The majority of breast cancer patients are treated with adjuvant chemotherapy often in combination with other systemic treatment [1,2]. Weight gain commonly occurs in western breast cancer patients who receive adjuvant chemotherapy [3-6]. Weight gain is also associated with cancer recurrence and poor prognosis [7-10].

Several studies have demonstrated that the majority of breast cancer survivors exhibited a mean body weight gain of 1-6 kg following chemotherapy and identified adjuvant chemotherapy as an independent prognostic factor for weight gain, with a potential longterm effect [11,12]. However, other studies did not report a significant difference in weight gain between breast cancer patients receiving adjuvant chemotherapy and healthy controls [3,13,14].

The causes of weight gain may include reduced physical activity and menopause prior to diagnosis. However, the exact mechanisms have not been fully elucidated. In addition, the previous observations were focused on patients from the USA and also patients from Western Europe [3].

There is lack of information associated with body weight decrease in advanced breast cancer patients following adjuvant chemotherapy in Indonesian population. Information about hematological parameter change in advanced breast cancer patients following adjuvant chemotherapy is also very limited.

Therefore, we conducted an observational analytical study among women treated with adjuvant chemotherapy for advanced breast cancer. The purpose of this study was to evaluate the body weight and hematological parameter change following adjuvant chemotherapy in advanced breast cancer.

Data collection

This study was conducted in the period of September 2016 to March 2017 in 50 patients who newly diagnosed with breast cancer and will get chemotherapy at the Hospital in Cirebon, West Java, Indonesia.

Diagnosis of breast cancer based on pathological anatomy result from patient undergoing mastectomy or biopsy. Breast cancer stage is determined based on the results of physical examination, anatomical pathology result and imaging.

We performed body weight and height assessment as well as complete laboratory examination including hematology parameter before chemotherapy. Data on body weight and hematological parameters are followed up during patients undergoing first and second cycle of chemotherapy.

We collected pathological anatomic diagnosis, age, body weight, body height and hematological parameter including hemoglobin, leucocyte, differential count and thrombocyte on adult patient newly diagnosed with advanced breast cancer (stage IIIB and IV) and undergoing chemotherapy with doxorubicin and cyclophosphamide regimen.

Data analysis

Data processing using the program SPSS version 21.0 for windows. Categorical data is presented with the number/frequency and percentage whereas the numerical data is presented with the mean, median, standard deviation and range.

Numerical data were analyzed using Kolmogorov Smirnov test to determine the data distribution the data were analyzed by using the Repeated Anova test if the data were normally distributed and Friedman's test if the data were not normally distributed.

Body mass index, hemoglobin and TLC data are normally distributed so that the Repeated Anova test is performed while body weight, BSA, platelets, leukocytes and ANC data are not normally distributed. So, Friedman test is performed. The significance criterion is determining using p value. The p value is statistically significant if p ≤ 0.05 and not statistically significant if p>0.05.

A number of 50 patients with advanced breast cancer (stage IIIB and IV) were treated with doxorubicin and cyclophosphamide adjuvant chemotherapy in the participating hospitals. The mean age of the study subjects was 46.44 ± 9.68 years, whereas the mean body weight and BMI of the subjects before the illness were 60.98 ± 13.10 kg and 26.05 ± 4.65, respectively (Table 1).

Table 1: Baseline characteristics. Categorical data presented in number/frequency or percentage while numerical data presented in mean, median, standard deviation and range.

Based on the study results, the subject body weight was decrease after first and second cycles chemotherapy from 60.06 ± 11.16 kg to 61.33 ± 16.61 and 58.69 ± 10.41 kg (p<0.05), respectively. The BMI was also decrease from 25.66 ± 4.10 kg/m² to 25.33 ± 4.12 and 25.05 ± 4.12 kg/m² (p<0.05), respectively. Body surface area also decrease from 1.58 ± 0.16 m² to 1.58 ± 0.16 and 1.57 ± 0.15 m² (p<0.05), respectively (Table 2).

Table 2: Comparison of body weight, BMI, and BSA in chemotherapy group before cycle I, II and III. For numerical data p value is tested by Repeated Anova test if normal distributed data and Friedman alternative test if the data is not normally distributed. The significance value is based on the p value <0.05. The * mark shows the value of p<0.05 means statistically significant.

Hemoglobin levels in the group before chemotherapy, after first and second cycle of chemotherapy had an average of 12.04 ± 1350, 11.29 ± 1.32, and 10.97 ± 1.47, respectively. Platelet levels in the group before chemotherapy, after first and second cycle of chemotherapy had an average of 363380.00 ± 108989.24, 404788.00 ± 127744.36, and 381276.00 ± 122192.573, respectively. Total lymphocyte count in the group before chemotherapy, after first and second cycle of chemotherapy had an average of 2235.61 ± 701.02, 1916.42 ± 670.776 and 1894.82 ± 712.13, respectively. Hemoglobin level decrease from 12.04 ± 1.35 g/dL to 11.29 ± 1.32 and 10.97 ± 1.47 g/dL (p<0,05), and TLC decrease from 2235.61 ± 701.02/mm³ to 1916.42 ± 670.77 and 1894.82 ± 712.13/mm³ (p<0,05), respectively. Base on study result, Hemoglobin, thrombocyte and TLC level significantly decrease before and after chemotherapy. (Table 3).

Table 3: Comparison in Hemoglobin level, Thrombocyte level and TLC in chemotherapy group before cycle I, II and III. For numerical data p value is tested by Repeated Anova test if normal distributed data and Friedman alternative test if the data is not normally distributed. The significance value is based on the p value

Leukocyte levels in the group before chemotherapy, after first and second cycle of chemotherapy had an average of 9129.40 ± 3081.53, 8252.60 ± 3167.50, and 7713.60 ± 2815.23, respectively. The ANC in the group before chemotherapy, after first and second cycle of chemotherapy had an average of 6817.82 ± 4824.36, 5756.96 ± 3023.06, 5262.68 ± 2439.06, respectively. Leukocyte level decrease from 9129.40 ± 3081.538, 8252.60 ± 3167.507, and 7713.60 ± 2815.230/mm³ (p=0.062), respectively, while the ANC level also decrease from 6817.82 ± 4824.366, 5756.96 ± 3023.061 and 5262.68 ± 2439.062/mm³ (p=0.568), respectively. Base on study result, there is no significant decrease in leukocyte and ANC level after first and second cycles of chemotherapy (Table 4).

Table 4: Comparison in Leucocyte level and ANC in chemotherapy group before cycle I, II and III. For numerical data p value is tested by Repeated ANOVA test if normal distributed data and Friedman alternative test if the data is not normally distributed. The significance value is based on the p value

Studies have demonstrated that adjuvant chemotherapy correlates with weight gain in Western breast cancer patients following adjuvant chemotherapy [15,16]. In our study, patients with advanced stage breast cancer exhibited significant decrease in body weight (60.06 ± 11.16 to 58.69 ± 10.4, p<0.05), BSA (1.58 ± 0.16 to 1.57 ± 0.15, p<0.05), and BMI (25.66 ± 4.10 to 25.05 ± 4.12, p<0.05) following two cycles of adjuvant chemotherapy with doxorubicin and cyclophosphamide regimen. Thus, unlike the dominant weight gain observed in Western populations, patients in our study have a significant decrease in body weight, BSA and BMI.

There are several factors contributing to weight change following adjuvant chemotherapy, such as age and weight at diagnosis, menopausal status, chemotherapeutic regimen, receptor status, clinical stage and number of chemotherapy cycles. Other factors, such as lifestyle, educational level and economic status were also shown to affect weight gain [17]. We observed that patients age over 40 years were more likely to decrease in body weight compared to those aged less than 40 years. This study also shown that patient’s body weight over 60 kg before chemotherapy may be associated with the greatest weight loss than patient’s age less than 60 kg (Data not shown).

The menopausal status was previously reported to be a positive predictor for weight gain in women receiving adjuvant chemotherapy [18-20]. Although it was also reported that menopausal status did not affect body weight [21]. Our study does not analyse the correlation of menopausal status and hormonal receptor status to body weight. However, all subjects in this did not receive hormonal therapy because they newly planned to get chemotherapy first and also did not have ovarian ablation. Our study did not analyse correlation between different chemotherapy regimen and body weight change because all subject have the same chemotherapy regimen (doxorubixin and cyclophosphamide).

Previous studies in animal have demonstrated that doxorubicin correlates with neutropenia and thrombocytopenia [22,23]. Metaanalysis study also shown that doxorubicin and cyclophosphamide causing neutropenia and thrombocytopenia [24]. Our study found that there is influence of chemotherapy on hematological parameters. Hemoglobin, platelet and TLC levels decreased significantly after chemotherapy but no significant decrease in leukocyte and ANC counts.

Our study had several limitations, due to it’s from a single centre and the relatively small sample size and we involve analyses only of two cycle of chemotherapy with doxorubicin and cyclophosphamide regimen. We did not assess additional factors which would potentially affect weight change, including energy intake, exercise, education and psychological status. Further multicentre, long-term and random casecontrol studies are required to further address these issues. However, this study was the first to report that adjuvant chemotherapy in advanced breast cancer may be associated with weight change in Indonesian breast cancer patients. The differences between Asian and Western populations may be attributed to racial genetic differences, a subject that requires further investigation.

Body weight, body mass index and body surface area is significantly decreased during chemotherapy in advanced breast cancer patients even when given dietary recommendations. Hemoglobin and including TLC level also decrease during chemotherapy. There is no significant decrease in leukocyte and ANC level after first and second cycles of chemotherapy. Appropriate weight management interventions with nutritional follow-up and physical activity programs are needed.