Estrogen Receptor (ER) mRNA and ER-Related Gene Expression in Breast Cancers That Are 1% to 10% ER-Positive by Immunohistochemistry

• Published in: Journal of clinical oncology Vol. 30; no. 7; pp. 729 - 734
• Main Authors: IWAMOTO, Takayuki, BOOSER, Daniel, MATSUOKA, Junji, YANG, Elliana J, HORTOBAGYI, Gabriel N, HATZIS, Christos, FRASER SYMMANS, W, PUSZTAI, Lajos, VALERO, Vicente, MURRAY, James L, KOENIG, Kimberly, ESTEVA, Francisco J, UENO, Naoto T, JIE ZHANG, WEIWEI SHI, YUAN QI
• Format: Journal Article
• Language: English
• Published: Alexandria, VA American Society of Clinical Oncology 01-03-2012
• Subjects: Adjuvants; Biological and medical sciences; Breast cancer; Breast Neoplasms - drug therapy; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Chemotherapy; Estrogen Receptor alpha - biosynthesis; Estrogen Receptor alpha - genetics; Estrogen Receptor alpha - metabolism; Estrogen receptors; Female; Gene Expression; Gene Expression Profiling; Gynecology. Andrology. Obstetrics; Humans; Immunohistochemistry; Mammary gland diseases; Medical sciences; Probes; Randomized Controlled Trials as Topic; RNA, Messenger - biosynthesis; RNA, Messenger - genetics; Survival; Tumors; Immunohistochemistry; Mammary gland diseases; Estrogen receptor; Anatomic pathology; Breast disease; Cancerology; Messenger RNA; Breast cancer; Malignant tumor; Gene expression; Cancer; Hormonal receptor
• ISSN: 0732-183X; 1527-7755
• DOI: 10.1200/JCO.2011.36.2574

We examined borderline estrogen receptor (ER) -positive cancers, defined as having 1% to 10% positivity by immunohistochemistry (IHC), to determine whether they show the same global gene-expression pattern and high ESR1 mRNA expression as ER-positive cancers or if they are more similar to ER-negative cancers.
ER status was determined by IHC in 465 primary breast cancers and with the Affymetrix U133A gene chip. We compared expressions of ESR1 mRNA and a 106 probe set ER-associated gene signature score between ER-negative (n = 183), 1% to 9% (n = 25), 10% (n = 6), and more than 10% (n = 251) ER-positive cancers. We also assessed the molecular class by using the PAM50 classifier and plotted survival by ER status.
Among the 1% to 9%, 10%, and more than 10% ER IHC-positive patients, 24%, 67%, and 92% were also positive by ESR1 mRNA expression. The average ESR1 expression was significantly higher in the ≥ 10% ER-positive cohorts compared with the 1% to 9% or ER-negative cohort. The average ER gene signature scores were similar for the ER-negative and 1% to 9% IHC-positive patients and were significantly lower than in ≥ 10% ER-positive patients. Among the 1% to 9% ER-positive patients, 8% were luminal B and 48% were basal-like; among the 10% ER-positive patients, 50% were luminal. The overall survival rate of 1% to 9% ER-positive patients with cancer was between those of patients in the ≥ 10% ER-positive and ER-negative groups.
A minority of the 1% to 9% IHC ER-positive tumors show molecular features similar to those of ER-positive, potentially endocrine-sensitive tumors, whereas most show ER-negative, basal-like molecular characteristics. The safest clinical approach may be to use both adjuvant endocrine therapy and chemotherapy in this rare subset of patients.