TY - JOUR
T1 - Lynch syndrome-associated breast cancers
T2 - Clinicopathologic characteristics of a case series from the colon cancer family registry
AU - Walsh, Michael D.
AU - Buchanan, Daniel D.
AU - Cummings, Margaret C.
AU - Pearson, Sally Ann
AU - Arnold, Sven T.
AU - Clendenning, Mark
AU - Walters, Rhiannon
AU - McKeone, Diane M.
AU - Spurdle, Amanda B.
AU - Hopper, John L.
AU - Jenkins, Mark A.
AU - Phillips, Kerry D.
AU - Suthers, Graeme K.
AU - George, Jill
AU - Goldblatt, Jack
AU - Muir, Amanda
AU - Tucker, Kathy
AU - Pelzer, Elise
AU - Gattas, Michael R.
AU - Woodall, Sonja
AU - Parry, Susan
AU - Macrae, Finlay A.
AU - Haile, Robert W.
AU - Baron, John A.
AU - Potter, John D.
AU - Le Marchand, Loic
AU - Bapat, Bharati
AU - Thibodeau, Stephen N.
AU - Lindor, Noralane M.
AU - McGuckin, Michael A.
AU - Young, Joanne P.
PY - 2010/4/1
Y1 - 2010/4/1
N2 - 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.
AB - 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.
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U2 - 10.1158/1078-0432.CCR-09-3058
DO - 10.1158/1078-0432.CCR-09-3058
M3 - Article
C2 - 20215533
AN - SCOPUS:77950655236
SN - 1078-0432
VL - 16
SP - 2214
EP - 2224
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 7
ER -