Anemia is a frequent complication in cancer patients, both with solid and haematological tumors, and negatively influences the quality of life, the performance status and the prognosis of these patients. It is important to recognise this condition rapidly and to manage and treat it, and consequently to improve the quality of life, the tolerability and adherence to citotoxic treatment and the response to oncologic treatments.
The data available show that the frequency of anemia in cancer patients is very high. A study in Europe in the early 2000’s, with a total of 15,000 patients diagnosed with solid and haematological malignancies, showed an anemia prevalence at the study entry of 39%, and in the follow-up period of the study anemia was found in 67% of the assessed patients(1). The increased incidence of anemia in oncologic patients is associated with the type of oncologic disease, the advanced stage of the disease and previous treatments. As for the type of disease, anemia is more common in haematological diseases compared to solid tumors. In solid neoplasia, anemia is commonly associated with bronchopulmonary, breast, gastrointestinal and gynecological cancers(2,3).
1. Mechanisms involved in anemia and iron deficiency in oncologic patients
The mechanisms involved in the occurrence of anemia in cancer patients are multiple and complicated, with several mechanisms responsible for anemia occurring at the same time or at different times(4).
By reviewing the most important mechanisms of anemia, these may be acute or chronic bleeding, commonly found in gynecological tumors and digestive tract. The nutritional deficiencies of iron, vitamin B12 and folate, determined by malnutrition or malabsorption, are other common causes of anemia in these patients. Bone marrow infiltration by metastatic disease is frequently found in patients with anemia and breast or prostate cancer. Other causes in patients with neoplastic disease is the decline in the production of endogenous erythropoietin, seen in patients with cancer and associated chronic renal disease, or due to decreased response to bone marrow erythropoietin(2,5,6).
In terms of iron deficiency, it is classified into two types – absolute and functional. Absolute deficiency appears when the iron storage are low and depleted. Functional deficiency is present when iron reserve is normal or increased, but the disponibility of iron for erythropoiesis is low due to inflammatory processes that cause iron blocking in macrophages and enterocytes.
In oncologic patients, the predominant deficiency is the functional type, and data from literature show that functional iron deficiency is present in aproximately 50% of cancer patients(7).
The mechanism of functional iron deficiency in cancer patients is well known. Iron is taken by the transferrin from duodenal enterocytes or macrophages that recycle the iron from aging erythrocytes and it is transported to the bone marrow(8). These mechanisms are controlled by hepcidin, which is an amino acid produced in the liver by peptic hepcidin anti-microbial genes at chromosome 19, in the presence of cancer or chemotherapy-induced inflammation. Hepicidin has the role of maintaining iron homeostasis(9). Hepcidin block the release of iron from the macrophages in the bone marrow by blocking ferroportin, which has the role to transfer the iron from the gastric mucosa to the transferrin. The functional deficiency of iron occurs following the release of cytokines, especially interleukin-6, in the presence of inflammation, which results in hepcidin production increased in the liver. High levels of hepcidin are found in many types of hematological and solid cancers. Low levels of hepcidin have been observed in patients with hepatic metastases(10-13).
2. Evaluation of patients with anemia and iron deficiency
Iron deficiency in cancer patients is a common state. But it is very difficult to recognize it. As shown in trials, the incidence of iron deficiency in cancer patients is about 42%(1). Evaluating the profile of patients with iron deficiency, data available from studies show that patients with tumors of the colon, rectum, pancreas and pulmonary syndrome have a very frequent iron deficiency. Also, patients with advanced disease and chemotherapeutic treatment have iron deficiency. It may be present even in the absence of anemia, it can influence the performance status of patients and may cause fatigue, an important and frequent sign(1,2).
In healthy people, ferritin values show the status of iron stores. Other parameters, such as transferrin saturation, the percentage of hypochromic erythrocytes, the soluble transferrin receptor and the reticulocyte hemoglobin content, show the amount of iron that is biologically available. All these markers are modified in cancer patients. Particularly ferritin, which is an acute phase protein, may not properly reflect iron deposits in cancer patients who have an inflammatory status. Transferrin saturation assessment is recommended, but it has also limitations in cancer patients, because of the presence of inflammation or malnutrition that causes transferrin levels to be reduced, so normal or elevated false values may occur(14,15).
The measurement of circulating hepcidin levels appears to be a useful tool in the diagnosis of iron deficiency in these patients, but is still under evaluation(16).
Iron deficiency in cancer patients is an important issue, with an impact on the patients’ quality of life, on adherence to oncologic therapies and ultimately on the prognosis of these patients. Moreover, the functional iron deficiency is difficult to diagnose and often remains unnoticed and consequently untreated. It is therefore important to evaluate in details the iron profile of the patients, in order to highlight the presence of iron deficiency. Additional studies are also needed to evaluate more precisely the biomarkers that can be used in the diagnosis of iron deficiency, especially the functional deficiency.
Conflict of interests: The authors declare no conflict of interests.