Evaluation of Peripheral Blood Smear for Myelodysplasia in Breast Cancer Patients who

Objective: Therapy-related myeloid neoplasms (t-MN) account for approximately 10% to 20% of all cases of AML (acute myeloid leukemia), MDS (myelodysplastic syndrome) and MDS/MPN (myelodysplastic syndrome/myeloproliferative neoplasms), MDS, and MDS/MPN. In our study, we evaluated peripheral blood smear samples and hemogram values in breast cancer patients who were receiving adjuvant anthracycline regimens and were in remission. Materials and Methods: A total of 78 patients receiving anthracycline-based adjuvant chemotherapy treatment from Kayseri Research and Training Hospital and Mersin State Hospital were enrolled in the study. Their adjuvant treatments had been completed at least 18 months prior to the study. Results: Two patients complained of anemia (2.2%) (Hb<11 mg/dl), leukopenia was observed in seven patients (7.7%) (leukocytes<4000/ mm3), and thrombocytopenia was observed in four patients (4.4%) (PLT<150.000/mm3). In the blood smear samples, the following were observed: ovalomacrocytes (14%), macrocytes (37%), acanthocytes (1%), stomatocytes (12%), teardrops (12%), nucleated erythrocytes (1%), basophilic stippling (14%), and Howell-Jolly bodies (1%). Additionally, hypo-granulation (38%), Pelger-Huet abnormalities (26%), hypersegmentation (20%), immature granulocytes (8%), and blasts (6%) were observed. We also confirmed the presence of giant platelets (50%) and platelet hypogranulation (19%). Conclusion: According to the peripheral blood smear assessments in our study, we suggest that breast cancer patients should be evaluated for MDS in the early stages, starting from month 18, even if the automated blood counts are normal.


Introduction
Breast cancer is the most common tumor type in women [1].The use of adjuvant chemotherapy to treat breast cancer has been extended over the past years from node-positive women to lower-risk patients [2,3].Anthracycline-containing chemotherapy has been shown to be more efficacious than alkylating-based chemotherapy and is currently the gold standard [4].
Generally, topoisomerase-II inhibitors (e.g., mitoxantrone, anthracyclines, and epipodophyllotoxins) are significantly associated with an increased risk of AML/MDS.Several studies have suggested that anthracyclines and mitoxantrone increase the risk of AML and MDS in women who receive chemotherapy for breast cancer [8][9][10][11][12].
The latency period varies according to the chemotherapeutic agents administered.For example, after exposure to alkylating agents or radiation therapy, t-MN may occur in approximately five to seven years [13,14].After the use of topoisomerase II inhibitors, t-MN can develop after a shorter latency period of one to three years [15][16][17].
In our study, we evaluated peripheral blood smear samples and hemogram measurements in breast cancer patients who were receiving adjuvant anthracycline regimens and had been in remission for at least 18 months.

Materials and Methods
In our study, patients receiving anthracycline-based adjuvant chemotherapy treatment were evaluated.A total of 78 patients from Kayseri Research and Training Hospital and Mersin State Hospital were enrolled in the study.Their adjuvant treatments had been completed at least 18 months prior to the study.No patients had either chronic or infectious diseases.Patients with abnormal ferritin, vitamin B12 or folate levels were excluded from the study.The peripheral smear samples were evaluated by a hematologist.For statistical evaluations, SPSS 16.0 software was used.

Results
Patient characteristics are summarized in Table 1.All patients underwent 3, 4 or 6 courses of anthracycline-based adjuvant chemotherapy; 70% of the patients received epirubicin, and 30% were treated with adriamycin.Table 2 shows CBC parameters.The evaluations of peripheral blood smears are shown in Table 3.

Discussion
Recent MDS studies have generally enrolled patients with a median age of ≥65 years; there were more male patients than female patients [18,19].In MDS cases, subject to treatment, the median age of diagnosis was 61 [20].The average age of the patients was 51 years old.
At the time of initial diagnosis, approximately 50% of MDS cases were asymptomatic [21,22].Some of the symptoms of MDS include anemia, neutropenia, thrombocytopenia, and bi-or pancytopenia.Anemia is observed in more than 80% of all MDS cases, leukopenia is established in 25-70% of all  [21,23,24].In our study, two patients complained of anemia (2.2%) (Hb<11 mg/dl), leukopenia was observed in seven patients (7.7%) (leukocytes<4000/mm 3 ), and thrombocytopenia was observed in four patients (4.4%) (PLT<150.000/mm 3 ).In our study, the number of patients with cytopenia was much lower than the number of patients diagnosed with MDS.However, because the patients in our study did not have co-morbidities, the percentage of cytopenia cases seemed to be important.
Giant platelets and platelet anisocytosis are the most important signs of dysthrombopoiesis that can be observed in the peripheral blood [23].We observed the presence of giant platelets (50%) and platelet hypogranulation (19%).In another study, giant platelets and platelet anisocytosis were identified at frequencies of 46% and 26%, respectively [25].
The diagnosis of myelodysplasia must be made based on the evaluation of a peripheral smear.Granulocytic hypogranulation and hyposegmentation, hypochromia, polychromasia, nucleated and fragmented erythrocytes, macrocytosis, thrombocytic anisocytosis and giant platelets found in peripheral smears are important signs for establishing a diagnosis of myelodysplasia.However, an accurate diagnosis requires bone marrow aspiration and biopsy.Cytogenetic examination may help in making a diagnosis; however, normal results do not exclude the diagnosis.Chromosomal abnormalities are identified in 80% of t-MDS cases.In particular, in 70% of cases, 5q.7q and 20q deletions are observed.The chromosomal analysis will be required in this same group of patients.
Finally, according to the peripheral blood smear assessments of our study, we suggest that breast cancer patients should be evaluated for MDS in the early stages, starting from month 18, even if the automated blood counts are normal.

Table 1 . Patient characteristics
*Number of Cures; it means that number of regimen with antracycline that patients received.Abb: ER: Estrogen receptor, PR: Progesterone receptor cases, and thrombocytopenia can be observed in 40-65% of all cases