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Anemia Triples Risk of Local Recurrence in Breast Cancer Patients

THURSDAY April 3, 2008 -- Breast cancer patients who develop anemia during chemotherapy face almost three times the risk of a recurrence in the same area of the affected breast, new research suggests.

The Austrian study was a re-analysis of information from a clinical trial that took place in the 1990s. Importantly, the findings also indicated that anemia did alter overall survival or significantly increase the risk of cancer occurring in a patient's other breast or spreading elsewhere in the body. Anemia, a common side effect of chemotherapy, is a low red blood cell count that can cause fatigue and reduced quality of life.

"This study is definitely not aimed at changing current practice," said study author Dr. Peter Dubsky, of the Medical University of Vienna. "This is a retrospective analysis that has yielded quite controversial data. The conclusion from our study is aimed at experimental and clinical oncologic research. Anemia is associated with a high likelihood of tumor hypoxia [too little oxygen in the blood]."

The chemotherapy used in the study was a combination of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). The problems of anemia and related local recurrence are probably not limited to just this form of chemotherapy, noted Dr. Douglas Yee, director of the University of Minnesota Cancer Center. "I think this effect would be seen with any chemotherapy."

CMF is no longer commonly used in the treatment of breast cancer and has been replaced by other forms of chemotherapy such as taxanes, added Dr. Barry C. Lembersky, a clinical associate professor of medicine at the University of Pittsburgh School of Medicine. Also, there is a trend in breast cancer treatment to use chemotherapy less often, he said.

"Nowadays, there is a more selective use of chemotherapy, which tends to be used when a tumor is not stimulated by estrogen, lymph nodes are involved, or the genetic/clinical profile is suited for chemotherapy," he explained.

In the Austrian study, CMF therapy was used as an additional treatment in 424 patients who were premenopausal and who underwent surgery as their main treatment for early-stage breast cancer. All had estrogen receptor-positive malignancies. The findings were published in the April 1 issue of Clinical Cancer Research.

The surgery was either a breast-conserving lumpectomy, which required additional radiation, or a modified radical mastectomy, for which radiation was optional. The radiation was given in the middle of chemotherapy treatment process, which is now an outdated method, Yee noted. "We tend not to do this kind of sandwich technique anymore," he explained.

After an average follow-up of 61 months, 39 local relapses occurred among the 424 women: 6.9 percent in patients without anemia and 19.5 percent in patients with anemia. The five-year rates of local relapse were 8.2 percent among patients without anemia and 19.6 percent among patients with anemia.

In addition to anemia, two other factors -- an older age at diagnosis and positive lymph node status -- significantly increased the risk of a local recurrence of breast cancer. According to an analysis of the range of factors examined in the study, patients with anemia had a 2.96-fold increased relative risk of a local recurrence.

Since the Austrian research was conducted, the treatment of anemia in breast cancer patients has become controversial, Lembersky noted.

"Erythropoietin-stimulating agents are indicated for use by the FDA [U.S. Food and Drug Administration] when red blood cell counts are too low," he said. "However, there is now controversy about their use due to the possible increase in tumor growth in breast cancer."

Dubsky agreed.

"I am sure you are aware of the recent pitfalls in the use of erythropoiesis-stimulating agents (ESAs)," he said. "Given this context, we should start discussing anemia more in the context of tumor hypoxia and look for targets that are distinct from erythropoiesis."

More information

Here's more on the treatment of early-stage breast cancer.

Posted: April 2008


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