Clinical and Pathological Features of Breast Cancer in Systemic Sclerosis: Results from the Sclero-Breast Study

Abstract

Systemic Sclerosis (SSc) is a chronic disease associated with a 1.5-fold increase in cancer risk, including lung cancer, hematological malignancies, and breast cancer (BC). This is a retrospective study aiming to explore the clinical and pathological features of BC developed by SSc patients. A total of 54.5% of patients developed BC before SSc (median interval: 5 years), whereas 45.5% of patients developed BC after SSc (median delay: 8 years). A total of 93.1% of patients were diagnosed with an early stage tumor. Among invasive carcinomas, 70.8% presented with a low Mib1, 8.3% with a tubular histotype, and 42.8% with a Luminal A-like phenotype. A total of 66.6% of patients underwent breast-conserving surgery and 55.5% RT. A total of 40% of patients developed interstitial lung disease after RT and 20% diffuse cutaneous SSc. The cause of death of the six deceased patients was PAH. A significant association was observed between the use of immunosuppressive therapy and diffuse skin extension, negative ACA, positive Anti-Scl-70, and interstitial lung disease, but not BC status. SSc patients developed BC at a good prognosis, suggesting a de-escalation strategy of cancer therapies. In particular, ionizing radiation and chemotherapeuticals should be limited to higher-risk cases. Finally, proper screening is mandatory in order to allow for early cancer detection in SSc patients.

Diseases of the musculoskeletal system and connective tissue and risk of breast cancer: Mendelian randomization study in European and East Asian populations

“…In another population-based cohort of 318 patients with scleroderma in Italy, 12 cases of BC were recorded, SIR of BC in SSc patients was 2.10 (95% CI: 1.13-3.90), compared with the general population ( 44 ). Among 33 cases of SSc with BC from an observational retrospective multicenter study in northern Italy, 75% of BC were ER+ and 25% of BC were ER- ( 45 ). In our MR analysis, there was no causal relationship between SSc and BC, neither ER+ BC nor ER- BC, which was the same as most of the previous studies.…”

Systemic Sclerosis Association with Malignancy

“…This study did not find differences in clinical and serological features between SSc patients with breast cancer and those without, except for a relatively shorter disease duration at the time of breast cancer diagnosis in the first group [ 39 ]. A more recent observational retrospective multicentre study enrolled 33 SSc women with breast cancer from January 2017 to December 2019, without confirming the temporal relationship between the two disorders [ 46 ]. In fact, 54.5% of these patients presented breast cancer before SSc onset (with a median of 5 years between the two diseases onset) and in 45.5% subjects SSc was diagnosed before the cancer with a median of 8 years.…”

“…In this population, 75% of invasive cancers were positive for hormone receptors, about 28% had HER2 positivity, and 19% were triple negative. Regarding SSc features, more than 50% of SSc patients had ILD and all 6 cases of death were SSc-related due to PAH [ 46 ]. At SSc onset, an association between breast cancer, age, and anti-RNA polymerase III (anti-RNA Pol III) antibodies was detected by a multivariable logistic regression (OR 1.07, p < 0.001 and OR 4.28, p = 0.018 respectively) [ 19 ].…”