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An update on breast cancer biomarkers.

Biomarkers are becoming key predictors of cancer outcomes, particularly in breast cancer. By identifying the presence of biomarkers in breast tumors, healthcare providers are better able to prescribe effective, personalized treatments that are more likely to result in positive outcomes for patients. In her article in the December 2010 issue of the Clinical Journal of Oncology Nursing, Maxwell discusses the three traditional breast cancer biomarkers and what they mean for breast cancer care, and offers highlights on emerging biomarkers that are still under investigation.



Traditional Biomarkers

Three biomarkers have historically been used in breast cancer care: estrogen receptor (ER), progesterone receptor (PR), and HER2. These markers have been such a reliable guide for treatment and predictor of breast cancer outcomes that the American Society of Clinical Oncology (ASCO) and National Comprehensive Cancer Network guidelines both recommend routine measurement of all three at diagnosis.

Estrogen receptor: "ER status is the most powerful individual predictive factor examined in breast cancer," Maxwell says. Two-thirds of patients younger than 50 years and 80% of patients older than 50 years have ER-positive tumors.

ER status is significant because it strongly predicts the efficacy of antiestrogen therapies such as tamoxifen and aromatase inhibitors. Patients whose tumors do not express ER are unlikely to benefit from these treatments and can therefore be spared from unnecessary therapies. In addition, among tumors that do express ER, higher expression predicts an even better response to tamoxifen.

Of note is that hormone status can differ in tumors based on site and stage of disease. For example, metastatic tumors can have a different status than primary tumors, or a tumor that started as ER-positive at diagnosis may become ER-negative at a later stage of disease.

Progesterone receptor: PR expression is related to estrogen, so tumors that are ER negative are usually negative for PR as well. Patients whose tumors are positive for both ER and PR usually have a greater five-year overall survival than those whose tumors are "double negative." This is because ERand PR-positive tumors are the most likely to respond to treatments such as tamoxifen.

Like with ER expression, PR expression can change within a tumor over the course of the disease. In fact, once a tumor has metastasized, 40% of those that were PR positive are found to be PR negative.

HER2: About 15%-30% of newly diagnosed breast cancers overexpress HER2 protein. HER2 overexpression is usually associated with poorer outcomes than in tumors that do not express the protein, but it also is a marker for tumors that are more likely to respond to certain treatments such as trastuzumab, tyrosine kinase inhibitors, and monoclonal antibodies. As with the other hormone markers, HER2 expression can vary over the disease course.

Emerging Biomarkers

Several new, potential biomarkers have been identified, which researchers are investigating intensively. For now, data are insufficient to support their routine use in practice, but they will likely be in the news in the future once their usefulness has been adequately verified.

Cancer stem cells: These are distinct subsets of cells that have stem cell-like properties which enable them to grow rapidly and form new tumors. Cancer stem cells make up only about 10%-20% of the cells in a tumor. In breast cancer, stem cells that are positive for CD44 and negative or low for CD24 are the most prolific: studies have shown that as few as 100 stem cells with this pattern of markers are sufficient to regenerate tumors. That pattern also was found to have an invasive nature that resulted in shorter metastasis-free and overall survival.

Circulating tumor cells: Circulating tumor cells (CTCs) with epithelial characteristics are present only in the blood of patients with cancer, rarely in healthy individuals or those with benign tumors. Researchers have found that CTCs have both prognostic and predictive value; for example, in patients with metastatic breast cancer, the number of CTCs could predict disease progression and survival earlier than traditional imaging techniques. One study showed that patients who had more than five CTCs in 7.5 ml of blood at initial diagnosis had shorter progression-free and overall survival.

More research needs to be completed before measuring CTCs becomes a routine part of practice. ASCO guidelines currently do not recommend that CTCs be used to diagnose breast cancer or influence treatment decisions.

Microtubule-associated protein tau: Breast cancers with high tau expression were found to be less susceptible to paclitaxel but possibly more responsive to ixabepilone.

Beta III-tubulin: Tumors that overexpress beta III-tubulin may be resistant to taxanes but may be more responsive to ixabepilone in the neoadjuvant setting.

Topoisomerase II: Studies have found that tumors with higher levels of topoisomerase II (topo-II) were more responsive to anthracyclines, but the reverse was also true, where tumors with topo-II deletion also had a high response. This confounds topo-II's use as a biomarker. Several studies have found that topo-II is coexpressed with HER2, and so research is focusing on this area.

Thymidine phosphorylase: Tumors that express thymidine phosphorylase (TP) are more aggressive but also more responsive to treatments such as radiation, anthracyclines, and taxanes. TP is also being studied as a marker for sensitivity to capecitabine treatment.

For more information about breast cancer biomarkers, refer to the full article by Maxwell (2010).

Key Definitions

Biomarker: an objectively measured characteristic that can be an indicator of normal biologic and pathogenic processes or therapeutic responses

Predictive biomarker: provides information on the effect of a therapeutic intervention or is the target of therapy

Prognostic biomarker: provides information about a patient's overall cancer outcome, independent of therapy

Five-Minute In-Service is a monthly feature that offers readers a concise recap of full-length articles published in the Clinical Journal of Oncology Nursing (CJON) or Oncology Nursing Forum. This edition summarizes "Biomarker Research in Breast Cancer," by Cathy Maxwell, RN, OCN[R], which was featured in the December 2010 issue of CJON. Questions regarding the information presented in this Five-Minute In-Service should be directed to the CJON editor at Photocopying of this article for educational purposes and group discussion is permitted.

Maxwell, C. (2010). Biomarker research in breast cancer. Clinical Journal of Oncology Nursing, 14, 771-783. doi: 10.1188/10.CJON.771-783

As Seen in the Clinical Journal of Oncology Nursing

[By Elisa Becze, BA, ELS, ONS Staff Writer]
COPYRIGHT 2011 Oncology Nursing Society
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Title Annotation:five-minute in-service
Author:Becze, Elisa
Publication:ONS Connect
Geographic Code:1USA
Date:Feb 1, 2011
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