BRCA1 and BRCA2 carriers with breast, ovarian and prostate cancer demonstrate a different pattern of metastatic disease compared with non-carriers: results from a rapid autopsy programme

Thorne, H; Devereux, L; Li, J; Alsop, K; Christie, L; van Geelen, CT; Burdett, N; Pishas, KI; Woodford, N; Leditschke, J; Izzath, Mhma; Strachan, K; Young, G; Jaravaza, RD; Madadin, MS; Archer, M; Glengarry, J; Iles, L; Rathnaweera, A; Hampson, C; Almazrooei, K; Burke, M; Bandara, P; Ranson, D; Saeedi, E; McNally, O; Mileshkin, L; Hamilton, A; Ananda, S; Au-Yeung, G; Antill, Y; Sandhu, S; Savas, P; Francis, PA; Luen, S; Loi, S; Jennens, R; Scott, C; Moodie, K; Cummings, M; Reid, A; Reed, AM; Bowtell, D; Lakhani, SR; Fox, S

Author(s): Thorne, H; Devereux, L; Li, J; Alsop, K; Christie, L; van Geelen, CT; Burdett, N; Pishas, KI; Woodford, N; Leditschke, J; Izzath, Mhma; Strachan, K; Young, G; Jaravaza, RD; Madadin, MS; Archer, M; Glengarry, J; Iles, L; Rathnaweera, A; Hampson, C; Almazrooei, K; Burke, M; Bandara, P; Ranson, D; Saeedi, E; McNally, O; Mileshkin, L; Hamilton, A; Ananda, S; Au-Yeung, G; Antill, Y; Sandhu, S; Savas, P; Francis, PA; Luen, S; Loi, S; Jennens, R; Scott, C; Moodie, K; Cummings, M; Reid, A; Reed, AM; Bowtell, D; Lakhani, SR; Fox, S;
Details: Publication Year 2023-03-31,Volume 83,Issue #1,Page 91-103
Journal Title: Histopathology
Abstract: AIM: To catalogue and compare the pattern of metastatic disease in germline BRCA1/2 pathogenic mutation carriers and non-carriers with breast, ovarian and prostate cancer from a rapid autopsy programme. METHODS AND RESULTS: The number of metastases in the major body systems and the proportion of participants with metastases were documented in 50 participants (19 germline mutation carriers). Analysis was conducted on the participants' pattern of disease for the different cancers and mutation subgroups. The four commonly affected organ systems were the digestive (liver only) (82%), respiratory (76%), gastrointestinal (65%) and reticuloendothelial (42%). There were significant differences in the pattern of metastatic breast cancer in BRCA1/2 germline carriers compared with non-carriers. Breast cancer carriers had significantly fewer organ systems involved (median n = 3, range = 1-3) compared with non-carriers (median n = 9, range = 1-7) (P = 0.03). BRCA1/2 carriers with ovarian carcinomas had significantly more organ systems with metastatic carcinoma (median n = 10, range = 3-8) than non-carriers (median n = 5, range = 3-5) (P < 0.001). There were no significant differences in the number of involved systems in BRCA2 carriers compared with non-carriers with prostate cancer (P = 1.0). There was an absence of locoregional disease (6.5%) compared with distant disease (93.5%) among the three cancer subtypes (P < 0.001). The majority of metastatic deposits (97%) collected during the autopsy were identified by recent diagnostic imaging. CONCLUSION: Even though a major limitation of this study is that our numbers are small, especially in the breast cancer carrier group, the metastatic patterns of breast and ovarian cancers may be impacted by BRCA1/2 carrier status, suggesting that tumours derived from patients with these mutations use different mechanisms of dissemination. The findings may focus clinical diagnostic imaging for monitoring metastases where whole-body imaging resources are scant.
Publisher: Wiley
Keywords: anatomy; autopsy; dissection; genes; hereditary cancer syndrome; neoplasm; tumour suppressor
Research Division(s): Cancer Biology And Stem Cells
PubMed ID: 36999648
Publisher's Version: https://doi.org/10.1111/his.14906
Open Access at Publisher's Site: https://doi.org/10.1111/his.14906
Terms of Use/Rights Notice: Refer to copyright notice on published article.

Creation Date: 2023-04-18 01:59:01

Last Modified: 2023-12-13 10:19:47