Treatment-associated anemia in early breast cancer is an important factor in local tumor control, concludes a new study by Austrian researchers. Premenopausal breast cancer patients who developed anemia during chemotherapy had nearly double the incidence of local recurrence as those who did not develop anemia, they report in the April 1 issue of Clinical Cancer Research.
Lead author Peter Dubsky, MD, from the Medical University of Vienna, in Austria, explained that it is already known that anemia interacts with chemotherapy and radiation, and that anemic patients usually showing less of a response. This was the basis for using erythropoietin-stimulating agents (ESAs), he pointed out, but “in view of the recent pitfalls in the treatment of cancer-associated anemia, the use of ESAs can hardly be recommended as a viable treatment option.”
What is new in this report is the clear correlation between anemia and local recurrence, Dr. Dubsky said. This is controversial data from a retrospective analysis, so it is too soon to draw any conclusions, he added. However, he hopes that the research will stimulate a new approach to anemia and take the focus away from erythropoiesis. “We should start discussing anemia more in the context of tumor hypoxia and look for targets that are distinct from erythropoiesis,” he commented in an email.
Anemia is associated with a strong likelihood of tumor hypoxia, and hypoxia is associated with biochemical events that can interact with adjuvant therapy, Dr. Dubsky explained. In addition, recent experimental studies have shown that hypoxia can lead to changes in both the phenotype and genomic stability of tumor cells. “There is even a molecular profile based on hypoxia that has shown prognostic value,” he said, “so this publication will ring a clinical bell for this type of research.”
Anemia Seen Only in Chemotherapy Group
For the current report, the authors conducted a retrospective analysis of data collected during the Austrian Breast and Colorectal Cancer Study Group Trial 5. They focused on the part of this trial that involved 424 premenopausal women with early-stage breast cancer and hormone-receptor-expressing tumors who had already undergone surgery and some radiotherapy. This part of the study compared endocrine therapy with tamoxifen and chemotherapy with cyclophosphamide, methotrexate, and 5-fluorouracil. This is quite a dated regimen, Dr. Dubsky commented; the trial was designed in late 1980s. Overall, the study showed superiority for the tamoxifen groups.
An analysis of blood samples collected during the study showed that anemia (<12 g/dL) developed within 3 months in 18% of patients undergoing chemotherapy, but was a very rare event (<1% patients) with endocrine therapy.
After a median follow-up of 5 years, local recurrence occurred in 19.5% of anemic patients, compared with 6.9% or 8.9% of nonanemic patients (P = .0006). Anemic patients had a 2.96-fold increased relative risk of developing local relapse compared with nonanemic patients. However, the overall relapse rate and the number of deaths were equal among anemic and nonanemic patients.
The authors point out that the 2 treatment groups were assigned randomly and patient characteristics (including type of surgery and use of radiotherapy) were well balanced between the 2 groups, so it is “most likely [the use of chemotherapy that is] responsible for the difference in the anemia rates.”
Dr. Dubsky commented that the team was surprised to see such a high rate of local recurrences in anemic patients, and were surprised that this finding did not extend to distant recurrences (metastases).
Young age and node involvement were also associated with local recurrences, but these 2 factors are well known among oncologists, Dr. Dubsky commented. Anemia might be a new factor, he added.
Anemia is Common, But Not Often Treated
Anemia occurs commonly during chemotherapy for breast cancer, but is often not treated, the authors comment. They cite data from an Austrian prospective chart review (Breast Cancer Res Treat. 2003;79:347-353), which found that nearly 60% of primary nonmetastatic breast cancer patients undergoing chemotherapy with multiagent nonplatinum-based agents became anemic (defined as hemoglobin levels <12 g/dL). The European Cancer Anemia Survey of more than 3000 breast cancer patients found similar results (Oncology. 2005;68:3-11). However, only 18.5% of patients in the Austrian study and 26% in the European survey received treatment for anemia, they note.
Reviewed by Dr. Ramaz Mitaishvili
