This study successfully identified clinical and demographic characteristics of breast cancer patients that are associated with anemia prevalence. We found that determinants such as the number of chemotherapy regimens used, dose reduction, and docetaxel were independent clinical prognostic indicators of anemia prevalence. Age and BMI were the independent demographic determinants.
Anemia is a frequent complication in critically ill and cancer patients. It has been linked to a reduction in quality of life as well as a poor prognosis (4). In addition, sadness, frustration, and exhaustion can all contribute to a patient’s feeling that life is pointless because of the lowered quality of life associated with anemia (23). Additional research has revealed an increased risk of mortality and complications such as pulmonary edema as a result of cancer related anemia (24, 25). Thus, identifying risk factors for anemia early may assist doctors in optimizing care for critically ill cancer patients (26).
Our data identified a high prevalence of anemia in patients with breast cancer admitted to the oncology departments and daycare centers of HKL, UMMC, and the NCI. Anemia was prevalent in 42.8% of patients at NCI, 30.5% at HKL, and 26.7% at UMMC.
Numerous researchers have previously reported a high prevalence of anemia in cancer patients in which their results were identical to the current study. For example, the ECAS (8) found that the incidence of anemia in cancer patients was 39.3% which is slightly lower than our finding. On the other hand, our results were lower than the study conducted by Chaumard N et al., (27) who stated that 64.8% of breast cancer patients developed anemia. This proportion varied between 11 and 88% in more detailed and specific research examining adjuvant therapy (28). We think that the difference is due to the different toxicity grading systems used in these studies: anemia was characterized as any recorded Hg level lower than 11 g/dl (28) or 10 g/dl (27), whereas the current study used a cutoff value of 12 g/dl in accordance with the National Cancer Institute grading system. Additionally, patients with cancer who are also anemic may require a different clinical management strategy for their anemia in order to improve their outcomes. Furthermore, the disparity in prevalence rates may be explained by clinical features of immunocompromised patients, such as bad performance status, acute physiologic changes, and inadequate nutrition due to the severity of illness, all of which can result in cancer-related anemia (8), particularly in those patients who have undergone more aggressive treatment.
Moreover, our findings indicated that obesity increases the risk of anemia in cancer patients. According to chi-square analysis, 57.5% of obese breast cancer patients develop anemia, while only 16.9% of non-obese patients do. Logistic regression analysis confirmed these findings, revealing that obese patients were 12.4 times more likely to develop anemia than non-obese breast cancer patients. Our findings are consistent with those of Aigner E, et al. (29) and Camaschella C (30), who established a statistically significant association between obesity and anemia. The suggested explanation could be that obesity impairs nutritional absorption from the duodenum, resulting in iron deficiency anemia (29). Also, heavy eating stimulates the immune system to release excessive amounts of pro-inflammatory cytokines via iron sequestration and suppresses bone marrow’s ability to produce RBCs (31). The body cannot use stored Fe because of inflammation, which also causes anemia.
We found that breast cancer patients who did not have their chemotherapy dose reduced were 1.4 times less likely to develop anemia than those who did have a detected reduced dose (Table 3). In Table 2, the chi-square analysis revealed a significant relationship between chemotherapy dose reduction and anemia prevalence (P < 0.05). Approximately 25% of the anemic breast cancer patients had their dose reduced (Table 2). This result is slightly lower than those reported in two recent studies, which indicated that 26% (20) and 48.2% (21) of all breast cancer patients with a dose reduction. Aside from that, our finding was greater than one study’s finding who reported that 8% of cancer patients had their dose reduced (32). This discrepancy could be explained by the fact that we defined chemotherapy dose reductions as at least a 10% reduction in dose from the first follow-up (21; 22), whereas Nagel C.I et al.,(32) defined them as dose modification from the first follow-up. Chemotherapy dose reductions occur most frequently during late cycles, particularly with FEC and docetaxel regimens (33). There are several possible explanations for this decrease. First, the doses of docetaxel and FEC may be higher than those required for each regimen’s efficacy, particularly in late cycles, resulting in severe toxicities that allowed the oncologist to decrease the chemotherapy dose. Second, most chemotherapy-sensitive cancer cells may be killed during the initial cycles, and then the dose may be reduced in late cycles to avoid or minimize any negative impact of the chemotherapy. There may be a decrease in the dosage of chemotherapy as a result of the increased incidence of anemia severity or some adverse effects of chemotherapy, such as neutropenia and neuropathy (33; 20).
The multitude of chemotherapy regimens used was found to be a clinical prognostic factor for anemia. This was expected, given chemotherapy’s well-documented bone marrow depressant and acute cytotoxic properties (34). Chemotherapy was associated significantly with anemia prevalence and the interactions we found point to the two subgroups of patients vulnerable to anemia: the elderly and obese breast cancer patients.
Additionally, our findings revealed a link between the type of chemotherapy used, such as docetaxel, and the prevalence of anemia. According to a logistic regression analysis, patients who received docetaxel developed anemia at a higher rate than those who did not receive docetaxel (Table 3). Correspondingly, similar findings indicated a significant relationship between doceatxel and anaemia (35). Despite the fact that anthracycline and taxane-based chemotherapeutic regimens have become the standard of care for breast cancer treatment, they have been shown to reduce mortality and improve survival rates. Docetaxel, on the other hand, has a number of side effects, including cardiac complications and anemia, which increases the prevalence of anemia in patients receiving these types of regimens (36). Furthermore, the mechanism of action of these regimens may result in bone myelosuppression, which causes bone marrow damage and impairs its ability to produce enough red blood cells, white blood cells, and platelets (37).
Cancer-related anemia (CRA) develops in part as a physiological response of the immune system to the action of many cytokines on various iron-homeostasis and erythrocyte-production pathways, which may result in bone marrow suppression (38). Anemia in hematologic cancer patients may be caused by the direct and indirect hemopoietic effects of uncontrolled leukocytosis and cytokine production (29). This would explain why the incidence of anemia is higher in elderly patients admitted to oncology hospitals in this study. While elderly cancer patients may be given less aggressive treatments than younger patients, more research is needed to better understand the determinants of incident anemia in elderly cancer patients requiring critical care.
There are numerous factors that contribute to the occurrence of anemia in cancer patients. Higher levels of inflammatory markers, interleukin-6 and leptin, hepcidin levels, ferritin levels, EPO levels, and reactive oxygen species (ROS) all contribute to the incidence of anemia in cancer patients (13). Anemia is caused by pro-inflammatory cytokines, which directly inhibit the production of red blood cells from the bone marrow (40, 41). Other factors such as poor nutrition, folate deficiency, lengthy hospitalization, and bleeding history, all contributed to anemia incidence in cancer patients (1; 42; 43).
Our study has limitations due to a lack of information regarding anemia treatment. Erythropoietin-stimulating agents (ESAs), for example, were not administered to all patients and only few patients received blood transfusions. Considering that some patients received anemia treatment, such as iron therapy, we detected a rather high prevalence of anemia in our study sample. We understand that anemia can be caused by a number of factors, including underlying cause, cancer relapse or exacerbation, infection, or renal failure.
Our study recommends all oncologists and health care professionals to follow the protocol of NCCN Clinical Practice Guidelines in Oncology and ESMO guidelines which both recommend to treat cancer related anemia based on the etiological causes and anemia severity. If anemia is severe (Hb < 7-8 g/dL), it should be treated with blood transfusion, if moderate (Hb 8-10 g/dL), it should be treated with ESAs and if mild (Hb 10-12 g/dL), it should be treated with iron therapy or multivitamins. ESAs should be added when necessary particularly if anemia is symptomatic and iv iron therapy is added only to improve the efficacy of ESAs and to reduce the need for red blood cell transfusion (45; 46).