Breast

Hormone receptors


Editorial Board Member: Kristen E. Muller, D.O.
Deputy Editor-in-Chief: Gary Tozbikian, M.D.
Joshua J.X. Li, M.B.Ch.B.

Last author update: 16 November 2022
Last staff update: 16 November 2022

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PubMed Search: Hormone receptors

Joshua J.X. Li, M.B.Ch.B.
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Cite this page: Li JJX, Tse GM. Hormone receptors. PathologyOutlines.com website. https://www.pathologyoutlines.com/topic/breastmalignanthormonereceptors.html. Accessed February 8th, 2023.
Definition / general
  • The most clinically important hormone receptors in breast cancer are estrogen, progesterone, and to a lesser extent, androgen receptors
  • Hormone receptor status is strongly associated with histology, prognosis and treatment response
Essential features
  • Clinically used hormone receptor markers for breast cancers include estrogen, progesterone and androgen receptors
  • Expression of hormone markers is associated with favorable prognostic features and less aggressive histologic features
  • Estrogen and progesterone expression select breast cancer patients for hormone therapy
Terminology
  • Estrogen receptor alpha
    • ERα is the routinely used marker in a clinical setting
    • Predictive value in prognostication and treatment response is better established in ERα compared to ERβ (Biomark Res 2020;8:39)
    • ER immunostain usually refers to ERα unless otherwise specified
Pathophysiology
Clinical features
Interpretation
  • Estrogen, progesterone and androgen receptors are nuclear stains
  • Interpretation of ER and PR outlined by ASCO / CAP guideline on estrogen and progesterone receptor testing in breast cancer (J Clin Oncol 2020;38:1346)
    • Staining is considered positive regardless of intensity
    • Reported as percentage of tumor nuclei positive (0 - 100%)
    • 1 - 100% staining considered as positive, < 1% staining considered as negative
    • ER low positive category (1 - 10% staining) introduced in the latest ASCO / CAP Guideline
  • Other scoring methods (Ann Oncol 2013;24:47)
    • Allred score
      • Summation of proportion (0 - 5) and intensity (0 - 3) of ER positive tumor cells into a score of 0 to 8 out of 8
      • Proportion
        • 0: 0%
        • 1: < 1%
        • 2: 1 - 10%
        • 3: 11 - 33%
        • 4: 34 - 66%
        • 5: > 66%
      • Intensity
        • 0: negative
        • 1: weak
        • 2: moderate
        • 3: strong
      • Scores 0 and 2 interpreted as negative; scores 3 to 8 interpreted as positive
    • H score
      • Score of 0 to 300 from multiplying proportion as percentage (0 - 100) and intensity (0 - 3) of ER positive tumor cells
      • % of tumor cells with weak staining x 1 + % of tumor cells with moderate staining x 2 + % of tumor cells with strong staining x 3
  • Pitfalls in ER and PR assessment are not uncommon and should be avoided (Pathobiology 2022 Mar 4 [Epub ahead of print])
    • Positive staining in nonneoplastic or entrapped breast tissue, proliferative and in situ lesions should be excluded
    • Prolonged cold ischemia time can decrease ER and PR expression
    • ER and PR antigenicity are also sensitive to tissue processing, fixation protocol and decalcification
Uses by pathologists
  • Routine assessment of breast cancer
    • For prognostication of breast cancers
    • Selecting ER positive breast cancers for hormonal therapy
    • ER and PR are components of the surrogate classification for breast cancer subtyping (Breast 2016;29:181)
      • ER / PR positivity indicates luminal-like breast cancers
  • Differentiating hyperplastic and neoplastic breast lesions
    • Homogenous uniform ER staining indicates clonality and favors a neoplastic process (Mod Pathol 2010;23:S1)
      • Homogenous uniform ER staining: columnar cell change, columnar cell hyperplasia, flat epithelial atypia, atypical ductal hyperplasia and carcinoma in situ
      • Heterogenous ER staining: normal breast epithelium, usual ductal hyperplasia and florid epithelial hyperplasia
    • AR can be used to demonstrate apocrine differentiation, usually with coexpression of GCDFP15 (Pathol Res Pract 1997;193:753, BMC Cancer 2014;14:546)
  • There are many other uses to ER and PR, including assessment of metastatic carcinomas and gynecological lesions
Prognostic factors
Microscopic (histologic) description
  • The most common type of ER positive (and PR, AR positive breast cancers which are correlated with ER expression) breast cancer is low grade invasive breast carcinoma of no special type (IBC, NST) (Breast Care (Basel) 2020;15:327)
    • Features include prominent tubule formation, mild nuclear pleomorphism and a low mitotic count
    • Other histological features include fewer tumor infiltrating lymphocytes, less lymphovascular invasion and more fibrotic foci (Br J Cancer 2020;123:1223, Ann Surg Oncol 2013;20:2842)
  • Special types of breast cancer which are commonly ER positive include lobular, micropapillary, mucinous, papillary and tubular carcinomas (Breast Care (Basel) 2020;15:327)
Microscopic (histologic) images

Contributed by Joshua J.X. Li, M.B.Ch.B. and Gary M. Tse, M.B.B.S.
Low grade IBC, NST Low grade IBC, NST

Low grade IBC, NST

Invasive lobular carcinoma

Invasive lobular carcinoma

Papillary carcinoma

Papillary carcinoma

Estrogen receptor

Estrogen receptor

Progesterone receptor

Progesterone receptor


Androgen receptor

Androgen receptor

Apocrine carcinoma

Apocrine carcinoma

Androgen receptor

Androgen receptor

Atypical ductal hyperplasia

Atypical ductal hyperplasia

Estrogen receptor

Estrogen receptor

Columnar cell change

Columnar cell change


Estrogen receptor

Estrogen receptor

Florid epithelial hyperplasia

Florid epithelial hyperplasia

Estrogen receptor

Estrogen receptor

Estrogen receptor low positive Estrogen receptor low positive Estrogen receptor low positive

Estrogen receptor low positive


Estrogen receptor low positive

Estrogen receptor low positive

Virtual slides

Images hosted on other servers:

Invasive lobular carcinoma

Low grade IBC, NST

ER immunostaining

Positive staining - normal
Positive staining - disease
Negative staining
  • Estrogen receptor:
  • Progesterone receptor and androgen receptor expression is closely related to estrogen receptor expression in most breast lesions, with the exception of apocrine lesions (see Positive staining - disease)
Sample pathology report
  • Left breast, biopsy:
    • Invasive breast carcinoma of no special type (see comment)
    • Comment: Immunostaining shows that the invasive tumor cells are ER positive (strong [3+] intensity, 70%) and PR positive (strong [3+] intensity, 70%).
Board review style question #1

Which of the following is a histological feature associated with estrogen receptor positivity in breast cancers?

  1. Abundant intratumoral and stromal lymphocytes
  2. Frequent mitotic figures
  3. Highly pleomorphic nuclei
  4. Lymphovascular invasion
  5. Prominent tubule formation
Board review style answer #1
E. Prominent tubule formation. ER positivity is associated with low grade features (Breast Care (Basel) 2020;15:327). Lymphovascular invasion, medullary features and tumor infiltrating lymphocytes are associated with ER negativity (Br J Cancer 2020;123:1223, Cancer Biol Med 2020;17:293).

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