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Guidelines Released for Managing Metastatic Breast Cancer

November 4, 2009

Written By Mary Alice Hartsock
Reviewed By Virginia F. Borges, MD, MMSc

The European School of Oncology’s Metastatic Breast Cancer Task Force released new international guidelines for managing metastatic breast cancer in the Journal of the National Cancer Institute.

The task force said both combination and sequential single-agent chemotherapy are "reasonable options" for treating advanced breast cancer because they demonstrate similar survival outcomes. However, sequential single-agent therapy should be the "preferred choice" because it is associated with fewer side effects, the task force said. Clinicians may consider a switch to combination therapy if, despite single-agent therapy, the cancer grows quickly, becomes life-threatening or requires immediate symptom control.

Research that directly compares the two approaches is needed to settle this question, the task force said. You and your doctors may consider these guidelines when discussing your treatment options.

The Evidence

Cancer researchers continue to debate whether it is better to treat metastatic breast cancer with sequential single-agent chemotherapy (a series of medicines with one chemotherapy given at a time) or with combination chemotherapy (several chemotherapies given at the same time).

In early-stage breast cancer, researchers have issued "consensus statements" about chemotherapy treatment, guidelines they develop based on findings from clinical trials. Doctors take consensus statements into account when planning your care.

In metastatic breast cancer, no consensus statements exist on the use of chemotherapy. To address this gap, in 2005 the European School of Oncology (ESO) and the European Breast Cancer Conference (EBCC) formed a Metastatic Breast Cancer Task Force. Both ESO and EBCC represent oncologists from around the world.

The task force discussed the treatment controversy at its 2009 meeting, examining numerous studies of:

  • An anthracycline (such as doxorubicin, or Adriamycin) taken alone versus combination therapy
  • A taxane (such as docetaxel, or Taxol) taken alone versus combination regimens
  • Capecitabine (brand name: Xeloda) alone versus combination therapy
  • Vinorelbine (brand name: Navelbine) alone versus combination therapy

What the Task Force Found

Very few trials directly compared single-agent to combination chemotherapy. However, eight randomized trials offered a balanced comparison of sequential single-agent therapy versus combination therapy.

Six of these trials suggested similar overall survival in both therapies, though combination therapy caused more side effects. One study showed single-agent therapy to be more effective than combination therapy at delaying time to progression and increasing the rate of response to treatment; however, the therapies were equivalent in overall survival. The final trial, a very small, unpublished study, suggested a better survival outcome with combination therapy.

Overall, combination therapy was associated with better response rate and increased time to disease progression compared to single-agent therapy. But women who took combination therapies often experienced more side effects than women who took single-agent chemotherapy—without increasing their survival.

Because metastatic disease can require ongoing chemotherapy, the task force noted the importance of maintaining quality of life when choosing treatments. It concluded that single-agent therapy is preferable to combination therapy for women who do not have rapid disease progression, life-threatening tumors in the liver or lung or an urgent need to control symptoms.

Future Research

Future studies are needed that compare combination and single-agent therapies for quality of life and overall survival, the group said. These studies may help doctors to determine which women are most likely to benefit from a combination approach.

The task force proposed conducting a multiple-institution trial of sequential single-agent chemotherapy and combination chemotherapy and using questionnaires or interviews of participants to record side effects. It also recommended new research to uncover how to lessen the side effects associated with chemotherapy.

What Does this Study Mean for Me?

Every cancer is unique, so the choice of combination versus single-agent chemotherapy should be made by you and your doctor, the task force said. Among the issues it recommended you and your team consider: your age, the availability of medicines, the traits of the breast cancer, how the cancer responded to previous treatments, the number of cancer sites and your lifestyle.

An important note: this new guideline did not contain recommendations about targeted (also called biologic) therapies, which usually are given in combination with chemotherapy. Often, targeted therapies only work effectively when given with chemotherapy medicines. Be sure to ask your doctors to explain what types of medicines they recommend and why it makes sense to give them in combination. They can help you understand the potential side effects and schedules of each treatment. This information could help you weigh the possible advantages and disadvantages of each treatment against your personal goals and quality-of-life needs.

F. Cardoso, et al. International Guidelines for Management of Metastatic Breast Cancer: Combination vs Sequential Single-Agent Chemotherapy. J Natl Cancer Inst 2009; 101: 1174-1181.

Read more about combination versus sequential therapy in metastatic breast cancer.