-fold higher (95% CI 1.16 – 2.85) in patients who received trastuzumab. Conclusion The results from this meta-analysis are sufficiently compelling to consider 1 year of adjuvant trastuzumab treatment for women with HER-2-positive EBC based on the risk: benefit ratio demonstrated in these studies. Adequate assessment of HER-2/neu status is critical, and careful cardiac monitoring is warranted because of cardiac toxicity. Clinical trials should be designed to answer unsolved questions.

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Clinical relevance of HER2 overexpression/amplification in patients with small tumor size and node-negative breast cancer.

Aron Goldhirsch, Elisabetta Munzone, Franco Nolè … (2009)

To assess the prognostic role of HER2 overexpression/amplification in patients with node-negative, pT1a-b breast cancers. All patients with HER2-positive breast cancer were identified among a population of 2,130 patients whose diseases were staged as pT1a-b, pN0 and who underwent surgery at the European Institute of Oncology from 1999 to 2006. A matched cohort was selected by using variables of hormone receptor status, age, and year of surgery. We estimated rates of local and distant recurrence, disease-free survival (DFS), and overall survival (OS) in the two groups. We identified 150 consecutive patients with pT1a-b, pN0, HER2-positive tumors. No patient received adjuvant trastuzumab. The median follow-up was 4.6 years (range, 1.0 to 9.0 years). In the hormone receptor-positive group, 5-year DFS rates were 99% (95% CI, 96% to 100%) for HER2-negative disease and 92% (95% CI, 86% to 99%) for HER2-positive disease. In the hormone receptor-negative group, 5-year DFS rates were 92% (95% CI, 84% to 100%) for HER2-negative disease and 91% (95% CI, 84% to 99%) for HER2-positive disease. Overall, the hazard ratio (HR) associated with HER2 overexpression was 2.4 (95% CI, 0.9 to 6.5; P = .09). After analysis was adjusted for pT1 stage, hormone receptor-positive disease with HER2-positive status was associated with a worse prognosis (HR, 5.1; 95% CI, 1.0 to 25.7). OS in HER2-positive, pT1a-b, pN0 breast cancer was similar irrespective of the hormone receptor status (P = .93). Patients with node-negative, HER2 positive, pT1a-b breast cancer have a low risk of recurrence at 5 years of follow-up. In patients with hormone receptor-positive disease and pT1a-b, N0 tumors, HER2 overexpression was associated with a worse DFS.

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Author and article information

Journal

Journal ID (nlm-ta): Br J Cancer

Title: British Journal of Cancer

Publisher: Nature Publishing Group

ISSN (Print): 0007-0920

ISSN (Electronic): 1532-1827

Publication date (Print): 03 January 2012

Publication date (Electronic): 22 November 2011

Volume: 106

Issue: 1

Pages: 32-38

Affiliations

[1 ]Department of Clinical Oncology, Velindre Cancer Centre, Whitchurch , Cardiff CF14 2TL, UK

[2 ]Department of Pathology, University Hospital of Wales , Cardiff, UK

Author notes

[* ]E-mail: Websterrm@ 123456cardiff.ac.uk

Article

Publisher Item ID: bjc2011506

DOI: 10.1038/bjc.2011.506

PMC ID: 3251855

PubMed ID: 22108523

SO-VID: 983a452c-8274-4989-bd13-82548f9ee061

History

Date received : 09 August 2011

Date revision received : 18 October 2011

Date accepted : 24 October 2011

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Exploring the use and impact of adjuvant Trastuzumab for HER2-positive breast cancer patients in a large UK cancer network Do the results of international clinical trials translate into a similar benefit for patients in South East Wales?

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Abstract

Background:

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Results:

Conclusion:

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Karger: Oncology

Most cited references 10

High risk of recurrence for patients with breast cancer who have human epidermal growth factor receptor 2-positive, node-negative tumors 1 cm or smaller.

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

Clinical relevance of HER2 overexpression/amplification in patients with small tumor size and node-negative breast cancer.

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