Recurrence Score (RS) results, clinicopathologic characteristics, treatments, and outcomes in primary versus subsequent breast cancer (BC): Exploratory analysis of the Clalit Health Services (CHS) registry.
Authors: Shachar Shlomit Strulov , Leviov Michelle , Yerushalmi Rinat , Drumea Karen , Tokar Margarita , Soussan-Gutman Lior , Bareket-Samish Avital , Sonnenblick Amir , Ben Baruch Noa , Evron Ella , Gal-Yam Einav Nili , Paluch-Shimon Shani , Bar-Sela Gil , Goldvaser Hadar , Stemmer Salomon M 
Published: June 2022

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Background: In this exploratory analysis of the CHS registry we investigated differences in RS results and clinicopathologic characteristics between a primary and subsequent BC as well as the association with treatments received (after the first BC) and clinical outcomes. Methods: The analysis included all ER+ HER2-negative BC pts who were RS-tested through CHS between 1/2006 and 12/2020, had ≤3 positive lymph nodes in their first BC, and ≥2 RS results > 1 yr apart. Results: The analysis included 60 pts (all had second BC, 2 also had a third BC). All were female; the median age at diagnosis of the first BC was 56 (IQR, 44-62) yrs and at the subsequent diagnosis, 61 (50-67) yrs. In the first diagnosis, 46/14 pts (77%/23%) were N0/node-positive; in the subsequent BC, it was 50/9 pts (81%/15%), (missing data for 3 pts [5%]). Of the 46 N0 pts at the first BC, 37 (80%) were N0 in the subsequent BC. Tumor characteristics were similar between the first and the subsequent BC tumors. No statistically significant differences were observed between the first and subsequent tumors with respect to tumor size, grade, histology, and the proportion of N0 vs N1/N1mi pts. The RS results were statistically significantly higher in the subsequent BC vs the first (mean [SD] of 24 [12)] vs 19 [10]; P =.00062, Mann-Whitney test). In the first BC, 7 (12%), 44 (73%), and 9 (15%) had RS 0-10, 11-25, and 26-100, respectively. In the subsequent BC, the distribution shifted with more pts in the higher RS category (5 [8%], 32 [52%], and 25 [40%], respectively; P =.0072, χ2-test). The differences in the RS between the first and subsequent BC varied considerably between pts (median difference, 6; IQR, -0.25 to 11.0; range, -50 to 56). Of the 46 pts with N0 at the first BC, 36 (78%) received endocrine therapy (ET), 34 (74%) received radiation therapy (RT), and 5 (11%) received CT after the first BC diagnosis; of the 14 N1mi/N1 pts, 12 (86%) received ET, 12 (86%) RT, and 4 (29%) CT after the first BC diagnosis. In 45 N0 pts with available information, higher RS in the subsequent BC was observed more often in irradiated breasts (pts who received RT to the breast that was subsequently diagnosed with second/third BC, n = 23) vs non-irradiated breast (pts with no RT or pts with subsequent BC in the opposite breast, n = 22): 83% vs 55%, P =.042; χ2-test. No other statistically significant associations were observed between treatments received after the first diagnosis and RS differences between the first and subsequent BC diagnoses. With a median (IQR) follow up of 4.2 (1.6-8.2) yrs from the latest diagnosis, 5 distant recurrences were reported: 2 in pts with RS≤25 in their second BC (of whom one had N1 BC), and 3 in pts with RS > 25 in their second BC. Conclusions: In ER+ HER2-negative BC pts, the RS in a second/third BC is generally higher than the first, particularly if the breast involved was irradiated.