INTRODUCTION

Breast cancer remains the second leading cause of cancer death among women in the United States1. Screening mammography reduces breast cancer mortality2–6, and current guidelines recommend mammography every 1–2 years for women over 40 years of age7,8.

Obesity has increased over the past 2 decades among women in the US9 and has disparate effects on pre- and postmenopausal breast cancer. Excess body weight may actually decrease the risk of premenopausal breast cancer10,11, but the relationship between obesity and premenopausal breast cancer mortality is ambiguous11,12. However, obesity is an important risk factor for both the development of10,11,13–15 and mortality from16–19 postmenopausal breast cancer. Obesity may also worsen breast cancer morbidity, including risk of breast cancer recurrence20, contralateral breast cancer21, wound complications after breast surgery22, and lymphedema23,24.

The mechanism by which obesity leads to poorer prognosis of breast cancer is not well understood and may be related to tumor characteristics, hormonal mechanisms, suboptimal diet and physical activity, or delay in diagnosis16. Studies of the relationship between obesity and stage at breast cancer diagnosis are conflicting25,26.

Several observational studies suggest that obese women may be less likely to report recent mammography27–39, but the relationship between obesity and screening mammography remains unclear40–43. Some studies suggest the problem may be confined to white women31–33,36.

Therefore, we conducted a systematic review and meta-analysis to determine whether overweight or obese women are less likely to have recent mammography than their normal-weight counterparts. We also studied the effect of race on the relationship between weight and recent mammography.

METHODS

Search Strategy

Our overall search strategy addressed a broader question regarding the association between obesity and screening for breast, cervical, and colon cancer. For this study, we searched the PubMed, CINAHL, and Cochrane Library electronic databases from inception to July 2008 to identify original articles evaluating the relationship between body weight and recent mammography in the US using search terms for breast cancer screening, breast cancer, and body weight (Appendix Table 5). We manually searched the references of included articles and the tables of contents of 11 key medical journals from August 2006 through November 2006 and then updated our manual search from April 2008 to July 2008. General medical, cancer, women’s health, and prevention journals were selected based on the origin of the included articles and the topic itself to avoid missing articles due to any delays in electronic indexing. Searchers were physician investigators and included a senior obesity researcher (J.M.C.), an investigator with systematic review experience (S.B.), and a post-doctoral epidemiology trainee with relevant clinical experience (N.M.M). Two reviewers conducted title and abstract reviews independently. If a title was selected by either investigator, it was advanced to abstract review. Title and abstract reviews were designed to be sensitive; if there was any question of an article exploring weight as a predictor of screening upon title or abstract review, we advanced the article to the next level of review. Of 273 abstracts, there were 62 conflicts (23%) in abstract review, which we resolved by consensus through discussion. Disagreements usually pertained to misreading on the part of one of the investigators, and disagreements in judgment were rare.

Study Selection

We included published original articles if they reported the prevalence of mammography by body weight in adults ≥18 years of age and were written in English. We defined original articles as articles in which the authors analyzed raw data and thus excluded reviews, commentaries, editorials, and consensus statements. We excluded studies conducted outside of the US since other countries may have different screening guidelines and resources, and the relationship between weight and mammography might differ based on cultural norms. We also excluded studies of screening in special populations since there may be different screening expectations for some populations (e.g., participants presenting to a cancer screening clinic, HIV-positive patients, those with a history of breast cancer, and those involved in a study of interventions to improve screening). Two investigators reviewed articles independently. Of 101 articles, there were 3 disagreements (3%), which were resolved through discussion.

Data Abstraction and Quality Assessment

Two reviewers sequentially abstracted the data on population characteristics, the exposure, and the outcome using standardized data abstraction forms. Two studies included body mass index (BMI) in models when exploring determinants of screening, but did not explicitly report mammography prevalence by BMI; the authors kindly provided these results34,39.

Two reviewers evaluated study quality independently using a quality form (Appendix A) based on the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) Statement, Checklist of Essential Items version 3 (September 2005)44, which was published recently45. We assumed that the importance of any confounding variable varied according to study design. Therefore, we did not expect each study to handle confounding in the same fashion and assessed quality as being adequate, fair, or inadequate on an individual basis. We resolved disagreements in data abstraction and quality evaluation through discussion.

Data Synthesis and Analysis

First, we created tables to describe all studies qualitatively. We reported results of adjusted analyses when available. In order to obtain generalizable combined estimates for the association between weight and mammography, we conducted unstratified meta-analyses and meta-analyses stratified by white and black race for studies that: (1) had nationally representative data and (2) reported BMI in five standard categories according to the World Health Organization46 and the National Institutes of Health47: (normal: 18.5–24.9 kg/m2, overweight: 25–29.9 kg/m2, class I obesity: 30–34.9 kg/m2, class II obesity: 35–39.9 kg/m2, and class III obesity: ≥ 40 kg/m2). We contacted the authors of articles that did not report results for mammography by BMI in five standard categories; two authors provided the quantitative results requested28,40. Two authors were unable to provide quantitative results stratified by race30,33.

Using the DerSimonian and Laird method48, we used random-effects models to calculate combined odds ratios and 95% confidence intervals for mammography by BMI category using normal BMI as the reference category. For the study that reported adjusted proportions33, we calculated odds ratios. We converted the relative risk to an odds ratio49 for another study32. One study provided results stratified by race only31, and we included the results from the white and black cohorts separately in our main and race-specific analyses.

We tested for heterogeneity using the I 2 statistic50 with an I2 value of >50% signifying “substantial heterogeneity”51. We chose a random-effects model as a more conservative approach to account for potential between-study variability.

We tested for publication bias using the tests of Begg and Mazumdar52 and Egger and colleagues53. All analyses were completed using STATA (StataCorp. 2005. Stata Statistical Software: Release 9. College Station, TX: StataCorp LP).

We conducted several sensitivity analyses. We examined the effect of the removal of any one study on the combined estimate for the unstratified analyses. Also, two35,37 of the seven studies30–33,35,37,38 that were based on nationally representative data and reported BMI in five categories used the same 2000 National Health Interview Survey (NHIS) data but performed slightly different analyses. We included the study with more conservative results in the main meta-analysis35. We included the other, less conservative estimate from the other study37 in a separate analysis. In another analysis, we included all studies that provided BMI in five standard categories regardless of whether they were nationally representative.

RESULTS

Literature Search Results

Of 5,047 titles identified in the overall search, 17 articles met our inclusion criteria and addressed mammography (Fig. 1). Seven30–33,35,37,38 of the 17 studies were sufficiently homogeneous (i.e., used nationally representative survey data and provided information for mammography by five standard categories of BMI) to include in the unstratified meta-analyses. Two of these studies were based on the same 2000 NHIS data35,37; thus, six studies were included in our main meta-analyses. Five nationally-representative studies30–33,35 reported race-stratified analyses, and two of these30,33 did not report the necessary quantitative results to allow their inclusion in the meta-analyses; thus, we included three studies in our race-stratified meta-analysis. Six studies were not nationally representative and were conducted in primarily non-white populations34,39,40,42,43 or reported race-stratified results36.

Figure 1
figure 1

Study flow diagram. *Search terms for breast cancer, cervical cancer, colon cancer, body weight, breast cancer screening, cervical cancer screening, and colon cancer screening were used to conduct the search of electronic databases. Specific terms are provided in Appendix Table 5. †Manual searching involved searching of references of included and key articles and searching of tables of contents of the following journals: Cancer, Journal of General Internal Medicine, Annals of Internal Medicine, Obesity, Ethnicity and Disease, Cancer Detection and Prevention, Journal of Health Care for the Poor and Underserved, Preventing Chronic Disease, Journal of Women’s Health, American Journal of Public Health, Preventive Medicine, and American Journal of Epidemiology. ‡Reasons for exclusion add up to more than abstracts or articles excluded since reviewers could have more than one reason for exclusion. §Studies included in the main meta-analysis reported nationally-representative results in five standard body mass index categories (normal 18–24.9 kg/m2, overweight 25–29.9 kg/m2, class I obesity 30–34.9 kg/m2, class II obesity 35–39.9 kg/m2, class III obesity ≥ 40 kg/m2). A seventh study37 met these criteria, but was based on the same data as another study35 and therefore was only included in a sensitivity analysis. ║Studies included in the race-specific meta-analysis reported nationally representative results in five standard body mass index categories (normal 18–24.9 kg/m2, overweight 25–29.9 kg/m2, class I obesity 30–34.9 kg/m2, class II obesity 35–39.9 kg/m2, class III obesity ≥40 kg/m2).

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Study Characteristics

The 17 included studies, which comprised approximately 276,034 participants, are described in Tables 1 and 2. Sixteen studies were cross-sectional27–38,40–43, and one was longitudinal39. All studies used BMI as the measure of excess body weight. Thirteen studies defined the outcome as mammography in the last 2 years28–33,35–38,40,42,43, two as mammography in the last year27,34, one as mammography in the last 3 years41, and one as mammography every 2 years over a 6-year period39. Ten27,29–33,35,37,38,41 of the 17 studies (59%) were based on nationally representative surveys, the NHIS, Behavioral Risk Factor Surveillance System (BRFSS), or Health and Retirement Survey. Most subjects were white. Reported absolute screened proportions ranged from 53.2% to 85.6%29,30,32–34,36–41,43.

Table 1 Description of Studies Included in Qualitative and Quantitative Analyses*
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Table 2 Results of Studies Included in Qualitative and Quantitative Analyses
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Sixteen of the 17 studies27–39,41–43 (94%) relied on self-reported BMI and mammography. Fourteen studies accounted for confounding adequately27,29–41, and one study did not adjust for any confounding factors28. Reported survey response rates ranged from 55% to 88%. Eight studies did not report missing data27,31,32,35,37,39,41,43, seven had <10% missing data28–30,32,34,36,42, and two reported >20% missing data38,40. All studies provided an adequate exposure description, and all but one27 provided an adequate outcome description. Ten studies used nationally representative surveys27,29–33,35,37,38,41, and 14 did not report the validity of the surveys used27,29–33,35–39,41–43. See Table 3.

Table 3 Quality Review of Included Studies*
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Quantitative Assessment of Mammography by BMI

Fourteen27–39,43 of 17 studies reported an inverse association between recent mammography and increasing BMI that was statistically significant in five27,29,31,36,37. Seven studies30–33,35,37,38 used nationally representative surveys with BMI in five standard categories. Using the six studies based on unique data, class III obesity was inversely associated with the likelihood of having recently undergone mammography compared to women with a normal BMI. The seventh study by Ferrante et al.37 was excluded from the main analysis because it was based on the same data as the study by Zhu et al.35 Combined odds ratios for mammography (95% confidence interval) by BMI category were 1.01 (0.95 to 1.08), 0.93 (0.83 to 1.05), 0.90 (0.78 to 1.04), and 0.79 (0.68 to 0.92) for overweight, class I, class II, and class III obese women, respectively, compared to women with a normal BMI (Fig. 2). We found statistical evidence of heterogeneity for the class I and II obesity categories; I2 statistics were 41%, 74%, 59%, and 42% for the overweight, and class I, II, and III obesity categories, respectively. The exclusion of any one study did not change the results of the meta-analyses substantially (data not shown). No statistically significant publication bias was found, although evaluation was limited by the relatively small number of studies.

Figure 2
figure 2

Meta-analyses of nationally representative studies with BMI in five categories. Note: Included studies: 30–33,35,38; BMI categories: overweight 25–29.9 kg/m2, class I obesity 30–34.9 kg/m2, class II obesity 35–39.9 kg/m2, class III obesity ≥40 kg/m2. *Data from analysis of white women. **Data from analysis of black women. BMI, body mass index; OR, odds ratio; CI, confidence interval.

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Sensitivity Analyses

We obtained similar results when we excluded the article by Zhu et al.35 and instead included the article by Ferrante et al.37, which used the same data. Results were also similar when we included all nine studies with BMI in five categories including three that were not based on nationally representative surveys (data not shown)30–36,38,40.

Effect of Race

Five nationally representative studies30–33,35 evaluated the effect of race on the relationship between BMI and recent mammography. Compared to women with a normal BMI, meta-analyses of the three race-stratified studies using five categories of BMI31,32,35 revealed an inverse association between class II and III obesity and recent mammography for white women, but a positive association between overweight and recent mammography among black women (Table 4). We found statistical evidence of heterogeneity for class I obesity in the analyses for white women and for class I and II obesity in the analyses for black women. There was no statistical evidence of publication bias.

Table 4 Combined Odds Ratios for Mammography by BMI for Race-Stratified Analyses*†
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Four studies conducted in primarily non-white populations did not find a statistically significant association between BMI and recent mammography34,39,42,43. One study based on a chart review of patients (86% non-white) of urban family practices reported an increased odds of recent mammography among overweight and class II obese patients compared to patients with a normal BMI40. A study of baseline data from the Southern Community Cohort Study found that compared to women with a normal BMI, white women with class III obesity were less likely to report recent mammography, but overweight and class I and II obese black women were more likely to report recent mammography36.

DISCUSSION

This systematic review demonstrates an inverse relationship between class I, II, and III obesity and recent mammography that was statistically significant for class III obesity. Compared to their lean counterparts, women with class III obesity were 20% less likely to report recent mammography. In white women, we found a statistically significant negative association between class II and III obesity and being up-to-date with mammography. We did not find this association between BMI and mammography among black women.

Two of the three studies that did not report an inverse association between recent mammography and increasing BMI were not nationally representative. One was a chart review from family practices in New Jersey with primarily non-white patients40, and the other was a Harlem survey among mostly non-Hispanic blacks42. The findings of these two studies are consistent with the results of our meta-analyses in which we observed no significant inverse relationship between obesity and mammography in non-whites. The third negative study41 included women <40 years of age. These results may be confounded by age since younger women are more likely to have a lower BMI54 and to report a lower prevalence of mammography since it is not routinely recommended for them.

Obese women may experience several possible barriers to mammography. Prior data show that obese women may delay medical care55 because of poor self-esteem and body image, embarrassment29,30,55,56, a perceived lack of respect from health-care providers, or to avoid unwanted weight loss advice28. Obesity may be a marker for sub-optimal health behavior in general, of which lack of mammography is simply one facet30,33. Also, beliefs regarding cancer screening may vary by BMI33. There could be physical limitations to obtaining mammography for obese women, but obesity is associated with a higher content of fat in the breast tissue that actually increases the sensitivity of mammography for detecting breast cancer57,58. Finally, obesity is associated with lower socioeconomic status59, which may decrease access to preventive care.

There are also many physician-related factors that may decrease screening mammography among obese women. Obesity-related co-morbid conditions may hinder referral for purely preventive services41,60,61. In addition, providers have reported difficulty and inadequate resources and education in providing care for obese women28. Finally, physicians may have biases against obese women, resulting in less screening62–64.

Obesity did not appear to affect the report of recent mammography in black women. This may be due to racial differences in obesity-related body image65–67. In particular, it has been reported that overweight or obese white, but not black, women were more likely to feel worthless, which may impact willingness to undergo mammography32. Black women may have a similar risk of developing breast cancer68,69, but higher breast cancer mortality21,68–71. They tend to present with a higher stage of breast cancer69,71, which has been linked to (1) less follow-up for abnormal exams72, (2) higher rates of obesity72–75, (3) socioeconomic factors76, (4) cultural beliefs (e.g., belief in herbal treatments)76, and possibly, lower likelihood of screening77–79, although this is controversial68,80–82. Our findings, the first meta-analyses by race, suggest that rates of mammography in black women do not vary significantly by BMI.

We included only 6 of 17 studies in our meta-analyses based on the provision of unique nationally representative data and BMI in five standard categories. However, 14 of the 17 studies reported a negative association between BMI and report of mammography. Also, we obtained similar results when we included all nine studies that reported BMI in five standard categories.

Most of the included studies were cross-sectional and cannot establish causality, but it is unlikely that failure to undergo mammography would contribute to weight gain. Also, we relied on the use of observational studies, which are susceptible to residual and unmeasured confounding. In particular, socioeconomic factors and health behaviors may confound the relationship between obesity and breast cancer and are difficult to account for fully. Although we did not find publication bias, we had limited power with a small number of studies. However, our search also included articles in which body weight was not the primary exposure, and thus, the potential for publication bias should be low.

The included studies used self-report of BMI as the measure of body weight, which has several limitations: It may underestimate obesity, especially in women83, but may also overestimate obesity, especially in blacks83. Self-report of height and weight may differ by survey type (telephone versus in-person), age, and BMI84. Overall, the included studies may have placed more obese participants into less obese categories, which would bias our results toward the null or result in finding an inverse association in overweight or milder obesity. However, the overall qualitative association between body weight and mammography would be unchanged.

Most of the included studies also relied upon self-report of mammography. A recent meta-analysis found that self-report of mammography had a sensitivity of 93% and specificity of 62%85. While this study reported similar sensitivities for self-reported mammography in blacks and whites, the specificity of self-reported mammography was only 49% among blacks85. Thus, mammography results are likely inflated above their actual rates with the degree of inflation higher for blacks. There is no evidence that the accuracy of self-report of mammography varies by BMI, but if it does, our results would also be biased.

The included studies did not stratify on menopausal status, but only one study included women under the age of 40 years41. It seems unlikely that menopausal status would affect willingness to be screened in women over age 40. While the relationship between obesity and premenopausal breast cancer risk and mortality is unclear10–12, obesity increases postmenopausal breast cancer risk10,11,13–15 and mortality16–19.

Finally, our search strategy may have been susceptible to selection bias given that we included a small number of full articles from the total citations reviewed, we manually searched only 11 key journals, and we had limited success obtaining full results from contacted authors. However, the qualitative results matched our meta-analytic results, we included no new articles from the manual search of 11 journals, and we were very sensitive in promoting a title or abstract to full article review (i.e., if an article discussed risk factors associated with mammography, we promoted that to full article review). Additionally, we re-reviewed a random sample of 2.5% of the full articles excluded at title review and 5% of the full articles excluded at abstract review and did not find any additional articles that satisfied our inclusion criteria.

Our study also has several strengths. This is the first systematic review with meta-analyses exploring the relationship between obesity and mammography and the only one to examine the effect of race on this association. We comprehensively searched multiple electronic databases in addition to manual searching. Also, we contacted authors for data leading to additional results from four studies. Finally, the meta-analyses were based on nationally representative surveys and thus are generalizable to the US population.

The main implication of our study is that a lack of routine screening mammography may explain some of the increased breast cancer mortality in obese postmenopausal women. Clinicians should be aware of this disparity in evaluating their own practices. Future research should determine why obese women are less likely to report recent mammography, including the investigation of a lack of health care access due to perceived bias or lack of insurance as a possible cause and explore whether there are consistent differences by race.