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Association between body mass index and clinical characteristics, as well as with management, in Chinese patients with breast cancer

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The Journal of International Medical Research
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Objective Body mass index (BMI) is a risk factor associated with breast cancer in postmenopausal women. This study aimed to identify the associations of BMI with clinical characteristics and management of breast cancer in female Chinese patients. Methods Clinicopathological information on 1296 women who were diagnosed with breast cancer was collected at our hospital. We recorded the clinicopathological characteristics, molecular phenotypes, manner of diagnosis, implementation rate of preoperative examinations, and surgical method used. Results Significant differences were found in the tumor size, disease stage, manner of diagnosis, implementation rate of preoperative examinations, and the surgical method among different BMI groups. In premenopausal patients, significant differences were found in the distribution of molecular phenotypes and surgical approach among different BMI groups. In postmenopausal patients, different BMI groups showed significant differences in the tumor size, disease stage, distribution of molecular phenotypes, manner of diagnosis, rate of implementation of preoperative mammography, and surgical method. Conclusion Higher BMI is associated with a larger tumor size, more advanced disease stage, diagnosis by physical examination, higher implementation rate of preoperative examinations, and lower radical surgery rate in Chinese women with breast cancer. However, the relationship between BMI and molecular phenotypes differs between pre- and postmenopausal women.
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Retrospective Clinical Research Report
Association between body
mass index and clinical
characteristics, as well as with
management, in Chinese
patients with breast cancer
Bin Wang
1,
*, Lizhe Zhu
1,
*, Siyuan Jiang
1
,
Lizhi Zhao
2
, Yuhui Zhou
1
, Ligang Niu
1
,YuYan
1
and Ke Wang
1
Abstract
Objective: Body mass index (BMI) is a risk factor associated with breast cancer in postmeno-
pausal women. This study aimed to identify the associations of BMI with clinical characteristics
and management of breast cancer in female Chinese patients.
Methods: Clinicopathological information on 1296 women who were diagnosed with breast
cancer was collected at our hospital. We recorded the clinicopathological characteristics, molec-
ular phenotypes, manner of diagnosis, implementation rate of preoperative examinations, and
surgical method used.
Results: Significant differences were found in the tumor size, disease stage, manner of diagnosis,
implementation rate of preoperative examinations, and the surgical method among different BMI
groups. In premenopausal patients, significant differences were found in the distribution of molec-
ular phenotypes and surgical approach among different BMI groups. In postmenopausal patients,
different BMI groups showed significant differences in the tumor size, disease stage, distribution
of molecular phenotypes, manner of diagnosis, rate of implementation of preoperative mammog-
raphy, and surgical method.
Conclusion: Higher BMI is associated with a larger tumor size, more advanced disease stage,
diagnosis by physical examination, higher implementation rate of preoperative examinations, and
lower radical surgery rate in Chinese women with breast cancer. However, the relationship
between BMI and molecular phenotypes differs between pre- and postmenopausal women.
1
Department of Breast Surgery, The First Affiliated
Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi
Province, China
2
Department of Oncosurgery, Hanzhong Central
Hospital, Hanzhong, Shaanxi Province, China
*These authors contributed equally to this work.
Corresponding author:
Ke Wang, Department of Breast Surgery, The First
Affiliated Hospital of Xi’an Jiaotong University, 277 Yanta
Western Road, Xi’an, Shaanxi Province 710061, China.
Email: 979915080@qq.com
Journal of International Medical Research
48(8) 1–15
!The Author(s) 2020
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DOI: 10.1177/0300060520949041
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Keywords
Breast cancer, body mass index, molecular phenotype, tumor size, menopausal, mammography
Date received: 15 March 2020; accepted: 21 July 2020
Introduction
Currently, breast cancer is one of the
most common malignant tumors in women.
In recent decades, the incidence of breast
cancer has been showing a rising trend
worldwide,
1
especially in the Asian region.
2
The incidence of breast cancer was increased
by 38.5% and the number of breast cancer-
related deaths was 13,000 in China in 2005.
3
Epidemiological studies have shown that the
increase in the incidence of breast cancer is
associated with changes in various breast
cancer-related risk factors, and body mass
index (BMI) is an important factor.
4
Furthermore, a number of clinical studies
have indicated that BMI is an important
risk factor associated with breast cancer in
postmenopausal women.
5
Some researchers have shown that
there are certain differences in the effect of
BMI in Western and Asian populations.
6
The CBCS and Washington state studies
showed that, in postmenopausal women,
BMI increased the risk for luminal A and
basal-like breast cancer.
7
However, in
Japanese postmenopausal patients, the corre-
lation between increased BMI and the risk of
breast cancer was limited to patients with
estrogen receptor-positive (ERþ) breast
cancer, and there was no correlation with
triple-negative (TN) or basal-like breast
cancer.
8
This difference might be related to
many factors, including regional differences,
ethnic background, living habits, diet
structure, the level of economic development,
and the education level among others.
9
This study aimed to study the effects
of BMI on the clinicopathological charac-
teristics, implementation rate of preopera-
tive clinical examinations, and surgical
approach in Chinese female patients with
breast cancer in the Shaanxi area.
Hopefully, the results of our study may
reflect to a certain extent the trend in
breast cancer in other developing countries.
Therefore, our findings could help other
developing countries to formulate preven-
tion strategies for breast cancer that cater
to a developing economy.
Methods
Patients
This retrospective study included female
patients with pathologically confirmed pri-
mary breast cancer from the First Affiliated
Hospital of Xi’an Jiaotong University
between February 2016 and January 2019.
This hospital is representative of the local
Shaanxi area, which is undergoing rapid
economic development.
10
All of the cases
were reviewed and the patients’ information
was collected using a case report form. All
of the patients enrolled in this study met
two main inclusion criteria as follows: (1)
pathologically confirmed primary breast
cancer and (2) previous treatment (surgery)
2Journal of International Medical Research
for breast cancer. The exclusion criterion
was distant metastasis at diagnosis.
According to the conventions of the
World Health Organization,
11
the enrolled
patients were classified into four groups
according to their BMI as follows: under-
weight, BMI <18.5 kg/m
2
; normal weight,
BMI ¼18.5 to 24.99 kg/m
2
; overweight,
BMI ¼25.0 to 29.99 kg/m
2
; and obese,
BMI 30.0 kg/m
2
. BMI was calculated as
follows:
BMI ¼weight kg
ðÞ
=height squared m
ðÞ
2
Pathological diagnostic criteria
Histological subtype categories were based
on the 1981 and 2003 World Health
Organization histological classification crite-
ria.
12
Staging of breast cancer was per-
formed according to the American Joint
Committee on Cancer tumor-node-
metastasis (TNM) staging system of 1997.
13
By convention, TNM stages I and II were
classified as early breast cancer, and stage III
was regarded as advanced breast cancer.
10
Immunohistochemistry and molecular
typing
The expression levels of ER, progesterone
receptor (PR), human epidermal growth
factor receptor 2 (Her2), and Ki-67 (cell pro-
liferation marker) in cancer tissue samples
were examined using immunohistochemistry
by experienced pathologists. ER and PR
expression was considered to be positive
if >1% of the cells showed positive nuclear
staining in a single section. The intensity and
pattern of Her2 staining in the membrane of
tumor cells were evaluated using a scoring
system for the categorization of tumors. In
brief, the scoring system was as follows:
scores of 0 and 1þ(weak immunostaining
in <30% of the tumor cells) were considered
Her2-negative; a score of 2þ(complete,
strong membranous staining in at least 10%,
but in <30%, of the tumor cells) was consid-
ered as equivocal; and a score of 3þ
(uniform intense membranous staining in
30% of the tumor cells) was considered as
Her2-positive. Tumors that were scored 2þ
were further assessed by fluorescence in situ
hybridization (FISH). If positive staining
was observed in FISH analysis, tumors with
a2þscore were designated as Her2-positive.
14
Using the newly recommended method
for categorizing breast cancer subtypes,
15
the tumors were grouped into four subtypes
as follows: (1) luminal A (ER- and/or PR-
positive, Her2-negative, and Ki-67 <14%);
(2) luminal B (ER- and/or PR-positive,
Her2-negative, and Ki-67 14%; or ER-
and/or PR-positive, Her2-positive, and
any expression of Ki-67); (3) Her2þ(Her2
overexpression, and ER- and PR-negative);
and (4) triple-negative ([TN] ER- and PR-
negative, Her2-negative, and any expression
of Ki-67).
Data collection and quality control
The following data were systematically col-
lected for all enrolled patients via a review
of their medical records: (1) general infor-
mation, including date of diagnosis, visits to
other health care professionals, inpatient
admission date, diagnosis at admission,
and manner of detection; (2) demographic
characteristics at the time of diagnosis/
admission; (3) data on a clinical breast
examination; (4) diagnostic imaging data,
including molybdenum target X-ray (mam-
mography) and B-ultrasound data; (5) data
on characteristics of the tumor, including
primary location of the tumor, primary
tumor quadrant, tumor size, tumor
Wang et al. 3
invasion, lymph node metastasis, and
tumor staging; (6) data on surgical interven-
tion; and (7) data on pathological charac-
teristics, including findings from
preoperative cytological and pathological
examinations, intraoperative pathological
evaluation, postoperative pathological eval-
uation, and ER, PR, Her-2, and Ki-67
expression.
All patients’ information was retrieved
from medical records by trained clerks
and added to a paper-based case report
form. Two data input clerks were recruited
for double entry of data from paper to a
computer-based database (FoxPro soft-
ware; FoxPro Inc., Lewiston, PA, USA)
independently. All of the complete double-
entry databases were validated by running
EpiData (The Epidata Association, Odense,
Denmark). Any inconsistencies found
between the two databases were reported
to the clerks for adjudication until both
databases were in agreement. As a final
check, one of the databases was chosen
for a final consistency check. Logistical mis-
takes were returned to the data collectors,
who checked the original medical records
and returned a revised database for the
final analysis. During the consistency
check, 5% of the medical records were ran-
domly selected on the basis of the study ID,
and sent for quality control review.
Data analysis
The frequencies of variables related to clin-
ical and pathological characteristics, imple-
mentation of the clinical examination, and
various treatment patterns were calculated
to indicate their distribution in the total
population and in different BMI groups.
Differences in the distribution of variables
among different groups were examined
using the chi-square test, the rank-sum
test, and Fisher’s exact test to obtain
Pvalues for the non-association tests.
Measurement data are expressed as mean
standard deviation. The case-only odds
ratio (OR) was used to evaluate the relative
strength of the association between BMI
and the tumor molecular subtype (i.e., lumi-
nal B, Her2þ, or TN) versus luminal A,
which is the most common subtype.
16
SPSS statistical software version 22.0
(IBM Corp., Armonk, NY, USA) was
used to analyze the data. Statistical signifi-
cance was assessed by two-tailed tests with
an alevel of 0.05.
Ethics
This study was approved by the Medical
Ethics Committee of Xi’an Jiaotong
University. Patient consent was not
required for this study because there were
no anticipated risks for the participants. All
patient identifiers were removed from the
data, according to approved procedures,
and the anonymized data were maintained
in a secure database that only members of
the research team could access. All of the
data are reported in aggregate.
Results
General information
Data for 1296 cases were collected, includ-
ing data on 127 cases in which we were
unable to distinguish between luminal A
and B types because the level of Ki-67
expression was not detected, 34 cases in
which immunohistochemistry showed an
Her2 score of 2þ, but Her2 expression
was not determined with FISH analysis,
and 95 cases in which the clinical and path-
ological information was incomplete.
Therefore, 256 cases were excluded, with a
final number of cases in this study of 1040.
4Journal of International Medical Research
The mean (standard deviation) age of the
women was 42 2 years. Basic clinical
and pathological information of all of the
patients is shown in Table 1. In this study,
more than half of the patients had a tumor
diameter of 2 to 5 cm. A higher number of
patients had advanced breast cancer than
early stage cancer. The main pathological
pattern was invasive ductal carcinoma.
The most common molecular subtype was
luminal A (>50%), followed by the TN
type, and the Her2þtype was the least
common. Finally, based on the
BMI, >60% patients were assigned to the
normal weight group, while the underweight
and obese groups contained only approxi-
mately 5% of patients in each group.
Comparison of the clinical and
pathological features of breast cancer
among the different BMI groups
There were significant differences in the
clinical and pathological features of the
different BMI groups. With regard to
tumor size, in the underweight group,
50% of the patients had a tumor diameter
2 cm, and the percentage of patients with
a tumor diameter 2 cm gradually
decreased with an increase in BMI.
Therefore, the tumor diameter significant-
lyincreasedwithanincreaseinBMI
(P<0.01). Similar to the trend in tumor
size, the proportion of patients with
early-stage breast cancer gradually
decreasedwithanincreaseinBMI,while
the proportion of patients with advanced
stage breast cancer gradually increased
(P¼0.04). There were no significant dif-
ferences in the other pathological features
(axillary lymph node status, pathological
diagnosis, tumor site, and molecular type)
among the BMI groups (Table 2).
Effect of BMI on the manner of detection
of breast cancer and the implementation
rate of preoperative examinations
Differences in social factors affect the dis-
tribution of BMI in the population, and this
difference might also have an effect on the
manner of detection and implementation of
the preoperative examination. With an
Table 1. Clinical characteristics and molecular
subtypes in the study population.
Characteristics n %
Tumor size
2 cm 391 37.6
2–5 cm 553 53.2
>5 cm 96 9.2
Axillary lymph nodes
Negative 531 51.1
Positive 509 48.9
TNM stage
Early (I þII) 465 44.7
Advanced (III) 575 55.3
Pathological diagnosis
Ductal carcinoma 849 81.6
Lobular carcinoma 93 8.9
Others 98 9.4
Tumor site
Left 535 51.4
Right 505 48.6
Molecular subtype
Luminal A 529 50.9
Luminal B 177 17.0
Her2þ111 10.7
TN 223 21.4
BMI group
UW 66 6.3
NW 642 61.7
OW 277 26.6
OB 55 5.3
TNM, tumor-node-metastasis; Her2, human epidermal
growth factor receptor 2; TN, triple-negative; BMI, body
mass index; UW, underweight; NW, normal weight; OW,
overweight; OB, obese.
Wang et al. 5
increase in BMI, the proportion of patients
in whom breast cancer was detected by a
physical examination and by accident grad-
ually increased, while the proportion in
which it was detected on the basis of symp-
toms decreased (P¼0.002) (Table 3). With
regard to preoperative examinations, the
overall implementation rate for mammog-
raphy was much lower than the average
rate in developed Western countries. The
implementation rate of B-ultrasound was
significantly higher than that of mammog-
raphy (P<0.01). The implementation
rate of these two most commonly used pre-
operative techniques showed the same
trend. With an increase in BMI, the imple-
mentation rate of mammography gradually
increased (P¼0.06), as did the implementa-
tion rate of B-ultrasound (P<0.01).
Table 2. Comparison of clinical and pathological features of breast cancer among the different body mass
index groups.
Characteristics
UW
n (%)
NW
n (%)
OW
n (%)
OB
n (%)
Subtotal
n (%)
66 642 277 55 1040
Tumor size
2 cm 33 (50.0) 236 (36.8) 111 (40.1) 11 (20.0) 391 (37.6)
2–5 cm 28 (42.4) 359 (55.9) 128 (46.2) 38 (69.1) 553 (53.2)
>5 cm 5 (7.6) 47 (7.3) 38 (13.7) 6 (10.9) 96 (9.2)
Pvalue <0.01**
Axillary lymph nodes
Negative 38 (57.6) 329 (51.2) 140 (50.5) 24 (43.6) 531 (51.1)
Positive 28 (42.4) 313 (48.8) 137 (49.5) 31 (56.4) 509 (48.9)
Pvalue 0.499*
TNM stage
Early (I þII) 31 (47.0) 307 (47.8) 105 (37.9) 22 (40.0) 465 (44.7)
Advanced (III) 35 (53.0) 335 (52.2) 172 (62.1) 33 (60.0) 575 (55.3)
Pvalue 0.04**
Pathological diagnosis
Ductal carcinoma 53 (80.3) 529 (82.4) 221 (79.8) 46 (83.6) 849 (81.6)
Lobular carcinoma 7 (10.6) 54 (8.4) 27 (9.7) 5 (9.1) 93 (8.9)
Others 6 (9.1) 59 (9.2) 29 (10.5) 4 (7.3) 98 (9.4)
Pvalue 0.955***
Tumor site
Left 32 (48.5) 339 (52.8) 136 (49.1) 28 (50.9) 535 (51.4)
Right 34 (51.5) 303 (47.2) 141 (50.9) 27 (49.1) 505 (48.6)
Pvalue 0.724*
Molecular subtype
Luminal A 34 (51.5) 322 (50.2) 143 (51.6) 30 (54.5) 529 (50.9)
Luminal B 9 (13.6) 118 (18.4) 42 (15.2) 8 (14.5) 177 (17.0)
Her2þ7 (10.6) 74 (11.5) 26 (9.4) 4 (7.3) 111 (10.7)
TN 16 (24.2) 128 (19.9) 66 (23.8) 13 (23.6) 223 (21.4)
Pvalue 0.799*
UW, underweight; NW, normal weight; OW, overweight; OB, obese; TNM, tumor-node-metastasis; Her2, human epi-
dermal growth factor receptor 2; TN, triple-negative. *Chi-square test; **rank-sum test; ***Fisher’s exact test.
6Journal of International Medical Research
Effect of BMI on the surgical approach
BMI also affected the surgical approach.
With an increase in BMI, the implementation
rate of radical surgery (modified radical mas-
tectomy) decreased, and the implementation
rate of advanced surgical methods (sentinel
lymph node biopsy [SLNB] or breast conser-
vation surgery [BCS]) gradually increased
(P<0.01) (Table 4).
Effect of BMI on the clinical and
pathological features, manner of
detection, implementation rate
of preoperative examinations, and
surgical approach in the
premenopausal population
To determine whether BMI is associated
with the occurrence of breast cancer in pre-
menopausal and postmenopausal women in
Table 3. Effect of body mass index on the manner of detection and the implementation rate of preoper-
ative examinations.
Characteristics
UW
n (%)
NW
n (%)
OW
n (%)
OB
n (%)
Subtotal
n (%)
66 642 277 55 1040
Detection
Physical examination 2 (3.0) 40 (6.2) 22 (7.9) 7 (12.7) 71 (6.8)
Accidental 33 (50.0) 422 (65.7) 193 (69.7) 30 (54.5) 678 (65.2)
Symptom based 31 (47.0) 180 (28.1) 62 (22.4) 18 (32.7) 291 (28.0)
Pvalue 0.002***
Molybdenum target X-ray
Used 9 (13.6) 124 (19.3) 65 (23.5) 21 (38.2) 219 (21.1)
Not used 52 (78.8) 501 (78.0) 204 (73.6) 32 (58.2) 789 (75.9)
Not clear 5 (7.6) 17 (2.6) 8 (2.9) 2 (3.6) 32 (3.1)
Pvalue 0.06***
B-ultrasound
Used 49 (74.2) 501 (78.0) 217 (78.3) 36 (65.5) 803 (77.2)
Not used 17 (25.8) 129 (20.1) 55 (19.9) 16 (29.1) 217 (20.9)
Not clear 0 (0.0) 12 (1.9) 5 (1.8) 3 (5.5) 20 (1.9)
Pvalue 0.01*
UW, underweight; NW, normal weight; OW, overweight; OB, obese. *Chi-square test; ***Fisher’s exact test.
Table 4. Effect of body mass index on the surgical approach.
Surgical approach
UW
n (%)
NW
n (%)
OW
n (%)
OB
n (%)
Subtotal
n (%)
66 642 277 55 1040
Radical mastectomy 0 (0.0) 17 (2.6) 14 (5.1) 3 (5.5) 34 (3.3)
Modified radical mastectomy 60 (90.9) 592 (92.2) 223 (80.5) 39 (70.9) 914 (87.9)
Simple mastectomy þSLNB 5 (7.6) 26 (4.0) 26 (9.4) 9 (16.4) 66 (6.3)
Breast-conserving surgery 1 (1.5) 7 (1.1) 14 (5.1) 4 (7.3) 26 (2.5)
Pvalue 0.01*
UW, underweight; NW, normal weight; OW, overweight; OB, obese; SLNB, sentinel lymph node biopsy. *Chi-square test.
Wang et al. 7
Table 5. Effect of body mass index on the clinical and pathological features, manner of detection, imple-
mentation rate of preoperative examinations, and surgical approach in the premenopausal population.
Characteristics
UW
n (%)
NW
n (%)
OW
n (%)
OB
n (%)
Subtotal
n (%)
35 292 103 24 454
Molecular subtype
Luminal A 21 (60.0) 155 (53.1) 49 (47.6) 9 (37.5) 234 (51.5)
Luminal B 6 (17.1) 63 (21.6) 17 (16.5) 2 (8.3) 88 (19.4)
Her2þ4 (11.4) 27 (9.2) 13 (12.6) 2 (8.3) 46 (10.1)
TN 4 (11.4) 47 (16.1) 24 (23.3) 11 (45.8) 86 (18.9)
Pvalue 0.003*
Surgical approach
Radical mastectomy 0 (0.0) 7 (2.4) 5 (4.9) 1 (4.2) 13 (2.9)
Modified radical mastectomy 33 (94.3) 269 (92.1) 81 (78.6) 19 (79.2) 402 (88.5)
Simple mastectomy þSLNB 2 (5.7) 12 (4.1) 11 (10.7) 3 (12.5) 28 (6.2)
Breast conservation surgery 0 (0.0) 4 (1.4) 6 (5.8) 1 (4.2) 11 (2.4)
Pvalue 0.015***
UW, underweight; NW, normal weight; OW, overweight; OB, obese; Her2, human epidermal growth factor receptor 2;
TN, triple-negative; SLNB, sentinel lymph node biopsy. *Chi-square test; ***Fisher’s exact test.
Table 6. Effect of body mass index on the clinical and pathological features, manner of detection, imple-
mentation rate of preoperative examinations, and surgical approach in the postmenopausal population.
Characteristics
UW
n (%)
NW
n (%)
OW
n (%)
OB
n (%)
Subtotal
n (%)
31 350 174 31 586
Tumor size
2 cm 13 (41.9) 112 (32.0) 69 (39.7) 1 (3.2) 195 (33.3)
2–5 cm 16 (51.6) 213 (60.9) 82 (47.1) 28 (90.3) 339 (57.8)
>5 cm 2 (6.5) 25 (7.1) 23 (13.2) 2 (6.5) 52 (8.9)
Pvalue 0.021**
TNM stage
Early (I þII) 13 (41.9) 158 (45.1) 51 (29.3) 11 (35.5) 233 (39.8)
Advanced (III) 18 (58.1) 192 (54.9) 123 (70.7) 20 (64.5) 353 (60.2)
Pvalue 0.006**
Molecular subtype
Luminal A 13 (41.9) 167 (47.7) 94 (54.0) 21 (67.7) 295 (50.3)
Luminal B 3 (9.7) 55 (15.7) 25 (14.4) 6 (19.4) 89 (15.2)
Her2 þ3 (9.7) 47 (13.4) 13 (7.5) 2 (6.5) 65 (11.1)
TN 12 (38.7) 81 (23.1) 42 (24.1) 2 (6.5) 137 (23.4)
Pvalue 0.049*
Detection
Physical examination 0 (0.0) 19 (5.4) 15 (8.6) 5 (16.1) 39 (6.7)
Accidental 10 (32.3) 237 (67.7) 121 (69.5) 16 (51.6) 384 (65.5)
Symptom based 21 (67.7) 94 (26.9) 38 (21.8) 10 (32.3) 163 (27.8)
Pvalue <0.01***
(continued)
8Journal of International Medical Research
Table 6. Continued.
Characteristics
UW
n (%)
NW
n (%)
OW
n (%)
OB
n (%)
Subtotal
n (%)
Molybdenum target X-ray
Used 4 (12.9) 62 (17.7) 42 (24.1) 15 (48.4) 123 (21.0)
Not used 23 (74.2) 280 (80.0) 127 (73.0) 14 (45.2) 444 (75.8)
Not clear 4 (12.9) 8 (2.3) 5 (2.9) 2 (6.5) 19 (3.2)
Pvalue <0.01***
Surgical approach
Radical mastectomy 0 (0.0) 10 (2.9) 9 (5.2) 2 (6.5) 21 (3.6)
Modified radical mastectomy 27 (87.1) 323 (92.3) 142 (81.6) 20 (64.5) 512 (87.4)
Simple mastectomy þSLNB 3 (9.7) 14 (4.0) 15 (8.6) 6 (19.4) 38 (6.5)
Breast conservation surgery 1 (3.2) 3 (0.9) 8 (4.6) 3 (9.7) 15 (2.6)
Pvalue <0.01***
UW, underweight; NW, normal weight; OW, overweight; OB, obese; TNM, tumor-node-metastasis; Her2, human epi-
dermal growth factor receptor 2; TN, triple-negative; SLNB, sentinel lymph node biopsy. *Chi-square test; **rank-sum
test; ***Fisher’s exact test.
Table 7. Case-only ORs and 95% CIs from logistic regression models of the associations between breast
cancer tumor subtypes and BMI.
BMI
Luminal A
comparison Luminal B Her2þTN
n n OR 95% CI n OR 95% CI n OR 95% CI
UW 34 9 1.00 Reference 7 1.00 Reference 16 1.00 Reference
NW 322 118 1.38 0.65–2.97 74 1.12 0.48–2.62 128 0.85 0.45–1.58
OW 143 42 1.11 0.49–2.50 26 0.88 0.35–2.20 66 0.98 0.51–1.90
OB 30 8 1.01 0.35–2.94 4 0.65 0.17–2.43 13 0.92 0.38–2.22
Subtotal 529 177 111 223
Premenopausal
UW 21 6 1.00 Reference 4 1.00 Reference 4 1.00 Reference
NW 155 63 1.42 0.55–3.69 27 0.92 0.29–2.87 47 1.59 0.52–4.87
OW 49 17 1.21 0.42–3.51 13 1.39 0.41–4.77 24 2.57 0.79–8.33
OB 9 2 0.78 0.13–4.62 2 1.17 0.18–7.56 11 6.42** 1.61–25.64
Subtotal 234 88 46 86
Postmenopausal
UW 13 3 1.00 Reference 3 1.00 Reference 12 1.00 Reference
NW 167 55 1.43 0.39–5.19 47 1.22 0.33–4.46 81 0.53 0.23–1.20
OW 94 25 1.15 0.31–4.36 13 0.60 0.15–2.39 42 0.48 0.20–1.15
OB 21 6 1.24 0.26–5.83 2 0.41 0.06–2.81 2 0.10** 0.02–0.54
Subtotal 295 89 65 137
OR, odds ratio; CI, confidence interval; BMI, body mass index; Her2, human epidermal growth factor receptor 2; TN,
triple-negative; UW, underweight; NW, normal weight; OW, overweight; OB, obese.
*P<0.05; **P<0.01 vs the UW group.
Reference: luminal A is regarded as the reference as the most common subtype.
Wang et al. 9
the current population, we divided our
patients into premenopausal and postmen-
opausal groups (Table 5). BMI had a sig-
nificant effect on the molecular subtype and
surgical approach in premenopausal
women as follows. In the underweight and
normal weight groups, the proportion of
luminal A type cancer was >50%, and in
the overweight and obese groups, the pro-
portion of patients with the TN type
was higher compared with that in the
underweight and normal weight groups
(P¼0.003). In the overweight and obese
groups, the proportion of patients who
underwent SLNB and BCS was higher
than that in the underweight and normal
weight groups, while the proportion of
patients who underwent radical procedures
showed the opposite trend (P¼0.015).
The other pathological features (tumor
size, axillary lymph node status, and stag-
ing) and the implementation rate of preop-
erative examinations showed no significant
differences among the BMI groups (data
not shown).
Effect of BMI on the clinical and
pathological features, manner of
detection, implementation rate of
preoperative examinations, and
surgical approach in the
postmenopausal population
BMI had a distinct effect in the postmeno-
pausal populations (Table 6). In postmeno-
pausal women, the proportion of patients
with early-stage breast cancer was higher
in the underweight and normal weight
groups than in the overweight and obese
groups (P¼0.006). The proportion of
patients with a tumor size <2cmwas
slightly higher in the overweight group
than in the normal weight group.
Moreover, the proportion of patients with
a tumor size <2 cm was higher in the
underweight group than in the obese
group (P¼0.021). Overall, the trend for
tumor size and tumor stage was similar.
The tumor diameter gradually increased
and the tumor stage gradually became
more advanced with an increase in BMI.
With regard to the molecular phenotype,
as BMI increased, the proportion of
patients with the luminal A type gradually
increased, while the proportion of those
with the TN type gradually decreased
(P¼0.049). The proportion of patients in
whom tumors were found by a physical
examination or by accident was significant-
ly higher in the obese group than in the
underweight group. Similarly, the propor-
tion of such patients was higher in the over-
weight group than in the normal weight
group (P<0.01). The proportion of
patients who underwent mammography
also gradually increased with an increase
in BMI (P<0.01). The proportion of
patients who underwent modified radical
mastectomy was significantly lower in the
overweight and obese groups compared
with the normal weight and underweight
groups. However, the proportion of
patients who underwent SLNB and BCS
was significantly higher in the overweight
and obese groups than in the normal
weight and underweight groups (P<0.01).
No significant differences were observed in
other clinicopathological characteristics
and the implementation rate of preopera-
tive B-ultrasound examinations among the
BMI groups (data not shown).
Analysis of the associations between
breast cancer subtypes and BMI
In the population of premenopausal women
with breast cancer, the TN type was signif-
icantly more frequent than the luminal A
type in the obese group compared with the
underweight group (P<0.01) (Table 7). In
the postmenopausal population, the oppo-
site trend was observed, where the TN type
was significantly less frequent than the
10 Journal of International Medical Research
luminal A type in the obese group com-
pared with the underweight group
(P<0.01).
Discussion
At present, most research on the association
between BMI and breast cancer has been
carried out in Western developed coun-
tries.
17
However, research on this associa-
tion in the Asian population, especially East
Asian populations, such as the Chinese, is
relatively less than that in Western coun-
tries.
18
There is a large difference between
Western and East Asian populations
regarding dietary habits and sociocultural
factors.
19
Therefore, the effect of BMI on
the occurrence and development of breast
cancer is also likely to differ between these
countries, and this in turn should be
reflected in the national prevention strate-
gies for breast cancer. Additionally, find-
ings in the Chinese population can be
applied to other developing countries
because certain socioeconomic factors are
similar among developing countries.
In our study, we found that the distribu-
tion of the BMI subgroups was different
compared with that in Western popula-
tions. The normal weight group comprised
more than 60% of the population, followed
by the overweight (26.6%), and finally, the
underweight and obese groups (approxi-
mately 5% in each group). The proportion
of BMI in the normal weight group was
significantly higher and that in the obese
group was significantly lower than those
in Western populations.
20
Furthermore,
the distribution of BMI is similar to that
reported by other Chinese and Japanese
scholars.
4,16
This difference between
Western and Eastern populations may be
attributable to factors related to social
background, living habits, and income.
19
These differences should be reflected in the
manner of detection, the treatment method,
and therefore, the clinicopathological
features and distribution of the molecular
phenotype. This was indicated by the find-
ings in the present study.
In our study, the tumor diameter signif-
icantly increased, the proportion of patients
with the early stage of breast cancer gradu-
ally decreased, and the proportion of
patients with the advanced stage of breast
cancer gradually increased with an increase
in BMI. These results are similar to those of
a recent study conducted by other Chinese
scholars.
16
A possible reason for these find-
ings is that a lower BMI represents less
breast volume, and therefore, earlier discov-
ery of breast masses. This could explain the
higher proportion of patients with early-
stage breast cancer with a low BMI.
In a previous study, we found that demo-
graphic factors affected the manner of diag-
nosis and treatment.
21
Therefore, in the
present study, we also examined the effect
of BMI on the diagnosis and treatment of
breast cancer because BMI is also closely
related to patients’ demographic factors.
Detection at the time of a regular physical
examination means that the chances of
diagnosing breast cancer at its early stages
are higher. Therefore, these patients receive
timely medical care. With a gradual
increase in the tumor mass, and therefore,
disease stage, the chances of accidental dis-
covery by patients while taking a shower or
changing clothes are higher. Therefore, the
chances of delayed diagnosis are higher.
With further progression of disease, symp-
toms (e.g., mass ulceration, skin involve-
ment, nipple retraction, and pain) will
gradually appear, and there is a further
delay in diagnosis. In this study, we found
that with an increase in BMI, the propor-
tion of patients in whom breast cancer was
found by a physical examination or by
chance significantly gradually increased,
and that of patients in whom this disease
was detected on the basis of symptoms
gradually decreased. In the Chinese popu-
lation, the income of most individuals who
Wang et al. 11
are obese or overweight is higher than that
of individuals who are underweight, who
are mostly manual workers and rural dwell-
ers.
19
Because rural medical and health con-
ditions are poor compared with city
conditions, this difference in income and
medical and health resources could explain
the difference in the manner of diagnosis.
22
However, lean women are likely to have less
breast volume and thus are more likely to
detect masses on their own. This could
explain why the incidence of tumor detec-
tion through a physical examination was
low in the underweight group.
The two most common preoperative
examinations reflected a similar trend
across the BMI groups in our study With
an increase in BMI, the implementation
rate of mammography gradually increased,
and B-ultrasound examinations also
showed a similar trend. This trend may be
related to the economic conditions of the
patients. Because the cost of mammogra-
phy is high, lower income populations
cannot afford it. Furthermore, people with
a lower income usually live in low-income
communities, and community hospitals in
such areas usually cannot afford such
advanced and expensive equipment.
Shaanxi is a low-income area. Therefore,
delayed diagnosis and infrequent breast
cancer screening are common. We hope
that these findings emphasize the need for
more frequent breast cancer screening pro-
grams and thus timely diagnosis and better
implementation of preoperative
examinations.
Socioeconomic conditions of the patients
and their locality affect the surgical
approach. In this study, we found a signif-
icant difference in the type of treatment
used across different BMI populations.
With an increase in BMI, the implementa-
tion rate of radical surgery (modified radi-
cal mastectomy) gradually decreased, and
the implementation rate of advanced surgi-
cal techniques (SLNB or BCS) increased.
The higher rates of SLNB and BCS in the
higher BMI groups could be explained by
the higher income and ability to accept new
ideas and new technology in these groups.
23
Furthermore, the lower income population
(mostly comprised the underweight group)
might not have been able to afford the cost
of radiotherapy after BCS. Additionally,
this part of the population usually lives in
poorer areas, where radiotherapy is not
easily available. Another important point
is that patients with a relatively large
breast volume (from the overweight and
obese groups) are more likely to undergo
BCS. At present, SLNB and BCS are the
main operative modes for treating breast
cancer in developed countries.
24
The results
of this study suggest that developed coun-
tries should provide medical assistance to
less developed areas, so that patients in
these regions can benefit from technological
advances in this field.
The female menopausal age is usually
approximately 51 years in China and the
retirement age for women is 50 years.
25
Therefore, differences in the economic abil-
ity of women are likely to exist before and
after retirement, which would be reflected in
the diagnosis and treatment of breast
cancer. Our study showed that, in premeno-
pausal patients, there was a considerable
difference in the choice of surgical opera-
tion between the BMI groups. A higher
number of patients in the overweight and
obese groups than in the underweight and
normal weight groups selected SLNB
and BCS, while an opposite trend was
observed for radical surgery. These results
were similar to those of the total patient
population. In postmenopausal patients,
the BMI groups showed significant differ-
ences in the tumor size, stage, manner of
detection, implementation rate of preoper-
ative examinations, and surgical approach.
The overall trend in differences was in
accordance with the trend in the total pop-
ulation. Finally, the results of the stratified
12 Journal of International Medical Research
analysis showed that the Chinese retirement
system does not appear to be associated
with implementation of diagnosing breast
cancer and treatment strategies in women.
We also investigated another important
factor, which was the relationship between
BMI and the molecular phenotype of
cancer. This is currently a hot research
topic in related fields. At present, most
scholars believe that increased BMI is a
risk factor for breast cancer only in post-
menopausal women, and that it mainly
increases the risk of hormone receptor-
positive breast cancer;
26
However, other
scholars believe that this increased risk is
not necessarily limited to certain molecular
subtypes.
16
Additionally, some researchers
have found that increased BMI in premeno-
pausal women with breast cancer is mainly
found in those with TN type cancer,
7
but
this correlation is not observed in postmen-
opausal patients. In contrast, some scholars
have found an association between BMI
and the TN type in postmenopausal
patients,
4
and some scholars have even
found that the TN type is negatively corre-
lated with an increase in BMI.
27
In our
study, we observed a relationship between
BMI and the molecular type of the breast
cancer in the overall patient population, as
well as in the premenopausal and postmen-
opausal patient populations. In the overall
patient population, the BMI subgroups and
molecular subtype were not obviously cor-
related, but in the premenopausal and post-
menopausal populations, remarkable
differences were observed in the distribu-
tion of molecular phenotypes between the
BMI groups. Case-only OR analysis
showed that, in the premenopausal popula-
tion, the TN type was more likely to be
found in the obese group, while in the post-
menopausal population, the luminal A type
was more likely to appear in the obese
group. This finding is consistent with most
reported studies.
4,7
This association is prob-
ably attributable to the positive relationship
between BMI and endogenous estrogen
levels because adipose tissue is the primary
source of estrogen in postmenopausal
women. Increased endogenous estrogen
levels can increase the risk of luminal type
breast cancer. Obesity among premeno-
pausal women is associated with lower
estrogen levels, possibly due to irregular
menstruation and anovulation. This may
explain why an elevated BMI increased
the risk of TN type tumors. The reason
for the diverse research results is probably
attributable to differences in race, social
background, and research method, among
other factors, used across different studies.
There are some potential limitations to
our study. First, a total of 256 (256/1296,
19.8%) patients were excluded because the
tumor cells had a 2þHer2 score and were
not assessed by FISH, and some clinico-
pathological data were missing. Second,
we did not set a healthy population as the
control. Third, most of our patients were
from Shaanxi Province, which is in the
center of China, and this may not have
been completely representative of the
entire Chinese ethnic population. Finally,
the classification of tumor subtypes as
defined in our study is not identical to
other published data because of a lack of
information on other tumor markers, such
as cytokeratin 5/6 and epidermal growth
factor receptor.
Conclusions
Our study shows that a higher BMI is asso-
ciated with a larger tumor size, more
advanced disease stage, diagnosis by a
physical examination, higher implementa-
tion rate of preoperative examinations,
and lower radical surgery rate in Chinese
women with breast cancer. These effects
differ between the premenopausal and post-
menopausal populations. Furthermore, the
relationship between BMI and the molecu-
lar phenotype of the cancer is not entirely
Wang et al. 13
consistent across the population, especially
between pre- and postmenopausal women.
In premenopausal patients, the TN type is
more likely to be found in obese women,
and in postmenopausal women, the luminal
A type is more likely to appear in obese
women. The findings from this study can
be applied to other developing countries.
In particular, our findings shed light on
the need for more screening programs to
ensure timely detection of breast cancer
and the introduction of advanced techni-
ques to ensure proper treatment in develop-
ing regions.
Acknowledgement
We would like to thank the native English-
speaking scientists of Elixigen Company for edit-
ing our manuscript.
Declaration of conflicting interest
The authors declare that there is no conflict of
interest.
Funding
The authors disclosed receipt of the following
financial support for the research, authorship,
and/or publication of this article: This study
was funded by the National Natural Science
Fund of China (number: 81702633).
Authors’ contributions
BW, LZZ, SYJ, LZZ, YHZ, LGN, YY, and KW
managed the study, conducted the literature
review, and prepared the manuscript. KW,
BW, LZZ, and SYJ designed the study and per-
formed statistical analysis. BW, LZZ, SYJ, LZZ,
YHZ, LGN, and YY contributed to the study
material, interpretation of data, and critical revi-
sion of the manuscript.
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Wang et al. 15
... However, some former reports are susceptible to potential biases that are less concerning in prospective cohorts because they were based on mostly case-control studies [15,[67][68][69] and a pooled analysis of women under the age of 50 based on studies of mixed design [62]. Moreover, when the comparison group turned to luminal A tumors, obesity appeared to significantly increase the risk of the TNBC subtype with statistical significance (Chen et [71,72]. As a result, the relationship between obesity and premenopausal TNBC appears to be complicated, and it seems difficult to provide a precise identification of the relationship between obesity and premenopausal TNBC to the extent of a single variable based on current studies. ...
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