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11-protein signature predicted prognosis in triple-negative breast cancer
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A prognostic protein signature for triple-negative breast cancer may better identify patients who should undergo adjuvant chemotherapy, according to study results.
Researchers evaluated frozen primary tumor samples from 126 lymph node-negative and adjuvant therapy-naive patients with advanced triple-negative breast cancer.
Median follow-up for good-prognosis patients — defined as patients who remained free of distant metastasis for at least 5 years after surgery — was 117 months for the training set (n=63) and 108 months for the test set (n=63).
Researchers used global proteome profiling of the training set to develop an 11-protein signature, which included CMPK1, AIFM1, FTH1, EML4, GANAB, CTNNA1, AP1G1, STX12, AP1M1, CAPZB and MTHFD1.
When evaluated in the test site, the signature demonstrated 89.5% sensitivity (95% CI, 69.2-98.1), 70.5% specificity (95% CI, 61.7-74.2) and 56.7% positive predictive value (95% CI, 43.8-62.1).
The signature demonstrated 93.9% negative predictive value (95% CI, 82.3-98.9) among poor-prognosis patients.
Results of univariate analyses indicated that predicted poor-prognosis patients were more likely to develop distant metastasis (HR=13.15; 95% CI, 3.03-57.07) and die of breast cancer (HR=22.78; 95% CI, 3-173.08) than predicted good-prognosis patients.
After accounting for age, menopausal status, tumor size and grade, as well as the prognosis of the 11-protein signature, the associations remained significant for distant metastasis (HR=12.45; 95% CI, 2.67-58.11) and breast cancer-related death (HR=36.08; 95% CI, 4-325.67).
Researchers determined high percentages of good-prognosis patients from the analysis would have been defined as high risk and would have subsequently received adjuvant chemotherapy according to the St. Gallen (91%) and NIH (95%) treatment guidelines. Thirty percent of good-prognosis patients would have received adjuvant chemotherapy according to the 11-protein signature. Therefore, the signature would have reduced by 60% the number of patients in the test set who would have been spared adjuvant chemotherapy.
“Our signature could aid in clinical practice to avoid unnecessary treatment with adjuvant chemotherapy of [lymph node-negative triple-negative breast cancer] patients,” the researchers wrote. “Future prospective clinical trials are needed to further consolidate the validity of the 11-protein signature.”
Disclosure: The researchers report no relevant financial disclosures.
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