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    • RS testing has been extensively validated in patients with

    2021-11-29

    RS testing has been extensively validated in patients with early stage, ER+, HER2− patients. TAILORx, a randomized controlled trial to evaluate the role of adjuvant chemotherapy by RS, found no recurrence or survival benefit to the addition of chemotherapy to endocrine therapy in patients with intermediate or low scores. However, this study and previous studies focused on patients with HER2− breast cancer. In the initial validation study of RS testing by Paik et all, HER2+ and HER2− patients were included. The study found a statistically insignificant greater proportion of patients with distant recurrence at 10 years among patients with HER2+ tumors versus those without. However, on multivariate analysis, which included ER, PR, and HER2 status, RS was the only significant predictor of distant recurrence. Subsequent studies of RS have thus only focused on the HER2− population, and clinically patients with HER2+ breast cancer receive HER2-targeted therapy in addition to chemotherapy. Current NCCN and American Society of Clinical Oncology guidelines recommend the use of RS testing in select patients with early stage, ER+ HER2− breast cancer, but not in patients with HER2+ breast cancer.8, 15 As patients with HER2+ tumors have a more aggressive disease and carry a worse prognosis, they are believed to derive a greater benefit from HER2-directed therapy and chemotherapy; therefore, RS testing is not recommended in this cohort. Nonetheless, we saw that approximately 5% of the patients in the United States with ER+, HER2+ breast cancer underwent RS testing. Use of RS testing occurred more frequently in elderly patients, and thus may be an attempt to find patients with a low or intermediate score in order to forego chemotherapy, as seen by the decreased rates of chemotherapy use in these populations. Using genomic testing to further characterize risk Fmoc-His(Boc)-OH.CHA mg and assist with treatment decisions was similarly studied in the MINDACT (Microarray in Node negative Disease may Avoid ChemoTherapy) trial. The MINDACT study, which evaluated the use of the 70-gene signature test in patients with early stage breast cancer, compared clinical versus genomic risk stratification. Patients with discordant risk stratifications were randomized to treatment by either their clinical or genomic risk stratification. Survival without distant metastases was 94.7% among all high clinical risk but low genomic risk patients who were randomized to no chemotherapy, which was comparable to that of those who received chemotherapy. Although the study included mostly patients with ER+, HER2− breast cancer, pioneer community did include 501 women with ER+, HER2+ disease. Of these 501 patients, 211 were found to have low genomic risk by the 70-gene assay. Furthermore, the study found much lower use of chemotherapy when using genomic stratification. Taken together, the use of genomic testing in patients classically deemed high risk may be able to spare some patients adjuvant chemotherapy without detrimental oncologic outcomes; however, these results cannot specifically be extrapolated to the subgroup of ER+, HER2+ patients. Among the tested HER2+ patients in our study, 17% received a high-risk score, 49% intermediate-risk, and 34% low-risk by the TAILORx cutoffs. In a review of the SEER database of patients with stage I to III, ER+ HER2− patients, Kizy et al reported the RS distributions using TAILORx cutoffs were; high-risk, 14%; intermediate-risk, 60%; and low-risk, 26%. In the TAILORx trial of HER2− patients, 14% of patients had a high-risk RS, 69% of patients had an intermediate RS, and 17% of patients had a low-risk RS. In our present study of HER2+ patients, the proportion of patients categorized as high-risk was slightly higher than reported in HER2− patients, but the majority of tested patients were still low and intermediate risk. We found increased utilization of chemotherapy among patients who had high-risk RS compared to those with a low- or intermediate-risk RS. In fact, most patients with HER2+ breast cancer with either low- or intermediate-risk RS did not receive chemotherapy. Previous studies have shown that clinician’s use of chemotherapy is correlated with and impacted by RS.18, 19, 20, 21, 22, 23 Although the use of chemotherapy between those not tested and those who received a high-risk RS was comparable, there was a sizable decrease in chemotherapy use among those with low- and intermediate-risk scores. Thus, despite current guidelines, receipt of a low or intermediate RS score in HER2+ patients appears to correlate with a decreased use of chemotherapy.