July 2013 Edition Vol.11, Issue 7

Breast and Lung Cancer Biomarker Research at ASCO: Changing Treatment Patterns

Breast and Lung Cancer Biomarker Research at ASCO:
Changing Treatment Patterns

By Julie Katz, MPH, MPhil

Biomarkers played a prominent role in the research presented in a number of tumor types at the 2013 American Society of Clinical Oncology (ASCO) annual meeting. New data presented at ASCO 2013 showed novel clinical implications of biomarkers, including estrogen receptor (ER), progesterone receptor (PR), and HER2 in breast cancer, and EGFR and EML4-ALK in lung cancer. In our post-ASCO discussion, we illustrate the influence of biomarkers on testing and treatment, of genetic changes throughout the course of disease, acquired resistance and treatment patterns, and biopsy practices and plasma DNA testing methods. All of these issues have potentially profound implications on a tumor’s behavior and sensitivity throughout the course of the disease. The biomarker research presented represents different approaches to cancer treatment.

The Biomarker France Study

One of the most exciting and promising presentations on biomarkers was the Biomarkers France study (Barlesi F. J Clin Oncol. 2013;31 [suppl]; abstr 8000)—the largest biomolecular study ever conducted. Investigators analyzed the mutation status of 10,000 advanced non-small cell lung cancer (NSCLC) patients and provided molecular profiling of EGFR, HER2, KRAS, BRAF and PIK3CA mutations as well as EML4-ALK translocation. This study demonstrated the feasibility of NSCLC tumor profiling and indicated the feasibility of a similar profiling study for other tumors. Moreover, tumor profiling in this study identified a known therapeutic target in 46% of the samples. Tumor profiling helped manage NSCLC patients in 57% of the cases and in 70% of the EGFR-mutant patients. Upon study completion, 19,000 patients will be included in the final analysis. The authors conclude that the study provides solid data on the value of a nationwide biomarker screening policy for NSCLC patients.

Breast Cancer Biomarkers

Three abstracts at ASCO reported investigations of new clinical uses of estrogen-receptor (ER) status, progesterone-receptor (PR) status and HER2 amplification status. ER, PR and HER2 were the first three predictive biomarkers identified historically, representing three of 11 unique biomarkers in oncology that are currently recommended to guide choice of drug regimen.  Beyond the predictive and prognostic role of ER, PR and HER2 in breast cancer, these studies demonstrate important considerations about how biomarkers may change throughout the course of disease and through different disease states, and the impact this may have in guiding treatment decisions and informing prognosis. 

Concordance between the Primary Tumor and Recurrence

A Japanese study of 117 consecutive cases investigated changes in biomarkers ER, PR, HER2 and Ki-67 between the primary tumor and a recurrence after breast-conserving surgery (Okumura Y et al. J Clin Oncol. 2013;31 [suppl]; abstr 1116). Patients in this study with an ipsilateral breast cancer tumor recurrence (IBTR) without distant metastases underwent surgery for IBTR between 1989 and 2008. The percentage of cases with concordance in breast cancer subtype (luminal A, luminal B/HER2-negative, luminal B/HER2-positive, HER2, triple negative) between primary and recurrent lesions was 62.1%. The PR-positive rate decreased significantly (p=0.01) and the mean Ki-67 index increased significantly (p=0.047) from the primary tumor to the recurrence. Discordance in the Ki-67 index between the primary tumor and IBTR was associated with a lower distant disease-free survival (DDFS), and this association was statistically significant among patients with a recurrence in the same quadrant of the ipsilateral breast.

A Korean study also examined biomarker agreement, comparing the primary breast tumor and a metastatic recurrence (Shin HC et al. J Clin Oncol. 2013;31 [suppl]; abstr 1039)). This study of 193 patients looked at the triple receptor status (ER, PR and HER2) and divided the patients into three groups: concordant non-triple-negative (TN), concordant TN, and a discordant group (Figure 1).

Source: Shin HC et al. J Clin Oncol. 2013;31 [suppl]; abstr 1039.

The study compared long-term outcomes, systemic recurrence-free survival (SRFS), overall survival (OS) from primary and OS from metastasis. The highest OS rate from primary was among the concordant non-TN group, followed by the discordant group; the concordant TN group had the lowest OS rate from primary. Similarly, the OS rate from metastasis was highest among the concordant non-TN group. However, the OS rate from metastasis was not significantly different between the discordant group and the concordant TN group. The relative risk of 2.5 (95% CL: 1.2 to 5.3) among the discordant group showed it to be an independent prognostic factor for death after metastasis.

These studies raise important questions about biomarker testing during the course of disease and treatment. Biopsy and biomarker testing at recurrence may be necessary to detect a change in the biomarker status of the recurrence compared to the primary tumor and could influence patient prognosis and treatment decisions. These data provide further support for the National Comprehensive Cancer Network (NCCN) recommendation to retest patients who were negative or unknown at initial biomarker testing (http://www.nccn.org/professionals/physician_gls/f_guidelines.asp#breast, Accessed June 25, 2013).

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Article Comments

Nguyen Nguyen

quotes Hello Ms. Katz, In the article "Breast and Lung Cancer Biomarker Research at ASCO", for breast cancer you wrote "...representing three of 11 unique biomarkers in oncology that are currently recommended to guide choice of drug regimen." Could you please list the names of these 11 biomarkers? Thank you very much, Nguyen quotes

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