Estrogen/Progesterone Receptors

Sample for Estrogen/Progesterone Receptors 

1. This procedure is done on the paraffin blocks of Breast cancer cases.
2. This can also be done on fresh biopsy tissue. Place the tissue on ice or in formalin.
3. Controls are a must and need to run.

Indications for Estrogen/Progesterone Receptors 

1. Estrogen/progesterone receptors are done on breast cancer to find hormone sensitivity and therapy.
2. ER/PR is used as a prognostic factor.

Precautions for Estrogen/Progesterone Receptors

1. Delayed fixation may cause deterioration of the receptors and produce a lower result.
2. Hormones should be discontinued before the biopsy.
3. Tamoxifen therapy may cause a false-negative result.
4. Contraceptives or menopausal estrogen, when given, lower the result.

Pathophysiology of Estrogen/Progesterone Receptors 

1. Biochemical concept:
   1. ER/PR receptors are cellular proteins with high affinity and great specificity for these hormones.
   2. These receptor proteins are present in other target organs like the uterus, pituitary gland, hypothalamus, and breast.
   3. Estrogen stimulates the biochemical process in the target cells that normally contain estrogen-receptor; a reduction in blood estrogen level is expected to reduce the biochemical activity of these cells.
   4. This is the accepted rationale for using endocrine therapy in females with breast carcinoma.

ER/PR receptor role in the treatment of breast cancer

ER/PR response to anti-hormone therapy:

1. ER/PR are the biomarkers of breast cancers. These can be prognostic, predictive (response to the therapy), or both.
2. Higher the ER content positivity, the higher the response rate to endocrine therapy.
3. In carcinoma of the breast, 60% of the cases are estrogen receptor-positive.
4. Roughly two-thirds of the cases of ER-positive respond to anti-hormone therapy.
5. In 95% of the cases, negative ER-receptor fails to respond to anti-hormone therapy.
6. Breast cancer ER-positive or PR positive are twice sensitive to anti-hormonal therapy (70 % response to anti-hormonal treatment).
7. While ER/PR negative cases have a 10% response rate.
8. ER/PR-positive cases have more disease-free survival.
9. Hormone receptors should be done on all breast cancers.
10. ER/PR is more favorable in a menopausal group than in younger patients.

PR- receptor:

1. It is useful to help in the assay of the ER receptors.
2. Metastatic cancer with ER and PR receptor-positive tumors has a response rate of 75% to endocrine therapy.
3. If the ER-positive and PR-negative tumors have a 40% response rate.
4. The only response rate of ER-negative and PR-positive patients is 25% for endocrine therapy.
5. In the case of ER and PR negative, the response rate is only 5%.
6. The percentage of positive cases in postmenopausal women is greater than the premenopausal women.

Normal

• Negative case = <5 % cells stains for receptors.
• Positive case  = >5% of the cells stain for receptors.

Another source

ER/PR receptors assay on tissue:

1. Negative = <3 fmol/mg cytosol protein.
2. Borderline = 3 to 9 fmol/mg cytosol protein.
3. Positive = >10 fmol/mg cytosol protein.

Interpretations of Estrogen/Progesterone Receptors 

1. This subjective interpretation depends on the staining intensity and the number of positive cell nuclei.
2. Only the cell nuclei staining is considered positive.

Estrogen/Progesterone Receptors: ER/PR positive cells

3. Favorable response >20 % cell stain.
4. The borderline response is 11 to 20 % of the cell stain.
5. The unfavorable response is < 10 % cell stain.
6. ASCO guideline is:
   1. Positive for ER/PR if  ≥ 1% of the tumor cell nuclei are immunoreactive.
   2. Negative ER/PR if  <1% of tumor cells nuclei are immunoreactive.
7. Allred scoring: This replaced the early scoring system.
   1. ER-positive tumor cells have > 10% positive cells.
      1. ER-negative tumor cells are 1 to 9% positive cells.

8. The hormone receptor positivity varies in different patients:
   1. ER+ =  80% of the cases.
   2. ER+ PR+  = 65% of the cases.
   3. ER+ PR-  = 13% of the cases.
   4. ER-  PR+  = 2% of the cases.
   5. ER-  PR-  = 25% of the cases.

Response to anti-hormone therapy:

• >50% of the ER-positive cases respond to chemotherapy like tamoxifen, estrogen, androgens, oophorectomy, and adrenalectomy.
  • Positivity increases when PR is positive.
• The advantage is that Endocrine, anti-hormone (tamoxifen) therapy is highly effective and relatively non-toxic. It is more tolerable than other modalities like radiation and chemotherapy.
• The disadvantage is that ER/PR-negative breast cancer cases have no anti-hormone-positive role.

The brown color indicates a positive reaction (ER/PR+)

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