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

2021 ◽  
Vol 11 (6) ◽  
pp. 580
Author(s):  
Angela Toss ◽  
Amelia Spinella ◽  
Chrystel Isca ◽  
Caterina Vacchi ◽  
Guido Ficarra ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Early Stage ◽  
Fold Increase ◽  
Breast Conserving Surgery ◽  
Pathological Features ◽  
Luminal A ◽  
Clinical And Pathological Features

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.

scholarly journals Impact of Lung Function Decline on Time to Hospitalisation Events in Systemic Sclerosis-associated Interstitial Lung Disease (SSc-ILD): a Joint Model Analysis

2021 ◽  
Author(s):  
Michael Kreuter ◽  
Francesco Del Galdo ◽  
Corinna Miede ◽  
Dinesh Khanna ◽  
Wim A. Wuyts ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Function ◽  
Lung Disease ◽  
Fold Increase ◽  
Phase Iii ◽  
Lung Function Decline ◽  
Related Hospitalisation ◽  
The Relationship ◽  
Increase In Risk

Abstract Background: Interstitial lung disease (ILD) is a common organ manifestation in systemic sclerosis (SSc) and is the leading cause of death in patients with SSc. A decline in forced vital capacity (FVC) is an indicator of ILD progression and is associated with mortality in patients with SSc-associated ILD (SSc-ILD). However, the relationship between FVC decline and hospitalisation events in patients with SSc-ILD is largely unknown. The objective of this post-hoc analysis was to investigate the relationship between FVC decline and clinically important hospitalisation endpoints.Methods: We used data from SENSCIS®, a Phase III trial investigating the efficacy and safety of nintedanib in patients with SSc-ILD. Joint models for longitudinal and time-to-event data were used to assess the association between rate of decline in FVC% predicted and hospitalisation-related endpoints (including time to first all-cause hospitalisation or death; time to first SSc-related hospitalisation or death; and time to first admission to an emergency room [ER] or admission to hospital followed by admission to intensive care unit [ICU] or death) during the treatment period, over 52 weeks in patients with SSc-ILD.Results: There was a statistically significant association between FVC decline and the risk of all-cause (n=78) and SSc-related (n=42) hospitalisations or death (both P<0.0001). A decrease of 3% in FVC corresponded to a 1.43-fold increase in risk of all-cause hospitalisation or death (95% confidence interval [CI] 1.24, 1.65) and a 1.48-fold increase in risk of SSc-related hospitalisation or death (95% CI 1.23, 1.77). No statistically significant association was observed between FVC decline and admission to ER or to hospital followed by admission to ICU or death (n=75; P=0.15). The estimated slope difference for nintedanib versus placebo in the longitudinal sub-model was consistent with the primary analysis in SENSCIS®.Conclusions: The association of lung function decline with an increased risk of hospitalisation suggests that slowing FVC decline in patients with SSc-ILD may prevent hospitalisations. Our findings also provide evidence that FVC decline may serve as a surrogate endpoint for clinically relevant hospitalisation-associated endpoints.Trial registration: Clinialtrials.gov, NCT02597933. Registered 8 October 2015, https://clinicaltrials.gov/ct2/show/study/NCT02597933.

Elevated Serum Krebs von den Lungen-6 in Early Disease Predicts Subsequent Deterioration of Pulmonary Function in Patients with Systemic Sclerosis and Interstitial Lung Disease

2016 ◽  
Vol 43 (10) ◽  
pp. 1825-1831 ◽  
Author(s):  
Masataka Kuwana ◽  
Yuichiro Shirai ◽  
Tsutomu Takeuchi
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Early Stage ◽  
Characteristic Curve ◽  
Elevated Serum ◽  
Initial Assessment ◽  
Baseline Serum ◽  
Disease Modifying Drugs ◽  
Highly Correlated

Objective.To identify predictors of poor prognosis in patients with systemic sclerosis (SSc) associated with interstitial lung disease (ILD).Methods.Fifty patients with early-stage SSc-ILD who had never received disease-modifying drugs and were either observed for ≥ 10 years or died from ILD-related causes were enrolled. The baseline variables of patients who developed endstage lung disease (ESLD) were compared with those of patients who remained ESLD-free, and the Cox proportional hazard model was used to identify initial factors that correlated with ESLD development.Results.Sixteen patients (32%) developed ESLD during 173.5 ± 64.7 months of followup. Elevated serum Krebs von den Lungen-6 (KL-6) at initial assessment was highly correlated with ESLD development (p = 0.0002). Receiver-operating characteristic curve analysis revealed that a KL-6 value of 1273 U/ml effectively discriminated patients who developed ESLD from those who did not. Patients with KL-6 > 1273 U/ml were less likely to remain ESLD-free compared with those with lower KL-6 levels (p < 0.0001). Multivariate analysis showed that KL-6 > 1273 U/ml was the most reliable predictor of ESLD development (OR 51.2, 95% CI 7.6–343, p < 0.0001). Finally, the initial KL-6 level correlated with the forced vital capacity (FVC) decline rate (r = 0.58, p < 0.0001).Conclusion.The natural course of SSc-ILD is highly variable. Baseline serum KL-6 is a biomarker potentially useful for predicting FVC decline.

scholarly journals AB0425 CLINICAL AND PATHOLOGICAL FEATURES OF BREAST CANCER IN PATIENTS WITH SYSTEMIC SCLEROSIS: PRELIMINARY DATA FROM THE SCLERO-BREAST STUDY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 1241.1-1241
Author(s):  
A. Spinella ◽  
A. Toss ◽  
C. Isca ◽  
C. Vacchi ◽  
A. Iannone ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Cause Of Death ◽  
Preliminary Data ◽  
Pulmonary Function Tests ◽  
Endocrine Treatment ◽  
Pathological Characteristics ◽  
Kidney Involvement

Background:Systemic Sclerosis (SSc) is a rare and life-threatening connective tissue disease characterized by vascular dysfunction, specific autoimmune abnormalities and fibrosis of the skin and internal organs. Previous studies have shown a 1.5-fold increase in cancer risk in SSc patients compared with the general population, including breast cancer (BC). The relationship between BC and SSc has long been discussed but past research has been contradictory and inconclusive on this topic.Objectives:The aim of our project was to analyze clinical and pathological characteristics of BC developed by SSc subjects and possible correlations with scleroderma features. Here we present the preliminary data from the Sclero-Breast study.Methods:Our observational retrospective multicenter study enrolled 33 SSc women with a personal history of BC identified at two Rheumatology/SSc Units in the north of Italy between January 2017 and December 2019 (lc/dcSSc 23/9, 1 unknown; mean age at SSc onset 57 years, range 32-73). All patients underwent general and instrumental assessment: smoking habits; presence of skin ulcers, calcinosis, teleangectasia; presence of gastro-intestinal and kidney involvement; interstitial lung disease (at HR-CT); pulmonary function tests; ECG abnormalities; echocardiographic assessment of pulmonary arterial hypertension (PAH); videocapillaroscopic pattern; autoantibody profile; exposure to immunosuppressive and vasoactive therapies; status at last follow-up evaluation and cause of death. Clinical and pathological characteristics of BC were also evaluated: age at diagnosis; menopausal status; histotype; hormone receptor status; MIB1, HER2 expression; clinical and pathological stage at diagnosis; metastatic sites; type of loco-regional treatment (surgery and radiotherapy); type of systemic treatment (neoadjuvant/adjuvant chemotherapy and endocrine treatment); other cancers and time from diagnosis of the first disorder to the second one.Results:A total of 54.5% of subjects developed BC before SSc (median interval of 5 years), whereas 45.5% of patients developed BC after SSc (median delay of 8 years). 54.5% of patients showed interstitial lung disease and the cause of death of the 6 deceased subjects was PAH. A significant association (p<0.05) was observed between the use of immunosuppressive therapy and diffuse skin extension, negative ACA, positive Anti-Scl-70 and interstitial lung disease, but not with BC status. 93.1% of patients were diagnosed with an early-stage tumor, 70.8% of invasive carcinomas with a low MIB-1, 8.3% with a tubular histotype, while 42.8% presented with a Luminal A-like tumor. 66.6% underwent breast conserving surgery and 55.5% RT after surgery. 40% of patients developed interstitial lung disease after RT and 20% dcSSc.Conclusion:According to our preliminary data, SSc patients developed BC at good prognosis, suggesting a de-escalation strategy of cancer therapies. On these grounds, a proper screening is mandatory in order to allow for early cancer detection in SSc patients. Further investigations on larger numbers of patients are needed. First of all, they would further clarify the intriguing relationship between BC and SSc. Secondly, they would help to explore the common biological and molecular pathways at the basis of these two disorders, with the aim to improve BC diagnosis and prognosis and to personalize oncological targeted treatments in this subset of fragile patients.Disclosure of Interests:None declared

Rapidly Progressive Systemic Sclerosis–associated Interstitial Lung Disease After Intravesical Bacillus Calmette-Guérin Therapy for Early-stage Bladder Cancer

2021 ◽  
pp. jrheum.201625
Author(s):  
Gonçalo Boleto ◽  
Jérôme Avouac ◽  
Yannick Allanore
Keyword(s):  
Bladder Cancer ◽  
Systemic Sclerosis ◽  
Respiratory Failure ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Early Stage ◽  
Wide Spectrum ◽  
Progressive Systemic Sclerosis ◽  
Bacillus Calmette Guerin ◽  
Common Cause

Despite recent advances in the management of systemic sclerosis–associated interstitial lung disease (SSc-ILD), it remains the most common cause of death and a significant contributor to morbidity.1,2 SSc-ILD is characterized by a wide spectrum of disease courses, with some patients having limited nonprogressive fibrosis, whereas others develop rapid and extensive fibrosis leading to respiratory failure.3

scholarly journals Impact of lung function decline on time to hospitalisation events in systemic sclerosis-associated interstitial lung disease (SSc-ILD): a joint model analysis

2022 ◽  
Vol 24 (1) ◽  
Author(s):  
Michael Kreuter ◽  
Francesco Del Galdo ◽  
Corinna Miede ◽  
Dinesh Khanna ◽  
Wim A. Wuyts ◽  
...  
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Function ◽  
Lung Disease ◽  
Fold Increase ◽  
Lung Function Decline ◽  
Link Type ◽  
Related Hospitalisation ◽  
The Relationship ◽  
Increase In Risk

Abstract Background Interstitial lung disease (ILD) is a common organ manifestation in systemic sclerosis (SSc) and is the leading cause of death in patients with SSc. A decline in forced vital capacity (FVC) is an indicator of ILD progression and is associated with mortality in patients with SSc-associated ILD (SSc-ILD). However, the relationship between FVC decline and hospitalisation events in patients with SSc-ILD is largely unknown. The objective of this post hoc analysis was to investigate the relationship between FVC decline and clinically important hospitalisation endpoints. Methods We used data from SENSCIS®, a phase III trial investigating the efficacy and safety of nintedanib in patients with SSc-ILD. Joint models for longitudinal and time-to-event data were used to assess the association between rate of decline in FVC% predicted and hospitalisation-related endpoints (including time to first all-cause hospitalisation or death; time to first SSc-related hospitalisation or death; and time to first admission to an emergency room [ER] or admission to hospital followed by admission to intensive care unit [ICU] or death) during the treatment period, over 52 weeks in patients with SSc-ILD. Results There was a statistically significant association between FVC decline and the risk of all-cause (n = 78) and SSc-related (n = 42) hospitalisations or death (both P < 0.0001). A decrease of 3% in FVC corresponded to a 1.43-fold increase in risk of all-cause hospitalisation or death (95% confidence interval [CI] 1.24, 1.65) and a 1.48-fold increase in risk of SSc-related hospitalisation or death (95% CI 1.23, 1.77). No statistically significant association was observed between FVC decline and admission to ER or to hospital followed by admission to ICU or death (n = 75; P = 0.15). The estimated slope difference for nintedanib versus placebo in the longitudinal sub-model was consistent with the primary analysis in SENSCIS®. Conclusions The association of lung function decline with an increased risk of hospitalisation suggests that slowing FVC decline in patients with SSc-ILD may prevent hospitalisations. Our findings also provide evidence that FVC decline may serve as a surrogate endpoint for clinically relevant hospitalisation-associated endpoints. Trial registration ClinicalTrials.govNCT02597933. Registered on 8 October 2015.

scholarly journals Circulating biomarkers of systemic sclerosis – interstitial lung disease

2020 ◽  
Vol 5 (2_suppl) ◽  
pp. 41-47 ◽  
Author(s):  
Anna-Maria Hoffmann-Vold ◽  
Håvard Fretheim ◽  
Chantal Meier ◽  
Britta Maurer
Keyword(s):  
Systemic Sclerosis ◽  
Interstitial Lung Disease ◽  
Lung Disease ◽  
Clinical Application ◽  
Topoisomerase I ◽  
Early Stage ◽  
Organ Damage ◽  
Disease Diagnosis ◽  
Surfactant Protein D ◽  
Circulating Biomarkers

Interstitial lung disease is a frequent organ manifestation in systemic sclerosis and is associated with high mortality. It is crucial to diagnose interstitial lung disease in systemic sclerosis and to assess severity and identify patients prone to progression at an early stage to ultimately decrease organ damage and improve outcome. Circulating anti-topoisomerase-I autoantibodies have long been associated with the presence and development of systemic sclerosis – interstitial lung disease, evidence on their potential to further predict the clinical course of systemic sclerosis is however conflicting. C-reactive protein is a marker of infection and systemic inflammation with widespread clinical application and is elevated in systemic sclerosis with a tendency towards higher abundancy in patients with early disease. The role of other circulating biomarkers is promising but hampered by the lack of standardized criteria and guidelines for sample/data collection, analyses, reporting and validation and has not reached prime time for clinical application. However, epithelial markers including Krebs von den Lungen-6 and surfactant protein D and several cytokines and chemokines including CCL2 and CCL18 for severity assessment of systemic sclerosis – interstitial lung disease patients at the time of interstitial lung disease diagnosis and to predict interstitial lung disease progression have been reported and seem to be promising candidate biomarkers in the future.

scholarly journals Tumour response 3 months after neoadjuvant single-fraction radiotherapy for low-risk breast cancer

2020 ◽  
Vol 27 (3) ◽  
Author(s):  
D. Tiberi ◽  
P. Vavassis ◽  
D. Nguyen ◽  
M. C. Guilbert ◽  
A. Simon-Cloutier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Tumour Response ◽  
Breast Conserving Surgery ◽  
Early Stage Breast Cancer ◽  
Primary Breast Tumor ◽  
Luminal A ◽  
Single Fraction ◽  
Novel Approach ◽  
Microscopic Evaluation

Introduction Standard treatment for early-stage invasive breast cancer consists of breast-conserving surgery (BCS) and several weeks of adjuvant radiotherapy (RT). Neoadjuvant single-fraction RT is a novel approach for early-stage breast cancer. We sought to investigate the effect of delaying surgery after neoadjuvant RT with respect to the rates pathological response (PR).   Materials and Methods Women aged 65 years or older with a new diagnosis of stage I, luminal A, breast cancer were eligible for inclusion. A single dose of 20 Gy to the primary breast tumor was given followed by BCS 3 months later. The primary endpoint was the rate of PR as assessed by microscopic evaluation using the Miller-Payne system.   Results 10 patients were successfully treated to date. The median age of the patients was 72 years (65-84). 8 patients had a pathological tumor response (PR) to neoadjuvant RT with a median residual cellularity of 3%. No immediate RT complications were noted other than mild dermatitis. Conclusions This study demonstrates a method for delivering single fraction RT that can lead to high levels of PR in most patients. Continued accrual of this study and subsequent trials are needed to determine the feasibility, safety and role of this novel technique in the management of early-stage breast cancer.  

scholarly journals Interstitial lung disease associated with adjuvant and neoadjuvant chemotherapy in early breast cancer

2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Kenji Tezuka ◽  
Kotaro Miura ◽  
Yusuke Nakano ◽  
Takahiro Ueda ◽  
Kyoko Yagyu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Interstitial Lung Disease ◽  
Neoadjuvant Chemotherapy ◽  
Lung Disease ◽  
Early Stage ◽  
Pulse Therapy ◽  
Clinicopathological Characteristics ◽  
Breast Cancer Patients ◽  
Steroid Pulse ◽  
Dose Dense

Abstract Background Interstitial lung disease (ILD) is a rare adverse event in patients receiving adjuvant or neoadjuvant chemotherapy (NAC) for breast cancer. Few studies have reported the frequency of ILD in detail, and only small numbers of cases have been described in the literature. Given these previous findings concerning ILD, we retrospectively examined the clinicopathological characteristics of five cases of ILD who had received epirubicin and cyclophosphamide (EC) and compared their findings with non-ILD cases. Methods The present single-center retrospective study included breast cancer patients who underwent adjuvant chemotherapy or NAC at our hospital between January 2014 and January 2021. Results Thirty-nine patients who had received EC for operable breast cancer were enrolled in this study. ILD developed 5 out of 39 patients (12.8%). The incidence of ILD in patients with non-dose-dense (dd) or dd chemotherapy was statistically significantly different (p = 0.0149). ILD occurred in three patients during dd EC treatment and two during weekly paclitaxel (wPTX) after dd EC. ILD was detected in one patient with high Krebs von den Lungen-6 (KL-6) levels, in two patients with continuous pyrexia, and in two patients from computed tomography imaging, which was taken to estimate the efficacy of chemotherapy, in two patients. Three of the 5 ILD patients underwent bronchoalveolar lavage, and 2 of these patients were diagnosed with Pneumocystis jirovecii pneumonia (PCP). There were no cases of serious ILD that required steroid pulse therapy. Conclusions Dd chemotherapy may be associated with an increased ILD frequency, which may reflect developing PCP. Careful monitoring and a timely diagnosis are useful for detecting early-stage ILD.

Sign in / Sign up

Export Citation Format

Share Document