Decipher the Meaning of BRCA, ER/PR, and Her2

Decipher the Meaning of BRCA, ER/PR, and Her2

Familiarize yourself with genetic mutations and the tests that detect them to improve your breast cancer coding.

Unless you deal with the tests for breast cancer (BRCA), estrogen receptor (ER)/progesterone receptor (PR), and human epidermal growth factor receptor 2 (Her2) — or have gone through a diagnosis of breast cancer or know someone who has — you may not be familiar with them and their use in diagnosing and treating breast cancer. Let’s shed some light on these acronyms and their use.

BRCA1 and 2

BRCA1 and 2 are genes that have been identified in the production of tumor suppressor proteins. These genes are integral to repairing damaged deoxyribonucleic acid (DNA). Mutations of these genes increase the risk of breast and ovarian cancers. One study found that approximately 72 percent of women who inherit a BRCA1 mutation and approximately 69 percent of women who inherit a BRCA2 mutation will develop breast cancer by the age of 80.
The following CPT® codes can be used for BRCA1 and 2 mutation testing:
81211     BRCA1, BRCA2 (breast cancer 1 and 2) (eg, hereditary breast and ovarian cancer) gene analysis; full sequence analysis and common duplication/deletion variants in BRCA1 (ie, exon 13 del 3.835kb, exon 13 dup 6kb, exon 14-20 del 26kb, exon 22 del 510bp, exon 8-9 del 7.1kb)
81162                  full sequence analysis and full duplication/deletion analysis)
81212                  185delAG, 5385insC, 6174delT variants
81213                  uncommon duplication/deletion variants
BRCA 1 mutation testing is coded with:
81214     BRCA1 (breast cancer 1) (eg, hereditary breast and ovarian cancer) gene analysis; full sequence analysis and common duplication/deletion variants (ie, exon 13 del 3.835kb, exon 13 dup 6kb, exon 14-20 del 26kb, exon 22 del 510bp, exon 8-9 del 7.1kb)
81215                  known familial variant
BRCA 2 mutation testing is coded with:
81216     BRCA2 (breast cancer 2) (eg, hereditary breast cancer and ovarian cancer) gene analysis; full sequence analysis
81217                  known familial variant
The U.S. Preventive Services Task Force recommends women with family members having breast, ovarian, fallopian tube, or peritoneal cancer to be evaluated for a family history associated with increased risk of harmful BRCA mutations.
A positive BRCA result does not mean the patient has cancer, only that she is at an increased risk of developing certain kinds of cancer. The American Cancer Society and National Comprehensive Cancer Network recommend annual screening with both mammography and magnetic resonance imaging (MRI) for women at high risk of breast cancer, including BRCA1 or 2 positive.
BRCA1 and/or 2 positive results are assigned either ICD-10-CM code Z15.01 Genetic susceptibility to malignant neoplasm of breast or Z15.02 Genetic susceptibility to malignant neoplasm of ovary, depending on family history.
Other gene mutations include TP53, CDH1, and CHEK2, associated with breast cancer and RAD51C, RAD51D, and STK11, associated with an increased risk for ovarian cancer.
Biomarkers such as ER, PR, and Her2 can be prognostic, predictive, or both. Prognostic markers are associated with a patient’s overall clinical outcome. Predictive markers determine response to therapy. All primary invasive breast cancers should be tested for ER, PR, and Her2.


ER and PR testing aid in therapy planning, and are performed on breast cancer tissue. The results and frequencies can be classified, as shown in Table 1.
Table 1

Receptor Percent Occurrence
ER+ 80 percent Breast cancer cells have estrogen receptors.
ER+/PR+ 65 percent Breast cancer cells have both estrogen and progesterone receptors.
ER+/PR- 13 percent Breast cancer cells have only estrogen receptors.
ER-/PR+ 2 percent Breast cancer cells have only progesterone receptors.
ER-/PR- 25percent Breast cancer cells have neither estrogen nor progesterone receptors.

A positive result generally triggers the use of hormonal therapy. ER and PR are weak prognostic markers, but strong predictive indicators. ER/PR positive cancers are responsive to endocrine therapies such as tamoxifen. Endocrine therapy is highly effective and relatively non-toxic.


Her2 is an enzyme receptor seen in 15-20 percent of invasive breast cancers. A Her2 positive cancer is treated with Her2 targeted therapy, including Herceptin® (J9355 Injection, trastuzumab, 10 mg), Tykerb® (J8999 Prescription drug, oral, chemotherapeutic, nos), Perjeta® (J9306 Injection, pertuzumab, 1 mg), and Kadcyla® (J9354 Injection, ado-trastuzumab emtansine, 1 mg).
There are two FDA-approved methods for Her2 testing:

  • Immunoactivity detects the presence of Her2 protein on breast cancer tissue.
  • In-situ hybridization measures the number of copies of Her2 inside breast cancer cells.

Her2 is both a prognostic and predictive indicator. Her2 expression is associated with a diminished prognosis. Her2 positive patients are generally treated with anthracyclines and taxane-based chemotherapies and Her2 targeted therapies such as Herceptin® (J9355).
ER, PR, and Her2 testing may be reported with a variety of codes, depending on the methodology. Table 2 provides the available coding.
Table 2

CPT® Description ER PR Her2
84233 Receptor assay; estrogen X
84234                progesterone X
88360 Morphometric analysis, tumor immunohistochemistry (eg, Her-2/neu, estrogen receptor/progesterone receptor), quantitative or semiquantitative, per specimen, each single antibody stain procedure; manual X X X
88361                using computer assisted technology X X X
88342 Immunohistochemistry or immunocytochemistry, per specimen; initial single antibody stain procedure X X X
+88341 each additional antibody stain procedure (List separately in addition to code for primary procedure) X X X

Although ICD-10-CM codes are not available for PR and Her2 status, Z17.0 Estrogen receptor positive status [ER+] and Z17.1 Estrogen receptor negative status [ER-] report ER test results.

Triple Negative

Triple negative breast cancers (ER-/PR-/Her2-) occur in 10-20 percent of all breast cancers (and are more common in BRCA1 mutations). Women with triple negative breast cancer have tumor cells that do not contain receptors for ER, PR, or Her2. These tumors are treated with a combination of therapies, including surgery, chemotherapy, radiation therapy, and non-Her2 targeted therapy.
Examples of breast cancer chemotherapy drugs include anastrozole (S0170 Anastrozole, oral, 1 mg), bevacizumab (J9035 Injection, bevacizumab, 10 mg), capecitabine (J8521), cisplatin (J9060 Capecitabine, oral, 500 mg), cyclophosphamide (J9070 Cyclophosphamide, 100 mg), and doxorubicin (J9000 Injection, doxorubicin hydrochloride, 10 mg).

Breast Cancer Staging

Breast cancer can be coded by accounting the stage of the cancer. Breast cancer staging is based on the TNM system developed by the American Joint Committee on Cancer from seven key pieces of information:

  • Size of the tumor (T)
  • How many lymph nodes has the cancer spread to (N)
  • Has the cancer metastasized to other sites (M)
  • Is ER positive (ER)
  • Is PR positive (PR)
  • Is Her2 positive (Her2)
  • Grade of cancer (G)

Using these criteria, which include ER, PR, and Her2, breast cancers are assigned to one of five stages (0 through IV). Staging ranges from Stage 0 (non-invasive cancers that have not spread) to Stage IV (invasive cancers that have metastasized to other parts of the body). There are many combinations and circumstances that will cause a cancer to fall into each stage. Additionally, staging can be broken down to sub-stages for further delineation.

Breast Cancer Grading

Cancers cells are given grades based on how much the cancer looks like normal cells:

  • Grade 1 cells are slower growing, well differentiated, and look more like normal breast tissue.
  • Grade 2 cells are growing at a speed between grades 1 and 3, moderately differentiated, and look between grades 1 and 3 cells.
  • Grade 3 cells look very different from normal cells, and grow and spread faster.

Put Your Breast Cancer Coding to the Test

Example A: A 49-year-old woman with suspected breast cancer was biopsied. The pathology report found evidence of a ductile carcinoma in situ. Staining identified the tissue as ER/PR positive and Her2 negative based on manual morphometric analysis. Based on the patient’s history and pathology results, she was assigned as stage I.
Using the pathology results, you would report the diagnosis using ICD-10-CM codes Z17.0 and D05.10 Intraductal carcinoma in situ of unspecified breast, and the test with CPT® 88360 x 3.
Example B: A 23-year-old woman with a known family history of breast cancer was seen by her primary care provider. It was suggested she be tested for BRCA1 and 2 to determine her risk for developing cancer. Testing revealed she was BRCA1 positive.
Using the pathology results, you would report the diagnosis using ICD-10-CM Z15.01 and the test with CPT® 81211.

John Hopkins Medicine. Breast Center, Breast Pathology
NIH National Cancer Institute. BRCA Mutations: Cancer Risk and Genetic Testing

Frank Mesaros
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No Responses to “Decipher the Meaning of BRCA, ER/PR, and Her2”

  1. Sara says:

    What if a patient is being treated for primary breast cancer that is ER + who now has mets to the liver that is triple negative? Is it appropriate to code both Z17.0 and Z17.1?

  2. Frank says:

    I believe you would code the the current status that is effecting treatment.