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The Impact of Bariatric Surgery on Breast Cancer Recurrence: Case Series and Review of Literature

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Background Excess body weight has been associated with worsening breast cancer survival. While bariatric surgery has been associated with less incident of breast cancer, the role that bariatric surgery plays after breast cancer diagnosis in terms of both feasibility and in preventing breast cancer recurrence is unclear. Methods We report the outcomes of 13 individuals who underwent bariatric surgery after definitive breast cancer treatment at a single institution. Results Thirteen females diagnosed with breast cancer (69.2% stage I, 23.1% stage II) at a median age of 42 years received bariatric surgery between 2001 and 2017. The median age of bariatric surgery was 52 years. Of the 13 patients, 46.2% underwent laparoscopic Roux-en-Y gastric bypass and 38.5% laparoscopic sleeve gastrectomy. The median time from breast cancer treatment to bariatric surgery was 3 years. The procedures were well tolerated. One female developed an abdominal wall hematoma. The average weight loss after 1 year and 2 years was 28.1% and 28.2%, respectively. There was a single breast cancer recurrence with a median follow-up of 11.7 years after breast cancer diagnosis and 5.3 years after bariatric surgery. Conclusions Bariatric surgery after breast cancer treatment is feasible and well tolerated. Prospective trials evaluating bariatric surgery in obese breast cancer survivors should be considered.
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BRIEF COMMUNICATION
The Impact of Bariatric Surgery on Breast Cancer Recurrence: Case
Series and Review of Literature
Shijia Zhang
1
&Sayeed Ikramuddin
2
&Heather C. Beckwith
1
&Adam C. Sheka
2
&Keith M. Wirth
2
&Anne H. Blaes
1
#The Author(s) 2019
Abstract
Background Excess body weight has been associated with worsening breast cancer survival. While bariatric surgery has been
associated with less incident of breast cancer, the role that bariatric surgery plays after breast cancer diagnosis in terms of both
feasibility and in preventing breast cancer recurrence is unclear.
Methods We report the outcomes of 13 individuals who underwent bariatric surgery after definitive breast cancer treatment at a
single institution.
Results Thirteen females diagnosed with breast cancer (69.2% stage I, 23.1% stage II) at a median age of 42 years received
bariatric surgery between 2001 and 2017. The median age of bariatric surgery was 52 years. Of the 13 patients, 46.2% underwent
laparoscopic Roux-en-Y gastric bypass and 38.5% laparoscopic sleeve gastrectomy. The median time from breast cancer
treatment to bariatric surgery was 3 years. The procedures were well tolerated. One female developed an abdominal wall
hematoma. The average weight loss after 1 year and 2 years was 28.1% and 28.2%, respectively. There was a single breast
cancer recurrence with a median follow-up of 11.7 years after breast cancer diagnosis and 5.3 years after bariatric surgery.
Conclusions Bariatric surgery after breast cancer treatment is feasible and well tolerated. Prospective trials evaluating bariatric
surgery in obese breast cancer survivors should be considered.
Keywords Bariatric surgery .Weight loss .Breast cancer .Recurrence
Introduction
It is estimated that overweight and obesity could account for
14% of all deaths from cancer in males and 20% of those in
females in the USA [1]. For those with a body mass index
(BMI) between 27.529.9 kg/m
2
, the risk of cancer increases
by 12%, while those with a BMI over 40 kg/m
2
have a 70%
increased risk of cancer compared to those with a normal BMI
[2]. On the contrary, dramatic weight loss from bariatric sur-
gery is associated with reduced cancer mortality by approxi-
mately 40% [3]. This suggests that promoting healthy weight
change in adults can have important health benefits and out-
comes from a cancer perspective.
Our interest is to look at the impact of weight loss on breast
cancer survivors. A recent meta-analysis of 82 studies that
included 213,075 women with breast cancer demonstrated
that for each 5 kg/m
2
increment in BMI, there was a 14 to
29% increased risk of breast cancerspecific mortality and an
8 to 17% increased risk of overall mortality [4]. Multiple trials
have been initiated to look at the impact of lifestyle interven-
tion and dietary modification to produce weight loss in
*Anne H. Blaes
blaes004@umn.edu
Shijia Zhang
shijia@umn.edu
Sayeed Ikramuddin
ikram001@umn.edu
Heather C. Beckwith
einho003@umn.edu
Adam C. Sheka
sheka015@umn.edu
Keith M. Wirth
wirth129@umn.edu
1
Division of Hematology, Oncology and Transplantation, Department
of Medicine, University of Minnesota, 420 Delaware Street, SE,
MMC 480, Minneapolis, MN 55455, USA
2
Department of Surgery, University of Minnesota, Minneapolis, MN,
USA
Obesity Surgery
https://doi.org/10.1007/s11695-019-04099-6
Table 1. Characteristics of patients in our cohort
No. Age at
BC dx
BMI at
BC dx
Stage ER
+
PR
+
HER2
+
BC surgery CT CT regimen RT ET Age
at
BS
Yrs from
BC dx to
BS
BMI
at BS
Type of BS Post-op
complications
from BS
%wt
loss in
1yr
%wt
loss in
2yrs
BC
recurrence
1 50 32.6 IA Y N N Right
lumpecto-
my
NY Y 56 6.0 37.1 Lap sleeve
gastrectomy
None 23.5 20.2 N
2 30 52.6 IIA N N N Bilateral
mastecto-
mies
Y Doxorubicin +
cyclophosphamide
then paclitaxel
N N 33 3.0 52.3 Lap adjustable
gastric band
None 18.7 18.7 N
3 47 37.8 IA Y Y N Left
lumpecto-
my
Y Doxorubicin +
cyclophosphamide
Y Y 52 5.5 43 Lap sleeve
gastrectomy
None 26.5 26.0 N
4 57 39.4 IA Y Y N Bilateral
mastecto-
mies
NN Y 59 2.7 38.9 Lap
Roux-en-Y
gastric by-
pass
Abdominal
wall
hematoma
14.7 10.8 N
5 35 NA IIAYYN Left
mastecto-
my
Y Cyclophosphamide +
methotrexate
+5-fluorouracil
N Y 43 7.5 40.2 Lap
Roux-en-Y
gastric by-
pass
None 31.6 36.8 Y
6 50 31.0 IA Y Y N Bilateral
mastecto-
mies
Y Cyclophosphamide +
paclitaxel
N Y 52 2.3 36.4 Lap sleeve
gastrectomy
None 40.1 37.9 N
7 36 36.9 IA Y Y Y Right
lumpecto-
my
Y Doxorubicin +
cyclophosphamide
Y Y 45 9.2 39.3 Lap sleeve
gastrectomy
None 21.1 19.8 N
8 42 35.0 IIA Y Y N Left
lumpecto-
my
Y Paclitaxel then
doxorubicin +
cyclophosphamide
Y Y 43 1.3 36.6 Lap sleeve
gastrectomy
None 35.8 24.3 N
9 42 44.0 IA Y Y N Bilateral
mastecto-
mies
NN Y 43 1.1 42.4 Lap
Roux-en-Y
gastric by-
pass
None 33.5 46.7 N
10 41 44.3 IA Y Y N Bilateral
mastecto-
mies
Y Cyclophosphamide +
methotrexate
+5-fluorouracil
N Y 44 2.2 46.9 Lap
Roux-en-Y
gastric by-
pass
None 35.0 43.5 N
11 53 43.7 IA Y Y N Right
lumpecto-
my
NY Y 56 2.4 43.8 Lap
Roux-en-Y
gastric by-
pass
None 29.2 28.8 N
12 42 NA NA NA NA NA Left
lumpecto-
my
Y NA Y NA 55 13.3 38.2 Lap duodenal
switch
None 38.0 38.7 N
13 49 NA IA N N N Y NA N N 63 14.2 33.8 Lap
Roux-en-Y
None 17.5 14.2 N
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patients with a history of breast cancer. The results of these
trials have been disappointing due to poor compliance with
the proposed intervention producing only modest weight loss
and questionable results in terms of local recurrence improve-
ment. Bariatric surgery has been shown to be the most effec-
tive tool to achieve and maintain long-term weight loss. In a
large multisite cohort study, the risk of postmenopausal breast
cancer was significantly lower (hazard ratio [HR] 0.58, 95%
confidence interval [CI] 0.440.77, P< 0.001) among patients
who had undergone bariatric surgery compared with matched
nonsurgical controls [5]. While bariatric surgery can improve
obesity-related health problems, such as type 2 diabetes, hy-
pertension, and sleep apnea, the impact on recurrence of breast
cancer is unclear. The aim of this study was to examine the
safety of bariatric surgery after breast cancer treatment on
breast cancer recurrence. Here, we report the outcomes of 13
patients, who had bariatric surgery after definitive breast can-
cer therapy.
Methods
Following approval from the Institutional Review Board of
our institution, a computerized search from the electronic
medical records of the University of Minnesota and
Fairview Health Systems was performed for patients who
have had a diagnosis of breast cancer and underwent bariatric
surgery from 2001 to 2017. Medical records of patients who
had definitive breast cancer treatment prior to bariatric surgery
were reviewed for data collection. Descriptive statistics were
used to describe the features of the data.
Case Series
Patients included in this analysis had to meet the following
two criteria: (1) had bariatric surgery (Roux-en-Y gastric by-
pass, sleeve gastrectomy, adjustable banding, or duodenal
switch) between 2001 and 2017, and (2) had definitive treat-
ment of breast cancer prior to bariatric surgery (Table 1). A
total of 13 patients met the study criteria. All were female. The
median age of initial breast cancer diagnosis was 42 (range
3057) years. At the time of breast cancer diagnosis, 2
(15.4%) patients had BMI in the range of 3034.9 kg/m
2
,4
(30.8%) in the range of 3539.9 kg/m
2
, 4 (30.8%) in range of
40 kg/m
2
and above, and 3 (23.1%) with unknown BMI. At
least 10 (76.9%) of these patients were obese (BMI 30 kg/
m
2
) when they were diagnosed with breast cancer. Nine
(69.2%) patients had stage I breast cancer and 3 (23.1%) had
stage II disease. The breast cancer staging of 1 (7.7%) patient
was unknown. One (7.7%) patient had a tumor that was hor-
mone receptor (HR)positive and human epidermal growth
factor receptor 2 (HER2)positive, 9 (69.2%) HR-positive
Tab l e 1. (continued)
No. Age at
BC dx
BMI at
BC dx
Stage ER
+
PR
+
HER2
+
BC surgery CT CT regimen RT ET Age
at
BS
Yrs from
BC dx to
BS
BMI
at BS
Type of BS Post-op
complications
from BS
%wt
loss in
1yr
%wt
loss in
2yrs
BC
recurrence
Bilateral
mastecto-
mies
gastric by-
pass
BC, breast cancer; BMI, body mass index; BS, bariatric surgery; CT, chemotherapy; dx, diagnosis; ET, endocrine therapy; lap, laparoscopic; NA, not available; RT, radiation therapy; wt, weight; yr,year
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and HER2-negative, 2 (15.4%) triple negative, and 1 (7.7%)
with unknown HR and HER2 status. All patients had surgery
for breast cancer: 6 (46.2%) patients underwent lumpectomy,
1 (7.7%) unilateral mastectomy, and 6 (46.2%) bilateral mas-
tectomies. Six (46.2%) patients had radiation therapy, and 9
(69.2%) patients received adjuvant chemotherapy. Ten
(76.9%) patients were treated with adjuvant endocrine
therapy.
The median age at bariatric surgery was 52 (range 3363)
years. The median time from breast cancer diagnosis to bariatric
surgery was 3 (range 1.114.2) years. At the time of bariatric
surgery, 1 (7.7%) patient had BMI in the range of 3034.9 kg/
m
2
, 6 (46.2%) in the range of 3539.9 kg/m
2
, and 6 (46.2%) in
the range of 40 kg/m
2
and above. For those with available BMI
at breast cancer diagnosis, 7 out of 10 (70%) gained weight
between the time of breast cancer diagnosis and the time of
bariatric surgery. Six (46.2%) patients underwent laparoscopic
Roux-en-Y gastric bypass, 5 (38.5%) laparoscopic sleeve gas-
trectomy, 1 (7.7%) laparoscopic adjustable gastric band, and 1
(7.7%) laparoscopic duodenal switch. These procedures were
generally well tolerated by the patients. In the postoperative
period, only 1 (7.7%) patient developed abdominal wall hema-
toma in the camera trocar site resulting in a large hemoglobin
drop that required red blood cell transfusions. For most patients,
the maximal weight loss occurred within 2 years of post-
bariatric surgery (Table 2). The average weight loss after 1 year
and 2 years was 28.1% (range 17.540.1%) and 28.2% (range
10.846.7%), respectively. Furthermore, most patients main-
tained durable weight loss (Fig. 1).
There was a single breast cancer recurrence with a median
follow-up of 11.7 (range 3.920.6) years after breast cancer
diagnosis and 5.3 (range 2.09.8) years after bariatric surgery.
This patient was diagnosed with stage IIA (T2N0M0), estro-
gen receptor (ER)-positive, progesterone receptor (PR)-posi-
tive, and HER-2-negative breast cancer at age 35. She was
found to be a carrier of BRCA2 mutation. She underwent left
mastectomy followed by chemotherapy (cyclophosphamide,
methotrexate, 5-fluorouracil). She was started on tamoxifen
and then switched to exemestane after she had total abdominal
hysterectomy and bilateral salpingo-oophorectomy at age 40.
She underwent laparoscopic Roux-en-Y gastric bypass at age
43 when her BMI was 40.2 kg/m
2
. About 4 weeks after her
bariatric surgery, she was found to have local recurrence of
breast cancer and then metastatic disease. She has received
multiple lines of therapy and has been doing well.
Discussion
As the worldwide obesity epidemic spreads, we are fac-
ing more and more challenges from diabetes, cardiovas-
cular diseases, cancers, and other health conditions re-
lated to obesity. Not only is the likelihood of develop-
ment of breast cancer linked to obesity; but equally as
concerning is the higher rate of reoccurrence following
definitive therapy for breast cancer. A meta-analysis of
43 studies showed that women who were obese at
breast cancer diagnosis had an approximately 33%
higher risk of mortality compared with normal-weight
women [6]. Attempts have been made to conduct pro-
spective interventional studies to look at the impact of
weight loss on overweight breast cancer survivors. The
Lifestyle Intervention in Adjuvant Treatment of Early
Table 2. Descriptive statistics of our cohort
Characteristic Overall (N=13)
Age, median (range)
At breast cancer diagnosis 42 (3057)
At bariatric surgery 52 (3363)
Years from BC dx to BS, median (range) 3.0 (1.114.2)
BMI at breast cancer diagnosis, N(%)
3034.9 2 (15.4)
3539.9 4 (30.8)
40 and above 4 (30.8)
Missing/NA 3 (23.1)
BMI at bariatric surgery, N(%)
3034.9 1 (7.7)
3539.9 6 (46.2)
40 and above 6 (46.2)
Type of bariatric surgery, N(%)
Laparoscopic Roux-en-Y gastric bypass 6 (46.2)
Laparoscopic sleeve gastrectomy 5 (38.5)
Laparoscopic adjustable gastric band 1 (7.7)
Laparoscopic duodenal switch 1 (7.7)
Post-op complication, N(%)
None 12 (92.3)
Abdominal wall hematoma 1 (7.7)
Breast cancer stage at diagnosis, N(%)
I9(69.2)
II 3 (23.1)
Missing/NA 1 (7.7)
Hormonal receptor (HR)/HER-2 status, N(%)
HR (+), HER-2 (+) 1 (7.7)
HR (+), HER-2 ()9(69.2)
HR (), HER-2 ()2(15.4)
Missing/NA 1 (7.7)
Breast cancer surgery type, N(%)
Lumpectomy 6 (46.2)
Unilateral mastectomy 1 (7.7)
Bilateral mastectomies 6 (46.2)
Treated with adjuvant chemotherapy, N(%)
Yes 9 (6 9 .2 )
No 4 (30.8)
Treated with radiation therapy, N(%)
Yes 6 (4 6 .2 )
No 7 (53.8)
Treated with endocrine therapy, N(%)
Yes 10 (76.9)
No 2 (15.4)
Missing/NA 1 (7.7)
Recurrence of breast cancer, N(%)
Yes 1 (7 . 7)
No 12 (92.3)
BC, breast cancer; BMI, body mass index; BS, bariatric surgery; dx,di-
agnosis; NA, not available
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Breast Cancer (LISA) trial randomized overweight
breast cancer survivors receiving adjuvant letrozole to
mail-based delivery of general health information ±
telephone-based lifestyle interventions over a period of
24 months. The primary endpoint was disease-free sur-
vival. Unfortunately, the enrollment was discontinued
early at 338 of 2,150 planned participants because of
loss of funding. The average weight loss in the lifestyle
interventions arm was 5.5 vs 0.7% in the control arm
after 1 year, and 3.6% vs 0.4% after 2 years. The im-
pact of this modest weight loss on breast cancer recur-
rence and mortality remains unknown [7].
Bariatric surgery is the most robust and durable therapy
for obesity and its related complications. As shown in the
LISA study, the amount of weight loss mediated by life-
style intervention is usually modest (3.6% after 2 years).
On the contrary, in our cohort of breast cancer survivors,
bariatric surgery induced significantly greater and durable
weight loss (28.2% after 2 years) in most patients. In the
Diabetes Surgery Study Randomized Clinical Trial, pa-
tients in the Roux-en-Y gastric bypass group (N= 60) lost
26.1% vs 7.9% of their initial body weight at 1 year com-
pared with the lifestyle-medical management group (N=
60). The weight loss effect persisted at 5 years: 21.8% in
the Roux-en-Y gastric bypass group vs 9.6% in the
lifestyle-medical management group in an intent-to-treat
analysis (15% of the lifestyle intervention patients actual-
ly ended up getting bariatric surgery) [8].
Analysis of the International Breast Cancer Study
Group clinical trials IV with 4105 eligible participants
showed that the breast cancer-free rate was around 43%
for patients with ER-positive disease and 46% for those
with ER-negative disease 12 years from random assign-
ment (estimated from the breast cancer-free interval
curves), indicating high breast cancer recurrence rate [9].
In our cohort, the disease recurrence rate was 7.7% (1 out
of 13 patients) with a median follow-up of 11.7 years. It is
noteworthy that this patient was found to have breast can-
cer recurrence only 4 weeks after her Roux-en-Y gastric
bypass surgery. Therefore, it was likely too soon to evalu-
ate the impact of bariatric surgery. Also, she carries a
BRCA2 mutation and only had unilateral mastectomy,
making her at high risk for recurrent or new breast cancer.
Bariatric surgery appears to be relatively safe in patients
who had definitive breast cancer treatmentonly 1 (7.7%)
patient in our cohort had bleeding in the abdominal wall in
the postoperative period. Given the small sample size, it
would not be feasible to compare the postoperative complica-
tion rate with other large studies. In a study of 268,898 meta-
bolic and bariatric surgeries performed between 2007 and
2010, the 30-day serious complication rate was 1.25% for
gastric bypass, 0.96% for sleeve gastrectomy, and 0.25% for
gastric banding. The authors did not define serious compli-
cationin their abstract, and it is unclear if abdominal hema-
toma would qualify for serious complication[10].
This study is limited by small sample size, retrospective
analysis, and no patients with stage III breast cancer at
diagnosis. Although it appears relatively safe to have bar-
iatric surgery for breast cancer survivors and most of these
patients seem to have a good outcome from a breast cancer
perspective based on our study, larger studies are required
to confirm these results. Recently, we conducted a retro-
spective cohort study of breast cancer patients undergoing
bariatric surgery 20042017 using de-identified data from
a large U.S. commercial insurance database (OptumLabs®
Data Warehouse). The relative risk of breast cancer events
for patients who underwent bariatric surgery was 45% low-
er than the non-surgical group [11]. With these results,
proposing bariatric surgery for obese breast cancer survi-
vors in an effort not only to reduce comorbidities such as
diabetes and hypertension but also to help prevent breast
cancer recurrence should be considered [12].
20
25
30
35
40
45
50
55
60
0 yr 1 yr 2 yr 3 yr 4 yr 5 yr 6 yr 7 yr 8 yr 9 yr 10 yr
BMI (kg/m2)
Years aer bariatric surgery
Pt 1
Pt 2
Pt 3
Pt 4
Pt 5
Pt 6
Pt 7
Pt 8
Pt 9
Pt 10
Pt 11
Pt 12
Pt 13
Fig. 1 Body mass index (BMI) at
the time of bariatric surgery and
yearly after bariatric surgery
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Conclusion
In obese breast cancer survivors, weight management strate-
gies should be utilized to prevent recurrence. Our results sug-
gest that bariatric surgery is well-tolerated in breast cancer
patients who have undergone definitive treatment for their
malignancy. As bariatric surgery is significantly more effec-
tive in producing long-term weight loss than lifestyle manage-
ment, physicians should discuss this option with obese breast
cancer patients and refer appropriate patients to a bariatric
surgeon as part of ongoing preventative therapy. A random-
ized control trial of bariatric surgery versus best medical man-
agement in obese breast cancer survivors should be
considered.
Funding University of Minnesota Innovation Research Grant.
Compliance with Ethical Standards
Conflict of Interest Authors Shijia Zhang, Heather C. Beckwith, Adam
C. Sheka, Keith M. Wirth, and Anne H. Blaes have nothing to disclose.
Author Sayeed Ikramuddin received support from Medtronic for equip-
ment for research studies, and Reshape Lifesciences for the grant support
for clinical trials.
Ethical Approval All procedures performed in studies involving human
participants were in accordance with the ethical standards of the institu-
tional and/or national research committee and with the 1964 Helsinki
declaration and its later amendments or comparable ethical standards.
Informed Consent This was a retrospective de-identified study so in-
formed consent was not obtained.
Open Access This article is distributed under the terms of the Creative
Commons Attribution 4.0 International License (http://
creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
distribution, and reproduction in any medium, provided you give appro-
priate credit to the original author(s) and the source, provide a link to the
Creative Commons license, and indicate if changes were made.
References
1. Calle EE, Rodriguez C, Walker-Thurmond K, et al. Overweight,
obesity, and mortality from cancer in a prospectively studied cohort
of U.S. adults. N Engl J Med. 2003;348:162538.
2. Berrington de Gonzalez A, Hartge P, Cerhan JR, et al. Body-mass
index and mortality among 1.46 million white adults. N Engl J
Med. 2010;363:22119.
3. Sjostrom L, Narbro K, Sjostrom CD, et al. Effects of bariatric sur-
gery on mortality in Swedish obese subjects. N Engl J Med.
2007;357:74152.
4. Chan DS, Vieira AR, Aune D, 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;25:190114.
5. Schauer DP, Feigelson HS, Koebnick C, et al. Bariatric surgery and
the risk of cancer in a large multisite cohort. Ann Surg. 2019;269:
95101.
6. Protani M, Coory M, Martin JH. Effect of obesity on survival of
women with breast cancer: systematic review and meta-analysis.
Breast Cancer Res Treat. 2010;123:62735.
7. Goodwin PJ, Segal RJ, Vallis M, et al. Randomized trial of a
telephone-based weight loss intervention in postmenopausal wom-
en with breast cancer receiving letrozole: the LISA trial. J Clin
Oncol. 2014;32:22319.
8. Ikramuddin S, Korner J, Lee WJ, et al. Lifestyle intervention and
medical management with vs without Roux-en-Y gastric bypass
and control of hemoglobin A1c, LDL cholesterol, and systolic
blood pressure at 5 years in the Diabetes Surgery Study. JAMA.
2018;319:26678.
9. Colleoni M, Sun Z, Price KN, et al. Annual hazard rates of recur-
rence for breast cancer during 24 years of follow-up: results from
the International Breast Cancer Study Group Trials I to V. J Clin
Oncol. 2016;34:92735.
10. Morton J, Sherif B, Winegar D, Nguyen N, Ponce J, Blackstone R.
National comparisions of bariatric surgery safety and efficacy: find-
ings from the BOLD database 20072010. American Society for
Metabolic and Bariatric Surgery 29th Annual Meeting. San Diego,
CA. 2012.
11. Blaes A, Simon G, Ugurbil M, et al. Impact of bariatric surgery on
breast cancer disease burden in the obese breast cancer survivor. J
Clin Oncol. 2018;36:e13072.
12. Chen Y, Dutson E, Eibl G. Strategies to prevent obesity-related
cancer. JAMA. 2018;319:2442.
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... Important retrospective work has shown that patients who underwent bariatric surgery had reduced risk of both pre-menopausal and post-menopausal breast cancer with a 64% reduced risk in premenopausal ER-tumors, typically the most aggressive tumors with the worst outcomes (Feigelson et al., 2020). Furthermore, reduced recurrence and mortality from cancer have been observed in bariatric surgery patients (Aminian et al., 2022;Bruno and Berger, 2020;Zhang et al., 2020a) although underlying mechanisms remain unclear. A major question remains regarding whether reductions in cancer risk and outcomes are associated with weight loss per se or are due to bariatric surgeryspecific benefits, which are inherently challenging to delineate in patients (Schauer et al., 2017;Alvarez et al., 2018). ...
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Bariatric surgery is a sustainable weight loss approach, including vertical sleeve gastrectomy (VSG). Obesity exacerbates tumor growth, while diet-induced weight loss impairs progression. It remains unknown how bariatric surgery-induced weight loss impacts cancer progression or alters response to therapy. Using a pre-clinical model of obesity followed by VSG or diet-induced weight loss, breast cancer progression and immune checkpoint blockade therapy were investigated. Weight loss by VSG or weight-matched dietary intervention before tumor engraftment protected against obesity-exacerbated tumor progression. However, VSG was not as effective as diet in reducing tumor burden despite achieving similar weight and adiposity loss. Leptin did not associate with changes in tumor burden; however, circulating IL-6 was elevated in VSG mice. Uniquely, VSG tumors displayed elevated inflammation and immune checkpoint ligand PD-L1+ myeloid and non-immune cells. VSG tumors also had reduced T lymphocytes and markers of cytolysis, suggesting an ineffective anti-tumor microenvironment which prompted investigation of immune checkpoint blockade. While obese mice were resistant to immune checkpoint blockade, anti-PD-L1 potently impaired tumor progression after VSG through improved anti-tumor immunity. Thus, in formerly obese mice, surgical weight loss followed by immunotherapy reduced breast cancer burden. Finally, we compared transcriptomic changes in adipose tissue after bariatric surgery from patients and mouse models. A conserved bariatric surgery-associated weight loss signature (BSAS) was identified which significantly associated with decreased tumor volume. Findings demonstrate conserved impacts of obesity and bariatric surgery-induced weight loss pathways associated with breast cancer progression.
... Large cohort studies with fairly long follow-up, like WHI [25], suggest the importance of diet quality even after BC diagnosis to decrease specific and overall risk of death. However, to date, evidence on pharmacological or surgical treatment for weight management in BCS needs to be integrated, as data are provided only for small sample sizes and require further investigation [49]. ...
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Breast cancer (BC) represents the most common cancer in women, while overweight and obesity are the second preventable cause of cancer. Weight gain and fat accumulation are common after BC diagnosis; moreover, weight gain during the treatment decreases the survival rate and increases the risk of recurrence in breast cancer survivors (BCS). To reduce the risk of second primary cancer or BC recurrence, and all-cause mortality in BCS, multiple interventions have been investigated to obtain reduction in weight, BMI and/or waist circumference. The aim of this narrative review is to analyze evidence on BCS for their risk of recurrence or mortality related to increased weight or fat deposition, and the effects of interventions with healthy dietary patterns to achieve a proper weight and to reduce fat-related risk. The primary focus was on dietary patterns instead of single nutrients and supplements, as the purpose was to investigate on secondary prevention in women free from disease at the end of their cancer treatment. In addition, BC relation with insulin resistance, dietary carbohydrate, and glycemic index/glycemic load is discussed. In conclusion, obesity and overweight, low rates of physical activity, and hormone receptor-status are associated with poorer BC-treatment outcomes. To date, there is a lack of evidence to suggest which dietary pattern is the best approach for weight management in BCS. In the future, multimodal lifestyle interventions with dietary, physical activity and psychological support after BC diagnosis should be studied with the aim of reducing the risk of BC recurrence or mortality.
... 257 Bariatric surgery Given the various mechanisms by which obesity contributes to carcinogenesis, weight loss mediated by bariatric surgery has 259 A prospective trial is investigating the efficacy of bariatric surgery in reducing recurrence in breast cancer patients (NCT03946423). 260 Although additional randomised prospective data are needed, it seems that weight loss modulates many of the effects of obesity on carcinogenesis. ...
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Obesity is a risk factor for at least 13 different types of cancer, many of which are hormonally driven, and is associated with increased cancer incidence and morbidity. Adult obesity rates are steadily increasing and a subsequent increase in cancer burden is anticipated. Obesity-related dysfunction can contribute to cancer pathogenesis and treatment resistance through various mechanisms, including those mediated by insulin, leptin, adipokine, and aromatase signalling pathways, particularly in women. Furthermore, adiposity-related changes can influence tumour vascularity and inflammation in the tumour microenvironment, which can support tumour development and growth. Trials investigating non-pharmacological approaches to target the mechanisms driving obesity-mediated cancer pathogenesis are emerging and are necessary to better appreciate the interplay between malignancy, adiposity, diet and exercise. Diet, exercise and bariatric surgery are potential strategies to reverse the cancer-promoting effects of obesity; trials of these interventions should be conducted in a scientifically rigorous manner with dose escalation and appropriate selection of tumour phenotypes and have cancer-related clinical and mechanistic endpoints. We are only beginning to understand the mechanisms by which obesity effects cell signalling and systemic factors that contribute to oncogenesis. As the rates of obesity and cancer increase, we must promote the development of non-pharmacological lifestyle trials for the treatment and prevention of malignancy.
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Breast cancer is the most common and second deadliest malignancy in women. With rising obesity rates and building evidence for a strong association with obesity, the incidence of breast cancer can be expected to increase. Weight loss reduces breast cancer risk, the mechanisms of which are still poorly understood. As an effective therapy for obesity, bariatric surgery may be a powerful tool in breast cancer prevention and treatment. This review details the potential physiologic mechanisms that may underlie this association, as well as recently published studies that reinforce the link between bariatric surgery and a reduction in incident breast cancer. The use of bariatric surgery as an adjunct therapy in endometrial cancer also raises the potential for similar use in select breast cancer patients. Despite the expanding potential applications of bariatric surgery in this field, publications to date have been strictly observational, highlighting a need for future clinical trials.
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The prevalence of noncommunicable diseases has increased dramatically in North America and throughout the world and is expected to continue increasing in coming years. Obesity has been linked to several types of cancers and is associated with increased morbidity and mortality following cancer diagnosis. Bariatric surgery has emerged as the prominent model to evaluate the effects of intentional weight loss on cancer incidence and outcomes. Current literature, comprising prospective cohort investigations, indicates site-specific reductions in cancer risk with select bariatric procedures. Future research is required to establish evidence-based indications for bariatric surgery in the context of cancer prevention.
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Background Obesity is a major risk factor for breast cancer. This study examines whether bariatric surgery affects breast cancer incidence in women with obesity compared to BMI-matched controls. Methods EMBASE, MEDLINE, Web of Science, and CINAHL were searched. Primary studies on female breast cancer incidence after bariatric surgery were eligible. Results 11 studies were included (n = 1,106,939). The rate of cancer diagnosis was lower in the surgical group (0.54%) compared to control (0.84%; risk ratio (RR) 0.50, 95%CI 0.37–0.67, I² = 88%). The results were robust to sensitivity analyses for patient age and study size. Bariatric surgery was associated with increased risk of stage I cancer (RR 1.23, 95%CI 1.06–1.44) and reduced risk of stage III or IV cancer (RR 0.50, 95%CI 0.28–0.88). Hormone receptor characteristics were not affected. Conclusions Bariatric surgery is associated with reduced incidence and earlier stage at diagnosis of breast cancer in women with obesity compared to BMI-matched controls.
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Purpose: Obesity is associated with poor outcomes in women with operable breast cancer. Lifestyle interventions (LIs) that help women reduce their weight may improve outcomes. Patients and methods: We conducted a multicenter randomized trial comparing mail-based delivery of general health information alone or combined with a 24-month standardized, telephone-based LI that included diet (500 to 1,000 kcal per day deficit) and physical activity (150 to 200 minutes of moderate-intensity physical activity per week) goals to achieve weight loss (up to 10%). Women receiving adjuvant letrozole for T1-3N0-3M0 breast cancer with a body mass index (BMI) ≥ 24 kg/m(2) were eligible. Weight was measured in the clinic, and self-report physical activity, quality-of-life (QOL), and diet questionnaires were completed. The primary outcome was disease-free survival. Accrual was terminated at 338 of 2,150 planned patients because of loss of funding. Results: Mean weight loss was significantly (P < .001) greater in the LI arm versus the comparison arm (4.3 v 0.6 kg or 5.3% v 0.7% at 6 months and 3.1 v 0.3 kg or 3.6% v 0.4% at 24 months) and occurred consistently across strata (BMI 24 to < 30 v ≥ 30 kg/m(2); prior v no prior adjuvant chemotherapy). Weight loss was greatest in those with higher baseline levels of moderate-intensity physical activity or improvement in QOL. Hospitalization rates and medical events were similar. Conclusion: A telephone-based LI led to significant weight loss that was still evident at 24 months, without adverse effects on QOL, hospitalizations, or medical events. Adequately powered randomized trials with cancer end points are needed.
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Positive association between obesity and survival after breast cancer was demonstrated in previous meta-analyses of published data, but only the results for the comparison of obese versus non-obese was summarised. We systematically searched in MEDLINE and EMBASE for follow-up studies of breast cancer survivors with body mass index (BMI) before and after diagnosis, and total and cause-specific mortality until June 2013, as part of the World Cancer Research Fund Continuous Update Project. Random-effects meta-analyses were conducted to explore the magnitude and the shape of the associations. Eighty-two studies, including 213 075 breast cancer survivors with 41 477 deaths (23 182 from breast cancer) were identified. For BMI before diagnosis, compared with normal weight women, the summary relative risks (RRs) of total mortality were 1.41 [95% confidence interval (CI) 1.29-1.53] for obese (BMI >30.0), 1.07 (95 CI 1.02-1.12) for overweight (BMI 25.0-<30.0) and 1.10 (95% CI 0.92-1.31) for underweight (BMI <18.5) women. For obese women, the summary RRs were 1.75 (95% CI 1.26-2.41) for pre-menopausal and 1.34 (95% CI 1.18-1.53) for post-menopausal breast cancer. For each 5 kg/m(2) increment of BMI before, <12 months after, and ≥12 months after diagnosis, increased risks of 17%, 11%, and 8% for total mortality, and 17%, 18%, and 29% for breast cancer mortality were observed, respectively. Obesity is associated with poorer overall and breast cancer survival in pre- and post-menopausal breast cancer, regardless of when BMI is ascertained. Being overweight is also related to a higher risk of mortality. Randomised clinical trials are needed to test interventions for weight loss and maintenance on survival in women with breast cancer.
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Obesity is a risk factor for the development of new cases of breast cancer and also affects survival in women who have already been diagnosed with breast cancer. Early studies of obesity and breast cancer survival have been summarised in two meta-analyses, but the latest of these only included studies that recruited women diagnosed as recently as 1991. The primary aim of this study was to conduct a meta-analysis that included the more recent studies. A systematic search of MEDLINE, EMBASE and CINAHL was conducted to identify original data evaluating the effects of obesity on survival in newly diagnosed breast cancer patients. Adjusted hazard ratios (HR) from individual studies were pooled using a random effects model. A series of pre-specified sensitivity analyses were conducted on factors such as overall versus breast cancer survival and treatment versus observational cohort. The meta-analysis included 43 studies that enrolled women diagnosed with breast cancer between 1963 and 2005. Sample size ranged from 100 to 424168 (median 1192). The meta-analysis showed poorer survival among obese compared with non-obese women with breast cancer, which was similar for overall (HR = 1.33; 95% confidence interval (CI): 1.21, 1.47) and breast cancer specific survival (HR = 1.33; 95% CI: 1.19, 1.50). The survival differential varied only slightly, depending on whether body mass index (1.33; 1.21, 1.47) or waist-hip ratio (1.31; 1.08, 1.58) was used as the measure of obesity. There were larger differences by whether the woman was pre-menopausal (1.47) or post-menopausal (1.22); whether the cohort included women diagnosed before (1.31) or after 1995 (1.49); or whether the women were in a treatment (1.22) or observational cohort (1.36), but none of the differences were statistically significant. Women with breast cancer, who are obese, have poorer survival than women with breast cancer, who are not obese. However, no study has elucidated the causal mechanism and there is currently no evidence that weight loss after diagnosis improves survival. Consequently, there is currently no reason to place the additional burden of weight loss on women already burdened with a diagnosis of cancer. Further research should concentrate on assessing whether factors such as diabetes or type of chemotherapy modify the obesity effect and on understanding the causal mechanism, in particular the role of relative under-dosing.
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To the Editor The Viewpoint by Dr Massetti and colleagues emphasized the link between obesity and cancer and called for more robust clinical intervention to prevent and treat obesity.¹ The authors proposed that sustainable weight loss be achieved by comprehensive strategies that support patients’ efforts to make significant lifestyle changes. However, most published studies have shown that the long-term success rate of lifestyle changes is low. Although lifestyle changes may be sufficient to reduce body weight prior to sustained obesity, once obesity is established, body weight seems to become biologically fixed and lifestyle programs become less effective.
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Objective: To determine whether bariatric surgery is associated with a lower risk of cancer. Background: Obesity is strongly associated with many types of cancer. Few studies have examined the relationship between bariatric surgery and cancer risk. Methods: We conducted a retrospective cohort study of patients undergoing bariatric surgery between 2005 and 2012 with follow-up through 2014 using data from a large integrated health insurance and care delivery systems with 5 study sites. The study included 22,198 subjects who had bariatric surgery and 66,427 nonsurgical subjects matched on sex, age, study site, body mass index, and Elixhauser comorbidity index. Multivariable Cox proportional-hazards models were used to examine incident cancer up to 10 years after bariatric surgery compared to the matched nonsurgical patients. Results: After a mean follow-up of 3.5 years, we identified 2543 incident cancers. Patients undergoing bariatric surgery had a 33% lower hazard of developing any cancer during follow-up [hazard ratio (HR) 0.67, 95% confidence interval (CI) 0.60, 0.74, P < 0.001) compared with matched patients with severe obesity who did not undergo bariatric surgery, and results were even stronger when the outcome was restricted to obesity-associated cancers (HR 0.59, 95% CI 0.51, 0.69, P < 0.001). Among the obesity-associated cancers, the risk of postmenopausal breast cancer (HR 0.58, 95% CI 0.44, 0.77, P < 0.001), colon cancer (HR 0.59, 95% CI 0.36, 0.97, P = 0.04), endometrial cancer (HR 0.50, 95% CI 0.37, 0.67, P < 0.001), and pancreatic cancer (HR 0.46, 95% CI 0.22, 0.97, P = 0.04) was each statistically significantly lower among those who had undergone bariatric surgery compared with matched nonsurgical patients. Conclusions: In this large, multisite cohort of patients with severe obesity, bariatric surgery was associated with a lower risk of incident cancer, particularly obesity-associated cancers, such as postmenopausal breast cancer, endometrial cancer, and colon cancer. More research is needed to clarify the specific mechanisms through which bariatric surgery lowers cancer risk.
Article
Purpose: Predicting the pattern of recurrence can aid in the development of targeted surveillance and treatment strategies. We identified patient populations that remain at risk for an event at a median follow-up of 24 years from the diagnosis of operable breast cancer. Patients and methods: International Breast Cancer Study Group clinical trials I to V randomly assigned 4,105 patients between 1978 and 1985. Annualized hazards were estimated for breast cancer-free interval (primary end point), disease-free survival, and overall survival. Results: For the entire group, the annualized hazard of recurrence was highest during the first 5 years (10.4%), with a peak between years 1 and 2 (15.2%). During the first 5 years, patients with estrogen receptor (ER) - positive disease had a lower annualized hazard compared with those with ER-negative disease (9.9% v 11.5%; P = .01). However, beyond 5 years, patients with ER-positive disease had higher hazards (5 to 10 years: 5.4% v 3.3%; 10 to 15 years: 2.9% v 1.3%; 15 to 20 years: 2.8% v 1.2%; and 20 to 25 years: 1.3% v 1.4%; P < .001). Among patients with ER-positive disease, annualized hazards of recurrence remained elevated and fairly stable beyond 10 years, even for those with no axillary involvement (2.0%, 2.1%, and 1.1% for years 10 to 15, 15 to 20, and 20 to 25, respectively) and for those with one to three positive nodes (3.0%, 3.5%, and 1.5%, respectively). Conclusion: Patients with ER-positive breast cancer maintain a significant recurrence rate during extended follow up. Strategies for follow up and treatments to prevent recurrences may be most efficiently applied and studied in patients with ER-positive disease followed for a long period of time.
Article
The influence of excess body weight on the risk of death from cancer has not been fully characterized. In a prospectively studied population of more than 900,000 U.S. adults (404,576 men and 495,477 women) who were free of cancer at enrollment in 1982, there were 57,145 deaths from cancer during 16 years of follow-up. We examined the relation in men and women between the body-mass index in 1982 and the risk of death from all cancers and from cancers at individual sites, while controlling for other risk factors in multivariate proportional-hazards models. We calculated the proportion of all deaths from cancer that was attributable to overweight and obesity in the U.S. population on the basis of risk estimates from the current study and national estimates of the prevalence of overweight and obesity in the U.S. adult population. The heaviest members of this cohort (those with a body-mass index [the weight in kilograms divided by the square of the height in meters] of at least 40) had death rates from all cancers combined that were 52 percent higher (for men) and 62 percent higher (for women) than the rates in men and women of normal weight. For men, the relative risk of death was 1.52 (95 percent confidence interval, 1.13 to 2.05); for women, the relative risk was 1.62 (95 percent confidence interval, 1.40 to 1.87). In both men and women, body-mass index was also significantly associated with higher rates of death due to cancer of the esophagus, colon and rectum, liver, gallbladder, pancreas, and kidney; the same was true for death due to non-Hodgkin's lymphoma and multiple myeloma. Significant trends of increasing risk with higher body-mass-index values were observed for death from cancers of the stomach and prostate in men and for death from cancers of the breast, uterus, cervix, and ovary in women. On the basis of associations observed in this study, we estimate that current patterns of overweight and obesity in the United States could account for 14 percent of all deaths from cancer in men and 20 percent of those in women. Increased body weight was associated with increased death rates for all cancers combined and for cancers at multiple specific sites.