Gene assay facilitates personalizing extended endocrine therapy

VK Gadi

CHICAGO – The Breast Cancer Index, a gene assay that provides information about a patient’s risk for distant recurrence as well as the likelihood of benefit from extended endocrine therapy, may be an effective tool for physicians to use in determining which patients with early stage, hormone receptor-positive disease should prolong treatment with endocrine therapy, according to findings presented at the ASCO Annual Meeting.

Recent research, including results of the phase 3 MA.17R trial that were presented at last year’s ASCO meeting, demonstrates that extending endocrine therapy from 5 to 10 years in this patient population does reduce the risk of recurrence. However, this benefit appears to be most apparent in a specific set of patients, according to VK Gadi, MD, PhD, associate professor of medicine in the division of oncology at the University of Washington, associate member of the clinical research division at Fred Hutchinson Cancer Research Center and member of the Seattle Cancer Care Alliance.

“Last year at ASCO, we learned that an additional 5 years of aromatase inhibitor therapy with letrozole was feasible, but it benefited very few women,” Gadi told HemOnc Today. “The benefits were really restricted to new breast cancer events. The question then becomes: if we’re not going to deploy these strategies for all patients, who are the right patients? This is a space where biomarkers could really be helpful.”

BCI analyzes recurrence risk, benefit of extended therapy

The Breast Cancer Index, or BCI, uses two assays to assess the efficacy of extended endocrine therapy, according to Gadi. BCI Predictive examines the HOXB13:IL17BR ratio index to estimate how likely a patient is to benefit from extended endocrine therapy. BCI Prognostic uses an algorithm that combines the HOXB13:IL17BR ratio and the molecular grade index to assess an individual’s risk for late distant recurrence.

Gadi and colleagues used information from the Clinical Database for Correlative Studies, a collection of more than 50 clinicopathologic and molecular variables from cases that were analyzed with the BCI, to examine clinical and pathologic characteristics, prognostic and predictive assay results, and physician testing patterns in 14,463 patients. Median age was 58.2 years (range, 23-92); most women (73.9%) were aged 50 years and older.

Most patients included in the study had stage I or stage II disease (IA, 47.3%; IB, 3.5%; IIA, 29.1%; IIB, 14.1%), though a small portion (6%) did have stage III disease. Approximately half of the cases were grade 2 disease (51%); the remainder were grade 1 (29%) and grade 3 (20%). Nearly all patients had ER-positive, PR-positive disease (87.7%); only 11.3% of patients had ER-positive, PR-negative disease. Slightly more than 10% of patients had HER-2-positive disease (11.3%).

Extended endocrine therapy for 4 to 6 years after diagnosis was recommended for 55.7% of patients. Most women who received an order for extended therapy (23.1%) were treated for more than 6 years after diagnosis; 14.4% were treated for 1-4 years and 6.8% were treated for less than 1 year.

Clinical, personal factors affect treatment choice

The patient’s lymph node status – whether positive or negative – is an important factor in understanding the importance of these findings and determining how to incorporate this assay into practice, according to Gadi. The analysis included 3,395 patients who were lymph-node negative. Of those, BCI Prognostic classified 50.6% as low risk for late distant recurrence; 49.4% were identified as high risk. According to BCI Predictive results, 41% of lymph node-negative patients were highly likely to benefit from extended endocrine therapy; 59% were deemed to have a low likelihood of benefit.

Patients with lymph node-positive disease were tested with the BCIN+ Prognostic algorithm, which examined BCI score plus tumor size/grade. Of 818 patients included in this part of the analysis, 77.3% demonstrated a high risk for recurrence; 22.7% were considered low-risk. More than half of the patients with lymph node-positive disease (55.4%) were determined to have a low likelihood of benefit from extended endocrine therapy compared with 44.6% of patients shown to have a high likelihood of benefit, according to the BCI Predictive Analysis.

“There’s a general opinion that many of the patients who have this test done are node-negative,” Gadi said. “This makes sense, because patients with node-positive disease are, clinically, higher-risk, and providers often extend endocrine therapy in this group regardless of what the BCI reveals. It might not be smart or right, but that is standard prescribing behavior.”

Approximately three-quarters of patients with node-positive disease were very likely to experience disease recurrence, which Gadi called “surprising.”

“This is the group in whom you would consider extending endocrine therapy, especially if they’re tolerating the treatment reasonably well,” he said.

The ability to more accurately predict which patients are likely to recur – and which individuals are expected to benefit from extended endocrine therapy – enables the clinician and the patient to make more informed decisions.

“This test provides prognostic and predictive information,” Gadi said. “It enables you to have a discussion with patients about whether they would continue the therapy. If the patient says, ‘No, I wouldn’t consider extending the treatment,’ then the discussion is closed. However, if a patient is open to it, the BCI can help you understand the likelihood of benefit.”

The development of tools such as the BCI represent an ever-growing trend toward personalized medicine, which includes the ability to make decisions about de-escalating therapy in certain patients, Gadi continued.

“We’re in an era where, in certain diseases, we’re doing quite well, and we could, forevermore, increase the intensity of therapy to try and close the gap for the remaining patients who don’t respond,” he said. “However, when we do that, we’re exposing everyone to the same therapies, the same doses. A big question right now is how to de-escalate treatment in certain patients to preserve quality of life while maintaining efficacy. An assay like the BCI allows us to make treatment decisions confidently and to offer patients choices.” – by Julia Ernst, MS

References:

Breast Cancer Index. About breast cancer index. Available at: https://www.breastcancerindex.com/about-breast-cancer-index. Accessed August 17, 2017.

Breast Cancer Index. Biotheranostics presents first data from the BCI Clinical Database for Correlative Studies. Available at: https://www.breastcancerindex.com/biotheranostics-presents-first-data-from-the-BCI-clinical-database-for-correlative-studies-at-asbs17. Accessed August 17, 2017.

Mahtani RL, et al. Abstract 551. Presented at: ASCO Annual Meeting: June 2-6, 2017; Chicago.

Disclosures: Gadi reports that he has patients, royalties and other intellectual property with PNP Therapeutics and stock and other ownership interests with SEngine Precision Medicine; he also receives research funding through his institution from Genentech and Roche. Mahtani reports that she serves as a consultant or adviser to Amgen, Biotheranostics, Celgene, Genentech, Pfizer and Sandoz, that she receives research funding through her institution from Genentech and that she receives travel, accommodations and expenses from Amgen, Biotheranostics, Celgene, Genentech/Roche and Pfizer. Please see the full study for a list of all other researchers’ relevant financial disclosures