The 21-gene Recurrence Score (RS) assay significantly influenced clinicians' decisions to recommend breast cancer patients for adjuvant chemotherapy, analysis of a population-based dataset showed.
Used to predict disease recurrence and benefit of chemotherapy in estrogen receptor-positive, lymph node-negative early-stage breast cancer (EBC), the assay had the strongest association with recommendation for chemotherapy, with an adjusted odds ratio (aOR) of 83 for high assay scores and 12 for intermediate scores, both relative to low scores.
Test use was significantly associated with younger age, white race, academic centers, private insurance, and pT2/pN0(i+) grade 2 to 3 disease, Peter Kabos, MD, of the University of Denver, Aurora, CO, and colleagues reported online in the Journal of Clinical Oncology.
"Our study revealed that the RS assay is an important predictor of the use of adjuvant chemotherapy in EBC, [and] affected clinicians' decisions regarding recommending adjuvant chemotherapy more than other variables studied," the study authors wrote. "Furthermore, significant differences exist in the use of the test and receipt of chemotherapy on the basis of race, insurance status, and type of facility."
The study, which looked at patients with EBC diagnosed from 2004 to 2012 who were included in the National Cancer Data Base, showed that the RS assay was ordered for 54.0% of 143,032 patients.
But the analysis found that testing guidelines weren't applied equally to different racial groups. In particular, it showed that black patients (aOR 1.31; 95% CI 1.20-1.43) and those treated in community facilities (aOR 1.49; 95% CI 1.35-1.63) were more likely to be tested outside the National Comprehensive Cancer Network guidelines, the analysis demonstrated. In addition, younger black patients (aOR 1.33; 95% CI 1.16-1.54) were more likely to receive chemotherapy despite low assay scores.
This study highlights the differences in implementation of ASCO guidelines for biomarkers across different practices in the U.S., Mateusz Opyrchal, MD, PhD, at Roswell Park Cancer Institute, University of New York at Buffalo, said in an interview. Opyrchal was not affiliated with the study.
"Overall, it did show that use [of the 21-gene RS] did guide use of chemotherapy especially in elderly women," Opyrchal said.
The study also highlighted "an ongoing trend across many studies that African American women are less likely to be treated according to published guidelines," he told MedPage Today.
Black patients (aOR 1.51; 95% CI 1.31-1.69) and those with high tumor grade (aOR 30.76; 95% CI 26.48-35.73) also had significantly higher assay scores, a finding that could reflect use patterns or less favorable tumor biology for estrogen receptor-positive disease, said Kabos and colleagues.
"The differences among races in receiving chemotherapy were significant for low test scores and younger age, and they disappeared with older age and higher test scores, indicating that the former group receives chemotherapy despite their low scores on the RS assay," the investigators suggested.
They noted that in their earlier study looking at racial differences in testing, scores, treatment and outcome, results showed that minority patients were significantly less likely to be tested despite meeting the criteria. The 2012 study also indicated that black women were significantly more likely to be tested outside the recommended guidelines.
Prognostic for Progression, Survival
A second study in women with late-stage breast cancer showed that the RS assay is independently prognostic for both time to progression (TTP) (hazard ratio 1.40; 95% CI 1.05-1.86; P=0.02) and 2-year overall survival (HR 1.83; 95% CI 1.14-2.95; P=0.013) in ER-positive/HER2-negative de novo stage IV breast cancer.
"Given the growing body of evidence that demonstrates the ability of the 21-gene RS to predict prognosis and benefit from chemotherapy in both early-stage node-positive and node-negative disease, these findings suggest that biology is the major determinant of outcome and warrant further prospective investigation," Tari A. King, MD, of Memorial Sloan Kettering Cancer Center in New York City, and colleagues reported in the Journal of Clinical Oncology.
"Prospective validation is needed to determine the potential role for this assay in the clinical management of this patient subset," they said.
The study looked at patients out of the Translational Breast Cancer Research Consortium (TBCRC) 013 -- a prospective registry that evaluated the role of surgery of the primary tumor in patients with de novo stage IV breast cancer. TBCRC 013 enrolled 127 patients from 14 sites from July 2009 to April 2012.
The analysis cohort was made up of 109 (86%) of these patients who had pretreatment primary tumor diagnostic biopsy samples suitable for RS analysis. Median patient age was 52 years. A total of 72 patients had HER2-negative breast cancer and 20 patients had HER2-positive disease.
At a median follow-up of 29 months, median TTP was 20 months and median survival was 49 months. An RS generated for the 101 primary tumor samples indicated that 22 were low ris, 29 were intermediate risk, and 50 were high risk.
"The majority of women with de novo stage IV breast cancer have ER-positive/HER2-negative disease and experience durable responses to first-line physician-directed therapy," noted King and colleagues."Within this population which represented more than one-third of patients enrolled in PALOMA-3, the potential to individualized treatment on the basis of predictive markers remains an unmet clinical need," they added.
"We have known that tumor biology of breast cancer influences prognosis and more aggressive, hormone therapy resistant ER-positive tumors have much worse prognosis then slower growing, hormone responsive tumors even in metastatic disease," Opyrchal commented. "21-gene RS assay is one of methods to help physicians determine the tumor biology better then pathologic assessment alone. Therefore, it is not surprising the patients with higher scores do not do as well as patients with lower score," he told MedPage Today.
"We will be looking into results looking at predictive value of the test in use of hormone and chemo-therapies in this patient population as it already does to some degree in the adjuvant setting," he added.
The authors in the first study disclosed relationships with Oncothyreon (Inst), Incyte (Inst), Abbott Laboratories/AbbVie (Inst), Galena Biopharma (Inst), Merrimack Pharmaceuticals (Inst), Genentech, Medivation (Inst), Astellas Pharma (Inst), CytRx (Inst), Eisai Medical Research (Inst), Johnson & Johnson (Inst), ImClone Systems (Inst), Covance/Bayer Healthcare (Inst), Angiochem (Inst), AstraZeneca (Inst), Eli Lilly (Inst) and Pfizer (Inst).
The authors in the second study disclosed relationships Genomic Health, Pfizer, Genentech, Carl Zeiss, Eisai (Inst), Seattle Genetics (Inst), Celgene (Inst), Veridex (Inst), Clearbridge Biomedics (Inst), Novartis (Inst), Myriad Genetics (Inst), Bayer (Inst), Merck, Eli Lilly, and The Breast Cancer Research Foundation.
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