Is there an Association of Glycosylated Haemoglobin A1c and Anthropometric Measurements in Premenopausal and Postmenopausal Breast Cancer Patients?

Introduction

The most common form of cancer among women, now days is breast cancer. It is the second most common cause of cancer death in affluent countries and a prominent cause in less developed nations. The burden differs significantly between nations and is steeply rising globally. Breast cancer incidence and mortality rates dropped in countries like the USA [1], but they are rapidly rising in China and South Korea. This difference could be explained by improved public health awareness, effective preventive measures, and more accessible healthcare. With an expected 2.3 million cases and 685,000 fatalities in 2020 [2], breast cancer has overtaken lung cancer as the most frequently diagnosed cancer for the first time. Breast cancer ranks fifth among all causes of cancer mortality globally. By 2070 cases are likely to reach 4.4 million [3]. Breast cancer ranks first for incidence and mortality in the majority of the world’s countries in 2020 [2], accounting for 24.5% of all cancer cases and 15.5% of cancer deaths. According to GLOBOCON data from 2020 [2], breast cancer caused 10.6% (90408) of all deaths in India and represented 13.5% (178361) of all cancer cases (Figures 1-17).

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Increased risk factor prevalence, planned or unplanned mammographic screening detections, population increase, and ageing are all potential contributors to elevated incidence rates of breast cancer [4]. But differences in the primary risk factors, screening procedures, and population numbers or structures of different geographical locations contributed to discrepancies in the burden of breast cancer [5].

Materials and Methods

The prospective observational study was conducted at the tertiary care hospital between December 2020 and November 2022 at Jawaharlal Nehru Medical College, Aligarh Muslim University, Aligarh, INDIA. The study was approved by the Institutional Ethics Committee.

Results

The study was conducted for 23 months from December 2020 to November 2022.

Discussion

Glycosylated haemoglobin A1c (HbA1c) tests were adopted as a diagnostic tool for diabetes by the American Diabetes Association (ADA) [8]. The chronic glycemic exposure marker HbA1c shows the average blood glucose levels over a period of two to three months [8, 9]. Overall breast carcinoma is the 2nd most common malignancy seen worldwide and the most common malignancy in females. Over hundred years the associations of breast carcinoma with other co-morbidities were being studied to identify various etiologies and associated morbidity and mortality. This study was undertaken with the aim to study the association of glycosylated haemoglobin A1c with anthropometric measurements & tumour characteristics in carcinoma breast. Results from our study showed that prediabetic patients with no history of diabetes made up the majority of the breast cancer patients in this series. This is especially interesting because prior research suggested that many diabetes cases would go untreated until a breast cancer diagnosis was obtained. In our study the mean age was 47.75±11.77 SD years. The youngest was 18 years old and eldest was 80 years all of whom were females. In our study maximum patients 62% belonged to 40-59 years age group (p value 0.069) which not statistically significant. 84 (84%) patients were married and 13 (13%) patients were widow and only 3 (3%) were single. Our study is in agreement with study of Nehad M Ayoub, et al. [10] average age of the patients was 49.9±10.3 SD years (range 27 to 80 years). In their study maximum patients 62.3% belonged to 40-59 years age group. 74% patients were married 16.6% were widow and 8.5% were single. In our study 36 (36%) patients were pre-menopausal and 64 (64%) patients were post-menopausal. In pre-diabetic group 70% patients were postmenopausal and in diabetic group 93% patients were postmenopausal. In the study by Nehad M Ayoub, et al. [10] 32% patients were pre-menopausal and 67.7% were post-menopausal. Study indicated a significant association between HbA1c and menopausal status. Postmenopausal women presented with higher mean levels of HbA1c

compared to premenopausal patients. The results were similar and comparable to our study. In our study HbA1c levels were positively and significantly correlated with waist circumference, hip circumference and BMI but were not significantly correlated with waist to hip ratio. In agreement to our findings Million Women Study [11] which followed 1.2 million UK women aged 50 to 64 years for a mean of 5.4 years, including 45,037 with breast cancer, and identified a nearly 30% higher risk of developing postmenopausal breast cancer with obesity. An increased risk of breast cancer in postmenopausal women with diabetes was reported in study by Talamini, et al. [12]. Our findings revealed that on the basis of HbA1c % levels, most patients were classified as prediabetics (58%). In agreement with study of Nehad M Ayoub, et al. [10] HbA1c % levels revealed that most patients classified as prediabetics (44.4%). 6% patients in our study were known cases of diabetes. Our study is in agreement with the study of Juhua Luo, et al. [13] of women with invasive breast cancer, in which 9.0 % had pre-existing treated diabetes before breast cancer diagnosis. In our study 52 (52%) patients had right sided disease, 47 (47%) had left sided disease and 1 (1%) patient had bilateral disease (p value 0.434) which was not statistically significant. Our study is in agreement with study of Shao-Ang Cheng, et al. [14] in the case of invasive carcinoma of breast. The right breast was more commonly affected than the left in young (<40 years old) patients whereas the opposite trend was found in old (≥40 years old) patients. In our study 2 (2%) patient had T1 tumour; 23 (23%) patients had T2 tumour; 51 (51%) had T3 tumour; and rest 24 (24%) had T4 tumour. 56% patients had clinically palpable lymph nodes while 44% did not. In this study 1% had stage I carcinoma of breast; 43% had stage II and 56% had stage III carcinoma of breast. Most of the pre-diabetic and diabetic patients had stage III breast cancer (55.1% and 56% respectively) with p value 0.879 which was not statistically significant. In this study pathological grading of disease was done by Nottingham histological grading system. 13% patients had grade I; 57% had grade II and 18% had grade III disease. Maximum patients were seen as grade II in pre-diabetic and diabetic HbA1c patients (53.4% and 64.3% respectively; p value 0.858) which was not statistically significant. In pre- diabetic and diabetic patients lymphovascular invasion was identified in 48.3% and 42.9%, respectively; (p value 0.888) which was not statistically significant. 77 (77%) patients had invasive ductal carcinoma – no special type (NST) as breast carcinoma subtype which failed to exhibit sufficient morphological features to be classified as specific histological types. Our study is in agreement with study of Barbara, et al. [15] grading which showed that most tumours were moderately differentiated, i.e., grade II in 67 patients (73%) and were followed by low-differentiated, i.e., grade III in 19 patients (21%); (p value 0.0698). Our study is in agreement with study of the Bronsveld, et al. [16] in which they did not find an association between any of the clinicopathological breast cancer subtypes and diabetes in postmenopausal breast cancer patients compared to the non-diabetic. Our study is in agreement with study of Yancik, et al. [17] in which there was no association seen between diabetes and breast cancer stage in menopausal women. Our study deviates from the study of Fleming, et al. [18] which evaluated women older than 67 years with breast cancer using Surveillance, Epidemiology, and End Results-Medicare data and found an increased risk of late-stage disease in women with diabetes. Our study differs from the study of Srokowski, et al. [19] which demonstrated that a higher percentage of women with diabetes presented with a more advanced stage than their nondiabetic counterparts. In our study 36 (36%) patients had positive ER status; while 55 (55%) had negative ER status. In pre-diabetic and diabetic patients; 60.3% and 42.9% had negative ER status respectively (p value 0.567). In our study 88 (88%) patients had negative PR status. In our study 47 (47%) patients had positive Her2 neu receptor status and 44 (44%) had negative Her2 neu. In pre-diabetic and diabetic 50% and 57.1% had positive Her2 neu status respectively; (p value 0.585). In agreement to our study Karlin, et al. [20] also reported no significant differences in breast cancer grade, stage, and receptor positivity between diabetic and non-diabetic patients. In contrast to our study Julie R. Palmer, et al. [21] demonstrated positive association with diabetes for ER negative breast cancer but not for ER positive cancer. The impact of HbA1c on breast clinicopathologic characteristics was inconsistent. HbA1c status in this study did not significantly correlate with tumour clinicopathologic features.

Conclusion

Our study demonstrated that a considerable proportion of breast cancer patients in this study were prediabetic. Glycaemic status and HbA1c was clearly associated with measures of visceral obesity in carcinoma of breast patients. Postmenopausal patients in this study had higher levels of HbA1c compared to premenopausal cases. However; clinicopathological and tumour characteristics in our study didn’t demonstrate any significant correlation with glycaemic status and need more research and randomized controlled trials. Collectively, findings from our study call for appropriate assessment for glycaemic status in breast cancer patients on presentation, particularly emphasizing the need to control hyperglycemia and identify vulnerable groups of breast cancer patients who might benefit from interventions to improve glycaemic control.

Ethical Approval

The study was approved by the Jawaharlal Nehru Medical College and Hospital Institutional Ethics Committee.