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Mammostrat score helps predict residual risk in postmenopausal ER-positive patients
The Mammostrat score predicted distant recurrence-free survival for breast cancer patients treated with exemestane, as well as patients treated with tamoxifen followed by exemestane regardless of nodal status and chemotherapy, according to results of a large retrospective analysis.
John M.S. Bartlett, PhD, FRCPath, of the Ontario Institute for Cancer Research, and colleagues tested the efficacy of the Mammostrat test in the Tamoxifen versus Exemesetane Adjuvant Multicenter (TEAM) trial. This novel multigene test, which uses five histochemical markers to stratify patients according to recurrence risk, has been validated recently in several retrospective clinical trial cohorts.
The researchers collected pathology blocks from 4,598 TEAM patients at a central laboratory and constructed tissue microarrays. Bartlett and colleagues were able to assign a Mammostrat risk score to 3,837 cases, which was 83.7% of the target population. This group comprised the primary analysis set.
Multivariate regression analyses, which the researchers corrected for conventional clinicopathologic markers, showed that Mammostrat offered significantly more information on distant recurrence-free survival after endocrine therapy in estrogen receptor-positive node-negative patients (n=1,226) who did not receive chemotherapy (P=.004). In addition, analyses on patients not exposed to chemotherapy, regardless of nodal status (n=2,559) and in the entire cohort (n=3,837), indicated that Mammostrat scores offered more information on DRFS in these groups. The researchers saw no differences between the two endocrine treatment regimens.
In node-negative patients with a low-risk Mammostrat score who were not receiving chemotherapy, the 5-year DRFS was 96%. There was no difference between treatment groups. Patients with medium-risk scores were at a 58% increased risk compared with patients who had low-risk scores. Those with high-risk scores were at 159% increased risk of distant relapse or death compared with those who had low-risk scores.
“Thus, the Mammostrat risk score adds significant information on residual risk after endocrine therapy in ER-positive breast cancer when corrected for conventional clinicopathologic features, including nodal status,” the authors wrote. “To our knowledge, this is the largest single study to assess the potential of this marker panel to provide information on residual risk, and analysis showed that this panel was effective for postmenopausal patients treated with an aromatase inhibitor (exemestane) for 5 years and patients given tamoxifen followed by an aromatase inhibitor in a switch strategy.”
In an accompanying editorial, Rohit Bhargava, MD, Adam M. Brufsky, MD, PhD, and Nancy E. Davidson, MD, all of the University of Pittsburgh, noted that, until recently, oncologists struggled to determine prognosis and make chemotherapy decisions in patients with early-stage, ER-positive breast cancer.
“Now, with a plethora of tests to choose from, the dilemmas are which test to request and how to assimilate information from different tests,” they wrote. “Most assays work well at the extremes (ie, determining and separating low risk from high risk) but tend to show variable results for patients who fall in the middle. We must complete our efforts to improve the categorization of patients in the intermediate zone, realizing that in these patients, treatment will ultimately be guided on the basis of individual assessment of benefits and risks.
“The future of diagnostic testing in ER-positive breast cancer likely will rely on devising and reliably deploying assays that predict for benefit of additional therapy such as newer targeted therapies,” they added. “It is certain that no particular technology holds the key, and all possible avenues need to be explored.”
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