Schizophrenia Tied to Elevated Breast Cancer Risk

Batya Swift Yasgur, MA, LSW

March 07, 2018

Rates of breast cancer are higher in women with schizophrenia than in women in the general population, new research shows.

Investigators in China and Maryland conducted a meta-analysis of studies that included more than 120,000 women and found that schizophrenia was associated with a significantly higher risk for breast cancer, although there was also significant heterogeneity found between the studies.

I think the association with breast cancer in female patients with schizophrenia is an important focus for clinicians, first author Chuanjun Zhuo, MD, PhD, Department of Psychiatric Laboratory, Tianjin Medical University, China, told Medscape Medical News.

I think clinicians should screen women with schizophrenia and monitor cancer markers frequently, he said.

The study was published online March 7 in JAMA Psychiatry.

Cancer Risk "Uncertain"

The risk of cancer in patients with schizophrenia remains uncertain, the authors write.

This population suffers from numerous chronic health conditions that typically are risk factors for the development of cancer (eg, smoking, alcohol and substance abuse, obesity, and lack of exercise), but results of epidemiologic studies have been inconsistent regarding the cancer risk, the investigators note.

Several analyses have shown that increased risk may be associated not only with factors related to an unhealthy lifestyle but also with genetic mechanisms and other potential factors that may be involved in the interaction between schizophrenia and cancer pathogenesis.

Because schizophrenia has been associated with a lower risk for certain types of cancer (eg, colorectal cancer, malignant melanoma, and prostate cancer), it is possible that genetic factors involved in schizophrenia pathogenesis may be protective against cancer, the authors write.

However, some studies have suggested an increased risk for breast cancer in schizophrenia patients, compared with the general population, and other studies have had mixed results or have used flawed statistical methods that did not adequately account for heterogeneity.

In the current study, the investigators set out to perform an updated meta-analysis to lead to better prevention and early treatment of breast cancer in women with schizophrenia.

In the meta-analysis, only cohort studies were included. In addition, studies had to be published as a full-length article in English, include adult women (age ≥18 years), have schizophrenia exposure identified at baseline, have a control group consisting of women from the general population without schizophrenia, have a documented incidence of breast cancer on follow-up, and report the standardized incidence ratios (SIRs), at least adjusted for age and corresponding 95% confidence intervals (CIs) for breast cancer incidence in women with schizophrenia, compared with control persons.

The researchers used several statistical approaches to the data. They extracted data of SIRs and established the lower and upper limits of 95% CIs to calculate log SIRs and their corresponding standard errors (SEs).

These logarithmically transformed SIRs and their corresponding SEs were used to stabilize the variance and normalize the distribution.

To evaluate the heterogeneity among the included cohort studies, the researchers used the Cochran Q test and the I 2 statistic, as well as a random-effects model, for meta-analyzing the SIR, because this model is considered to produce a more generalized result by considering heterogeneity between studies.

Shared Mechanisms?

The researchers identified 11 studies published between 1992 and 2016 that met the inclusion criteria. Participants (n = 125,760) were drawn from Europe, the United States, and Asia.

Of the 12 cohorts, five included hospitalized patients with schizophrenia; the remaining studies did not specify the source of the patients.

Study sizes ranged from 1388 to 446,447 patients with schizophrenia; the number of breast cancer cases ranged from 42 to 1042.

Six of the studies excluded breast cancer cases that were present prior to the diagnosis of schizophrenia. The remaining studies did not specify whether those cases were excluded.

Schizophrenia was found to be associated with a significantly increased risk for breast cancer in women (SIR, 1.31; 95% CI, 1.14 - 1.50; P < .001), with significant heterogeneity (P < 0.001; I 2 = 89%).

Because of the substantial between-study variance, which was reflected by the wide prediction interval (PI; 0.81 - 2.10), it is possible that a future study will show a decreased breast cancer risk in women with schizophrenia, compared with the general population, the authors comment.

The researchers investigated sensitivity of the findings by omitting one study at a time, but this did not significantly alter the results. The SIR varied between 1.29 and 1.38 (all Ps < .01).

The subgroup analyses found that the association between schizophrenia and increased breast cancer incidence was significant in studies in which breast cancer occurred before the diagnosis of schizophrenia was excluded (SIR, 1.34; 95% CI, 1.20 - 1.51; P < .001; I 2 = 84%) as well as studies with >100 breast cancer cases (SIR, 1.31; 95% CI, 1.18 - 1.46; P < 0.001; I 2 = 84%).

However, the association between schizophrenia and breast cancer incidence was not significant in studies that did not specify the exclusion of breast cancer cases that occurred prior to the diagnosis of schizophrenia (SIR, 1.38; 95% CI, 0.89 - 2.14; P = 0.15; I 2 = 91%) or in studies with <100 breast cancer cases (SIR, 1.50; 95% CI, 0.78 - 2.87; P = 0.23; I 2 = 93%)

The differences between subgroups were not statistically significant.

The researchers determined on the basis of the Egger regression test that there was no potential publication bias (P = .64).

The authors speculate that several potential mechanisms may be involved in the association between schizophrenia and increased breast cancer risk, including obesity and nulliparity, and possible shared pathophysiologic factors, including pathways involved in angiogenesis and cell-cycle regulation.

Increased prolactin levels, which have been observed in women with schizophrenia, may raise the risk for breast cancer, particularly in women receiving certain antipsychotics, they suggest.

Most psychiatrists focus only on treatment of positive and negative symptoms in patients with schizophrenia and tend to neglect the physical status, especially in female patients, said Dr Zhuo.

But psychiatrists should not ignore cancer markers and should remain aware of them, he added.

Be on the Lookout

Commenting on the study for Medscape Medical News, Gail Daumit, MD, MHS, professor of medicine, psychiatry, and behavioral sciences, epidemiology, health policy and management, and mental health, Johns Hopkins Medical Institutions, Baltimore, Maryland, who was not involved with the study, called it a nicely done meta-analysis.

One limitation was that the analysis incorporated studies that measured cancer incidence in different ways, such as the use of cancer registries and the use of billing data, she noted.

Nevertheless, the analysis shows a signal of increased risk of cancer in this population that should prompt clinicians to be on the lookout and make sure that women with schizophrenia get the recommended breast cancer screening appropriate for their age and risk factors, since this population is often ignored in their physical needs.

Additionally, the potential role of prolactin in increasing breast cancer risk warrants further research.

Antipsychotic medications are widely used not only for schizophrenia but also for other conditions, and more work regarding a possible prolactin connection needs to be done, she said.

Zhuo noted that his future research will focus on cancers for which the incidence is lower in patients with schizophrenia than in the general population.

There is a high rate of smoking in people with schizophrenia, compared to the general population, but no higher rate of lung cancer, suggesting a possible protective factor, which I am interested in exploring, he said.

This work was supported by grants from the Tianjin Health Bureau Foundation and the Key Projects of the Natural Science Foundation of Tianjin, China. The authors and Dr Daumit have disclosed no relevant financial relationships.

JAMA Psychiatry. Published online March 7, 2018. Full text

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