Interesting Study on Her2 + and Recurrence

[Sheila]

Study finds small HER2-positive tumors need Herceptin
Source: (cancerfacts.com)
Friday, November 06, 2009

CHICAGO – Nov. 6, 2009 – Early-stage breast cancer patients with small HER2 positive tumors are at significant risk of recurrence, compared to those with early-stage disease who are not HER2 positive, a new study shows.

Led by Dr. Ana, Gonzalez-Angulo, associate professor in M. D. Anderson's Departments of Breast Medical Oncology and Systems Biology, the findings stem from the first large study to analyze this group. The researchers say the results suggest a shift in the way women with early-stage HER2 positive breast cancer should be assessed for risk of recurrence and considered for treatment.

"Our findings show that women with early stage HER2 positive breast cancer have a 23 percent chance of recurrence. In contrast, the five-year survival rate of all women with such early-stage breast cancer is more than 90 percent," Gonzalez-Angulo said in a prepared statement. "The findings indicate that physicians need to consider offering these women Herceptin-based therapy in the post-operative, or adjuvant, setting."

The study was first presented at the San Antonio Breast Cancer Symposium in Dec., 2008 and was published this week online at the website of the Journal of Clinical Oncology.

Gonzalez-Angulo and her team used M. D. 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 (.39 in.); patients whose receptor status could not be analyzed and/or had received adjuvant chemotherapy or Herceptin 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 M. D. 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, 77.1 percent survived five years without recurrence, compared to 93.7 percent of those with HER2 negative tumors. Likewise 86.4 percent of women with HER2 positive tumors survived without a recurrence somewhere else in the body, compared to 97.2 percent in women with HER2-negative tumors. In other words, patients with HER2-positive tumors were 2.68 times more likely to have a recurrence than women with HER2-negative tumors, and 5.3 times more likely to a recurrence in another part of the body than those with HER2-negative tumors.

In addition, women with HER2-positive tumors were 5.09 times more likely to have recurrence and 7.81 times more likely to have distant recurrence than women with hormone receptor-positive tumors.

Herceptin, also known as trastuzumab, was approved for use in 1998 for women whose advanced breast cancer expresses Human Epidermal growth factor Receptor 2, or HER2. Approximately 15 percent to 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 Herceptin-based adjuvant therapy should be discussed with patients if the tumors are from six to 10 millimeters, Gonzalez-Angulo explained.

According to Gonzalez-Angulo, the number of patients with HER2 positive tumors smaller than one centimeter continues to increase as breast cancer surveillance and early detection become increasingly sophisticated.

"Before now, there's been no data regarding how to treat these women because they were excluded from all the definitive trials confirming Herceptin's benefit. This data strongly suggests 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."

The European subset confirmed the findings found from the analysis of the M. D. Anderson patients, said Gonzalez-Angulo.

"The risk of recurrence was much higher than we suspected. With this study, we now have concrete evidence to discuss with our HER2 positive patients with even the smallest of tumors, and Herceptin alone or combined with chemotherapy should be strongly considered as adjuvant therapy," said Dr. Jennifer Litton, assistant professor in M. D. Anderson Department of Breast Medical Oncology, and also an author on the study. "This data should also encourage this subset of patients to be included in ongoing clinical trials with HER2-targeted therapies."

Gonzalez-Angulo and Litton hope that a specific, three-arm clinical trial can be designed comparing observation, Herceptin, and Herceptin combined with chemotherapy.

Currently, M. D. Anderson is a study site for BETH (BEvacizumab and Trastuzumab Adjuvant Therapy in HER2-positive Breast Cancer), an international phase III trial investigating the benefits of combining Avastin and Herceptin, together with chemotherapy for early stage HER2-positive breast cancer.

The study was funded, in part, by an ASCO Career Development Award and NCI grant, both awarded to Dr. Gonzalez-Angulo, and by the Nellie B. Connally Breast Cancer Research Fund.

SOURCE: adapted from press materials provided by M.D. Anderson Cancer Research Center
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