| Cancer antigen (CA) 15-3 and CA 27.29 as markers for breast cancer as screening, diagnostic, or staging tests |
Present data are insufficient to recommend CA 15-3 or CA 27.29 for screening, diagnosis, and staging. There is no change from the guideline published in 2000. |
| CA 15-3 and CA 27.29 to detect recurrence after primary breast cancer therapy |
Present data do not support the use of CA 15-3 and CA 27.29 for monitoring patients for recurrence after primary breast cancer therapy. There is no change from the guideline published in 2000. |
| CA 15-3 and CA 27.29 to contribute to decisions regarding therapy for metastatic breast cancer |
For monitoring patients with metastatic disease during active therapy, CA 27.29 or CA 15-3 can be used in conjunction with diagnostic imaging, history, and physical examination. Present data are insufficient to recommend use of CA 15-3 or CA 27.29 alone for monitoring response to treatment. However, in the absence of readily measurable disease, an increasing CA 15-3 or CA 27.29 may be used to indicate treatment failure. Caution should be used when interpreting a rising CA 27.29 or CA 15-3 level during the first 4-6 weeks of a new therapy, since spurious early rises may occur. There is no change from the guideline published in 2000. |
| Carcinoembryonic antigen (CEA) for screening, diagnosis, staging, or routine surveillance of breast cancer patients after primary therapy |
CEA is not recommended for screening, diagnosis, staging, or routine surveillance of breast cancer patients after primary therapy. There is no change from the guideline published in 2000. |
| CEA to contribute to decisions regarding therapy for metastatic breast cancer |
For monitoring patients with metastatic disease during active therapy, CEA can be used in conjunction with diagnostic imaging, history, and physical examination. Present data are insufficient to recommend use of CEA alone for monitoring response to treatment. However, in the absence of readily measurable disease, an increasing CEA may be used to indicate treatment failure. Caution should be used when interpreting a rising CEA level during the first 4-6 weeks of a new therapy, since spurious early rises may occur. There is no change from the guideline published in 2000. |
| Estrogen receptors (ERs) and progesterone receptors (PgRs) |
ER and PgR should be measured on every primary invasive breast cancer and may be measured on metastatic lesions if the results would influence treatment planning. In both pre-and postmenopausal patients, steroid hormone receptor status should be used to identify patients most likely to benefit from endocrine forms of therapy in both the early breast cancer and metastatic disease settings. In patients with ductal carcinoma in situ (DCIS) who are candidates for hormonal therapy, data are insufficient to recommend routine measurement of ER and PgR for therapy recommendations. |
| DNA flow cytometry–based parameters |
Present data are insufficient to recommend use of DNA content, S phase, or other flow cytometry–based markers of proliferation to assign patients to prognostic groups. There is no change from the guideline published in 2000. |
| Immunohistochemically based markers of proliferation (Note: This topic is new to the guideline) |
Present data are insufficient to recommend measurement of Ki67, cyclin D, cyclin E, p27, p21, thymidine kinase, topoisomerase II, or other markers of proliferation to assign patients to prognostic groups. |
| Human epidermal growth factor receptor 2 (HER2) evaluation in breast cancer |
HER2 expression and/or amplification should be evaluated in every primary invasive breast cancer either at the time of diagnosis or at the time of recurrence, principally to guide selection of trastuzumab in the adjuvant and/or metastatic setting. Other utilities for HER2 evaluation are also discussed separately below. |
| HER2 to define prognosis for early stage breast cancer patients in the absence of systemic therapy |
HER2 amplification, overexpression, and the presence of HER2 extracellular domain are generally associated with a poorer prognosis. However, the value of this information in clinical practice is questionable and the use of HER2 for determining prognosis is not recommended. There is no change from the guideline published in 2000. |
| HER2 to select patients for anti-HER2–based therapy |
High levels of tissue HER2 expression or HER2 gene amplification should be used to identify patients for whom trastuzumab may be of benefit for treatment of breast cancer in the adjuvant or metastatic disease settings.
There is no change from the guideline published in 2000. |
| The utility of HER2 for predicting response to specific chemotherapeutic agents |
Level II evidence (prospective therapeutic trials in which marker utility is a secondary study objective) suggests that overexpression of HER2 (3+ by protein or >2.0 fluorescent in situ hybridization [FISH] ratio by gene amplification) identifies patients who have greater benefit from anthracycline-based adjuvant therapy. If a clinician is considering chemotherapy for a patient with HER2-positive breast cancer, it is recommended that an anthracycline be strongly considered, assuming there are no contraindications to anthracycline therapy. In the context of trastuzumab therapy, there is Level I evidence (single, high-powered, prospective, randomized, controlled trials specifically designed to test the marker or a meta-analyses of well-designed studies) that a nonanthracycline regimen may produce similar outcomes. At present, the Update Committee does not recommend that HER2 be used to guide use of taxane chemotherapy in the adjuvant setting. |
| HER2 to determine sensitivity to endocrine therapy |
HER2 should not be used to withhold endocrine therapy for a patient with hormone receptor–positive breast cancer, nor should it be used to select one specific type of endocrine therapy over another. There is no change from the guideline published in 2000. |
| Utility of circulating extracellular domain of HER-2 |
Measuring circulating extracellular domain of HER2 is not currently recommended for any clinical setting. There is no change from the guideline published in 2000. |
| p53 as a marker for breast cancer |
Present data are insufficient to recommend use of p53 measurements for management of patients with breast cancer. There is no change from the guideline published in 2000. |
| Urokinase plasminogen activator (uPA) and plasminogen activator inhibitor 1 (PAI-1) as a marker for breast cancer (Note: This topic is new to the guideline) |
uPA/PAI-1 measured by enzyme-linked immunosorbent assays (ELISAs) on a minimum of 300 mg of fresh or frozen breast cancer tissue may be used for the determination of prognosis in patients with newly diagnosed, node negative breast cancer. Immunohistochemistry (IHC) for these markers is not accurate, and the prognostic value of ELISA using smaller tissue specimens has not been validated. Low levels of both markers are associated with a sufficiently low risk of recurrence, especially in hormone receptor–positive women who will receive adjuvant endocrine therapy, that chemotherapy will only contribute minimal additional benefit. Furthermore, cyclophosphamide, methotrexate, and fluorouracil (CMF)-based adjuvant chemotherapy provides substantial benefit, compared with observation alone, in patients with high risk of recurrence as determined by high levels of uPA and PAI-1. |
| Cathepsin D as a marker for breast cancer |
Present data are insufficient to recommend use of cathepsin D measurements for management of patients with breast cancer. There is no change from the guideline published in 2000. |
| Cyclin E fragments as markers for breast cancer (Note: This topic is new to the guideline) |
Present data are insufficient to recommend use of whole length or fragment measurements of cyclin E for management of patients with breast cancer. |
| Proteomic analysis for breast cancer (Note: This topic is new to the guideline) |
Present data are insufficient to recommend use of proteomic patterns for management of patients with breast cancer. |
| Multiparameter gene expression analysis for breast cancer (Note: This topic is new to the guideline) |
In newly diagnosed patients with node-negative, estrogen-receptor positive breast cancer, the Oncotype DX assay can be used to predict the risk of recurrence in patients treated with tamoxifen. Oncotype DX may be used to identify patients who are predicted to obtain the most therapeutic benefit from adjuvant tamoxifen and may not require adjuvant chemotherapy. In addition, patients with high recurrence scores appear to achieve relatively more benefit from adjuvant chemotherapy (specifically [C]MF) than from tamoxifen. There are insufficient data at present to comment on whether these conclusions generalize to hormonal therapies other than tamoxifen, or whether this assay applies to other chemotherapy regimens. The precise clinical utility and appropriate application for other multiparameter assays, such as the MammaPrint assay, the "Rotterdam Signature," and the Breast Cancer Gene Expression Ratio are under investigation. |
| Bone marrow micrometastases as markers for breast cancer (Note: This topic is new to the guideline) |
Present data are insufficient to recommend assessment of bone marrow micrometastases for management of patients with breast cancer. |
| Circulating tumor cell assays as markers for breast cancer (Note: This topic is new to the guideline) |
The measurement of circulating tumor cells (CTCs) should not be used to make the diagnosis of breast cancer or to influence any treatment decisions in patients with breast cancer. Similarly, the use of the recently U.S. Food and Drug Administration (FDA)-cleared test for CTC (CellSearch Assay) in patients with metastatic breast cancer cannot be recommended until further validation confirms the clinical value of this test. |
