Title |
Breast cancer metastasis to gynaecological organs: a clinico‐pathological and molecular profiling study
|
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Published in |
The Journal of Pathology: Clinical Research, October 2018
|
DOI | 10.1002/cjp2.118 |
Pubmed ID | |
Authors |
Jamie R Kutasovic, Amy E McCart Reed, Renique Males, Sarah Sim, Jodi M Saunus, Andrew Dalley, Christopher R McEvoy, Liana Dedina, Gregory Miller, Stephen Peyton, Lynne Reid, Samir Lal, Colleen Niland, Kaltin Ferguson, Andrew P Fellowes, Fares Al‐Ejeh, Sunil R Lakhani, Margaret C Cummings, Peter T Simpson |
Abstract |
Breast cancer metastasis to gynaecological organs is an understudied pattern of tumour spread. We explored clinico-pathologic 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 vs. 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 5 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%, 87.5% respectively) and most patients had involved axillary lymph nodes (p<0.001). Primary tumours frequently co-expressed oestrogen receptor (ER) cofactors (GATA3, FOXA1) and harboured amplifications at 8p12, 8q24 and 11q13. In terms of phenotype conversion, ER status was generally maintained in metastases, FOXA1 increased, and expression of progesterone receptor (PR), 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. This article is protected by copyright. All rights reserved. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Spain | 1 | 17% |
Australia | 1 | 17% |
Ireland | 1 | 17% |
Portugal | 1 | 17% |
Unknown | 2 | 33% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 3 | 50% |
Practitioners (doctors, other healthcare professionals) | 1 | 17% |
Scientists | 1 | 17% |
Science communicators (journalists, bloggers, editors) | 1 | 17% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 47 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Bachelor | 8 | 17% |
Student > Master | 6 | 13% |
Researcher | 4 | 9% |
Student > Ph. D. Student | 4 | 9% |
Student > Postgraduate | 2 | 4% |
Other | 3 | 6% |
Unknown | 20 | 43% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 14 | 30% |
Biochemistry, Genetics and Molecular Biology | 5 | 11% |
Agricultural and Biological Sciences | 3 | 6% |
Psychology | 2 | 4% |
Unspecified | 1 | 2% |
Other | 1 | 2% |
Unknown | 21 | 45% |