Metastatic Breast Cancer With Discordant Tumors: Small Study Reports Treatment by Primary Status May Improve Survival

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The survival of these 14 patients was consistent with my hypothesis that patients with treatment plans based on the primary tumor receptor status have a longer median life expectancy.

T. Allen Pannell, Jr, PhD

In a small retrospective series, patients with metastatic breast cancer treated according to the receptor status of the primary tumor, not the metastatic one, had significantly longer median overall survival. The study was reported at the 2016 Miami Breast Cancer Conference by T. Allen Pannell, Jr, PhD, of Lincoln Memorial University, Knoxville, Tennessee.1 Dr. Pannell, a statistician, began researching the topic as a personal mission (see sidebar) and believes his may be the first report of how first-line treatment by receptor status may impact survival.

Little to No Evidence to Guide Decision-Making

A meta-analysis of 48 articles found discordance rates of 20% for the estrogen receptor, 33% for the progesterone receptor, and 8% for the HER2 oncogene.2 “The growing consensus is that hormone receptor status should be retested, but there is little to no evidence that utilizing the metastatic tumor receptor status test results improves the clinical outcome of patients,” said Dr. Pannell. “In fact, there is evidence that changes to treatment plans based on this retesting can be harmful to patient outcomes.”3

Dr. Pannell has estimated that based on breast cancer statistics, 12 women each day in the United States may face discordant receptor results and so must decide, with their oncologist, whether to base first-line treatment on the primary or metastatic tumor status. He added that at this time, recommendations to treat based on metastatic status are “at the lowest level of evidence or are an ‘opinion.’”

Dr. Pannell pointed to the 2nd ESO-ESMO (European School of Oncology–European Society for Medical Oncology) International Consensus Guidelines of the Advanced Breast Cancer Consensus Conference (2014), which states, “It is currently unknown which result should be used for treatment decision making.”4

In addition, he cited a study by Liedtke et al showing that patients with triple-negative breast cancer who have discordant tumors have significantly lower median progression-free survival than do patients with concordant tumors, “probably due to inappropriate use of targeted therapies,” the authors concluded.3

Treating According to Primary

To study this issue, Dr. Pannell conducted a retrospective analysis of the tumor registry and charts of patients at the University of Tennessee Cancer Center who had recurrent metastatic disease between 2000 and 2014. A total of 317 records were accessed, and 124 provided complete information. A total of 14 cases were found to have discordant hormone and/or HER2 receptor status; 8 patients were treated for metastatic disease based on their primary tumor status, whereas 6 were treated based on the metastatic status.

“The survival of these 14 patients was consistent with my hypothesis that patients with treatment plans based on the primary tumor receptor status have a longer median life expectancy,” Dr. Pannell said. Post-recurrence survival was 4.0 years for patients treated according to the primary tumor status vs 0.7 years for those treated by metastatic status (P = .049).

In a univariate analysis of 15 patient-, disease- and treatment-related factors, none were significantly different between patients who received treatment based on primary vs metastatic receptor status. There was a trend for patients receiving treatment based on the primary to have more nonvisceral disease.

Dr. Pannell acknowledged that his study is small, and therefore has limitations, and would like to see additional analyses from larger databases. He is in contact with other researchers. “Everyone’s been wonderful,” he revealed, “to answer an e-mail from a guy at a business school.” ■

Disclosure: Dr. Pannell reported no potential conflicts of interest. Dr. Pannell's dissertation is available here.


1. Pannell TA, Zaretzki R: Utilizing metastatic tumor receptors on relapse worsens patient outcomes. 2016 Miami Breast Cancer Conference. Presented March 11, 2016.

2. Aurilio G, Disalvatore D, Pruneri G, et al: A meta-analysis of oestrogen receptor, progesterone receptor and human epidermal growth factor receptor 2 discordance between primary breast cancer and metastases. Eur J Cancer 50:277-289, 2014.

3. Liedtke C, Broglio K, Moulder S, et al: Prognostic impact of discordance between triple-receptor measurements in primary and recurrent breast cancer. Ann Oncol 20:1953-1958, 2009.

4. Cordoso F, Costa A, Norton L, et al: ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2). Breast 23:489-502, 2014.

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