Changes in mammographic density following bariatric surgery

Changes in mammographic density following bariatric surgery

Surgery for Obesity and Related Diseases 15 (2019) 964–968 Original article: integrated health Changes in mammographic density following bariatric s...

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Surgery for Obesity and Related Diseases 15 (2019) 964–968

Original article: integrated health

Changes in mammographic density following bariatric surgery Ava Hosseini, M.D.a,*, Amal L. Khoury, M.D.b, Flora Varghese, M.D.b, Jonathan Carter, M.D.b, Jasmine M. Wong, M.D.b, Rita A. Mukhtar, M.D.b b

a Department of Surgery, University of California, San Diego, San Diego, CA Department of Surgery, University of California, San Francisco, San Francisco, CA

Abstract

Background: Obesity and high breast density both increase breast cancer risk but paradoxically are inversely related. Bariatric surgery decreases breast cancer risk, but its impact on mammographic breast density is not well understood. Objectives: We investigated how mammographic density changes after bariatric surgery and whether this change is related to weight loss. Setting: University of California, San Francisco Medical Center. Methods: We reviewed records from 349 prospectively collected patients who underwent bariatric surgery between 2013 and 2015 and identified 42 women with pre- and postoperative screening mammograms within 1.5 years of surgery. We recorded body mass index (BMI), height and Breast Imaging Reporting and Data System density and calculated BMI loss and total weight loss. Data were analyzed in Stata 14.2. Results: Average age was 54.2 years, mean preoperative BMI was 43.8 kg/m2, mean BMI lost was 30.9%, and total weight loss was 31.1% at 1.3 years. Over one-third had a change in mammographic breast density, which increased 93.3% of the time (P , .001). Amount of weight loss was not associated with a density change. Patients with the lowest mammographic density preoperatively were most likely to have a density change (P 5 .02). Conclusions: Most women with a mammographic change had an increase in breast density, despite bariatric surgery being associated with reduced breast cancer risk. Baseline breast density was associated with a density change, but amount of weight loss was not. These findings suggest the metabolic effects of bariatric surgery have an effect on breast parenchyma independent of absolute BMI reduction or weight loss. (Surg Obes Relat Dis 2019;15:964–968.) Published by Elsevier Inc. on behalf of American Society for Bariatric Surgery.

Key words:

bariatric surgery; breast density; breast cancer; obesity

Obesity has been associated with an increased risk of developing breast cancer [1,2]. This relationship is supported by studies showing a decrease in breast cancer risk after weight loss [3], with this reduced risk also found in women who undergo bariatric surgery [4]. Potential

* Correspondence: Ava Hosseini, M.D., 3855 Health Sciences Drive MC 0987, La Jolla, CA 92093. E-mail address: [email protected] (A. Hosseini).

mechanisms responsible for this link between weight and breast cancer risk include elevated estrogen levels in metabolic syndrome in both the body and breast [5] as well as direct communication between breast adipocytes and tumor cells [6]. Breast density, like obesity, has also been shown to be a risk factor for breast cancer [7]. Breast density is defined as the amount of fibroglandular tissue relative to fatty tissue in the breast on mammography and is reported per the Breast Imaging Reporting and Data System (BI-RADS)

https://doi.org/10.1016/j.soard.2019.03.037 1550-7289/Published by Elsevier Inc. on behalf of American Society for Bariatric Surgery.

Ava Hosseini et al. / Surgery for Obesity and Related Diseases 15 (2019) 964–968

guidelines [8]. The BI-RADS system classifies breast density into 4 categories: almost entirely fat (BI-RADS A), scattered fibroglandular densities (BI-RADS B), heterogeneously dense (BI-RADS C), and extremely dense (BIRADS D). Like weight, density is also a risk factor that is modifiable; therefore, changes in breast density may alter breast cancer risk [9]. Breast cancer risk assessment models that include mammographic breast density ascribe a 2- to 4fold increase in breast cancer risk as density increases [10]. However, the relationship between breast density and weight is not well understood. Studies have reached conflicting conclusions about whether breast density increases or decreases with weight loss [11–13]. We sought to determine how mammographic density changes after bariatric surgery and whether this change is related to amount of weight loss. Materials and Methods This study was approved by the Institutional Review Board of the University of California, San Francisco. We analyzed a prospectively collected database of patients who underwent bariatric surgery at the University of California, San Francisco, between 2013 and 2015. Inclusion criteria were female gender, having preoperative and postoperative screening mammograms within 1.5 years of surgery, and undergoing either Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). Exclusion criteria included history of breast cancer or ductal carcinoma in situ and undergoing laparoscopic adjustable gastric band placement. Out of 349 patients, 42 women were identified who met these criteria. We recorded patient data including age, race, and comorbidities. We documented type of surgery and body mass index (BMI) before and after surgery. We also recorded BIRADS density as reported by the radiologist on mammography report preoperatively and 1 to 1.5 years postoperatively. We calculated change in BMI (percentage) and

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total weight loss (TWL) (percentage). The primary outcome was change in mammographic breast density after bariatric surgery. Data were analyzed using Stata 14.2, using X2 tests for categorical variables and t tests for continuous variables. Results For the 42 women in our study group, the average age was 54.2 years, and the majority were Caucasian (Table 1). Preoperatively, 52.4% of the women had almost entirely fatty breasts, 33.3% had scattered fibroglandular densities, and 14.3% were heterogeneously dense. Mean preoperative BMI was 43.8 kg/m2 (standard deviation [SD] 6.7) and mean postoperative BMI was 30.3 kg/m2 (SD 5.5), with a mean reduction in BMI of 30.9%. Mean percentage TWL was 31.1% (SD 7.8). Most patients underwent RYGB (69%), and the remainder underwent SG. While patients who underwent RYGB had significantly higher baseline BMI, there was no difference in amount of TWL or BMI loss between the 2 groups (Table 2). Postoperative breast density showed 26.2% had almost entirely fatty breasts, 52.4% had fibroglandular scattered densities, and 21.4% were heterogeneously dense. When comparing pre- and postoperative mammograms, 35.7% of women had a change in breast density; among these, the density increased 93.3% of the time (P , .001). Figure 1 shows pre- and postoperative mammographic images from a single patient in this study to demonstrate typical mammographic density increase. Type of surgery was not associated with density change: 34.5% of the RYGB and 38.5% of the SG groups had density change (P 5 .53). The amount of weight loss was not associated with density change; in fact, total weight loss was slightly greater in those without a density change than in those with a density change (32.4% versus 28.9%, P 5 .18). There was also no difference in the number of patients with density change when comparing those in the highest quartile of weight loss to those in the lowest quartile of weight loss (27.3% versus

Table 1 Patient baseline characteristics

Mean age (yr) Race, n (%) Caucasian Black Hispanic Asian Other Incidence of diabetes, n (%) Incidence of HTN, n (%) Incidence of OSA, n (%) Incidence of OA, n (%)

Overall N 5 42

RYGB N 5 29

SG N 5 13

P value

54.2 (36.6–70.7)

53.4 (36.6–70.7)

56.1 (43.1–68.9)

.81 .3

22 (52.4) 14 (33.3) 2 (4.8) 1 (2.4) 3 (7.1) 12 (28.6) 26 (61.9) 11 (26.2) 28 (66.7)

14 (48.3) 11 (37.9) 1 (3.5) 0 (0.0) 3 (10.3) 5 (17.2) 17 (58.6) 9 (31.0) 18 (62.1)

8 (61.5) 3 (23.1) 1 (7.7) 1 (7.7) 0 (0.0) 7 (53.8) 9 (69.2) 2 (15.4) 10 (76.9)

.03 .73 .45 .49

RYGB 5 Roux-en-Y gastric bypass; SG 5 sleeve gastrectomy; HTN 5 hypertension; OSA 5 obstructive sleep apnea; OA 5 osteoarthritis.

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Ava Hosseini et al. / Surgery for Obesity and Related Diseases 15 (2019) 964–968 Table 2 Changes in weight and breast density after bariatric surgery

Mean, SD preoperative weight (kg) Mean, SD preoperative BMI (kg/m2) Mean, SD postoperative weight (kg) Mean, SD postoperative BMI (kg/m2) Mean, SD BMI reduction (%) Mean, SD total weight loss (%) Preoperative mammographic density, n (%) BI-RADS A: Entirely fatty BI-RADS B: Scattered densities BI-RADS C: Heterogeneously dense Postoperative mammographic density, n (%) BI-RADS A: Entirely fatty BI-RADS B: Scattered densities BI-RADS C: Heterogeneously dense No. (%) of patients with postoperative density change Mean, SD time from preoperative mammogram to postoperative mammogram (yr)

Overall N 5 42

RYGB N 5 29

SG N 5 13

P value

119.5, 17.5 43.8, 6.7 82.2, 14.6 30.3, 5.5 30.9, 7.9 31.1, 7.8

122.1, 17.3 44.8, 7.5 82.4, 15.1 30.3, 6.1 32.5, 8.3 32.5, 8.3

113.4, 17.4 41.7, 3.9 81.7, 14.0 30.3, 4.2 27.4, 5.7 28.0, 5.7

.97 .02 .78 .15 .15 .16 .59

22 (52.4) 14 (33.3) 6 (14.3)

16 (55.2) 10 (34.5) 3 (10.3)

6 (46.2) 4 (30.8) 3 (23.1)

11 (26.2) 22 (52.4) 9 (21.4) 15 (35.7)

9 (31.0) 15 (51.7) 5 (17.2) 10 (34.5)

2 (15.4) 7 (53.8) 4 (30.8) 5 (38.5)

.53

1.9, .55

2.0, .55

1.7, .52

.87

.51

RYGB 5 Roux-en-Y gastric bypass; SG 5 sleeve gastrectomy; BMI 5 body mass index; BI-RADS 5 Breast Imaging Reporting and Data System.

33.3%, P 5 .77). Density change was not associated with age, preoperative BMI, or time between mammograms. Preoperative BMI was significantly associated with mammographic breast density, with a mean preoperative BMI of 45.2, 42.8, and 41.1 kg/m2 in those with the BI-RADS A, B, and C density scores, respectively (P 5 .001). Those with the lowest baseline mammographic density (BI-RADS A) were most likely to have a density change, regardless of the absolute amount of weight loss (density change in 54.6%, 21.4%, and 0% of baseline

BI-RADS A, B, and C, respectively, P 5 .02). There was no relationship between baseline BMI or mammographic density and amount of weight loss. Discussion Obesity and high breast density are both established risk factors for breast cancer. Both are modifiable and therefore can be targeted for cancer risk reduction. Bariatric surgery is a well-established method of weight loss and confers a

Fig. 1. Pre– and post–bariatric surgery mammograms of one patient showing an increase in mammographic density from preoperative scattered densities (A) to postoperative heterogeneously dense (B) breasts.

Ava Hosseini et al. / Surgery for Obesity and Related Diseases 15 (2019) 964–968

number of metabolic changes and reduction in systemic inflammation [14], all of which may also affect cancer risk. Breast density has been shown to be modified through endocrine treatments already used for breast cancer treatment and prevention [15]. However, the relationship between weight loss, particularly the weight loss conferred via bariatric surgery, and breast density is not well understood. Because BMI and breast density are both risk factors for breast cancer, one would expect them to be directly correlated, which some studies have shown [13]. However, our study shows that after significant weight loss with bariatric surgery, the majority of women had no detectable change in mammographic breast density; however, when breast density did change, it was significantly more likely to increase. While we were unable to calculate individual breast cancer risk for this cohort, interestingly, the finding of increased breast density would be associated with an increased risk in breast cancer risk assessment models that include breast density. This is contrary to the known association between weight loss surgery and reduced breast cancer risk and warrants further study. Since the amount of change in BMI and total weight did not correlate with likelihood of changing breast density, these findings suggest that bariatric surgery has an impact on the breast parenchyma independent of fat loss alone. We hypothesize that bariatric surgery may induce other changes in breast tissue, such as reduction in local inflammation or tissue stiffness, that might reduce breast cancer risk [16,17]. The finding that patients with the lowest breast density were most likely to have a density change is consistent with published reports [18]. The limitations of our study include a small sample size, which resulted from limiting our inclusion criteria to women who had undergone mammograms within 1.5 years of surgery. We felt this was important since breast density can change over time, and examining a relatively short period allows us to determine a more independent effect of the surgical intervention and weight change. While it may be advantageous to use mammographic density as determined by radiologists, given this is the clinically applicable method, a quantitative method could be more sensitive in detecting changes and could account for discrepancies among the few studies that have examined this question. A quantitative method also has the advantage of being able to analyze changes in breast volume and any potential effects this may have on overall breast density. By using the BI-RADS density as reported by radiologists, we were not able to measure interrater reliability and acknowledge this is not a completely objective measurement, another limitation of our study. Future work will include analysis of a larger population and comparison of breast density changes after weight loss from bariatric surgery versus nonsurgical weight loss.

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Conclusions In our study population, the women who had a mammographic change after bariatric surgery had an increase in breast density, despite bariatric surgery being associated with reduced breast cancer risk. Interestingly, the amount of weight loss was not associated with change in breast density. These findings suggest the metabolic effects of bariatric surgery may have an effect on the breast parenchyma independent of absolute BMI reduction or weight loss. Our findings, along with those emerging in this field, highlight the need for further investigation into how bariatric surgery modifies breast cancer risk. Disclosures The authors have no commercial associations that might be a conflict of interest in relation to this article. References [1] Esposito K, Chiodini P, Colao A, Lenzi A, Giugliano D. Metabolic syndrome and risk of cancer: a systematic review and meta-analysis. Diabetes Care 2012;35(11):2402–11. [2] Bhandari R, Kelley GA, Hartley TA, Rockett IR. Metabolic syndrome is associated with increased breast cancer risk: a systematic review with meta-analysis. Int J Breast Cancer 2014;2014:189384. [3] Hardefeldt PJ, Penninkilampi R, Edirimanne S, Eslick GD. Physical activity and weight loss reduce the risk of breast cancer: a metaanalysis of 139 prospective and retrospective studies. Clin Breast Cancer 2018;18(4):e601–e12. [4] Schauer DP, Feigelson HS, Koebnick C, et al. Bariatric surgery and the risk of cancer in a large multisite cohort. Ann Surg 2019;269(1):95–101. [5] Cleary MP, Grossmann ME. Minireview: obesity and breast cancer: the estrogen connection. Endocrinology 2009;150(6):2537–42. [6] Blucher C, Stadler SC. Obesity and breast cancer: current insights on the role of fatty acids and lipid metabolism in promoting breast cancer growth and progression. Front Endocrinol (Lausanne) 2017;8:293. [7] McCormack VA, dos Santos Silva I. Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev 2006;15(6):1159–69. [8] Hooley RJ. Breast density legislation and clinical evidence. Radiol Clin North Am 2017;55(3):513–26. [9] Kerlikowske K, Ichikawa L, Miglioretti DL, et al. Longitudinal measurement of clinical mammographic breast density to improve estimation of breast cancer risk. J Natl Cancer Inst 2007;99(5):386–95. [10] Tice JA, Cummings SR, Smith-Bindman R, Ichikawa L, Barlow WE, Kerlikowske K. Using clinical factors and mammographic breast density to estimate breast cancer risk: development and validation of a new predictive model. Ann Intern Med 2008;148(5):337–47. [11] Vohra NA, Kachare SD, Vos P, et al. The short-term effect of weight loss surgery on volumetric breast density and fibroglandular volume. Obes Surg 2017;27(4):1013–23. [12] Mokhtari TE, Rosas US, Downey JR, Miyake KK, Ikeda DM, Morton JM. Mammography before and after bariatric surgery. Surg Obes Relat Dis 2017;13(3):451–6. [13] Williams AD, So A, Synnestvedt M, et al. Mammographic breast density decreases after bariatric surgery. Breast Cancer Res Treat 2017;165(3):565–72. [14] Frikke-Schmidt H, O’Rourke RW, Lumeng CN, Sandoval DA, Seeley RJ. Does bariatric surgery improve adipose tissue function? Obes Rev 2016;17(9):795–809.

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