Metastatic progression of breast cancer: Insights from 50 years of autopsies

Cummings, Margaret C., Simpson, Peter T., Reid, Lynne E., Jayanthan, Janani, Skerman, Joanna, Song, Sarah, McCart Reed, Amy E., Kutasovic, Jamie R., Morey, Adrienne L., Marquart, Louise, O'Rourke, Peter and Lakhani, Sunil R. (2014) Metastatic progression of breast cancer: Insights from 50 years of autopsies. Journal of Pathology, 232 1: 23-31. doi:10.1002/path.4288

Author Cummings, Margaret C.
Simpson, Peter T.
Reid, Lynne E.
Jayanthan, Janani
Skerman, Joanna
Song, Sarah
McCart Reed, Amy E.
Kutasovic, Jamie R.
Morey, Adrienne L.
Marquart, Louise
O'Rourke, Peter
Lakhani, Sunil R.
Title Metastatic progression of breast cancer: Insights from 50 years of autopsies
Journal name Journal of Pathology   Check publisher's open access policy
ISSN 0022-3417
Publication date 2014-01-01
Year available 2013
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1002/path.4288
Open Access Status Not yet assessed
Volume 232
Issue 1
Start page 23
End page 31
Total pages 9
Place of publication Chichester, West Sussex, United Kingdom
Publisher John Wiley and Sons Ltd
Language eng
Subject 2734 Pathology and Forensic Medicine
Abstract There remain no clear guidelines for the optimal management of patients with metastatic breast cancer. To better understand its natural history, we undertook a detailed examination of 197 autopsies performed on women who died of breast cancer. We reviewed clinical, treatment and pathological aspects of all cases and, additionally, pathological features and biomarker expression (ER, PgR, HER2, EGFR, p53, Ki67, c-Kit, CK AE1/AE3) were assessed in detail for the primary tumour and matched metastases for 55 of the cases. Genomes of the primary tumour and multiple metastases were analysed by array-based comparative genomic hybridization for six cases##. 945 metastatic deposits were identified, with a median of four/patient. The most common organs involved were lung/pleura (80%), bone (74%), liver (71%) and non-axillary lymph nodes (55%). Major findings included: (a) patients with CNS metastases were more likely to have bone metastases (p < 0.013); (b) younger age was associated with metastasis to the liver (≤ 49 years; p < 0.001) and to gynaecological organs (≤ 49 years; p = 0.001); (c) surgical excision of the primary tumour was associated with metastasis to the liver (p = 0.002); and (d) ER and PgR showed down-regulation during progression in a non-random manner, particularly in lung/pleura (ER; p < 0.001), liver and bone metastases. Genomic analysis revealed DNA copy number variation between the primary tumour and metastases (e.g. amplification of 2q11.2-q12.1 and 10q22.2-q22.3) but little variation between metastases from the same patient. In summary, the association of CNS and bone metastases, liver and gynaecological metastases in young women and the risk of liver metastases following surgery have important implications for the management of patients with breast cancer. Clonal heterogeneity of the primary tumour is important in developing metastatic propensity and the change in tumour phenotype during progression/colonization highlights the importance of sampling metastatic disease for optimal treatment strategies.
Keyword Autopsy
Breast cancer
Intratumour heterogeneity
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 1017028
Institutional Status UQ

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: UQ Centre for Clinical Research Publications
Official 2014 Collection
School of Medicine Publications
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 38 times in Thomson Reuters Web of Science Article | Citations
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