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

Walsh MD, Buchanan DD, Cummings MC, Pearson SA, Arnold ST, Clendenning M, Walters R, McKeone DM, Spurdle AB, Hopper JL, Jenkins MA, Phillips KD, Suthers GK, George J, Goldblatt J, Muir A, Tucker K, Pelzer E, Gattas MR, Woodall S, Parry S, Macrae FA, Haile RW, Baron JA, Potter JD, Le Marchand L, Bapat B, Thibodeau SN, Lindor NM, McGuckin MA, Young JP (2010) Lynch syndrome-associated breast cancers: clinicopathologic characteristics of a case series from the colon cancer family registry. Clinical cancer research : an official journal of the American Association for Cancer Research 16:2214-2224

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="">