Public Release: 

Chemotherapy more effective when given before breast cancer surgery

Center for Advancing Health

Giving chemotherapy to women with operable breast cancer before they have surgery --not after -- helps physicians pin down the best treatment regimen and can reduce the extent of surgery, according to a new systematic review.

Preoperative chemotherapy reduced chemo-related infections by 4 percent and the need for mastectomies by 17 percent when compared to postoperative chemotherapy, found reviewers led by Sven Mieog, M.D., of Leiden University Medical Center in the Netherlands.

Mieog and colleagues looked at 14 studies that included 5,500 women with operable breast cancer. Half of the women received preoperative chemotherapy and the rest received chemotherapy after surgery.

The data revealed a higher cancer recurrence rate in women who had chemotherapy before surgery, although this did not affect survival rates, which were similar for both groups.

"Ten studies reported overall survival data on 4,620 women involving 1,139 estimated deaths," the authors write. "There was no detectable difference between preoperative and postoperative chemotherapy."

The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates research in all aspects of health care. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing trials on a topic.

One reason for giving chemotherapy first is to shrink tumors before surgery, the researchers say.

Moreover, preoperative chemotherapy allows doctors to see if a tumor is resistant to a particular drug and thus adjust the dose or switch to another drug after surgery. The patient might avoid toxic side effects while getting another chance to receive appropriate systemic treatment, Mieog said.

After surgery, doctors can no longer gauge chemotherapy's effect on tumor size.

"Concerns could be raised on the postoperative and thus 'blind' administration of chemotherapy to patients with tumors resistant to a specific chemotherapy regimen," Mieog said. "These patients will receive all chemotherapy courses while only experiencing the harmful side effects."

Side effects such as hair loss, cardiac symptoms, nausea and vomiting, and white blood cell disorders were similar for both groups, the Cochrane reviewers found.

"Initially, preoperative chemotherapy was set up to improve overall survival by not waiting for the surgical procedure and the subsequent recovery -- a couple of months means one or two [cancer] cell divisions," Mieog said.

He added, "The chemotherapy also increased the breast conservation rate; it is well known that conserving the breast as compared to mastectomy is associated with an increased recurrence rate, without, however, hampering long-term overall survival."

"It is important to evaluate issues of timing and specifically consider the advantages of preoperative chemotherapy," said Terry Mamounas, M.D., medical director of the Mount Sinai Center for Breast Health in Cleveland.

Earlier studies suggest "a correlation between tumor response with preoperative chemotherapy and relapse-free survival," Mamounas said. He added that the response to preoperative chemotherapy can give clues about the outcome of the therapy and help guide further treatment.

The Cochrane review showed that tumors shrank more in some of the women who received preoperative chemotherapy than in others. "Different factors could have influenced the reported rates," the researchers write, "including definition of response, blinding of assessor, method and type of assessment, study population and type of chemotherapy used."

"The most appropriate method of clinical tumor response assessment remains a matter of debate," they add.

The researchers say that preoperative chemotherapy is currently the standard of care in locally advanced breast cancer. The choice of whether women should receive preoperative chemotherapy depends on a variety of factors, according to Mieog, although cost is not an issue: "The costs of chemotherapy are not significantly different before or after surgery."

According to the Centers for Disease Control and Prevention, breast cancer is the most common cancer in women, regardless of race or ethnic background. The National Cancer Institute estimates that 192,000 American women are diagnosed with breast cancer each year.

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Mieog JSD, van der Hage JA, van de Velde CJH. Preoperative chemotherapy for women with operable breast cancer (Review). Cochrane Database of Systematic Reviews 2007, Issue 2.

The Cochrane Collaboration is an international nonprofit, independent organization that produces and disseminates systematic reviews of health care interventions and promotes the search for evidence in the form of clinical trials and other studies of interventions. Visit http://www.cochrane.org for more information.

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