Scleroderma Patients at Higher Risk of Lung, Breast and Blood Cancers

Study: SSc patients in Spain have 1.5 times higher overall cancer risk

Teresa Carvalho, MS avatar

by Teresa Carvalho, MS |

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People with scleroderma (SSc) in Spain have a 1.5 times higher overall risk of cancer than the general population, according to a new study. Further, these patients were found to have a higher rate of lung, breast, and blood cancers.

The risk of cancer is higher in patients with late-onset disease, lung involvement, or specific autoantibodies — self-reactive antibodies characteristic of scleroderma.

Researchers suggested that these results may aid in developing preventive programs and in determining those individuals at increased risk for specific cancers.

“These data may help to identify SSc patients at high-risk of cancer for screening,” the team wrote.

The study, “Standardized incidence ratios and risk factors for cancer in patients with systemic sclerosis: Data from the Spanish Scleroderma Registry (RESCLE),” was published in the journal Autoimmunity Reviews.

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Known link between scleroderma and cancer

Previous studies have shown increasing cancer prevalence among scleroderma patients, especially for lung, blood, and breast cancers. Exposure to immunosuppressive therapies — used to reduce scleroderma symptoms — and genetic susceptibility have been indicated as possible reasons for the higher number of new cancer cases in SSc compared with the general population.

Although a number of cancer risk factors have been identified among patients with scleroderma, the evidence is still limited. SSc-specific antibodies such as anti-RNAP III and anti-Scl-70 antibodies have been cited as risk factors for lung cancer, but factors such as sex, geographic location, and ethnicity still need to be investigated.

The new study was based on data collected until 2006 and then prospectively until 2018 from a nationwide multicenter SSc registry in Spain, called Registro Español de eSCLErodermia, or RESCLE. In all, 40 Spanish hospitals participated in the registry during the study period. The study involved 1,930 patients with SSc, of whom 206 (10.7%) had cancer.

The mean age at cancer diagnosis was 62 years, and patients with cancer had a mean age at SSc diagnosis of 57.8 years.

Data collected in RESCLE included disease onset, demographic and clinical features, mortality, the presence of SSc-related autoantibodies, diagnostic methods, and treatments. Cancer location, composition and structure of each tumor, and date of diagnosis also were evaluated.

SSc-related cancer was defined as a tumor that occurred between three years before to three years after the onset of scleroderma.

The presence of some SSc-associated complications also was assessed, including pulmonary hypertension (PH), interstitial lung disease (ILD), and primary biliary cholangitis (PBC), a type of autoimmune liver disease.

Both PH and ILD affect the lungs: PH is a progressive disease characterized by high blood pressure in the blood vessels that supply the lungs, while ILD is a group of lung disorders usually marked by progressive scarring of lung tissue.

The study also assessed possible associations between the risk of cancer and certain medications, such as calcium channel blockers — used to lower blood pressure — and aspirin.

Results showed that the general risk of cancer was about 1.5 times higher in patients with SSc compared with the general Spanish population. This increased risk was specifically observed in lung, blood, and breast cancers, and in colorectal cancer in women.

Breast cancer was the most frequently found cancer type in patients with SSc, affecting 22.8%. This was followed by lung (14.1%), blood (9.7%), colorectal (8.7%), and uterine cancers (6.8%).

“Our findings agree with reports that the most prevalent cancers in patients with SSc are breast, lung, and [blood] malignancies,” the researchers wrote. The team noted that the increased frequency of breast cancer was “facilitated by screening established in the last decade,” which may have contributed to a higher frequency of this type relative to previous studies.

The study also found that cancer was among the top three mortality causes among scleroderma patients, at a rate of 10.7%, following PH (16.6%), and ILD (11.3%).

“Cancer was the third leading cause of death in our series, and cancer diagnosis was associated with greater all-cause mortality. These findings are consistent with those from other cohorts, highlighting the relevance of this association,” the researchers wrote.

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Factors increasing cancer risk

Results also showed that patients who were older at SSc onset had their risk of developing cancer increased by 1.2 times. According to the team, this “may be explained by the likelihood that immunosenescence [gradual deterioration of the immune system as a person gets older] favors carcinogenesis [cancer development] in the context of this disease.”

The presence of the liver disease PBC was linked to a 2.35 times higher general risk of cancer and a 5.71 times increased risk of breast cancer. Although the researchers were not able to explain the link between autoimmunity and general or breast cancer, “the presence of PBC in patients with SSc can be considered to be a risk factor for the development of cancer,” they wrote.

Also, the general risk of cancer was almost twofold higher in ILD patients in whom a forced vital capacity (FVC, a measure of lung function) was less than 70% of the expected value. According to the researchers, “cancer development in this setting may be related to increased inflammation, although more data are needed to confirm this association.”

In contrast, the presence of anticentromere antibodies (ACAs), which have been linked to less severe SSc and increased survival, was found to lower the risk of cancer.

The study also revealed that other SSc-related autoantibodies — anti-Ro and anti-Scl-70 — were risk factors for breast and lung cancers, respectively.

“The detection of certain autoantibodies or combinations thereof may aid the identification of patients at greater risk of cancer,” the scientists added.

The findings also showed a lower cancer risk among patients who used calcium channel blockers and pulmonary vasodilators (blood vessel widening medications). Aspirin showed a protective effect against multiple cancers.

“In summary, our work clearly shows that patients with SSc have an increased risk of cancer compared with the general population,” the investigators concluded, noting that individuals at high risk should be identified for screening.