Lynch syndrome-associated breast cancers: clinicopathologic characteristics of a case series from the colon cancer family registry

Walsh, M.D., Buchanan, D.D., Cummings, M.C., Pearson, S.A., Arnold, S.T., Clendenning, M., Walters, R., McKeone, D.M., Spurdle, A.B., Hopper, J.L., Jenkins, M.A., Phillips, K.D., Suthers, G.K., George, J., Goldblatt, J., Muir, A., Tucker, K., Pelzer, E., Gattas, M.R., Woodall, S., Parry, S., Macrae, F.A., Haile, R.W., Baron, J.A., Potter, J.D., Le Marchand, L., Bapat, B., Thibodeau, S.N., Lindor, N.M., McGuckin, M.A., & Young, J.P. (2010) Lynch syndrome-associated breast cancers: clinicopathologic characteristics of a case series from the colon cancer family registry. Clinical Cancer Research, 16(7), pp. 2214-2224.

View at publisher


Purpose: The recognition of breast cancer as a spectrum tumor in Lynch syndrome remains controversial. The aim of this study was to explore features of breast cancers arising in Lynch syndrome families.

Experimental Design: This observational study involved 107 cases of breast cancer identified from the Colorectal Cancer Family Registry (Colon CFR) from 90 families in which (a) both breast and colon cancer co-occurred, (b) families met either modified Amsterdam criteria, or had at least one early-onset (<50 years) colorectal cancer, and (c) breast tissue was available within the biospecimen repository for mismatch repair (MMR) testing. Eligibility criteria for enrollment in the Colon CFR are available online. Breast cancers were reviewed by one pathologist. Tumor sections were stained for MLH1, PMS2, MSH2, and MSH6, and underwent microsatellite instability testing.

Results: Breast cancer arose in 35 mutation carriers, and of these, 18 (51%) showed immunohistochemical absence of MMR protein corresponding to the MMR gene mutation segregating the family. MMR-deficient breast cancers were more likely to be poorly differentiated (P = 0.005) with a high mitotic index (P = 0.002), steroid hormone receptor–negative (estrogen receptor, P = 0.031; progesterone receptor, P = 0.022), and to have peritumoral lymphocytes (P = 0.015), confluent necrosis (P = 0.002), and growth in solid sheets (P < 0.001) similar to their colorectal counterparts. No difference in age of onset was noted between the MMR-deficient and MMR-intact groups.

Conclusions: MMR deficiency was identified in 51% of breast cancers arising in known mutation carriers. Breast cancer therefore may represent a valid tissue option for the detection of MMR deficiency in which spectrum tumors are lacking

Impact and interest:

49 citations in Scopus
41 citations in Web of Science®
Search Google Scholar™

Citation counts are sourced monthly from Scopus and Web of Science® citation databases.

These databases contain citations from different subsets of available publications and different time periods and thus the citation count from each is usually different. Some works are not in either database and no count is displayed. Scopus includes citations from articles published in 1996 onwards, and Web of Science® generally from 1980 onwards.

Citations counts from the Google Scholar™ indexing service can be viewed at the linked Google Scholar™ search.

Full-text downloads:

72 since deposited on 20 Jan 2013
3 in the past twelve months

Full-text downloads displays the total number of times this work’s files (e.g., a PDF) have been downloaded from QUT ePrints as well as the number of downloads in the previous 365 days. The count includes downloads for all files if a work has more than one.

ID Code: 56555
Item Type: Journal Article
Refereed: Yes
Keywords: Lynch syndrome, Mismatch repair
DOI: 10.1158/1078-0432.CCR-09-3058
ISSN: 1557-3265
Subjects: Australian and New Zealand Standard Research Classification > MEDICAL AND HEALTH SCIENCES (110000) > ONCOLOGY AND CARCINOGENESIS (111200)
Divisions: Current > QUT Faculties and Divisions > Faculty of Health
Copyright Owner: Copyright 2010 American Association for Cancer Research
Deposited On: 20 Jan 2013 23:44
Last Modified: 19 Jul 2013 17:43

Export: EndNote | Dublin Core | BibTeX

Repository Staff Only: item control page