Metastatic progression of breast cancer: insights from 50 years of autopsies.

Cummings MC, Simpson PT, Reid LE, Jayanthan J, Skerman J, Song S, McCart Reed AE, Kutasovic JR, Morey AL, Marquart L, O'Rourke P, Lakhani SR.

Source

The University of Queensland, UQ Centre for Clinical Research, Herston, Brisbane, QLD 4029, Australia; Pathology Queensland: The Royal Brisbane & Women's Hospital, Brisbane, QLD 4029, Australia; The University of Queensland, School of Medicine, Herston, Brisbane, QLD 4006, Australia.

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 pathology aspects of all cases and additionally, pathology 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 analyzed by array-based comparative genomic hybridization for six cases. 945 metastatic deposits were identified with a median of four per patient. The most common organs involved were lung/pleura (80%), bone (74%), liver (71%), and non-axillary lymph nodes (55%). Major findings included: i) patients with CNS metastases were more likely to have bone metastases (p<0·013); ii) younger age was associated with metastasis to the liver (≤49 years; p<0·001) and to gynaecological organs (≤49 years; p=0·001); iii) surgical excision of the primary tumour was associated with metastasis to the liver (p=0·002) and iv) 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 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.

TimAllenMDJD

Tuesday, December 3, 2013