Ten-year clinical outcomes in N0 ER+ breast cancer patients with Recurrence Score-guided therapy

Salomon M Stemmer; Mariana Steiner; Shulamith Rizel; Noa Ben-Baruch; Beatrice Uziely; Debbie M Jakubowski; Julie Baron; Steven Shak; Lior Soussan-Gutman; Avital Bareket-Samish; Georgeta Fried; Ora Rosengarten; Amit Itay; Bella Nisenbaum; Daniela Katz; Michelle Leviov; Margarita Tokar; Nicky Liebermann; David B Geffen

doi:10.1038/s41523-019-0137-3

Ten-year clinical outcomes in N0 ER+ breast cancer patients with Recurrence Score-guided therapy

NPJ Breast Cancer. 2019 Nov 8:5:41. doi: 10.1038/s41523-019-0137-3. eCollection 2019.

Authors

Salomon M Stemmer^{1

2}, Mariana Steiner³, Shulamith Rizel¹, Noa Ben-Baruch⁴, Beatrice Uziely⁵, Debbie M Jakubowski⁶, Julie Baron⁶, Steven Shak⁶, Lior Soussan-Gutman⁷, Avital Bareket-Samish⁸, Georgeta Fried⁹, Ora Rosengarten¹⁰, Amit Itay¹¹, Bella Nisenbaum¹², Daniela Katz¹³, Michelle Leviov³, Margarita Tokar^{14

15}, Nicky Liebermann¹⁶, David B Geffen^{14

15}

Affiliations

¹ 1Davidoff Center, Rabin Medical Center, Petah Tikva, Israel.
² 2Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
³ Oncology Dept., Lin Medical Center, Haifa, Israel.
⁴ 4Oncology Dept., Kaplan Medical Center, Rehovot, Israel.
⁵ 5Sharett Institute of Oncology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
⁶ 6Genomic Health Inc, Redwood City, CA USA.
⁷ 7Oncotest Division, Teva Pharmaceutical Industries, Ltd, Shoham, Israel.
⁸ BioInsight Ltd, Zichron Yaakov, Israel.
⁹ 9Oncology Dept., Rambam Health Care Campus, Haifa, Israel.
¹⁰ Oncology Institute, Shaare Zedek Medical Center, Jerusalem, Israel.
¹¹ Oncology Dept., Sheba Medical Center at Tel HaShomer, Ramat Gan, Israel.
¹² 12Oncology Dept., Meir Medical Center, Kfar Saba, Israel.
¹³ 13Oncology Dept., Assaf Harofeh Medical Center, Zerifin, Israel.
¹⁴ 14Department of Oncology, Soroka University Medical Center, Beer Sheva, Israel.
¹⁵ 15Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva, Israel.
¹⁶ 16Community Division, Clalit Health Services, Tel Aviv, Israel.

Abstract

The 21-gene Recurrence Score (RS) assay is a validated prognosticator/predictor of chemotherapy (CT) benefit in early-stage estrogen receptor (ER)-positive breast cancer (BC). Long-term data from real-life clinical practice where treatment was guided by the RS result are lacking. We performed exploratory analysis of the Clalit Health Services (CHS) registry, which included all CHS patients with node-negative ER+ HER2-negative BC who underwent RS testing between 1/2006 and 12/2009 to determine 10-year Kaplan-Meier estimates for distant recurrence/BC-specific mortality (BCSM) in this cohort. The analysis included 1365 patients. Distribution of RS results: RS 0-10, 17.8%; RS 11-25, 62.5%; RS 26-100, 19.7%. Corresponding CT use: 0, 9.4, and 69.9%. Ten-year distant recurrence rates in patients with RS 0-10, 11-25, and 26-100: 2.6% (95% confidence interval [CI], 1.1-6.2%), 6.1% (95% CI, 4.4-8.6%), and 13.1% (95% CI, 9.4-18.3%), respectively (P < 0.001); corresponding BCSM rates: 0.7% (95% CI 0.1-5.1%), 2.2% (95% CI, 1.3-3.7%), and 9.5% (95% CI, 6.0-14.9%) (P < 0.001). When the analysis included patients treated with endocrine therapy alone (95.5/87.5% of patients with RS 0-10/11-25), 10-year distant recurrence and BCSM rates for RS 0-10 patients were 2.7% (95% CI, 1.1-6.5%) and 0.8% (95% CI, 0.1-5.3%), respectively, and for RS 11-25 patients, 5.7% (95% CI, 3.9-8.3%) and 2.0% (95% CI, 1.1-3.7%), respectively. For RS 11-25 patients, no statistically significant differences were observed in 10-year distant recurrence/BCSM rates between CT-treated and untreated patients; however, this should be interpreted cautiously since the number of events was low and patients were not randomized. In conclusion, in node-negative ER+ HER2-negative BC patients, where treatment decisions in real-life clinical practice incorporated the RS, patients with RS 0-25 (~80% of patients, <10% CT use) had excellent outcomes at 10 years. Patients with RS 26-100 had high distant recurrence risk despite CT use and are candidates for new treatment approaches.

Keywords: Breast cancer; Cancer therapy.