The Impact of the 21-gene Recurrence Score Assay on Decision Making About Adjuvant Chemotherapy in Early-stage Estrogen-receptor-positive Breast Cancer in an Oncology Practice With a Unified Treatment Policy

D. B. Geffen; S. Abu-Ghanem; N. Sion-Vardy; R. Braunstein; M. Tokar; S. Ariad; B. Delgado; M. Bayme; M. Koretz

Disclosures

Ann Oncol. 2011;22(11):2381-2386. 

In This Article

Results

RS Effect on Chemotherapy Recommendation

Between February 2006 and June 2009, the 21-gene RS was obtained on 135 patients, including three men. Patient characteristics are shown in Table 2. Only 5.2% were high-grade tumors. Median RS was 19 (range 1–57). Figure 1A shows the distribution of the RS grouped by low, intermediate and high risk. The number of patients who were recommended for chemotherapy before and after obtaining the RS is shown in Figure 1B, along with the distribution of patients in each recommendation group by RS risk group. Of note, 43% of patients not recommended for chemotherapy before RS were found to have RS in the intermediate or high range; while 41% of chemotherapy recommended patients pre-RS were found to have a low-risk RS. For 24 patients [17.8%; 95% confidence interval (CI) 11.3% to 24.2%], treatment recommendations were changed after receiving the RS to endocrine therapy; while only 10 patients (7.4%; 95% CI 2.9% to 11.8%) had treatment recommendation changed to chemotherapy (P < 0.0001). Overall, treatment recommendations were changed in 34 patients (25.2%; 95% CI 17.9% to 32.5%). Figure 2A–D shows that the net changes in treatment were greatest for the high- (B) and low-RS (C) groups as opposed to the intermediate RS group (D)and the entire group (A). For the intermediate risk group, the RS was similar for both chemotherapy (n = 27) and nonchemotherapy (n = 24) post-RS recommended patients, with medians 21 (range 18–26), and 20.5 (range 18–29), respectively. The similar RS medians as well as the minimal net change in treatment recommendations reflect our policy of relying on traditional clinicopathological parameters in intermediate RS patients to decide on therapy. Even so, the RS influenced clinicians as seven patients in the intermediate RS group had treatment recommendations switched after obtaining RS, four to chemotherapy and three patients to no chemotherapy. Five patients were recommended for chemotherapy despite having a low-risk RS. Two were patients with positive nodes who presented when the validation of the RS in node-positive patients was available in abstract form only.[16]

Figure 1.

(A) Distribution of recurrence scores by risk group, N = 135. (B) Distribution of RS risk categories by % within treatment recommendation groups before and after obtaining RS. Intermed, intermediate; RS, recurrence score; CTX, chemotherapy recommended; No CTX, chemotherapy not recommended.

Figure 2.

Percentage of patients recommended for chemotherapy. (A) Entire study cohort, (B) high-risk group RS patients, (C) low-risk group RS patients, (D) intermediate risk group RS patients. CTX, recommended for chemotherapy; pts, patients; RS, recurrence score; Intermed, intermediate.

Change in Chemotherapy Recommendation by T Stage, N Stage and Histological Grade

We examined the impact of histological grade (Table 3), T stage and N stage on whether therapy was changed by RS. Histological grade and N stage had no significant impact (P = 0.569 and 0.707, respectively). There was a trend for more changes in therapy with higher T stage (P = 0.055). More than one-third of low-grade patients had RS of intermediate or high risk and almost half of patients with intermediate or undetermined histological grade had low-risk RS.

RS According to PR status

In the 23 PR-negative patients, the median RS was 24.5 (range 13–42), in contrast to the PR-positive group with a median RS of 15.5 (range 1–57). Table 4 shows that 57.7% of ER-positive PR-positive patients had low-risk RS, in contrast to only 13% low-risk RS ER-positive PR-negative patients. Genomic Health began providing single gene (SG) results for ER/PR only midway through the study period and for HER2 later on, so only 80 (59%) patients have SG ER/PR reports. SG assay for ER was positive in 79 of those 80 (all IHC ER positive) and the single remaining patient had an RNA expression score of 6.3, close to the 6.5 units lower limit for ER positivity. Of 11 PR-negative patients with a SG, 7 were confirmed as negative by the assay, while 4 were positive.

Correlation of RS and AO

AO-predicted 10-year mortality reduction for adding anthracyline-based chemotherapy calculated for all 135 patients showed a mean of 1.60% (SD ±1.31%) and median of 1.2% (range 0.1%–6.6%). Figure 3 shows the poor correlation (r = 0.140, P = 0.105) between RS and predicted 10-year mortality reduction by AO.

Figure 3.

Scatter plot of Adjuvant! Online predicted per cent 10-year mortality reduction from adding chemotherapy and recurrence score. RS, recurrence score.

Therapy Actually Received

Of the 49 patients for whom the RS resulted in a recommendation for chemotherapy, 14 refused chemotherapy. The chemotherapy most frequently given was the three-drug combination cyclophosphamide (C), doxorubicin (A) or epirubicin, and 5-flurouracil (n = 31, 86%); with two patients receiving CMF and three receiving AC-paclitaxel. Of the 86 patients recommended for endocrine therapy only, 2 (2.3%) insisted on receiving chemotherapy despite the RS result confirming our recommendation.

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