|Year : 2020 | Volume
| Issue : 8 | Page : 4190-4195
The association of body mass index and adverse clinicopathological characteristics in non-metastatic breast cancer
Atlal Abusanad, Bashayer Alghamdi, Reema Alghamdi, Raghad Khallaf, Konooz Faisal, Raghad Bishnaq
Department of Internal Medicine and Medical Oncology, Faculty of Medicine, King Abdulaziz University Hospital, Jeddah, Saudi Arabia
|Date of Submission||10-Apr-2020|
|Date of Decision||10-Jun-2020|
|Date of Acceptance||01-Jul-2020|
|Date of Web Publication||25-Aug-2020|
Dr. Atlal Abusanad
Associate Professor of Internal Medicine and Medical Oncology, Faculty of Medicine, King Abdulaziz University (KAU), Al Ehtifalat St, Jeddah - 21589
Source of Support: None, Conflict of Interest: None
Background: Obesity is a global health problem. It is becoming increasingly prevalent in Saudi Arabia. High body mass index (BMI) is a risk factor for many diseases, including cancer. Noticeably, breast cancer (BC) cases in Saudi Arabia occur at a younger age than in western countries. Different lifestyle behaviors such as maintaining healthy body weight and physical activity may play a role in this. In this study, we investigated the association between BMI and BC adverse clinicopathological features. Methods: This retrospective study was conducted by reviewing the records of women with non-metastatic BC over 4 years. The association between BMI and patients' demographics, BC histological type, receptor status, differentiation grade, tumor size, involvement of axillary lymph nodes, and performed procedures were analyzed. Result: 315 patients with non-metastatic BC were studied. The mean age at the time of diagnosis was 52.43 years ± 11.63. The mean BMI was 30.21 ± 5.77. The mean tumor size was 3.19 cm ± 3.52. The mean age of diagnosis is significantly higher in obese women than in other BMI groups (P = 0.025). Obese female patients aged ≥40 were more likely to present with larger tumor (P = 0.022) and numerically higher pathological axillary lymph nodes, trending toward statistical significance (P = 0.092). Conclusion: The relationship between BMI and developing more aggressive BC is still not clear; in this study, we found that obese patients presented at an older age, with larger tumor and more pathologic lymph nodes. Further research to understand the impact of this finding on outcomes is warranted.
Keywords: Body mass index, breast cancer, clinicopathologic characteristics, obesity, postmenopausal
|How to cite this article:|
Abusanad A, Alghamdi B, Alghamdi R, Khallaf R, Faisal K, Bishnaq R. The association of body mass index and adverse clinicopathological characteristics in non-metastatic breast cancer. J Family Med Prim Care 2020;9:4190-5
|How to cite this URL:|
Abusanad A, Alghamdi B, Alghamdi R, Khallaf R, Faisal K, Bishnaq R. The association of body mass index and adverse clinicopathological characteristics in non-metastatic breast cancer. J Family Med Prim Care [serial online] 2020 [cited 2020 Sep 24];9:4190-5. Available from: http://www.jfmpc.com/text.asp?2020/9/8/4190/293057
| Introduction|| |
Obesity is a prevalent global health problem, defined by a body mass index (BMI) ≥30.0 kilogram/meter squared. Overall, about 13% of the world's adult population (11% of men and 15% of women) were obese in 2016. In the Arab region, including Saudi Arabia, obesity has reached 66–75% among adults, which increases the risk of developing several diseases such as coronary artery diseases, hypertension, diabetes, hyperlipidemia, osteoarthritis, and cancer.,,
Breast cancer (BC) is the most common malignancy and the leading cause of cancer-related death among women worldwide., In Saudi Arabia, there is a significant increase in the number of BC cases that occurs at an earlier age than in Western countries, and with advanced stage of the disease. An unmatched case-control study from Saudi Arabia showed that the proportion of overweight/obese (BMI ≥25) females was significantly higher among breast cancer patients (75.8%) than among healthy controls (61.3%). However, it did not investigate the impact of increasing BMI on the adverse clinical and pathological features of breast cancer.
Breast cancer is a diverse disease with different clinical presentations that are classified differently according to hormonal receptor status, estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2)., Among the commonly described histology are ductal carcinoma in situ (DCIS), lobular carcinoma in situ (LCIS), invasive ductal carcinoma (IDC), invasive lobular carcinoma (ILC). Other miscellaneous histologies include but not limited to tubular, medullary, metaplastic and papillary. In recent meta-analysis, BC-specific death among obese women is higher compared to normal weight women. Another study among women aged 65–79 years old indicated that high BMI is associated with a higher risk of having IDC, although it was not statistically significant. As for hormonal receptor status, a study concluded that overweight/obese postmenopausal women develop hormone receptor (HR)-positive tumors more frequently. Altogether is supporting the need for better understanding of the means by which obesity causes poor outcomes in patients with BC.
Several reports from different populations showed a correlation between BMI and tumor grade, tumor size, and axillary lymph node involvement., We locally do not have evidence on the effect of increasing BMI on the adverse clinical and pathological presentation of breast cancers. This relationship is yet to be investigated in our population.
Our study aimed to investigate the potential association between BMI and adverse clinic pathological features (tumor size, lymph node involvement, hormonal receptors, grade and histological subtypes) in patients with non-metastatic breast cancer from Saudi Arabia, Jeddah.
| Methodology|| |
Study design and setting
We conducted a retrospective patients' record review at King Abdulaziz University Hospital (KAUH) in Jeddah, Saudi Arabia. Institutional Review Board (IRB) at KAUH approved the study after the satisfaction of the institutional requirements. All names and file numbers of patients were concealed, and only anonymous data were used to ensure privacy and confidentiality.
From February 2014 to February 2018, all females aged 18-year-old and above with non-metastatic BCs that were operated on before receiving preoperative chemotherapy were enrolled. We reviewed 766 medical records, and some patients were excluded due to the presence of a benign lesion, distant organ metastasis, and missing data. The final sample size was 315.
Data were collected from the electronic medical record system. The following variables were obtained, patients' demographics: (age at diagnosis and nationality), BMI, which is measured by the equation; weight in kilogram (kg) divided by height in meters (m), squared and defined as per World Health Organization (WHO): underweight BMI <19 kg/m2; normal BMI ≥19 and <25 kg/m2; overweight BMI ≥25 and <30 kg/m 2; obese BMI ≥30.0 kg/m2). Breast cancer histological types (DCIS, LCIS, IDC, ILC), receptor status (ER, PR, HER2), grade of differentiation (well (I), moderately (II) and poorly (III) differentiated), tumor size; was classified into three categories (tumor size ≤1 cm, 1–2 cm, and ≥2 cm), the involvement of axillary lymph node, and the surgical procedures performed; (modified radical mastectomy (MRM) or lumpectomy were recorded. Study cohort was sub-classified according to age.
Frequencies of categorical variables were computed and presented. Tumor characteristics were cross-tabulated among young patients <40 and older patients ≥40 years old. The relationship to BMI was assessed using univariate and multivariate analysis with a significance value (P ≤ 0.05 considered significant). Data were analyzed by the statistical package for the social sciences version 21 (SPSS).
| Result|| |
We studied 315 patients with non-metastatic breast cancer who fulfilled the inclusion criteria spanning 4 years from 2014 to 2018. The mean age at the time of diagnosis is 52.43 years ± 11.63 (range 25–85 years). Saudi patients accounted for 40.6% of our sample. The mean BMI is 30.21 ± 5.77 (range, 17- 55). Nearly half of our sample (47.9%) has a BMI of ≥30. Distribution of BMI based on age; ≥40 years and <40 years is shown in [Table 1]. A significant association between age and BMI was demonstrated as follow: the mean age of obese patients is 54.24 ± 11.09, overweight patients is 50.63 ± 11.90, normal-weight patients is 51.58 ± 12.10 and underweight patient is 42.75 ± 6.1 (P = 0.025).
Histological types and receptor status
Invasive ductal carcinoma is the most frequently reported histological type, reported in 237 (84.6%) among women aged 40 years and above, and in 29 (82.9%) of women aged <40 years [Table 2] and [Table 3]. ER-positive tumors are the most common in both age groups, with 185 (66.1%), 23 (65.7%) among ≥40 years and, <40 years, respectively. Interestingly, HER2/neu positive tumors accounted for more than one-third in both age groups [Table 2] and [Table 3].
|Table 2: Clinico-pathologic features in women aged less than 40 according to BMI distribution|
Click here to view
|Table 3: Clinico-pathologic features in women aged 40 and older according to BMI distribution|
Click here to view
The mean tumor size was 3.19 cm ± 3.52. Sixty-one patients (19.4%) had a tumor of ≤1 cm, 31 (9.8%) had a tumor size ranged from 1 to 2 cm, and 223 (70.8%) patients with a tumor size of ≥2 cm. Two-hundred and one patients (72%) aged 40 years and older has tumor size ≥2 cm with 50% (101 out of 201) were being obese patients P = 0.022 [Table 2] and [Table 3].
Lymph node involvement and grade
Lymph node metastasis was found in 171 patients; 154 of them (55%) were 40 year-old and older. Tumor grade was reported as follows: 173 (55%) patients had a moderately differentiated tumors followed by poorly differentiated tumors in 85 (%27), and well differentiated in 57 (18.1%).
Type of procedure
The majority of the patients underwent MRM 216 (68.6%), followed by lumpectomy in 99 patients (31.4%). In women aged 40 and above, 192 (68.6%) had MRM, and 88 (31.4%) had a lumpectomy. In women aged <40, 24 (68.6%) patients had MRM and 11 (31.4%) had a lumpectomy.
| Discussion|| |
Although the impact of BMI on developing BC is consistently described, the association between increasing BMI and adverse pathological features of breast cancer has been speculative. In this present study, we have found that obese women, especially those who are 40 years and older, tend to have a larger tumor. Our findings are consistent with what was described in other populations., Having an increased proportion of older women presenting with larger tumors can be explained by the increased activity of aromatase enzyme seen in women with BMI ≥30, which converts androstenedione to estrogens in peripheral adipose tissue, leading to an increase in the level of estrogen. Moreover, an elevated level of insulin-like growth factor (IGF) and other growth factors such as VEGF, TNF-a, Leptin, IL-6 that may enhance tumor growth, promote angiogenesis, accelerate metastasis, and inhibit apoptosis. Insulin itself stimulates ovarian synthesis of androgens, stimulates expression of growth hormone (GH) receptors, reduces liver production of sex hormone-binding globulin (SHBG) and two IGF-binding proteins (IGFBP-1 and -2), resulting in raising the bioavailability of sex hormones and IGF-1.,
Half of the older patients (aged ≥40) with hormone receptor (HR)-positive tumors were having BMI ≥30. However, no statistically significant relationship between hormone and HER2 receptors status and BMI was observed in the current study. Although HR-positive tumors were numerically more frequent, the statistical significance could not be demonstrated. This may imply that a larger number of patients is needed to demonstrate significance. Different studies showed a variable relationship between HR-status and body weight. Some correlated positively , while others did not show such correlation., All reported studies focused on having an increased number of positive HR among patients with increased BMI; however, the lack of HR expression is considered an adverse feature. Therefore, we ran an analysis in women who were ≥40 with HR- negative status and high BMI exploring the association. There was no statistical or numerical association between HR-negative tumor and high BMI in our sample.
Most of the patients with lymph node metastasis were obese. Lymph node involvement was more prominent in older patients and showed a trend toward statistical significance (P = 0.092). This finding is consistent with many studies.,, However, results from other studies are contradictory, for instance, Eichholzer M et al. found no association between BMI and tumor size or lymph node status in postmenopausal women. We observed that women with high BMI were older at diagnosis (mean age 54.24 ± 11.09) than the ones with average to low BMI (51.58 ± 12.10 and 42.75 ± 6.1, respectively). This finding might be explainable by the lack of health awareness in general among those patients, represented by an unhealthy lifestyle leading to obesity. Nonetheless, higher BMI is associated with more body fat, which makes the clinical palpation difficult; hence this results in women presenting with larger tumor size and more lymph node metastasis.
Modified radical mastectomy (MRM) accounted for the majority of the surgical option. Selection bias could have cofounded this finding as we selected patients who underwent upfront surgery in order to ascertain accurate pathologic staging based on the complete surgical specimen. Similar proportion in both age groups had MRM (68.6%) and lumpectomy (31.4%). The majority of both groups had a tumor ≥2 cm, considerably high percentage of lymph node involvement, and nearly one third with HER2 positive tumor and high grade, which possibly contributed to MRM being the most common procedure. Invasive ductal carcinoma was the most frequent type among our patients, and the majority were obese, but were not different from what observed in the average BMI group. Differentiation Grade of breast cancer was not significantly associated with increasing BMI in our study. Moderate differentiation was the predominant grade across all BMI groups.
The main limitation of this study was that body weight and height were the only anthropometric information found in the records at the time of diagnosis of breast cancer. This favored the use of BMI as a sign of general obesity. However, visceral obesity that is detected by waist-hip ratio and waist circumference could not be examined because these measures were not routinely reported. Although BMI is used as a marker of obesity, it does not distinguish between slim/fat mass or central/peripheral fat distribution.
The majority in this cohort presented with histologically invasive carcinoma, larger tumor and more pathological lymph nodes. There is a recognized need to advocate awareness of obesity and its impact on health in general and as a potential contributing factor for the development of breast cancer with probably more advanced and aggressive features.
The knowledge of how obesity can affect the risk of developing several morbidities including breast cancer, specifically breast cancer with more aggressive features, will help primary care and family practice physician in identifying the population in need for better awareness and education. Emphasizing the pivotal role of primary care providers in promoting healthy life style, healthy diet, and exercising to help maintain healthy body weight and avoid obesity-related complications.
| Conclusion|| |
Higher BMI showed an association with larger tumor size and pathological lymph nodes in older patients with breast cancer. Histological types, receptor status, and grade did not show statistically significant association. Obese women had an older age at diagnosis with BC than those with average BMI. Data from this research will help in investigating the impact of obesity on breast cancer (outcomes, presentation, prognosis) in Saudi Arabia.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Sun L, Zhu Y, Qian Q, Tang L. Body mass index and prognosis of breast cancer: An analysis by menstruation status when breast cancer diagnosis. Medicine (Baltimore) 2018;97:e11220.
DeNicola E, Aburizaiza OS, Siddique A, Khwaja H, Carpenter DO. Obesity and public health in the Kingdom of Saudi Arabia. Rev Environ Health 2015;30:191-205.
M Alqarni SS. A review of prevalence of obesity in Saudi Arabia. J Obes Eat Disord 2016;2:25. doi: 10.21767/2471-8203.100025.
Martin-Sanchez JC, Lunet N, Gonzalez-Marron A, Lidon-Moyano C, Matilla-Santander N, Cleries R, et al
. Projections in breast and lung cancer mortality among women: A bayesian analysis of 52 countries worldwide. Cancer Res 2018;78:4436-42.
Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin 2020;70:7-30.
Saggu S, Rehman H, Abbas ZK, Ansari AA. Recent incidence and descriptive epidemiological survey of breast cancer in Saudi Arabia. Saudi Med J 2015;36:1176-80.
Elkum N, Al-Tweigeri T, Ajarim D, Al-Zahrani A, Amer SM, Aboussekhra A. Obesity is a significant risk factor for breast cancer in Arab women. BMC Cancer 2014;14:788.
Sahin S, Erdem GU, Karatas F, Aytekin A, Sever AR, Ozisik Y, et al
. The association between body mass index and immunohistochemical subtypes in breast cancer. Breast 2017;32:227-36.
Makki J. Diversity of breast carcinoma: Histological subtypes and clinical relevance. Clin Med Insights Pathol 2015;8:23-31.
Chan DS, Vieira AR, Aune D, Bandera EV, Greenwood DC, McTiernan A, et al
. Body mass index and survival in women with breast cancer-systematic literature review and meta-analysis of 82 follow-up studies. Ann Oncol 2014;25:1901-14.
Li CI, Malone KE, Porter PL, Weiss NS, Tang MT, Daling JR. Reproductive and anthropometric factors in relation to the risk of lobular and ductal breast carcinoma among women 65-79 years of age. Int J Cancer 2003;107:647-51.
Biglia N, Peano E, Sgandurra P, Moggio G, Pecchio S, Maggiorotto F, et al
. Body mass index (BMI) and breast cancer: Impact on tumor histopathologic features, cancer subtypes and recurrence rate in pre and postmenopausal women. Gynecol Endocrinol 2013;29:263-7.
Gershuni V, Li YR, Williams AD, So A, Steel L, Carrigan E, et al
. Breast cancer subtype distribution is different in normal weight, overweight, and obese women. Breast Cancer Res Treat 2017;163:375-81.
Govind Babu K, Anand A, Lakshmaiah KC, Lokanatha D, Jacob LA, Suresh Babu MC, et al
. Correlation of BMI with breast cancer subtype and tumour size. Ecancermedicalscience 2018;12:845.
Daling JR, Malone KE, Doody DR, Johnson LG, Gralow JR, Porter PL. Relation of body mass index to tumor markers and survival among young women with invasive ductal breast carcinoma. Cancer 2001;92:720-9.
Loi S, Milne RL, Friedlander ML, McCredie MR, Giles GG, Hopper JL, et al
. Obesity and outcomes in premenopausal and postmenopausal breast cancer. Cancer Epidemiol Biomarkers Prev 2005;14:1686-91.
Ayoub NM, Yaghan RJ, Abdo NM, Matalka, II, Akhu-Zaheya LM, Al-Mohtaseb AH. Impact of obesity on clinicopathologic characteristics and disease prognosis in pre- and postmenopausal breast cancer patients: A retrospective institutional study. J Obes 2019;2019:3820759.
Petekkaya I, Sahin U, Gezgen G, Solak M, Yuce D, Dizdar O, et al
. Association of breast cancer subtypes and body mass index. Tumori J 2013;99:129-33.
Enger SM, Ross RK, Paganini-Hill A, Carpenter CL, Bernstein L. Body size, physical activity, and breast cancer hormone receptor status: Results from two case-control studies. Cancer Epidemiol Biomarkers Prev 2000;9:681-7.
Suzuki R, Rylander-Rudqvist T, Ye W, Saji S, Wolk A. Body weight and postmenopausal breast cancer risk defined by estrogen and progesterone receptor status among Swedish women: A prospective cohort study. Int J Cancer 2006;119:1683-9.
Gillespie EF, Sorbero ME, Hanauer DA, Sabel MS, Herrmann EJ, Weiser LJ, et al
. Obesity and angiolymphatic invasion in primary breast cancer. Ann Surg Oncol 2010;17:752-9.
Kaviani A, Neishaboury M, Mohammadzadeh N, Ansari-Damavandi M, Jamei K. Effects of obesity on presentation of breast cancer, lymph node metastasis and patient survival: A retrospective review. Asian Pac J Cancer Prev 2013;14:2225-9.
Eichholzer M, Huang DJ, Modlasiak A, Schmid SM, Schotzau A, Rohrmann S, et al
. Impact of body mass index on prognostically relevant breast cancer tumor characteristics. Breast Care (Basel) 2013;8:192-8.
[Table 1], [Table 2], [Table 3]