Patterns and predictors of early recurrence in postmenopausal women with estrogen receptor-positive early breast cancer

Abstract

Previous studies suggest that disease recurrence peaks at around 2 years in patients with early stage breast cancer (EBC), but provide no data regarding recurrence type. This retrospective analysis aimed to identify early recurrence types and risk factors in estrogen receptor-positive (ER?) EBC patients treated with adjuvant tamoxifen following breast cancer surgery. Postmenopausal women diagnosed with ER? EBC from 1995 to 2004 were evaluated. Annual hazard ratios (HR) for recurrence at different sites were calculated. Time-dependent Cox regression analysis was used to identify predictors of recurrence within 2.5 years of diagnosis, including factors that were more strongly predictive of early than later recurrence. Of 3,614 patients evaluated, 476 developed recurrence during the 5-year median follow-up. Cumulative recurrence rates at 2.5 years (95% confidence interval) were: overall 6.3% (5.5-7.1), locoregional 1.1% (0.7-1.5), contralateral 0.5% (0.3-0.7), and distant 4.8% (4.0-5.6). The annual HR of overall recurrence peaked at 2 years (4.3% per annum).The majority of this peak represented distant recurrence (3.4% per annum). In Cox regression analysis, tumor size and grade, lymph node involvement, lymphovascular invasion, and symptomatic presentation were significant independent predictors of early recurrence. Age at diagnosis was independently predictive of recurrence within 2.5 years of diagnosis but not later recurrence. This study identified an early recurrence peak at 2 years, most of which were distant recurrences. Implementing an aromatase inhibitor after an initial 2-3 years of tamoxifen fails to address this early peak of distant recurrence and the potential breast cancer-associated mortality.

Pattern of relapse after breast conserving therapy, a study of 1519 early breast cancer patients treated in the Central Region of Denmark 2000–2009

“…Several studies have investigated the pattern of recurrence. Although definitions of recurrence varied, and some studies include all breast cancer patients regardless of surgical modality, several suggest a pattern of recurrence after breast cancer with more than one peak [11,12] which could represent a difference in time to recurrence depending on tumor characteristics. We found that median time to DM for patients with ER negative tumors were shorter than for those having ER positive tumors (3.0 years vs. 4.5 years), and that for patients with ER negative tumors the majority of DM events would develop within three years, while the risk of developing DM for patients with ER positive tumor would persist.…”

Unfavourable pattern of metastases in M0 breast cancer patients during 1978-2008: a population-based analysis of the Munich Cancer Registry

“…[12,34] In this study the majority of metastases became manifest within 2.5 years of initial diagnosis, as observed by others. [11,13,35,36] The MCR hosts unique data on clinically evident metastases in follow-up, but the prevalence of metastases in the MCR is slightly underdocumented. Surgically treated and histopathologically confirmed metastases are obtained from pathology reports and are therefore nearly complete.…”

FACE: the barefaced facts of AI potency

“…22,23,25,27,28,30 Differences in the binding of letrozole and anastrozole to the aromatase enzyme (Figure 1), and their corresponding inhibitory activity, may in part underlie the more complete suppression of E 2 levels with letrozole versus anastrozole that has been observed in directly comparative clinical studies such as ALIQUOT (Figure 3). It is plausible that the more complete suppression of E 2 in plasma and tissues by letrozole in turn causes a greater eradication of distant micrometastatic breast cancer deposits, which can develop later into fulminant DM recurrences.…”

“…In a recently published study (N = 3614 PMW with operable, estrogen receptor-positive breast cancer receiving adjuvant tamoxifen), a peak of recurrence was reported at 2 years (4.3% per annum), and DM events were found to be the predominant type of early recurrence event at this peak (3.4% per annum). 30 Retrospective analyses from the ATAC and BIG 1-98 trials also confirmed that DM events constitute the majority of recurrence events at 2 years. 25,28 Prevention of DM recurrence is thus a key factor in improving survival and reducing death from breast cancer.…”