Breast cancer metastasis to gynaecological organs: a clinico‐pathological and molecular profiling study

Autor: Lynne Reid, Peter T. Simpson, Sunil R. Lakhani, Jamie R. Kutasovic, Stephen Peyton, Andrew Fellowes, Andrew J. Dalley, Gregory Miller, Renique Males, Christopher R McEvoy, Samir Lal, Fares Al-Ejeh, Colleen Niland, Sarah Sim, Liana Dedina, Amy E. McCart Reed, Kaltin Ferguson, Jodi M. Saunus, Margaret C. Cummings
Rok vydání: 2018
Předmět:
Adult
0301 basic medicine
Oncology
medicine.medical_specialty
Axillary lymph nodes
Population
Breast Neoplasms
Pathology and Forensic Medicine
Metastasis
03 medical and health sciences
breast cancer
0302 clinical medicine
Breast cancer
immunophenotyping
luminal subtype
Internal medicine
Progesterone receptor
genomics
Biomarkers
Tumor
medicine
metastasis
Humans
education
Aged
education.field_of_study
business.industry
Carcinoma
Ductal
Breast
GATA3
Original Articles
Middle Aged
medicine.disease
3. Good health
Gene Expression Regulation
Neoplastic
Androgen receptor
Carcinoma
Lobular
030104 developmental biology
medicine.anatomical_structure
Receptors
Estrogen
Lymphatic Metastasis
030220 oncology & carcinogenesis
Invasive lobular carcinoma
Original Article
ovary
Female
Neoplasm Recurrence
Local
Receptors
Progesterone
business
Zdroj: The Journal of Pathology: Clinical Research
ISSN: 2056-4538
DOI: 10.1002/cjp2.118
Popis: Breast cancer metastasis to gynaecological organs is an understudied pattern of tumour spread. We explored clinico‐pathological and molecular features of these metastases to better understand whether this pattern of dissemination is organotropic or a consequence of wider metastatic dissemination. Primary and metastatic tumours from 54 breast cancer patients with gynaecological metastases were analysed using immunohistochemistry, DNA copy‐number profiling, and targeted sequencing of 386 cancer‐related genes. The median age of primary tumour diagnosis amongst patients with gynaecological metastases was significantly younger compared to a general breast cancer population (46.5 versus 60 years; p < 0.0001). Median age at metastatic diagnosis was 54.4, time to progression was 4.8 years (range 0–20 years), and survival following a diagnosis of metastasis was 1.95 years (range 0–18 years). Patients had an average of five involved sites (most frequently ovary, fallopian tube, omentum/peritoneum), with fewer instances of spread to the lungs, liver, or brain. Invasive lobular histology and luminal A‐like phenotype were over‐represented in this group (42.8 and 87.5%, respectively) and most patients had involved axillary lymph nodes (p < 0.001). Primary tumours frequently co‐expressed oestrogen receptor cofactors (GATA3, FOXA1) and harboured amplifications at 8p12, 8q24, and 11q13. In terms of phenotype conversion, oestrogen receptor status was generally maintained in metastases, FOXA1 increased, and expression of progesterone receptor, androgen receptor, and GATA3 decreased. ESR1 and novel AR mutations were identified. Metastasis to gynaecological organs is a complication frequently affecting young women with invasive lobular carcinoma and luminal A‐like breast cancer, and hence may be driven by sustained hormonal signalling. Molecular analyses reveal a spectrum of factors that could contribute to de novo or acquired resistance to therapy and disease progression.
Databáze: OpenAIRE
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