Breast Cancer Screening in Women With Schizophrenia: A Systematic Review and Meta-Analysis

On average, individuals with serious mental illness, such as schizophrenia and bipolar disorder, die 15 to 20 years earlier than the general population, and the mortality gap is widening (1–3). The leading causes of death for this population are cardiovascular disease and cancer, suggesting that access to timely and appropriate preventive services could help reduce premature deaths. Therefore, gaining a better understanding of issues concerning early cancer detection is an important step in identifying potential causes of early mortality in individuals with serious mental illness.

Breast cancer detection is of particular importance, given that the 5-year survival rate for people with breast cancer is nearly 90%—thanks to substantial efforts to increase awareness and screening among American women (4). Although there is debate in the field regarding recommendations for mammography screening (5–8), the current U.S. Preventive Services Task Force (USPSTF) guidelines recommend biennial mammography screening for women ages 50 to 74 (9).

Unfortunately, evidence suggests that women with serious mental illness may not receive breast cancer preventive services in a timely and appropriate way (10). Recent work has found that breast cancer is identified at later stages among women with serious mental illness compared with women without these disorders (11). As a result, breast cancer among women with serious mental illness is characterized by larger and higher-grade tumors and more lymph node involvement.

In 2014, Mitchell and colleagues (12) conducted a meta-analysis examining breast cancer screening among women with mental distress or any mental illness and women without mental illness, finding that mammography screening rates were lower among women with mental illness. Upon further stratification of the sample with mental illness by diagnosis, they found that women defined as having serious mental illness were almost 50% less likely than women without mental illness to receive mammography. However, this study grouped multiple diagnoses under the category of serious mental illness, which may have masked some of the diversity and variation of presentation. For example, although the National Institute of Mental Health defines serious mental illness as a psychiatric disorder leading to severe functional impairment, the nature of symptoms and impairment in different psychiatric disorders—such as schizophrenia, bipolar disorder, and major depressive disorder—can vary widely. Notably, the type of mental illness appeared to affect breast cancer screening rates in some studies (13, 14).

Because of this limitation, we chose to focus on breast cancer screening among women with diagnoses of schizophrenia and other psychotic disorders (e.g., schizoaffective disorder), given robust evidence that this group is more likely to have severe functional impairment and may face additional challenges in accessing care because of cognitive impairment related to psychiatric symptoms (13). In addition, some studies have found that women with schizophrenia face greater stigma (15), are less likely to attend primary care visits (16, 17), and may have more difficulty communicating with unfamiliar providers (18) compared with women without schizophrenia. These contributing factors could make it particularly burdensome for these individuals to obtain access to the health care system and health education and arrange mammography screening.

This article aims to summarize the literature to date on mammography screening rates and focus on disparities in care for women with schizophrenia and other psychotic disorders. To our knowledge, this is the first systematic review to distinguish mammography screening rates for this specific population, quantifying the degree of disparity by a meta-analysis.

Methods

Protocol and Registration

This systematic review was conducted with reference to the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement, using a protocol registered at the PROSPERO International Prospective Register of Systematic Reviews database (https://www.crd.york.ac.uk/prospero) (19).

Eligibility Criteria and Study Selection

Studies had to meet the following inclusion criteria: report on the primary outcome measure of mammography screening, compare mammography screening rates to a control population of women meeting recommended breast cancer screening guideline criteria, and provide sufficient data to calculate relative-risk or odds ratios (ORs). As previously described, studies were eligible if they included women with a diagnosis of schizophrenia or a related psychotic disorder, such as schizoaffective disorder, as defined by DSM-5 (295.xx), ICD-10 (F20.x, F25.x), or other valid measure (20). We did not aim to analyze studies that reported mammography screening rates for women with mental distress, delirium, dementia, developmental disorders, eating disorders, nonpsychotic mood disorders, or substance use disorders. Of note, because breast cancer screening guidelines have changed over time, authors of included articles were expected to use screening guidelines that were applicable during the specific time frame of each study (9). Studies in any language were included. Rates of diagnosis of breast cancer and treatment are not reviewed in this article.

Search and Information Sources

With a research librarian who specializes in systematic reviews, one author (A.H.) conducted a search of the PubMed, Embase, Web of Science, and PsycINFO electronic databases using relevant keywords in the title, abstract, and subject descriptors. Databases were searched from their start date to September 14, 2018. An iterative process was used to determine the search terms, which were breast cancer, breast neoplasm, mammogram, and mammography combined with screening or routine and schizophrenia, schizophrenic, psychotic, psychosis, and severe mental illness. Titles and abstracts were then independently reviewed by two authors (A.H. and K.W.) to determine whether they met inclusion criteria. The same authors also manually reviewed reference lists and bibliographies of the included articles for additional relevant studies. Any disagreements were arbitrated by a third author (C.M.).

Data Extraction

Data were extracted independently by two authors (A.H. and K.W.) by using a predetermined spreadsheet. Categories extracted were country/location; setting; type of study; population; time period; sample size; data collection method; covariates; main outcome measures; and results, including adjustment for factors and statistical analysis. For any missing data or clarification, we attempted to contact authors directly up to three times.

Data Analysis

Quality was assessed by using the Newcastle Ottawa Scale, independently rated by two authors (A.H. and K.W.) (21). Quality ratings could range from 0 to 8, with points given for representativeness of the study population and comparison group, ascertainment of data, reported outcome, comparability, assessment of outcome, sufficient length of study, and adequacy of follow-up period. Studies receiving 7 or 8 points were considered high quality; 5or 6 points, medium quality; and 4 or fewer points, low quality.

The primary outcome of interest was rate of mammography screening for women with schizophrenia and psychotic disorders compared with rates in the general eligible population. We compared mammography screening rates for women with the specified diagnoses to the general population using ORs, including adjusted-risk estimates if these were available. If no risk estimates were reported, we calculated ORs from the raw number of women with schizophrenia and the general population. All analyses were conducted on the log scale by using a random-effects model. The meta-analyses results were graphically displayed in a forest plot. Statistical heterogeneity was assessed with the I² and Cochrane’s Q statistic. Publication bias assessment was done by using a funnel plot with Begg’s and Egger’s tests (22). We also performed subgroup analyses of the low- and medium-quality studies and reported these findings in addition to the primary study findings. All analyses were performed by using Stata, version 15.1.

Results

Identification and Description of Studies

Of 408 abstracts reviewed, 104 were duplicates and another 229 were excluded on the basis of title and abstract. In total, 75 articles were retrieved and assessed for eligibility, and 11 met the inclusion criteria. (14, 18, 23–31). (A literature search flow diagram is available in an online supplement.) Common reasons for exclusion were that the study was not comparative or that participants with diagnoses of schizophrenia or psychosis could not be extracted separately from others with severe mental illness.

Seven of the 11 studies were considered to be of high quality; three, medium quality; and one, low quality. The studies were conducted in a range of settings (inpatient and outpatient settings, community clinic, and multisite research centers) and with privately and publicly insured populations and included data from 446,475 participants in control groups and 25,447 women with diagnoses of schizophrenia or other psychotic disorders. Seven studies were conducted in the United States, two in the United Kingdom, one in Denmark, and one in Canada. Data were collected by using nationwide registries, administrative claims databases from insurers, and individual surveys. Three studies used survey responses linked with databases. (The final 11 studies included in this review are summarized in a table in the online supplement.)

Meta-analysis

The meta-analysis of the random-effects model found that women with schizophrenia and other psychotic disorders were about half as likely to receive mammography screening as the general population (pooled OR=0.50, 95% confidence interval [CI]=0.38–0.64, p<0.001) (Figure 1). The I² (96.4%) statistic indicated a high level of heterogeneity. On the basis of visual inspection, we found that the funnel plot was symmetrical, and neither the Begg (p=0.24) nor the Egger bias test (p=0.88) demonstrated evidence of publication bias.

Not all studies used locally comparable control populations. Salsberry et al. (29) and Thomas et al. (30) used national rates from the National Health Interview Survey from the time of study, whereas Domino’s (25) comparison population was individuals with other chronic medical conditions. In subgroup analyses that examined low- and medium-quality studies, overall findings did not change significantly (low- to medium-quality studies: OR=0.48, 95% CI=0.36–0.65, p<0.001; remaining high-quality studies: OR=0.51, 95% CI=0.31–0.85, p=0.009).

Discussion

Women with schizophrenia and other psychotic disorders were about half as likely to be screened for breast cancer as the general population. To our knowledge, this is the first meta-analysis to focus specifically on mammography screening rates for women with psychotic disorders. This study extends findings from previous reviews to highlight a disparity across four countries, in privately and publicly insured populations, at academic research centers and community clinics, and in inpatient and outpatient populations. Our review included nearly twice as many publications as a previous review on mammography screening for women with mental illness (12), enabling us to evaluate breast cancer screening provision for over 25,000 women with diagnoses of schizophrenia and other psychotic disorders.

There were a number of limitations of our study. First, all studies came from Western countries, primarily the United States, so findings may not be generalizable to other countries. However, four countries were included, reflecting screening rates in a Nordic country, in the Canadian and U.K. national health systems, and in private and public systems in the United States. Second, criteria for mammography screening varied across countries as well as across time, with the USPSTF recommending in 2009 that only women between the ages of 50 and 75 receive routine screening, a change from the earlier recommendation of routine screening for all women. However, the change in guidelines would not be expected to affect disparities in screening in our analyses, given that the comparisons were between women who were all receiving care under the guidelines in effect during that period. Third, there was considerable heterogeneity between studies. One reason for this may be that we could not determine severity of illness based on diagnosis. That is important, given that severity of mental illness, not a specific diagnosis, may be the more important factor in accessing preventive care services (14). Fourth, it is possible that low mammography screening rates among individuals with schizophrenia are driven by other factors, such as socioeconomic status, race-ethnicity, or access to primary care, although we used adjusted odds ratios when possible, and multiple studies attempted to control for demographic factors and comorbid illnesses. Despite these limitations, we found a strong summary result indicating that women with schizophrenia and other psychotic disorders receive mammography screening at lower rates than the general population. The result is consistent with prior studies showing lower rates of preventive health services for individuals with serious mental illness (32–34).

Lasser et al. (27) conducted the only study that found higher rates of mammography screening among women with psychosis compared with a control population, but theirs was also the smallest of the included studies, with only 12 women with a diagnosis of psychosis. It is possible that there was selection bias in the participants in this study, such that they were more engaged in health care services than other patients with similar diagnoses.

Lower screening rates could explain why women with schizophrenia and other serious mental illnesses are found to have more advanced breast cancer at time of diagnosis (11). In addition, poor screening is concerning in light of evidence from a recent literature review that women with schizophrenia have higher incidence of breast cancer and higher mortality rates due to breast cancer compared with the general population (35, 36). It is important to note that these studies of cancer incidence and mortality have considerable heterogeneity, however, and it can be difficult to account for confounding socioeconomic factors.

Some barriers to adequate screening may apply to populations with and without mental illness. Having a regular primary care provider appears to promote preventive care such as cancer screening in the general population, and utilization of primary care services increases mammography screening rates among women with serious mental illness (37, 38). Other studies of mammography utilization in the general population found lower probability of mammography screening receipt in areas affected by poverty and racial-ethnic segregation (39). Other barriers to cancer screening in the general population include lack of test awareness, fear of the procedure, poor communication about prevention and prognosis, and limited financial resources (40, 41).

However, individuals with serious mental illness may also face additional challenges in accessing appropriate cancer screening. In a survey of participants with psychiatric disorders at a community-based wellness center, the main barrier to mammography screening was not a lack of access to a primary care provider or to the screening procedure itself. Instead, the main barrier was that physicians did not suggest cancer screening to patients and failed to communicate the importance of screening (42). With time constraints, primary care providers and psychiatrists may not prioritize cancer screening for patients with serious mental illness. Rather, they may focus on monitoring of metabolic disorders, which are increasingly recognized as a side effect of psychotropic medications and a driver of early morbidity in this population (43). The increased focus on addressing psychiatric symptoms may lead to deferring routine preventive screening discussion for future visits, but the future discussion never occurs. Some providers might defer screening because they believe that individuals with serious mental illness will have difficulties following through with treatment such as radiation and chemotherapy (17).

Given that patients with serious mental illness may need more in-depth communication and guidance to follow up with cancer screening procedures, such as mammography and colonoscopy, creative models are needed for emphasizing the importance of preventive care for individuals with serious mental illness. As an inverse of the collaborative care model, a care manager, social worker, or nurse may be able to play a critical role in connecting these patients with necessary cancer screening services in specialty mental health settings (44, 45). As a recent Cochrane review indicates, an evidence-based intervention for increasing cancer screening rates for people with severe mental illness has yet to be identified (46). Clinical trials are underway to test new strategies integrating mental health and cancer treatment for the population with serious mental illness, but initial screening remains a barrier to timely and appropriate intervention (47).

Prior studies have found disparities in breast cancer screening rates on the basis of race-ethnicity and income, with results indicating that low-income women and women from racial-ethnic minority groups are less likely to receive screening consistent with guidelines. Our finding that women with schizophrenia and psychosis were about half as likely to be screened as the general population supports the argument that persons with severe mental illness should be designated as a health disparity population, with special funding to target disparities in care (48, 49). Future studies are needed to determine whether women who have schizophrenia experience further differences in mammography screening rates on the basis of race or ethnicity.

Conclusions

Given the high prevalence of breast cancer and the promising prognosis of breast cancer if detected early, mammography screening is a key first step in improving diagnosis and treatment for people living with schizophrenia. This review quantifies the inequity in breast cancer screening and highlights the need for novel strategies to promote mammography screening for women with schizophrenia.