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Guest column

Targeted therapy improves breast cancer prognosis

By V. UPENDER RAO
Published May 2, 2005

Herceptin (Trastuzumab) is a humanized monoclonal antibody that is engineered to target breast cancer cells that carry an excess number of copies of a growth-promoting oncogene known as Her2 Nu. Overexpression of the Her2 Nu oncogene accelerates tumor cell growth and is considered a marker of poor prognosis.

Interim results of two randomized clinical trials announced just a couple of days ago showed that the addition of Herceptin to standard chemotherapy increased the disease-free survival for early-stage breast cancer patients by 52 percent, as compared with those who received standard chemotherapy alone. The data monitoring committees overseeing these two trials said it was appropriate to release the interim results without waiting for the more mature data because the primary endpoint of increasing the disease-free survival was met.

Herceptin is currently approved by the FDA for treatment of metastatic or advanced breast cancer. The National Cancer Institute sponsored two clinical trials conducted by the National Surgical Bowel and Breast Project, the North Central Cancer Treatment Group and other research organizations to study the utility of Herceptin combined with standard chemotherapy in early-stage breast cancer.

Patients were accrued onto these two studies between April 2000 and March 2005. Analysis of more than 3,300 patients treated on these two studies yielded a disease-free survival advantage of 52 percent for patients with early-stage breast cancer and an overexpression of Her2 Nu oncogene when treated with Herceptin in addition to standard chemotherapy.

A majority of the patients studied had lymph node positive breast cancers, but a few were node negative. The results of these studies are, therefore, more pertinent to patients who have lymph node positive, Her2 Nu overexpressed early-stage breast cancers. This, however, should not be construed as meaning that Her2 Nu positive, node negative patients do not benefit from Herceptin: The number of Her2 Nu positive and lymph node patients in these two studies was so small that a statistically relevant number could not be expected, and therefore a separate analysis was not undertaken. Another study of node negative, Her2 Nu positive breast cancers with sufficient numbers to reach statistical power can address this issue properly.

Congestive heart failure emerged as a side effect in 3 to 4 percent of patients who received Herceptin in addition to chemotherapy. It is anticipated in 1 percent of patients who take chemotherapy alone. The extent to which the patients were symptomatic with this problem was not mentioned. This information is important because those with mild congestive heart failure can remain fully functional with treatment.

The details of these studies will be presented at the American Society of Clinical Oncology annual meeting in Orlando in a couple of weeks.

Two days after the NCI-sponsored studies' results were released, the Breast International Group announced the results of a Phase III study involving 8,000 patients in 39 countries. It showed a significant increase in disease-free survival for early-stage breast cancer patients with Her 2 Nu overexpression.

Various leaders in breast cancer research and treatment hailed these results as a major advance for thousands of women with breast cancer and a major turning point in the use of targeted therapies to eliminate suffering and death from cancer. Addition of Trastuzumab (Herceptin) to chemotherapy appears to virtually reverse the prognosis from unfavorable to good.

This news represents an important milestone in the fight against this aggressive type of breast cancer and for patients who faced a poor outlook.

Eight to 9 percent of women will develop breast cancer during their lives. This year, in the United States alone, an estimated 211,240 new cases and 40,110 deaths are anticipated. Worldwide, more than 1-million women develop breast cancer each year, and 400,000 deaths are attributed to it. About 20 to 30 percent - or 200,000 to 300,000 patients worldwide - will have Her 2 Nu overexpression and can be expected to benefit from Herceptin treatment for early-stage breast cancer. Many women with metastatic or advanced disease are already receiving and realizing favorable results from it.

--V. Upender Rao, MD, FACP, practices at the Cancer and Blood Disease Center in Lecanto.

[Last modified May 2, 2005, 01:35:17]