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What are the receptors tested in breast cancer?

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Key concept

Breast cancer is composed of several biological subtypes. Newly diagnosed breast cancers must be tested for estrogen receptor (ER) and progesterone receptor (PR) expression and for overexpression of human epidermal growth factor 2 (HER2) receptors. This information is critical for both prognostic and therapeutic purposes.1

Clinical scenario

A 51-year-old woman with stage I breast cancer presents after lumpectomy and sentinel lymph node biopsy surgery for discussion of systemic therapy. The ER/PR and HER2 neu status are pending.

Action items

The proportions of breast cancers with different receptor phenotypes were evaluated in one study and showed the following case distribution2:

  • Hormone receptor (ER and/or PR)–positive cancers: 80% of cases

  • HER2 overexpression: 23% of cases

    • Of these, 67% and 32% were hormone receptor–positive and –negative, respectively

  • ER, PR, and HER2–negative (triple-negative) cancers: 13% of cases

The frequency of subtypes varies according to race. Compared with white women, African-American women are less likely to have hormone receptor (ER/PR)–positive, HER2-negative disease (48% vs. 64%, respectively) and more likely to have ER/PR/HER2-negative disease (22% vs. 11%, respectively).3

Discussion

ER and PR expression are prognostic factors for invasive breast cancer, particularly in the first 5 years after the initial diagnosis. In addition, patients who are ER- and/or PR-positive are candidates for endocrine therapy as neoadjuvant or adjuvant treatment. ER positivity is defined by immunohistochemistry (IHC) for ER and PR in >1% of tumor cells.1

HER2 overexpression is present in 20% of patients and predicts those who will benefit from HER2-directed therapy. HER2 overexpression is detected by uniform intense membrane staining of >30% of invasive tumor cells (IHC 3+) or the presence of HER2 gene amplification by fluorescence in-situ hybridization (FISH) defined as a ratio of HER2/CEP17 (centromeric probe to chromosome 17) ratio ≥2.0.1

Assays for tumor expression of ER, PR, and HER2 neu have well-established utility in the clinical management of patients with both early stage and advanced breast cancer. They identify tumors for which endocrine and/or anti-HER2 therapies are valuable therapeutic options, and they should be routinely obtained on all tumor specimens.

Pearls
  • IHC has rapidly become the predominant method for measuring ER and PR in clinical practice4

  • Due to variability in ER and PR IHC assay caused by a variety of factors, national guidelines for testing have been developed4

References
  1. NCCN Clinical Practice Guidelines in Oncology for breast cancer. Available at: http://www.nccn.org.

  2. Parise CA, Bauer KR, Brown MM, et al. Breast cancer subtypes as defined by the estrogen receptor (ER), progesterone receptor (PR), and the human epidermal growth factor receptor 2 (HER2) among women with invasive breast cancer in California, 1999-2004. Breast J 2009; 15:593-602.

  3. O’Brien KM, Cole SR, Tse CK, et al. Intrinsic breast tumor subtypes, race, and long-term survival in the Carolina Breast Cancer Study. Clin Cancer Res 2010; 16:6100-10.

  4. Hammond ME, Hayes DF, Dowsett ...

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