HER2 in well differentiated breast cancer: is testing necessary?
BACKGROUND
In addition to providing a timely and accurate diagnosis, pathologists routinely provide prognostic and predictive information to assist in the treatment of patients with invasive breast cancer. As our understanding of breast cancer at the molecular and genetic level improves, sophisticated new treatment options have become available to patients. The demonstrated improvements in disease-free and overall survival with the use of trastuzumab (Herceptin) has made HER2 testing a standard of care in the evaluation of patients with breast cancer. Specialized breast centers have accumulated sufficient experience to recognize that HER2 positive tumors tend to be of higher grade and to be estrogen receptor negative, whereas well-differentiated breast cancers rarely are HER2 positive.


METHODS
To determine whether HER2 testing is necessary in well-differentiated breast cancer, we analyzed the frequency of HER2 positivity among 1,162 cases from 7 major breast centers or commercial laboratories in the United States and Europe.


RESULTS
Well-differentiated breast cancers, defined by either nuclear grading or the Scarff-Bloom-Richardson system, rarely are HER2 positive (mean 1.6%, range 0-2.8%).


CONCLUSIONS
Given the low rate of well differentiated HER2 positive tumors, falling within the range reported for false negative IHC tests for HER2, and the absence of published data demonstrating a beneficial effect of trastuzumab therapy in this subset of patients, HER2 testing should not be considered a standard of care for all patients with well-differentiated breast cancer.
Haines
G Kenneth
GK
Department of Pathology, Yale University School of Medicine, New Haven, CT 06510, USA. k.haines@yale.edu
Wiley
Elizabeth
E
Susnik
Barbara
B
Apple
Sophia K
SK
Frkovic-Grazio
Snjezana
S
Reyes
Carolina
C
Goldstein
Lynn C
LC
Dadmanesh
Farnaz
F
Gown
Allen M
AM
Nadji
Mehrdad
M
Bracko
Matej
M
Tavassoli
Fattaneh A
FA
D000911:Antibodies, Monoclonal / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D001943:Breast Neoplasms / Q000378:metabolism*; D002454:Cell Differentiation; D002467:Cell Nucleus / Q000378:metabolism; D005188:False Negative Reactions; D005784:Gene Amplification; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D017404:In Situ Hybridization, Fluorescence; D008495:Medical Oncology / Q000379:methods; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D012306:Risk; D000068878:Trastuzumab; D016896:Treatment Outcome
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018719:Erb-b2 Receptor Tyrosine Kinases; D011960:Receptors, Estrogen; D000068878:Trastuzumab