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Page 234 Puyana et al. J Transl Genet Genom 2022;6:223-239 https://dx.doi.org/10.20517/jtgg.2021.51

Despite the evident benefits of bariatric surgery in obese class II and III women with breast cancer, when
and how to integrate bariatric surgery into the breast cancer care continuum has not been explored. There is
some evidence to suggest that bariatric surgery may be well-tolerated in breast cancer survivors after
[98]
completing all treatments , but very few studies have examined the outcomes of bariatric surgery in this
population. Additionally, little is known about the impact of bariatric surgery on breast cancer recurrence
rates, metastasis, or mortality. Future studies should explore the optimal time to undergo bariatric surgery
after mastectomy, lumpectomy, chemotherapy, and/or radiotherapy. Longitudinal studies of the effects of
bariatric surgery on progression-free and overall survival are also warranted.

Our study has several limitations. First, study reliability is limited by the small sample size (n = 403) that was
highly enriched for HW women (65%). Findings may therefore not be generalizable to all populations. In
addition, our study focused solely on women with breast cancer and did not include a healthy control
group. Results must only be interpreted in the context of breast cancer patients. It is not clear how obesity
PRS and CRP levels in this sample compare to healthy women, and future case-control studies comparing
breast cancer populations to healthy populations will be essential to corroborate findings. Second, BMI may
be an oversimplified measure of adiposity, as it neither accounts for fat distribution nor distinguishes fat
from muscle [99,100] . Waist circumference may be a better reflection of obesity and associated breast cancer
risk [99,100] ; however, this is not routinely collected in the clinical setting, and our analysis was limited by the
data available in the electronic medical record. Third, CRP is a nonspecific marker of inflammation .
[101]
Although some studies suggest an association between high CRP and obesity or breast cancer, our results
must be interpreted cautiously, as spurious elevations in CRP may contribute to the observed trends. CRP
was the sole biomarker evaluated in the current study due to its known association with inflammation and
the economic feasibility of collection; however, oxidative stress is also known to play a critical role in the
pathogenesis of obesity and breast cancer . Future studies are warranted to evaluate whether our obesity
[102]
PRS may also be associated with biomarkers of oxidative stress. Lastly, nutritional intake, physical activities,
and other environmental factors may modify the genetic effects on obesity. However, we did not collect
such information; it is not possible to adjust for these variables in our regression analysis. Future studies
should collect such information for adjustment.

Our findings validate previous studies suggesting that aggregating polygenic risk into a PRS helps predict
obesity risk. In particular, our obesity PRS can identify breast cancer patients with a high genetic
predisposition to obesity who may benefit from aggressive weight-loss strategies, such as bariatric surgery.
Our study also highlights that obesity-associated SNPs may be related to racial and ethnic disparities in
obesity and subsequently, breast cancer outcomes. Together, racial/ethnic variation in obesity rates and high
obesity PRS may contribute to worse breast cancer outcomes observed in minority women, highlighting the
importance of intervention in this high-risk population. Additionally, we demonstrate an association
between genetic risk of obesity and inflammation that highlights one possible mechanism by which obesity
promotes carcinogenesis. Future studies utilizing larger sample sizes will be necessary to validate these
findings. Finally, we carefully propose that bariatric surgery may be considered as a prevention strategy for
breast cancer incidence and/or recurrence, and to improve the quality of life and overall survival in eligible
women. Additional studies should target racial/ethnic disparities in outcomes to examine the potential
benefits of introducing bariatric surgery into the breast cancer continuum of care.

DECLARATIONS
Acknowledgements
The authors are thankful to all women who participated in the study, the clinical staff at the breast cancer
and radiation oncology clinics, and Wei Zhao for statistical support.