Lynch syndrome-associated breast cancers: clinicopathologic characteristics of a case series from the colon cancer family registry.
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.
Walsh
Michael D
MD
Familial Cancer Laboratory, I Floor, Bancroft Centre, Queensland Institute of Medical Research, Herston Road, Herston, Queensland 4006, Australia. Michael.Walsh@qimr.edu.au
Buchanan
Daniel D
DD
Cummings
Margaret C
MC
Pearson
Sally-Ann
SA
Arnold
Sven T
ST
Clendenning
Mark
M
Walters
Rhiannon
R
McKeone
Diane M
DM
Spurdle
Amanda B
AB
Hopper
John L
JL
Jenkins
Mark A
MA
Phillips
Kerry D
KD
Suthers
Graeme K
GK
George
Jill
J
Goldblatt
Jack
J
Muir
Amanda
A
Tucker
Kathy
K
Pelzer
Elise
E
Gattas
Michael R
MR
Woodall
Sonja
S
Parry
Susan
S
Macrae
Finlay A
FA
Haile
Robert W
RW
Baron
John A
JA
Potter
John D
JD
Le Marchand
Loic
L
Bapat
Bharati
B
Thibodeau
Stephen N
SN
Lindor
Noralane M
NM
McGuckin
Michael A
MA
Young
Joanne P
JP
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