VCU news

By Lorraine Cichowski and Harry Bear

RICHMOND, Va. – A five-year, multi-site study that included more than 2,400 women with operable breast cancer shows that preoperative treatment with the anti-cancer drug, Taxotere, and a standard regimen of chemotherapy dramatically reduced tumor size and – in a notable number of patients  – eliminated cancer completely.

The study, by the renowned National Surgical Adjuvant Breast and Bowel Project (NSABP), advances research that has demonstrated the value of neoadjuvant, or preoperative, chemotherapy for the treatment of operable breast cancer. It also suggests a treatment strategy that eventually might improve survival rates for some breast cancer patients and make more patients eligible for breast-conserving lumpectomies instead of requiring mastectomies that remove the entire breast.

The findings are reported online as an Early Release by the Journal of Clinical Oncology (www.jco.org) and will be published in the journal’s Nov. 15 print edition.

“Giving chemotherapy before surgery has become increasingly common for patients with locally advanced or borderline inoperable breast cancer,” says Dr. Harry D. Bear, chair of surgical oncology at Virginia Commonwealth University and lead author of the NSABP study.  “As more effective drugs have become available, we’ve become interested in extending this approach to patients with less advanced or operable breast cancer. One of the most significant advantages of preoperative chemotherapy is that it allows us to observe the response of the tumor to treatment. We know that a patient’s long-term outcome, including overall survival rates and disease-free rates, correlates with clinical and, even more importantly, pathologic tumor response.”

A clinical complete response means doctors cannot feel or see a tumor in the breast or lymph nodes after treatment; a pathological complete response indicates that laboratory tests on tissue samples from the breast have found no trace of invasive cancer cells. 

Between December 1995 and December 2000, women with operable breast tumors treated at NSABP-affiliated institutions, including VCU’s Massey Cancer Center, were assigned randomly to one of three groups, if they agreed to participate in the clinical trial. The women’s tumors averaged almost two inches in diameter. More than half of the patients were under age 50, and 86 percent were younger than age 60. 

One group of patients (Group I) received four cycles of the chemotherapy drugs Adriamycin and Cytoxan, given every 21 days before surgery. A second group of patients (Group II), after completing treatment with Adriamycin and Cytoxan, received four courses of Taxotere, given every 21 days before surgery. Group III received Taxotere after surgery. In all three groups, patients who underwent lumpectomy were required to undergo a course of radiotherapy to the breast. 

Taxotere is produced by Aventis Pharmaceuticals.

The study showed that patients in Group II who were treated with a combination of Taxotere and standard chemotherapy before surgery had a significantly higher complete clinical response rate than the other two groups.  Clinicians could not feel or see a tumor in the breast or lymph nodes at the time of surgery in almost 64 percent of the patients in Group II, versus about 40% with a complete clinical response in Groups I and III.

Perhaps even more noteworthy, laboratory tests of tissue samples taken from Group II found that 26 percent of the patients treated before surgery with a combination of Taxotere and the other chemotherapy drugs had a pathological complete response – 19 percent of patients were cancer free at the time of surgery, and 7 percent had non-invasive cancer. That compared with a pathological complete response rate of about 14 percent in Groups I and III – about 10 percent with no tumor at the time of surgery and 4 percent with non-invasive cancer.

Group II’s 26 percent pathological complete response rate was also nearly double that achieved in a 1998 NSABP large randomized trial that compared four cycles of Adriamycin and Cytoxan given preoperatively to women with breast cancer versus the same drugs given postoperatively and demonstrated the safety of using preoperative chemotherapy to shrink large breast tumors so that breast conservation could be performed without compromising survival.

“Pathological complete response has been found to be a strong predictor of disease-free and overall survival rates,” says Bear.  “Until recently, however, there have been few agents available that could be added to standard chemotherapy to increase the pathologic response rate. We’re encouraged by the findings in this trial.”

Bear said researchers would study follow-up data from the study to determine if the increase in pathologic response rates in the breast and lymph nodes resulted in an increase in disease-free and overall survival of the patients.  Normally, researchers look at the five-year mark after surgery and treatment when assessing survival rates, but some survival results are reported after three years.

Preliminary results of the study were presented at the 24th Annual San Antonio Breast Cancer Symposium in December 2001.

The National Surgical Adjuvant Breast and Bowel Project is a clinical trial network supported by the National Cancer Institute. During its 40-year history, the project has influenced the way breast cancer is treated and prevented. NSABP breast cancer studies led to the establishment of lumpectomy plus radiation over radical mastectomy as the standard surgical treatment for breast cancer. It was the first to demonstrate that adjuvant, or post-surgery, therapy could increase survival rates and the first to demonstrate on a large scale that the drug, Tamoxifen, prevented breast cancer.