American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer (unabridged version).
OBJECTIVE
To develop a guideline to improve the accuracy of immunohistochemical (IHC) estrogen receptor (ER) and progesterone receptor (PgR) testing in breast cancer and the utility of these receptors as predictive markers.


METHODS
The American Society of Clinical Oncology and the College of American Pathologists convened an international Expert Panel that conducted a systematic review and evaluation of the literature in partnership with Cancer Care Ontario and developed recommendations for optimal IHC ER/PgR testing performance.


RESULTS
Up to 20% of current IHC determinations of ER and PgR testing worldwide may be inaccurate (false negative or false positive). Most of the issues with testing have occurred because of variation in pre-analytic variables, thresholds for positivity, and interpretation criteria.


CONCLUSIONS
The Panel recommends that ER and PgR status be determined on all invasive breast cancers and breast cancer recurrences. A testing algorithm that relies on accurate, reproducible assay performance is proposed. Elements to reliably reduce assay variation are specified. It is recommended that ER and PgR assays be considered positive if there are at least 1% positive tumor nuclei in the sample on testing in the presence of expected reactivity of internal (normal epithelial elements) and external controls. The absence of benefit from endocrine therapy for women with ER-negative invasive breast cancers has been confirmed in large overviews of randomized clinical trials.
Hammond
M Elizabeth H
ME
Intermountain Healthcare, University of Utah School of Medicine, Salt Lake City, UT, USA.
Hayes
Daniel F
DF
Dowsett
Mitch
M
Allred
D Craig
DC
Hagerty
Karen L
KL
Badve
Sunil
S
Fitzgibbons
Patrick L
PL
Francis
Glenn
G
Goldstein
Neil S
NS
Hayes
Malcolm
M
Hicks
David G
DG
Lester
Susan
S
Love
Richard
R
Mangu
Pamela B
PB
McShane
Lisa
L
Miller
Keith
K
Osborne
C Kent
CK
Paik
Soonmyung
S
Perlmutter
Jane
J
Rhodes
Anthony
A
Sasano
Hironobu
H
Schwartz
Jared N
JN
Sweep
Fred C G
FC
Taube
Sheila
S
Torlakovic
Emina Emilia
EE
Valenstein
Paul
P
Viale
Giuseppe
G
Visscher
Daniel
D
Wheeler
Thomas
T
Williams
R Bruce
RB
Wittliff
James L
JL
Wolff
Antonio C
AC
D000465:Algorithms; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry* / Q000188:drug therapy / Q000473:pathology; D005188:False Negative Reactions; D005189:False Positive Reactions; D005260:Female; D006801:Humans; D007150:Immunohistochemistry / Q000592:standards*; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D011960:Receptors, Estrogen / Q000032:analysis*; D011980:Receptors, Progesterone / Q000032:analysis*; D015203:Reproducibility of Results; D017211:Treatment Failure
D014408:Biomarkers, Tumor; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone