Abstract PS6-12: Prognostic significance of age, histologic subtype, tumor size and nodal status on breast cancer specific survival of “clinical low risk” grade 1 ER+/HER2- breast carcinoma patients - SEER analysis 2010-2012
Authors: Orucevic Amila , Bell John L 
Published: February 2021

Introduction: TAILORx and MINDACT clinical trials on ER+/HER2-/lymph node (LN) 0 or LN 1-3 positive breast carcinoma (BC) patients (pts) revealed that breast-cancer-specific-survival (BCSS) of pts with low Oncotype DX or MammaPrint genomic assay scores did not improve with addition of adjuvant chemotherapy (CTH) to endocrine therapy. Furthermore, pts from MINDACT trial with “clinical low risk” (CLow) BC had no benefit from the use of CTH regardless of the MammaPrint score (low or high), underscoring the importance of identifying these CLow patients who might not obtain value from genomic testing. CLow is defined as the 10-year probability of BCSS &gt;88% without CTH among women with ER+ tumors. MINDACT trial algorithm based on grade, tumor size and lymph node status is used to classify patients into CLow vs. “clinical high-risk” group. We investigated the significance of age, histologic subtype, tumor size, nodal and PR status on BCSS in a subgroup of CLow pts with grade 1 tumors ≤30 mm in size and N0-1 LN, utilizing Surveillance Epidemiology and End Results (SEER) database.

Methods: “Incidence, SEER research, 18 registries, Nov 2019 sub (2000-2017)” database was used to select female BC pts with ER(+)/HER2(-) BC diagnosed between 2010-2012 to allow for at least a 5-year follow-up (2010-2017). A subgroup of clinical low-risk pts was selected based on MINDACT trial algorithm: grade 1/N0/≤30 mm tumor size, or grade 1/N1/≤20 mm tumor size. Five invasive BC histologic types were selected: ductal (IDC), lobular (ILC), cribriform (ICC), tubular (ITC) and mucinous (IMC). Frequency statistics and a multivariate Cox regression were used for analyses of patient’s characteristics and BCSS using SPSS Version 25 (Armonk, NY: IBM Corp).

Results: From 132,822 female pts diagnosed with BC from 2010-2012, 20,677 pts (age range 19-85+) fulfilled above selection criteria. Age, tumor size, nodal status and ILC were significant (p&lt;0.05) predictors for BC death in a multivariate Cox regression analysis: pts ≥50, tumor size 21-30 mm, 1-3 LN positive, and ILC histologic type were respectively 2.9 (95% CI=1.8-4.7), 2.6 (95% CI=1.8-3.6), 2.7 (95% CI=2.1-3.6) and 1.4 (95% CI=1.1-1.9) times more likely to die from BC than pts &lt;50, tumor size 1-20 mm and negative LN (Table). IDC and IMC histologic types and PR status did not significantly influence BCSS, although PR status was borderline significant (0.05) in ILC histologic type. Cox regression analysis did not include ICC and ITC pts due to low number of BC caused death. A 5-year BCSS was the best for ITC and the worst for ILC pts, with 3/608 (0.5%) and 52/2047 (2.5%) pts dying from BC, respectively (Table), confirming ITC as an indolent, “good prognosis carcinoma”.

Conclusions: Our results show that 5-year breast cancer specific survival is significantly influenced by patient’s age, ILC histologic type, tumor size and nodal status even in the lowest risk of “clinical low risk” ER(+)/HER2(-), grade 1 BC pts. Since addition of CTH to endocrine therapy is not beneficial in these patients, further studies/clinical trials are needed to evaluate different endocrine therapy regimens for this subgroup of “clinical low-risk” patients in order to improve their BCSS.

Table:Clinicopathologic characteristics of a grade 1 subgroup of "clinical low-risk" ER+/HER2(-) patientsHistologic subtypesN=20,677 (100%)IDCILCICCITCIMCVariablesN=20,677 (100%)N (%)N (%)N (%)N (%)N (%)N=20,677; Mean +/- SE = 62 +/- 0.016; Median = 62Age (years)&lt;502568 (15.3)274 (13.1)17 (19.1)132 (21.6)118 (11.3)&gt;5014,265 (84.7)1825 (86.9)72 (80.9)479 (78.4)927 (88.7)N=20,677; Mean +/- SE = 11.27 +/- 0.041; Median = 10Tumor size (mm)1-2015,893 (94.4)1768 (84.2)83 (93.3)603 (98.7)864 (82.7)21-30940 (5.6)331 (15.8)6 (6.7)8 (1.3)181 (17.3)GradeGrade 116,833 (100)2099 (100)89 (100)611 (100)1045 (100)Lymph nodesNegative14,915 (88.6)1881 (89.6)81 (91)594 (97.2)1022 (97.8)1-3 Positive1918 (11.4)218 (10.4)8 (9.0)17 (2.8)23 (2.2)PRPositive15,553 (92.4)1800 (85.8)86 (96.6)542 (88.7)986 (94.4)Negative1280 (7.6)299 (14.2)3 (3.4)69 (11.3)59 (5.6)BCSSAlive16,584 (98.5)2047 (97.5)88 (98.9)608 (99.5)1028 (98.4)Dead from BC249 (1.5)52 (2.5)1 (1.1)3 (0.5)17 (1.6)Prognostic significance of age, tumor size, histologic subtype, lymph node and PR status on BCSS in a multivariate Cox regression analysisVariablep valueAdjusted Odds Ratio95% CI Lower95% CI UpperAge &gt;=50&lt;0.001*2.9431.8274.741Tumor size 21-30 mm&lt;0.001*2.5991.8843.587IDCReferentILC0.019*1.4431.0621.96IMC0.8111.0630.6461.748Lymph nodes 1-3 positive&lt;0.001*2.7592.0973.631PR negative0.11.3360.9451.887LegendN = Total number; % = percentage; IDC = Invasive ductal carcinoma; ILC = Invasive lobular carcinoma; ICC = Invasive cribriform carcinoma; ITC = Invasive tubular carcinoma; IMC = Invasive mucinous carcinoma; PR = Progesterone receptor; BCSS = Breast cancer specific survival; BC = Breast carcinoma; *= Significant

Citation Format: Amila Orucevic, John L Bell. Prognostic significance of age, histologic subtype, tumor size and nodal status on breast cancer specific survival of “clinical low risk” grade 1 ER+/HER2- breast carcinoma patients - SEER analysis 2010-2012 [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-12.