Breast carcinoma, rates of expression of steroid receptors

Oestrogen receptor (ER) status is a good predictor of clinical response to hormonal therapies: the likelihood and level of response increases with higher levels of receptor expression⁶. The best response is in patients with a tumour that is positive for both ER and progesterone receptors (PR). Progesterone receptors are an independent predictor of response and indicate a functioning oestrogen receptor pathway. Immunohistochemistry is equal or superior to ligand binding assay for the prediction of response to hormonal therapy with greater sensitivity and requiring less tissue⁶. However, variability arises from pre-analytical handing, the choice of antibody, antigen retrieval methodology, use of controls, interpretation and scoring⁶.

Oestrogen receptor estimation in core biopsies correlates well with expression in excised tumours but the score on core biopsy is higher, presumably because of the tendency to sample the periphery of the tumour, where expression is greater⁴.

Overall rates of expression of oestrogen (ER) and progesterone receptors (PR)¹:

	ER+	ER-
PR+	55%	3%	59%
PR-	20%	22%	44%
	75%	25%

The rate of expression increases with patient age and following the menopause⁶. Tamoxifen may reduce expression⁷.

Medullary carcinomas are usually negative for oestrogen receptors (positivity defined as >10% nuclei immunoreactive)²:

Typical medullary carcinoma	0/13
Atypical medullary carcinoma	3/24
Ductal carcinoma with medullary features	4/23

Apocrine ductal carcinoma in situ is characteristically positive for androgen receptors but negative for oestrogen and progesterone receptors³:

Androgen receptor	33/34
oestrogen receptor	2/35
progesterone receptor	1/34

Prolactin receptor is also expressed by breast tissue and tumours. Normal breast tissue shows consistent positivity of the luminal surface of epithelial cells, with negativity of the myoepithelial and stromal cells. Expression by tumours correlates with expression of oestrogen receptor but not with stage or tumour grade⁴:

fibrocystic disease	4/84
fibroadenoma	9/94
florid regular duct hyperplasia	0/34
intraduct papillomas	6/64
lactating adenoma	2/24
duct ectasia	2/34
gynaecomastia	5/64
ductal carcinoma	36/524
lobular carcinoma	3/44
tubular carcinoma	1/14
mucinous carcinoma	1/14
squamous carcinoma	0/14

Core biopsies are generally a good indicator of oestrogen receptor status:

	by Quick Score (four prognostic categories; negative, weakly positive, moderately positive, strongly positive: correlates well with anti-oestrogen therapy)	positive vs negative (determines anti-oestrogen therapy)
core versus wide local excision	48/59	55/59
core versus mastectomy	20/27	24/27
overall	68/86	79/86

The risk of brain metastases correlates with negativity for oestrogen receptors, along with high grade, expression of CK5/6, epidermal growth factor receptor and HER2⁸.

References

¹ Rhodes A, Jasani B, Balaton AJ et al. Frequency of oestrogen and progesterone receptor positivity by Immunohistochemical analysis in 7016 breast carcinomas: correlation with patient age, assay sensitivity, threshold value and mammographic screening. J Clin Pathol 2000;53:688-696.

² Jensen ML et al. Medullary breast carcinoma vs. poorly differentiated ductal carcinoma: an immunohistochemical study with keratin 19 and oestrogen receptor staining. Histopathology 1996;29:241-245.

³ Leal, C., Henrique, R., Monteiro, P., Lopes, C., Bento, M. J., De Sousa, C. P., Lopes, P., Olson, S., Silva, M. D., Page, D. L. Apocrine ductal carcinoma in situ of the breast: histologic classification and expression of biologic markers. Human Pathol 2001;32:487-493.

⁴ Douglas-Jones, A. G., Collett, N., Morgan, J. M., Jasani, B. Comparison of core oestrogen receptor (ER) assay with excised tumour: intratumoral distribution of ER in breast carcinoma. J Clin Pathol 2001;54:951-955.

⁵ Graham AD, Loane J. Oestrogen receptor assays in breast cancer: correlation between core biopsies and resection specimens. Pathological Society July 2004.

⁶ Diaz LK,Sneige N .Estrogen receptor analysis for breast cancer: current issues and keys to increasing testing accuracy. Adv Anat Pathol 2005; 12:10-9

⁷ Verghese et al. Mitotic rate, ER and bcl-2 expression in short term Tamoxifen treated breast cancer. J Pathol 2001:193(suppl):31^A.

⁸ Hicks DG, Short SM, Prescott NL, et al. Breast Cancers With Brain Metastases are More Likely to be Estrogen Receptor Negative, Express the Basal Cytokeratin CK5/6, and Overexpress HER2 or EGFR. Am J Surg Pathol 2006; 30:1097-1104

This page last revised 23.9.2006.

©SMUHT/PW Bishop