Factors Predicting Late Recurrence for Estrogen Receptor–Positive Breast Cancer

Abstract

BackgroundAdjuvant endocrine therapy beyond 5 years reduces recurrence in patients with estrogen receptor–positive breast cancer. We have previously shown that immunohistochemical markers (IHC4) and two gene expression profile tests (recurrence score [RS] and PAM50 risk of recurrence [ROR]) are associated with time to distant recurrence, and we have now assessed the value of each of these scores and routine clinical variables for predicting outcome, specifically in years 5 to 10.MethodsWe used univariate and multivariable proportional hazards models to determine the prognostic value of all variables and scores (IHC4, RS, ROR) for distant recurrence, separately in years 0 to 5 and specifically for years 5 to 10 for all patients. All statistical tests were two-sided.ResultsNodal status and tumor size were at least as strong in years 5 to 10 as in years 0 to 5 (nodal status, years 5–10: χ2 = 21.72 vs years 0–5: χ2 = 11.08, both P < .001; tumor size, years 5–10: χ2 = 10.52 vs years 0–5: χ2 = 10.82, both P = .001). Ki67 and the overall IHC4 score were the only statistically significant biomarkers related to distant recurrence univariablely in the 5 to 10 year period (χ2 = 8.67, χ2 = 13.22, respectively). The ROR score was the strongest molecular prognostic factor in the late follow-up period (χ2 = 16.29; P < .001), whereas IHC4 (χ2 = 7.41) and RS (χ2 = 5.55) were only weakly prognostic in this period. Similar results were seen for all subgroups and for all recurrences.ConclusionsNone of the IHC4 markers provided statistically significant prognostic information in years 5 to 10, except for nodal status and tumor size. ROR gave the strongest prognostic information in years 5 to 10. These results may help select patients who could benefit most from hormonal therapy beyond 5 years of treatment.

Utility of Molecular Tools for Extended Adjuvant Endocrine Therapy Decisions in Early Breast Cancer

“…In the transATAC clinical trial, the ROR score was highly prognostic for overall distant relapses and provided independent prognostic information to classical clinical parameters [16]. More recently, the ROR score was investigated for prediction of late distant relapses in the transATAC clinical trial [10]. Interestingly, it was shown that the ROR score was the strongest prognostic factor in all patient subgroups when compared with the oncotype DX RS and it significantly added prognostic information for late recurrences.…”

“…The prognostic value of the oncotype DX RS for late distant recurrence (>5 years) was first evaluated in the transATAC (NCT00849030) trial [10]. In this analysis, oncotype DX was not prognostic for late distant relapse after adjustment for classical clinical-pathological factors.…”

Clinical Utility of Multigene Profiling Assays in Early-Stage Breast Cancer

“…Based on the tumour-marker utility grading system 7,8 , all five studies 2,9-12 were assessed as category B and were found to support the overall prognostic role of Oncotype dx for tumour recurrence at an evidence level of IB (Table v). When comparing distant with local recurrence, four of five studies were determined to provide level IB evidence supporting the ability of Oncotype dx to prognosticate distant recurrence 2,9,11,12 . The fifth study was category B, but evaluated only the ability of the Oncotype dx assay to prognosticate locoregional recurrence 10 .…”

“…Six studies evaluated the prognostic ability of the Prosigna (formerly PAM50) assay 11,12,[15][16][17][18] (Tables vi and v). Based on the tumour marker utility grading system 7,8 , all six studies were assessed as category B and as supporting the overall prognostic role of the Prosigna assay; that evidence is considered to be level IB ( Table v).…”

General St. Gallen-2015 guidelines for the treatment of early breast cancer (adapted by the experts of the Russian Society of Breast Oncologists)

“…Органосохраняющее лечение после неоадъювантной химиотерапии возможно даже при мультифокальной или мультицентричной опухоли при условии достижения «чистых» краев резекции или в случае, если в результате неоадъювантного лечения был достигнут полный патоморфологический регресс опухоли (рCR) [42] Местно-регионарная лучевая терапия Обзор 3 последних исследований по лучевой терапии, включавших N-позитивных пациентов (pN+), показал превосходный контроль за заболеванием и более высокие показатели выживаемости при включе-нии в поля облучения зон регионарного лимфооттока [7] М а м м о л о г и я [43]. Тем не менее в исследовании ATAC он не являлся предиктором отдаленного рецидива после эндокринотерапии, в то время как шкала PAM-50 ROR ® и основанная на ИГХ шкала IHC4 ® являлись прогностически значимыми и после завершения 5 лет эндокринотерапии [44,45]. Кроме того, в австрий-ских исследованиях ABCSG 6 и ABCSG 8 молекулярный маркер EndoPredict ® был прогностически значимым спустя 5 лет, особенно в сочетании с клиническими факторами [46].…”