How Risky Are Small HER-2-Positive Tumors?
The major adjuvant trials of trastuzumab have centered on high-risk, node-negative or node-positive breast cancer. The benefit of trastuzumab in patients with small, node-negative but HER-2-positive cancers is not well established because the natural history of these lesions is not well known. Investigators from the M.D. Anderson Cancer Center reported on outcomes of tumors 1 cm or smaller as a function of HER-2 status.
[4] This observational cohort did not receive either chemotherapy or trastuzumab, and thus the study does not permit one to know how each of these interventions might be of benefit. What was observed, however, was that prognosis clearly depended on HER-2 status. For HER-2-negative tumors, the 10-year risk for recurrence-free survival with T1abN0 breast cancer was 88% if the tumor was ER positive and was 80% if "triple negative." However, if the tumor was HER-2 positive, 10-year recurrence-free survival was only 62%.
This observation suggests that even small tumors that are HER-2 positive carry a substantial risk for recurrence and might benefit from adjuvant treatment with chemotherapy and trastuzumab. This is consistent with current guidelines from the National Comprehensive Cancer Network, which suggest consideration of chemotherapy and trastuzumab for HER-2-positive tumors that measure between 6 and 10 mm. A prospective study conducted at the Dana-Farber Cancer Institute and affiliated sites is testing the effectiveness of paclitaxel plus trastuzumab for stage 1, HER-2-positive tumors.
Summary
Anti-HER-2 therapy remains a field of vital clinical investigation. New agents from both the antibody-based and small molecular/tyrosine kinase inhibitor-based domains are in development. Emerging data raise fascinating questions about the interplay of ER and HER-2 signaling pathways that are being explored in ongoing clinical trials. Meanwhile, the risk for HER-2-positive lesions continues to be marked in the absence of trastuzumab, underscoring the value of that agent in treating early-stage breast cancer.
This activity is supported by an independent educational grant from Susan G. Komen for the Cure.
References
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References
- Vukelja S, Rugo H, Vogel C, et al. A phase II study of trastuzumab-DM1, a first-in-class HER2 antibody-drug conjugate, in patients with HER2+ metastatic breast cancer. Cancer Res. 2009;69(suppl 2):71s. Abstract 33.
- Burstein HJ, Sun Y, Tan AR, et al. Neratinib (HKI-272), an irreversible pan erbB receptor tyrosine kinase inhibitor: phase 2 results in patients with advanced HER2+ breast cancer. Cancer Res. 2009;69(suppl 2):73s. Abstract 37.
- Johnston S, Pegram M, Press M, et al. Lapatinib combined with letrozole vs letrozole alone for front line postmenopausal hormone receptor positive (HR+) metastatic breast cancer (MBC): first results from the EGF30008 trial. Cancer Res. 2009;69(suppl 2):74s. Abstract 46.
- Rakkhit R, Broglio K, Peintinger F, et al. Significant increased recurrence rates among breast cancer patients with HER2-positive, T1a,bN0M0 tumors. Cancer Res. 2009;69(suppl 2):96s. Abstract 701.
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Author(s)
Harold J Burstein, MD, PhD
Associate Professor of Medicine, Harvard Medical School, Boston, Massachusetts
Disclosure: Harold J. Burstein, MD, PhD, has disclosed no relevant financial relationships.
Editor(s)
Margie Miller
Group Editorial Director, Medscape Hematology-Oncology
Disclosure: Margie Miller has disclosed no relevant financial relationships.
Emma Hitt, PhD
Freelance editor and writer, Marietta, Georgia
Disclosure: Emma Hitt, PhD, has disclosed no relevant financial relationships.
Jill W. Chamberlain
Editorial Director, Medscape Hematology-Oncology
Disclosure: Jill W. Chamberlain has disclosed no relevant financial relationships.
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CME Information
CME Released: 01/20/2009; Valid for credit through 01/20/2010
Target Audience
This activity is intended for oncologists and other healthcare providers who treat patients with breast cancer.
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The goal of this activity is to report and appraise new and emerging treatment regimens and clinical strategies for breast cancer; to enhance the care and outcomes of persons with breast cancer; and to support quality clinical practice of healthcare professionals involved in the management of patients with breast cancer.
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Upon completion of this activity, participants will be able to:
- Appraise the most recent clinical trial data on newer and emerging treatment options for patients with HER-2-positive breast cancer
- Evaluate newly reported clinical trial data on the use of endocrine therapy in the adjuvant setting in patients with early-stage breast cancer
- List the clinical characteristics of breast cancer stem cells and list potential therapeutic approaches that target such cells
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Contents of Highlights of SABCS 2008 All sections of this activity are required for credit.
- Highlights in HER-2-Positive Breast Cancer
- Highlights in Adjuvant Endocrine Therapy for Breast Cancer
- Breast Cancer Stem Cells as Novel Therapeutic Targets: An Expert Interview With Dr. Max S. Wicha
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