Significant Increased Recurrence Rates Among Breast Cancer Patients with HER2-positive, T1a,bN0M0 Tumors

Researchers at the University of Texas M. D. Anderson Cancer Center have released findings from a large retrospective study showing that women treated for early stage human epidermal growth factor receptor 2 (HER2)-positive breast cancer tumors ≤ 1cm have a significantly greater risk of recurrence than women whose tumors are HER2-negative. Led by Ranjay Rakkhit, MD, fellow, Department of Hematology and Oncology, investigators identified 965 patients treated for breast lesions < 1cm from 1990-2002. Patients were excluded from analysis if their receptor status was undetermined or if data indicated that they had received adjuvant chemotherapy or trastuzumab (Herceptin).

The median age of the women at diagnosis was 57 years, and records showed that 98 (~10%) had tumors that were HER2-positive. Of the remaining 867 patients, 77% were hormone-receptor positive and 13% were triple-receptor negative.

The rate of five-year disease-free survival was significantly lower for those women identified as having an HER2-positive tumor than for women whose tumors were found to be HER2-negative (77.1% vs 93.7%). In addition, the five-year risk of distant recurrence was 5.3 times greater for women with HER2-positive tumors than for women with HER2-negative tumors.

Investigators conducted a second retrospective analysis of 350 patients from European institutions who met the same criteria as patients in the M. D. Anderson cohort. According to the study’s authors, these data confirmed the reproducibility and validity of their earlier findings.

Breast cancer cells that produce excessive amounts of HER2 growth protein are generally more aggressive. Women with advanced HER2-positive breast cancer are often treated with trastuzumab, which binds to the HER2 growth factor on the surface of the cancer cells, thereby inhibiting tumor growth.

Ana M. Gonzalez-Angulo, MD, assistant professor, Department of Breast Medical Oncology and Systems Biology, M. D. Anderson Cancer Center and a senior author of the study, noted that for tumors < 5 mm, current guidelines recommend surgical excision followed by radiation and no adjuvant therapy. For patients whose tumors are

6 mm-10 mm, the guidelines call for discussing the option of trastuzumab therapy. Gonzalez-Angulo said the data from these analyses “strongly suggest that we need to rethink how we treat early stage breast cancer patients with HER2-positive tumors and likely offer anti-HER2 therapy in the adjuvant setting.”

Gonzalez-Angulo believes that as screening measures improve, more women will be identified with tumors < 1cm. She believes this “subset of patients [should] be included in ongoing clinical trials with HER2-targeted therapies,” and said she hopes a three-arm clinical trial can be designed that compares the effects of observation, adjuvant therapy with trastuzumab, and chemotherapy plus adjuvant therapy with trastuzumab.