title: Lynch syndrome-associated breast cancers: clinicopathologic characteristics of a case series from the colon cancer family registry.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
authors.affiliation: Familial Cancer Laboratory, I Floor, Bancroft Centre, Queensland Institute of Medical Research, Herston Road, Herston, Queensland 4006, Australia. Michael.Walsh@qimr.edu.au
authors.forename: Michael D
authors.initials: MD
authors.lastname: Walsh
authors.forename: Daniel D
authors.initials: DD
authors.lastname: Buchanan
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Cummings
authors.forename: Sally-Ann
authors.initials: SA
authors.lastname: Pearson
authors.forename: Sven T
authors.initials: ST
authors.lastname: Arnold
authors.forename: Mark
authors.initials: M
authors.lastname: Clendenning
authors.forename: Rhiannon
authors.initials: R
authors.lastname: Walters
authors.forename: Diane M
authors.initials: DM
authors.lastname: McKeone
authors.forename: Amanda B
authors.initials: AB
authors.lastname: Spurdle
authors.forename: John L
authors.initials: JL
authors.lastname: Hopper
authors.forename: Mark A
authors.initials: MA
authors.lastname: Jenkins
authors.forename: Kerry D
authors.initials: KD
authors.lastname: Phillips
authors.forename: Graeme K
authors.initials: GK
authors.lastname: Suthers
authors.forename: Jill
authors.initials: J
authors.lastname: George
authors.forename: Jack
authors.initials: J
authors.lastname: Goldblatt
authors.forename: Amanda
authors.initials: A
authors.lastname: Muir
authors.forename: Kathy
authors.initials: K
authors.lastname: Tucker
authors.forename: Elise
authors.initials: E
authors.lastname: Pelzer
authors.forename: Michael R
authors.initials: MR
authors.lastname: Gattas
authors.forename: Sonja
authors.initials: S
authors.lastname: Woodall
authors.forename: Susan
authors.initials: S
authors.lastname: Parry
authors.forename: Finlay A
authors.initials: FA
authors.lastname: Macrae
authors.forename: Robert W
authors.initials: RW
authors.lastname: Haile
authors.forename: John A
authors.initials: JA
authors.lastname: Baron
authors.forename: John D
authors.initials: JD
authors.lastname: Potter
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Bharati
authors.initials: B
authors.lastname: Bapat
authors.forename: Stephen N
authors.initials: SN
authors.lastname: Thibodeau
authors.forename: Noralane M
authors.initials: NM
authors.lastname: Lindor
authors.forename: Michael A
authors.initials: MA
authors.lastname: McGuckin
authors.forename: Joanne P
authors.initials: JP
authors.lastname: Young
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D018567:Breast Neoplasms, Male / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D003110:Colonic Neoplasms / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003123:Colorectal Neoplasms, Hereditary Nonpolyposis / Q000150:complications / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D053843:DNA Mismatch Repair / Q000235:genetics; D005190:Family; D005260:Female; D006580:Genetic Carrier Screening; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012042:Registries