Abstract P1-03-01: Differential distant disease-free intervals for mammography detected vs. clinical presentation invasive breast cancer: Early detection or lead time bias?
Authors: Kaplan HG , Malmgren JA , Atwood MK 
Published: May 2019

Abstract
Background: Distant recurrence metastatic breast cancer (rMBC) incidence has declined with coincident improved breast cancer (BC) survival over time. Lead time is time from screening diagnosis to diagnosis that would have been made without screening. The purpose of screening is to detect disease at an early more treatable stage. Lead time bias would indicate early detection led only to a perceived increase in survival time without affecting the course of BC progression. Our objective was to evaluate detection method and treatment changes to distant recurrence and survival over time.
Methods: In a longitudinal institutional cohort 1990-2011, we reviewed primary invasive stage I-III BC patients (n = 7991) for initial BC detection method by mammography (MamD) or patient/physician (ClinP), distant recurrence (rMBC), time from initial diagnosis to distant recurrence (DDFI) and distant disease specific survival (DDSS), follow up through 2016 updated annually. 856 patients with distant recurrence were identified and confirmed by imaging, biopsy or both. Diagnosis year time periods were set to coincide with significant treatment changes over time (1990-98, 1999-2004, 2005-2011). Chi square, mean ANOVA, DDSS and Cox proportional hazards analysis were conducted.
Results: 48% of the cohort were ClinP and 52% MamD with MamD BC increasing over time [1990-98 45%, 2005-2011 54%, p&lt;.001]. 72% of rMBC patients were ClinP BC. ClinP BC had shorter distant recurrence time, 4.99 years vs. 6.05 MamD BC (p = .001). Mean time from rMBC diagnosis to death was 2.88 years with no significant difference by detection method. In a Cox proportional hazards model adjusted for race, reduced risk of rMBC was observed for stage I/II, recent diagnostic years, hormone receptor positive, MamD, and low histologic grade [TNM I HzR .11, 95% CI .09, .14; TNM II HzR = .36, 95% CI = .31, .43; 1990-2004 HzR = .63, 95% CI = .53, .75; 2005-2011 HzR = .49, 95% CI = .41, .58; HR+ HzR = .70, 95% CI = .59, .82; MamD HzR = .68, 95% CI = .58, .81; low histologic grade HzR = .80, 95% CI = .67, .96; age &gt;40 HzR = .79, 95% CI = .65, .96]. No difference was observed for DDSS by detection method [5-year DDSS: ClinP = 22%, MamD = 21%; log rank test = .019, p = .892].
Conclusion: At initial diagnosis, the majority of rMBC cases are symptomatic, have shorter DDFI but DDSS equal to MamD BC. MamD BC cases have lower rMBC incidence and longer DDFI possibly due to more responsive earlier diagnosed initial disease, slower progression disease or as yet unidentified biologic/genomic differences. Lead time bias may partially explain lower rMBC incidence given the benefits owed to treatment of MamD invasive BC which preclude disease progression to clinically evident BC. Mammography detected/non-symptomatic and clinically detected/symptomatic BC have differential incidence of and time to distant recurrence but no difference in DDSS. Mammography detection appears to confer a distant disease risk reduction advantage independent of other known prognostic factors but the disease has the same virulence once it becomes metastatic. Our results indicate treatment changes by diagnosis year proxy and mammography detection are both associated with decreased rMBC risk.
Citation Format: Kaplan HG, Malmgren JA, Atwood MK. Differential distant disease-free intervals for mammography detected vs. clinical presentation invasive breast cancer: Early detection or lead time bias? [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P1-03-01.