Increased risk of recurrence for patients with early stage, HER2-positive breast cancer


Early-stage breast cancer patients with HER2 positive tumors one centimeter or smaller are at significant risk of recurrence of their disease, compared to those with early-stage disease who do not express the aggressive protein.

Trastuzumab, also known as Herceptin, was approved for use in 1998 for women whose advanced breast cancer expresses Human Epidermal growth factor Receptor 2, or HER2. Approximately 15-20 percent of breast cancer cells produce an excess amount of the HER2 growth protein on their surface, which makes the cancer more aggressive. Herceptin is a monoclonal antibody that latches on to these proteins and inhibits tumor growth.

Current guidelines call for no additional therapy after surgery and radiation if tumors are less than five millimeters and Trastuzumab-based adjuvant therapy should be discussed with patients if the tumors are from six to 10 millimeters.

For the retrospective study, Gonzalez-Angulo, and her team used MD Anderson's Breast Cancer Research Database to analyze 965 patients treated between 1990 and 2002. All of the patients' tumors were smaller than one centimeter; patients whose receptor status could not be analyzed and/or had received adjuvant chemotherapy or Trastuzumab at any time were excluded. The median age of the women at diagnosis was 57 years. To validate the findings, a second cohort of 350 patients from European institutions was also analyzed.

Of the MD Anderson patient population, more than 10 percent, or 98 patients, had HER2 positive tumors. In addition, 77 percent were hormone-receptor positive and 13 percent were triple receptor-negative.

In those analyzed with HER2 positive tumors, the five-year, recurrence-free survival was 77.1 percent; in contrast, HER2 negative patients' recurrence-free survival was 93.7 percent. Five-year distant recurrence-free survival was 86.4 percent in women with HER2 positive tumors compared to 97.2 percent in women with HER2-negative tumors. Patients with HER2-positive tumors had 2.68 times higher risk of recurrence and 5.3 times higher risk of distant recurrence than those with HER2-negative tumors.

In addition, women with HER2-positive tumors had 5.09 times the risk of recurrence and 7.81 times risk of distant recurrence than women with hormone receptor-positive tumors.

The European subset confirmed the MD Anderson findings and showed reproducibility.

Source: University of Texas MD Anderson Cancer Center, 2009

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