Locally advanced breast cancer is breast cancer that has spread to tissue near the breast, but not to distant locations in the body (such as bones or the brain). The study reviewed here found that Herceptin (chemical name: trastuzumab) given in combination with chemotherapy BEFORE surgery for HER2-positive locally advanced breast cancer improves survival without the breast cancer coming back (called "disease-free survival"). Treatments given before surgery are called neoadjuvant treatments. These results were presented at the 2008 San Antonio Breast Cancer Symposium.
Herceptin is a targeted therapy medicine commonly used AFTER surgery to treat HER2-positive breast cancers. HER2-positive cancers have too many copies of the HER2/neu gene that makes too much of the HER2 protein. About 1 out of every 4 breast cancers is HER2-positive. HER2-positive breast cancers tend to be more aggressive than HER2-negative breast cancers.
In this study, called the NOAH trial, half of 228 women diagnosed with HER2-positive locally advanced breast cancer got standard chemotherapy treatments before surgery. The other half of the women got standard chemotherapy treatments AND Herceptin before surgery. Because all the breast cancers were HER2-positive, all of the women were treated with Herceptin after surgery.
The results:
Most of the women who got Herceptin before surgery didn't have any serious side effects. Herceptin is given intravenously and may cause flu-like symptoms in about 40% of the people who receive it. Side effects are usually less severe after the first treatment. There is also a 5% to 30% risk that Herceptin can damage the heart's ability to pump blood effectively. The risk of serious heart damage goes up when Herceptin is given with other chemotherapy medicines known to cause heart damage. Adriamycin (chemical name: doxorubicin) is a chemotherapy medicine that can cause heart damage. In this study, 95% of the women who got Herceptin before surgery had no or very little effect on their hearts from the Herceptin.
Based on these results, adding Herceptin to the treatment plan before surgery for HER2-positive locally advanced breast cancer may make sense for many women. If you've been diagnosed with HER2-positive locally advanced breast cancer, Herceptin will likely be a part of your treatment plan after surgery. Consider talking to your doctor about this study and whether combining Herceptin with chemotherapy BEFORE surgery is a good choice for you. Together you and your doctor can decide on the best treatment based on your unique situation.
Visit the Breastcancer.org Targeted Therapies section to learn more about Herceptin and other targeted therapies used to treat breast cancer.
SAN ANTONIO, Dec. 14 (MedPage Today) -- Patients with locally advanced HER2-positive breast cancer had significant improvement in event-free survival when trastuzumab (Herceptin) was added to extensive neoadjuvant chemotherapy, investigators reported here.
Trastuzumab plus chemotherapy was associated with a three-year event-free survival of 70% compared with 53% for patients who received chemotherapy alone, Luca Gianni, M.D., of the National Cancer Institute in Milan, said at the San Antonio Breast Cancer Symposium.
Additionally, almost twice as many trastuzumab-treated patients had complete pathologic responses.
"These data establish neoadjuvant trastuzumab with chemotherapy as a standard treatment option in women with HER2-positive locally advanced breast cancer," said Dr. Gianni.
Locally advanced breast cancer is associated with a significantly worse survival compared with other types of cancer (three to six years versus more than 10), and they need better treatment, said Dr. Gianni.
Neoadjuvant chemotherapy has a key role in all treatment strategies for locally advanced breast cancer, he continued. Whether the addition of trastuzumab would improve neoadjuvant results had not been thoroughly examined.
In the international phase III NOAH trial, investigators studied 228 patients with HER2-positive breast cancer (T3N1 or any T plus N2 or N3). All the patients received standard neoadjuvant chemotherapy, starting with three cycles of doxorubicin-paclitaxel therapy, followed by four cycles of paclitaxel, and ending with four cycles of CMF (cytoxan/methotrexate/5-fluorouracil) combination therapy. The patients were then randomized to receive chemotherapy plus trastuzumab or to chemotherapy alone.
After eight months of neoadjuvant chemotherapy, all patients had surgery, followed by radiotherapy and adjuvant tamoxifen. Patients in the trastuzumab arm continued it to 52 weeks.
The study also included a group of 99 HER2-negative patients with locally advanced disease who received the same chemotherapy, followed by surgery, radiation, and tamoxifen.
The primary outcome was event-free survival, defined by progression on therapy, relapse after surgery, or death from any cause. The advantage in the trastuzumab-treated patients at three years translated into a hazard ratio of 0.55 compared with the HER2-positive patients who received only chemotherapy (P=0.006).
Subgroup analysis demonstrated a consistent advantage in favor of trastuzumab with respect to event-free survival.
The addition of trastuzumab to chemotherapy doubled the rate of complete pathologic responses (43% versus 23%, P=0.002). Dr. Gianni said 17% of the HER2-negative patients had complete pathologic responses. Overall response rates were 89% with trastuzumab and 77% with chemotherapy alone (P=0.02).
Three-year overall survival trended in favor of the trastuzumab group but did not achieve statistical significance (HR 0.65, P=0.18).
The neoadjuvant regimen was well tolerated, as few patients in any of the treatment groups had grade 3-4 adverse events. Noting concern about cardiotoxicity with trastuzumab, Dr. Gianni reported that 95% of patients who received the monoclonal antibody had common toxicity criteria values of 0-1 for cardiotoxicity.
"Herceptin, given before surgery, significantly extends survival without recurrence to patients with locally advanced, HER2-positive breast cancer," said Dr. Gianni. ""This most likely will translate into an advantage in terms of survival. The preoperative regimen was well tolerated with acceptable cardiac safety."
F. Hoffmann-La Roche co-sponsored the study with the Michelangelo Foundation.
Dr. Gianni has served as a consultant to Genentech and Roche and has received honoraria from Roche and GlaxoSmithKline.
Primary source: San Antonio Breast Cancer Symposium Source reference: San Antonio Breast Cancer Symposium. 2008 Abstracts. Abstract 31.
Breastcancer.org 7 East Lancaster Avenue, 3rd Floor Ardmore, PA 19003
Learn more about our commitment to your privacy
© 2009 Breastcancer.org - All rights reserved.
Breastcancer.org is a non-profit organization dedicated to providing information and community to those touched by this disease. Learn more about our commitment to providing complete, accurate, and private breast cancer information.
_tcm8-332386.jpg "wellness_dvd_promo")