Comparison of Hematological Parameters and the Associated Factors Among Women with and without Breast Cancer: A Case-Control Study

Introduction

Breast cancer (BC) is one of the most popular and dangerous cancers which is accompanied by a high mortality rate.^1–3 BC women represent up to 36% of cancer patients globally, and its incidence number has increased in the past four decades.^4,5 Furthermore, BC represents 31% of female tumors in the United States.⁶ In Yemen, BC is a public health disease that represents 16.6% of cancer patients and 30.3% of cancer among women.⁷ There has been an increase in BC numbers during the last few years in Yemen.⁸ There is a close relationship between tumors and hematological parameters.^1,9–12 The cancer induces an immune response resulting in changes in hematological parameters such as white blood cells (WBCs) and platelets.^13–17 Hematological parameters reflect the cell-mediated immune response to cancer, and changes in hematological parameters influence cancer progressions. Therefore, hematological parameters evaluation is reliable for the prognosis and diagnosis of several types of cancer, including breast cancer.^12,18–21 There is a need for more studies to understand the association of hematological parameters and BC prognosis.¹⁷ There is a restricted research achievement on hematological parameters of diseases in Yemen.²² Furthermore, there is no research conducted on BC and its effects on the hematological parameters in Yemen. Therefore, this research aimed to evaluate the hematological parameters and the associated factors among women with and without BC.

Materials and Methods

The population sources were the Life Center of Breast Cancer Control-Ibb branch from August 30, 2022 to August 30, 2023. The study followed a thumb role to detect sample size in each group, where 30 participants in each group were enough to distinguish the actual variations.²³ To increase the statistical power of the evaluation, the participant’s number was increased to 100 participants per group (100 women with breast cancer and 100 healthy control). The age of women with BC was ≥26 years, while the age of healthy women (control) was ≥21 years. The study experiments were analyzed in Zain Medical Laboratories. An Arabic-translated questionnaire was administered to participant women. The data collected involved participants’ number, weight, residence, age, education level, marital state, employment state, economic state, smoking, qat chewing, tobacco, regular exercise, following a strict diet, sleeping under light, consumption of animal fats, marital state and age, menarche age, menopause age, first pregnancy age, number of alive births, contraceptive use and type, breastfeeding period and estrogen and prolactin disorders. The whole blood samples were tested immediately for complete blood count (CBC) parameters, while the sera were used to screen cancer antigen (CA 15-3) and C-reactive protein (CRP).

Participants with pregnancy, childbirth bleeding disorder, renal disease and liver disease (hepatitis B and C viruses), and the use of blood pressure and diabetes medicines as well as aspirin were excluded. Moreover, The CA 15-3 marker and C-reactive protein (CRP) were screened to ensure the control group was BC and CRP-free, respectively Furthermore, the control group with appendicitis, arthritis or tonsillitis was excluded.

Statistical Analysis

GraphPad Prism 8.0.1 was used to analyze the data obtained from the laboratory tests and questionnaires. Kolmogorov-Smirnov test was applied to determine whether available data showed a normal distribution in which the data were calculated by an Unpaired t-test. Furthermore, in an abnormal distribution, the Mann–Whitney U-test was used. Fisher exact test or a chi-square test for trend was used to analyze the socio-demographic and reproductive characteristics. A P-value ≤0.05 means statistically significant.

Results

Socio-Demographic Characters of the Study Participants

In this study, 100 women with BC (cases) and 100 healthy women formed a control group. The standard deviation (SD), range, and mean were statistically analyzed for all variables revealed in the tables. In addition, the mean and SD of BC and healthy control group’s ages were 46.14±11.51 years and 33.43±11.42 years, respectively. Similarly, the mean and SD of BC and healthy control groups’ weight were 56.51±10.41 Kg and 50.96±9.905 Kg, respectively. Approximately 34% and 51% of the participants in the BC and control groups lived in urban areas. Furthermore, most of the BC group were housewife (89%) with an illiterate education level (67%). Most of the healthy control group were non-employed (58%) and had a university education level (68%). Besides, 60% and 82% of the BC and healthy control groups had a middle economic state. According to daily habits, the percentage of BC participants were qat chewers (51%), non-tobacco chewers (96%), non-smokers (82%), irregular exercise (51%), non-sleep under light (78%), non-follow a strict diet (80%) and consumption of animal fats (76%), respectively. Moreover, the percentage of the control group participants were non-qat chewers (56%), non-smokers (82%), non-tobacco chewers (100%), irregular exercise (90%), non-follow a strict diet (96%), non-sleep under light (84%) and consumption of animal fats (70%), respectively. In addition, most of the participants in the BC group (74%) and control group 82 (82%) had no history of family cancer as presented in Table 1.

Table 1 Socio-Demographic Characters of Women with BC and Control Groups

In the current study, as revealed in Table 1, there were significant differences between BC and healthy control groups in weight (P<0.0001), age (P<0.0001), residence (P=0.0218), employment state (P<0.0001), education levels (P<0.0001), economic state (P=0.0003), regular exercise (P<0.0001) and following a strict diet (P<0.0008). Nevertheless, the family history with cancer, smoking, tobacco chewing, qat chewing, sleep under light and consumption of animal fats were not statistically significant between the BC and the healthy control groups.

Reproductive Characters of Participant Women in Breast Cancer Group and Control Group

In brief, a total of 200 participant women (100 BC as cases and 100 healthy as a control) were involved. Out of BC participants, almost 87% were married, while out of the control group, 58% were married. In case of marital age, the group (16–20 years) represented the highest set among both BC and control groups. Marital state and marital age were statistically significant (P <0.0001 and 0.0008). As revealed in Table 2, menopause age was statistically significant (P=0.0002). Furthermore, number of live births was significant (P=0.0001). The contraceptive use revealed a significant difference between both groups (P<0.0001). Considering the most contraceptive used, out of 42 BC participants, 8 (19.05%) used an intrauterine device, 16 (38.1%) used a tablet, 3 (7.14%) used an implant and 15 (35.71%) used an injection, out of 8 participants in the control group, 2 (25%), 3 (37.5%), 2 (25%) and 1 (12.5%) used an intrauterine device, tablet, implant and injection, respectively. Furthermore, the disorders of estrogen and prolactin hormones were not statistically significant.

Table 2 Reproductive Characters of Women with BC and Control Group

Clinical Variables and Treatment History of BC Women and Control Group

In terms of BCperiod, the mean and SD of period were 3.184±2.43 years while the range was 3 months~10 years and most of the BC group had a period>1-5 years (53%). Additionally, approximately 64% of the participant women in BC group were CRP-negative. In case of inflammatory symptoms among BC group, 67%, 19% and 1% had arthritis, tonsillitis and appendicitis, respectively. Furthermore, the treatment profile of BC group showed that 13% of participants used blood pressure medication, 12% used diabetic medication and 9% used aspirin as seen in Table 3.

Table 3 Clinical Variables and Treatment History of Women with BC

Comparison of Hematological Parameters Between BC Women and Control Group

In the current study, there were statistically significant differences between mean and SD of BC and control groups concerning Hb level (P=0.0393) and the count of RBCs (P=0.0045), WBCs (P=0.0327), neutrophils (P=0.0441), lymphocytes (P=0.0098) and monocytes (P<0.0001) as revealed in Table 4.

Table 4 Comparison of Hematological Parameters Between Women with BC and Healthy Control

As shown in Table 4, the results showed that the mean and SD of PCV, MCV, MCH, MCHC, eosinophil, basophil, and platelets were not statistically significant between BC and control groups.

Discussion

BC in women is the most dangerous disease accompanied by a high rate of mortality.^1–3 The hematological parameters used in disease diagnosis include cancer.¹⁸ Additionally, there are diverse risk factors that play roles in BC development including delayed menopause, early menarche, and history of the family with breast cancer.^2,24 In the present study, weight, age, residence, employment state, educational level, economic state, regular exercise, and subsequent strict diet revealed a significant difference between BC and healthy control groups. In comparison with the current research, age, employment state, and education levels were significantly similar to those in a study conducted in Kolkata, India.²⁵ However, another study in Mumbai, India, reported that age and occupation were not found to be significant.²⁶ On the other hand, this study found no significant relation between the presence of family history with BC, which agreed with a study in India²⁵ and disagreed with two studies carried out in Ankara and Izmir, Turkey.^27,28 In the present study, sleep under light was not related to BC incidence (P=0.3676) due to the lack of good electricity in Yemen. However, different studies conducted by Sweeney et al,²⁹ Jaynes and Switzer,³⁰ James et al³¹ and Urbano et al³² showed a correlation between exposure to light and BC incidence.

In the present study, menarche and menopause ages were not significantly different between women with BC and control groups. This finding agreed with the one reported by a study in Ankara, Turkey,²⁷ and disagreed with an investigation conducted in India.²⁵ There was no correlation between the breastfeeding period and BC. This study agreed with studies in the USA and Turkey^27,33 and in disagreed with a study in India.²⁵

The current study showed that marital state and marital age were significant in BC group compared to the control group. This result is identical to a study performed in India, which showed that marital state was significant.²⁵ In this study, contraceptive usage showed a significant change, while studies conducted in India, USA, and Turkey revealed that contraceptive use was not significant.^25,27,34

This study contained a comparison of hematological parameters between a BC group and a healthy control group. In the current study, the hematological parameters Hb (P=0.0393), RBCs (P=0.0045), WBCs (P=0.0327), lymphocytes (P=0.0098), neutrophils (P=0.0441) and monocytes (P<0.0001) showed a statistically significant difference between both groups. Nevertheless, PCV (P=0.2393), MCV (P=0.7193), MCH (P=0.1168), MCHC (P=0.6816), eosinophils (P=0.5903), basophils (P=0.2841) and platelets (P=0.0893) were not significantly different. Hb and RBCs results were identical to results of studies conducted in Algeria and India.^2,35 In addition, a study carried out in Nigeria displayed statistically significant of Hb, WBCs, neutrophil, lymphocyte and PCV, while monocyte, eosinophil and platelet were not statistically significant.¹² In contrast, in a study carried out in Iran,³⁶ it was confirmed that Hb and RBCs were not statistically significant, while MCV, MCH and MCHC were statistically significant. Velidedeoglu and his et al in Turkey concluded that WBCs, neutrophils, lymphocytes and monocytes were significant, whereas Hb, platelets and eosinophil were insignificant.³⁷

The dissimilarities might be due to differences in the sample size, socio-economic state, geographical position, laboratory analytical method applied, reproductive and clinical characters, nutrition and regular activities.

Conclusion

This study concluded that there were statistically significant differences in some hematological parameters among women with BC compared to a control group. Our results present that contraceptive use, menopause age, marital state, and marital age may be associated with breast cancer incidence. Moreover, Hb, RBCs, WBCs, neutrophils, lymphocytes, monocytes, and other parameters scored high points of evidence for BC surveillance. The limitations of this study include the small number of participants and the absence of identification of hematological parameter differences and biochemical parameters after or during chemotherapy or mastectomy (wholly or partially). Similar studies are recommended in the other provinces to confirm the roles of hematological parameters in BC diagnosis in Yemen. Further studies are recommended to illustrate the hematological parameters between patients with invasive BC and non-invasive BC.