Chemotherapy-induced anaemia increases risk of local breast cancer recurrence

"We speculate that there may be an interaction between chemotherapy/radiotherapy and anaemia," said lead researcher Peter Dubsky, MD, a senior consultant in the department of surgery at the Medical University of Vienna, Austria. "Both treatment modalities have been shown to be less effective in anaemic patients. Since we do not see the effect in terms of relapse-free survival, the interaction with local adjuvant treatment may play a more important role."

Dubsky and his colleagues from the Austrian Breast and Colorectal Cancer Study Group examined data from a randomized, clinical trial comparing adjuvant hormonal treatment and tamoxifen with the standard treatment of cyclophosphamide, methotrexate and 5-fluorouracil (CMF). All women in the trial were premenopausal and had positive estrogen and/or progesterone receptor status. Patients who underwent breast-conserving surgery received mandatory radiation. Radiation was optional in women who underwent modified radical mastectomy.

For the current analysis, the researchers focused on anaemia data from the 424 patients in the CMF arm, as the rates of anaemia among those who received the hormonal treatment were low. They examined local relapse-free survival, relapse-free survival and overall survival.

Anaemia occurred in 18.2% of patients who received CMF chemotherapy. Anaemia was defined as an incidence of at least one serum haemoglobin level below 12 g/dL during chemotherapy through the first follow-up date three months after adjuvant treatment concluded.

After a median follow-up of 61 months, 39 local relapses occurred: 6.9% in patients without anaemia and 19.5% in patients with anaemia. The five-year rates of relapse were 8.2% among non-anaemic patients and 19.6% among anaemic patients. Patients without anaemia experienced a significantly longer local relapse-free survival than patients with anaemia, according to the study.

Other factors that significantly increased local relapse-free survival were younger age at diagnosis and negative lymph node status. Any relationship between anaemia and tumour size, postoperative radiation or type of surgery did not have an effect on local relapse-free survival, researchers say.

Relapse-free survival did not differ significantly with the presence or absence of anaemia. "There seemed to be no difference when distant or contralateral events were part of the analysis," said Dubsky. "The effect was limited to local recurrences. Any explanation of the limit is pure speculation."

No difference in overall survival was evident, but Dubsky says he doubted one would be seen given the number of patients and the length of follow-up. Follow-up of 10 to 15 years would be needed to observe any significant differences, he says.

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