Study of breast cancer incidence in patients of lymphangioleiomyomatosis

Núñez, Olivier; Román, Antonio; Johnson, Simon R.; Inoue, Yoshikazu; Hirose, Masaki; Casanova, Álvaro; Garibay, Gorka Ruíz de; Herranz, Carmen; Bueno-Moreno, Gema; Boni, Jacopo; Mateo, Francesca; Petit, Audrey; Climent, Fina; Soler, Teresa; Vidal, August; Sánchez-Mut, José Vicente; Esteller, Manel; López, José I.; García, Nadia; Gumà, Anna; Ortega, Raúl; Plà, M.J.; Campos, M. Calvo; Ansótegui, Emilio; Molina-Molina, María; Valenzuela, Claudia; Ussetti, Piedad; Laporta, Rosalía; Ancochea, Julio; Xaubet, Antoni; Pollán, Marina; Pujana, Miguel Ángel

doi:10.1007/s10549-016-3737-8

Cited by 11 publications

(9 citation statements)

References 23 publications

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“…Estrogens have been shown to boost the metastatic potential in a LAM cell model (21), and progesterone and estradiol synergistically interact in this process (22). The similarities between LAM and cancer might extend to shared disease susceptibility (23,24)…”

Section: Introductionmentioning

confidence: 99%

Heterogeneity and Cancer-Related Features in Lymphangioleiomyomatosis Cells and Tissue

Espín

Baiges

Blommaert

et al. 2021

Molecular Cancer Research

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Lymphangioleiomyomatosis (LAM) is a rare, low-grade metastasizing disease characterized by cystic lung destruction. LAM can exhibit extensive heterogeneity at the molecular, cellular, and tissue levels. However, the molecular similarities and differences among LAM cells and tissue, and their connection to cancer features are not fully understood. By integrating complementary gene and protein LAM signatures, and single-cell and bulk tissue transcriptome profiles, we show sources of disease heterogeneity, and how they correspond to cancer molecular portraits. Subsets of LAM diseased cells differ with respect to gene expression profiles related to hormones, metabolism, proliferation, and stemness. Phenotypic diseased cell differences are identified by evaluating LUM proteoglycan and YB1 transcription factor expression in LAM lung lesions. The RUNX1 and IRF1 transcription factors are predicted to regulate LAM cell signatures, and both regulators are expressed in LAM lung lesions, with differences between spindle-like and epithelioid LAM cells. The cancer single-cell transcriptome profiles most similar to those of LAM cells include a breast cancer mesenchymal cell model and lines derived from pleural mesotheliomas.Heterogeneity is also found in LAM lung tissue, where it is mainly determined by immune system factors. Variable expression of the multifunctional innate immunity protein LCN2 is linked to disease heterogeneity. This protein is found to be more abundant in blood plasma from LAM patients than from healthy women.Implications: This study identifies LAM molecular and cellular features, master regulators, cancer similarities, and potential causes of disease heterogeneity.

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Section: Introductionmentioning

confidence: 99%

Heterogeneity and Cancer-Related Features in Lymphangioleiomyomatosis Cells and Tissue

Espín

Baiges

Blommaert

et al. 2021

Molecular Cancer Research

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“…1,47,48 A hitherto the largest epidemiological study indicated that sporadic LAM patients were at a higher risk of developing invasive BC relative to those from the general population. 49 Recent study supported that high levels of serum CA-125 (an OC biomarker) were associated with disease progression of LAM. 50 Due to the low yield of the report of LAM disease linked with estrogen-dependent disease, such as BC or OC, misregulation of these genes are prospective research fields to elucidate novel pathogenesis of LAM in the future.…”

Section: Discussionmentioning

confidence: 91%

“…Moreover, isolated LAM cells from the lungs exhibit positive immunoreactivity for ER and PR . A hitherto the largest epidemiological study indicated that sporadic LAM patients were at a higher risk of developing invasive BC relative to those from the general population . Recent study supported that high levels of serum CA‐125 (an OC biomarker) were associated with disease progression of LAM .…”

Section: Discussionmentioning

confidence: 99%

Identification of driver genes and somatic mutations in cell‐free DNA of patients with pulmonary lymphangioleiomyomatosis

Zhang

Wang

et al. 2019

Intl Journal of Cancer

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Next‐generation sequencing of cell‐free circulating DNA (cfDNA) has emerged as promising technique for identifying minimally invasive genomic profiling of tumor cells recently. However, it remains relatively unknown in LAM disease. In our study, paired cfDNA and genomic DNA (gDNA) in blood samples were obtained from 23 LAM patients and seven healthy controls to explore mutations profiles of targeted 70 cancer‐related genes. As results, log2‐based allele frequencies of mutations in cfDNA were significantly different from those of gDNA. By comparing the mutual mutations identified both in cfDNA and gDNA, a significant correlation was also observed. After removing mutations in gDNA, distinct somatic mutation profiles of cfDNA were observed in LAM patients. Forty of 70 targeted genes had recurrent mutations, of which ATM, BRCA2 and APC showed the highest frequency. Based on the mutation, correlation network constructed of 40 mutated genes, 11 hub genes bearing intensive interactions were highlighted, including BRCA1, BRCA2, RAD50, RB1, NF1, APC, MLH3, ATM, PDGFRA, PALB2 and BLM. Expression of the hub genes showed significant clusters between LAM patients and controls and that RAD50 and BRCA2 had the strongest associations with subject phenotypes. Myogenesis and estrogen response were confirmed to be positively regulated in LAM patients. Collectively, our study provided a landscape of genomic alterations in LAM and discovered several potential driver genes, that is, BRCA2 and RAD50, which shed a substantial light on the clinical application of key molecular markers and potential therapy targets for precision diagnosis and treatment in the future.

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“…There have been few previously reported cases or studies on the incidence of breast cancer in patients with lymphangioleiomyomatosis (LAM). In 2016, Nunez et al analyzed the incidence of three patient cohorts with LAM from three different countries and identified an increased risk of breast cancer in these patient populations [6]. The patient in this case report had a previous diagnosis of angiomyolipoma 19 years previously, but the relevance of this is unclear.…”

Section: Discussionmentioning

confidence: 95%

A Case of Lymphangioleiomyomatosis (LAM) of the Lung in a Patient with a History of Breast Cancer

et al. 2019

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Patient: Female, 47 Final Diagnosis: Lymphangioleiomyomatosis Symptoms: Dyspnea Medication: — Clinical Procedure: — Specialty: Pulmonology Objective: Rare disease Background: Lymphangioleiomyomatosis (LAM) is a rare progressive cystic and nodular disease of the lung characterized by smooth muscle cell proliferation. LAM predominantly affects young premenopausal women. This report is of a case of LAM presenting in a 47-year-old woman with a past history of breast cancer and discusses the possibility of an association between the two conditions. Case Report: A 47-year-old woman presented as an emergency with an exacerbation of a four-month history of shortness of breath and dry cough. Her symptoms began following the start of anti-hormonal treatment with letrozole and goserelin acetate for a moderately differentiated (grade 2) invasive ductal carcinoma of the breast (pT2, pN0, M0) which was positive for expression of estrogen receptor (ER+), progesterone receptor (PR+), and human epidermal growth factor receptor 2 (HER2+). Until the previous four months, she had breast-conserving treatment with radiotherapy and tamoxifen therapy. Following hospital admission, she was found to be in type I respiratory failure. Chest X-ray, lung computed tomography (CT), and positron-emission tomography (PET) showed diffuse cystic and nodular lung lesions, consistent with a diagnosis of LAM, and antihormonal therapy was discontinued. She developed pericarditis that was treated with the anti-inflammatory agent, colchicine. Treatment with letrozole and sirolimus improved her respiratory symptoms. Conclusions: A rare case of LAM is presented in a woman with a recent history of breast cancer. Because both tumors were hormone-dependent, this may support common underlying gene associations and signaling pathways between the two types of tumor.

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Study of breast cancer incidence in patients of lymphangioleiomyomatosis

Cited by 11 publications

References 23 publications

Heterogeneity and Cancer-Related Features in Lymphangioleiomyomatosis Cells and Tissue

Heterogeneity and Cancer-Related Features in Lymphangioleiomyomatosis Cells and Tissue

Identification of driver genes and somatic mutations in cell‐free DNA of patients with pulmonary lymphangioleiomyomatosis

A Case of Lymphangioleiomyomatosis (LAM) of the Lung in a Patient with a History of Breast Cancer

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