Estrogen/Progesterone Receptor (ER/PR Receptors)

Sample

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.

Indication

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

Precaution

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

1. Biochemical concept:
   1. ER/PR receptors are a cellular protein with high affinity and great specificity for these hormones.
   2. These receptors 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 the use of endocrine therapy in females with breast carcinoma.

2. 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 ER-positive responds to anti-hormone therapy.
   5. 95% of the cases negative ER-receptor fails to respond to anti-hormone therapy.
3. Breast cancer ER-positive or PR positive are twice sensitive to anti-hormonal therapy (70 % response to antihormonal therapy).
4. While ER/PR negatives cases have a 10% response rate.
5. ER/PR positive cases have more disease-free survival.
6. Hormone receptors should be done on all breast cancers.
7. ER/PR is more positive in a menopausal group than younger patients.
8. PR- receptor is useful to help to the assay of the ER-receptors.
   1. Metastatic cancer with ER and PR receptor-positive tumors have a response rate of 75% to endocrine therapy.
   2. If the ER-positive and PR negative tumors have a 40% response rate.
   3. If ER-negative and PR-positive patient’s only response rate is 25% for endocrine therapy.
   4. In the case of ER and PR negative, the response rate is only 5%.
9. 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.

Interpretation

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

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.

Score	Positive cells %	Intensity	Intensity score
0Score	o	None	0
1	None	Week	1
2	1 to 10	Intermediate	2
3	11 to 33	Strong	3
4	34 to 66
5	66 to 100

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:

ER	PR	Response to hormones therapy
positive	positive	75 %
negative	positive	60 %
positive	negative	35 %
negative	negative	25 %

• >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 the other modalities like radiation and chemotherapy.
• The disadvantage is that In ER/PR negative breast cancers cases has no anti-hormone positive role.

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