Breast malignant, males, children
Breast cancer
Hormone receptors

Author: Monika Roychowdhury, M.D. (see Authors page)

Revised: 20 October 2016, last major update February 2012

Copyright: (c) 2002-2016, PathologyOutlines.com, Inc.

PubMed Search: Hormone receptors [title] breast

Cite this page: Hormone receptors. PathologyOutlines.com website. http://www.pathologyoutlines.com/topic/breastmalignanthormonereceptors.html. Accessed December 11th, 2016.
Definition / General
  • Estrogen receptors (ER) have alpha and beta subtypes
  • ER-alpha: “classic” functions of ER; may render breast epithelium susceptible to proliferative stimulation of estrogen; expressed in breast and endometrium; immunostains not specifically classified as ER-alpha or ER-beta are usually ER-alpha
  • ER-beta: provides “housekeeping” functions; expressed in normal ovary and granulosa cells, carcinoma of breast, colon, prostate; values differ from ER-alpha in BRCA1 associated breast carcinoma (BMC Cancer 2008;8:100)

ER/PR positive tumors
  • Includes most colloid carcinomas, most well differentiated tumors, bcl2+ tumors
  • ER+ tumors have lower microvessel density (Int Semin Surg Oncol 2007;4:22)
Clinical Features
  • Presence of estrogen (type alpha) and progesterone receptors correlates best with response to anti-estrogen treatment (tamoxifen or others) or chemotherapy
  • Expression of ER-beta in ER-alpha negative breast cancer patients is an independent marker for favorable prognosis after adjuvant tamoxifen treatment (Clin Cancer Res 2007;13:1987, Hum Pathol 2001;32:113); may have prognostic value in ER+/PR+ patients (APMIS 2009;117:644)
  • Otherwise, hormone expression correlates only weakly with prognosis; presence is associated with older age
  • Endocrine therapy responsiveness is observed even with low expression of ER (1 - 5%)
  • ER gene profiling (BMC Genomics 2008;9:239) or ER-beta mRNA (BMC Cancer 2007;7:131) may predict the 30 - 40% of ER+ tumors that will NOT respond to tamoxifen
  • Immunostaining is done on paraffin fixed tissue (previously required fresh tissue)
  • Recommended to fix tissue within 1 hour of receipt (Mod Pathol 2009;22:1457), and for at least 6 hours (for HER2, Arch Pathol Lab Med 2009;133:775)
  • ER antibodies SP1 and 1D5 give similar results (Am J Clin Pathol 2009;132:396)
  • Report % of tumor nuclei stained and intensity of staining (none, weak, moderate, strong)
  • Note: tumor staining may be heterogeneous
  • Note: must validate tumor protocols in each lab; SP2 antibody for PR may be less reliable (Am J Clin Pathol 2008;129:398)
  • Compared to ER, PR staining adds only a limited amount of additional predictive information for response to hormonal therapy (Mod Pathol 2004;17:1545)
  • Antigen retrieval techniques are required for ER if glyoxal fixative is used (Hum Pathol 2004;35:1058)
  • Metastases to skin are often positive for androgen receptor, even if ER- and PR- (Mod Pathol 2000;13:119)
  • ASCO/CAP recommendations for immunohistochemistry testing (Arch Pathol Lab Med 2010;134:930)

ER/PR negative tumors:
  • Tumors are usually moderate / poorly differentiated with axillary nodal metastases and poor prognosis (Arch Pathol Lab Med 2002;126:325)
  • Includes metaplastic, adenoid cystic, apocrine and acinic cell carcinomas; also comedocarcinoma, medullary carcinoma and basal-like carcinoma (which are typically triple negative [ER, PR, HER2])
  • Often occurs in premenopausal women
  • 30% of primary operable breast cancers are ER negative; of these, 94% are high grade, 85% are invasive ductal NOS (Mod Pathol 2005;18:26)
  • Amongst breast cancer subtypes, triple negative tumors have the worst overall survival and the worst disease free survival (Clin Med Res 2009;7:4)
  • BRCA1 pathway dysfunction is found in a substantial proportion of basal-like and triple negative breast cancers and can be exploited therapeutically (e.g., inhibitors of the PARP enzyme and cross-linking agents, link)
Micro Description
ER/PR negative tumors - Description for triple negative tumors (basal-like morphology)
  • Poorly differentiated with central fibrosis / necrosis
  • Usually lymphoid stroma, pushing margin
Micro Images

Images hosted on PathOut servers:
Contributed by Leica Microsystems, Biosystems Division:

Invasive ductal carcinoma - ER (6F11) with intense nuclear staining

Strong nuclear staining for PR



Images hosted on other servers:

ER+ (strong)

ER alpha+

ER beta+

ER+ (weak)



ER negative tumors have high microvessel density (CD34 staining)

PR+ in only a few cells

PR cytoplasmic staining is considered negative, Fig. B

PR membranous staining is considered negative, Fig. B

Positive Stains
ER/PR negative tumors:
Additional References