Distant Disease-specific Survival Research Articles

Breast cancer distant recurrence lead time interval by detection method in an institutional cohort

BackgroundLead time, the interval between screen detection and when a disease would have become clinically evident, has been cited to explain longer survival times in mammography detected breast cancer cases (BC).MethodsAn institutional retrospective cohort study of BC outcomes related to detection method (mammography (MamD) vs. patient (PtD)). Cases were first primary invasive stage I-III BC, age 40–74 years (n = 6603), 1999–2016. Survival time was divided into 1) distant disease-free interval (DDFI) and 2) distant disease-specific survival (DDSS) as two separate time interval outcomes. We measured statistical association between detection method and diagnostic, treatment and outcome variables using bivariate comparisons, Cox proportional hazards analyses and mean comparisons. Outcomes were distant recurrence (n = 422), DDFI and DDSS.Results39% of cases were PtD (n = 2566) and 61% were MamD (n = 4037). MamD cases had a higher percentage of Stage I tumors [MamD 69% stage I vs. PtD 31%, p < .001]. Rate of distant recurrence was 11% among PtD BC cases (n = 289) vs. 3% of MamD (n = 133) (p < .001). Order of factor entry into the distant recurrence time interval (DDFI) model was 1) TNM stage (p < .001), 2) HR/HER2 status (p < .001), 3) histologic grade (p = .005) and 4) detection method (p < .001). Unadjusted PtD DDFI mean time was 4.34 years and MamD 5.52 years (p < .001), however when stratified by stage, the most significant factor relative to distant recurrence, there was no significant difference between PtD and MamD BC. Distant disease specific survival time did not differ by detection method.ConclusionWe observed breast cancer distant disease-free interval to be primarily associated with stage at diagnosis and tumor characteristics with less contribution of detection method to the full model. Patient and mammography detected breast cancer mean lead time to distant recurrence differed significantly by detection method for all stages but not significantly within stage with no difference in time from distant recurrence to death. Lead time difference related to detection method appears to be present but may be less influential than other factors in distant disease-free and disease specific survival.

Abstract P1-03-01: Differential distant disease-free intervals for mammography detected vs. clinical presentation invasive breast cancer: Early detection or lead time bias?

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&amp;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 &amp;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.

Examination of a paradox: recurrent metastatic breast cancer incidence decline without improved distant disease survival: 1990\u20132011

PurposeDistant relapse metastatic breast cancer (rMBC) incidence and survival are vital measures of breast cancer diagnosis and treatment progress over time.MethodsWe conducted a retrospective cohort study of stage I–III invasive breast cancer, 1990–2011, follow-up through 2016 [N = 8292, rMBC = 964 (12%)] at a community-based institution. Patient and tumor characteristics (treatment, distant recurrence, vital status) from BC registry data were evaluated. Survival analysis and Cox proportional hazards (HzR) with 95% confidence intervals (95% CI) were calculated using distant recurrence and distant disease-specific survival (DDSS) endpoints.ResultsBoth 5- and 10-year distant relapse (rMBC) declined over time from 1990–1998 to 2005–2011 [11% to 5%, 16% to 8% (p < 0.001)]. Proportionately, HER2 + BC distant relapse decreased 9% and triple negative (HR−/HER2−) increased 8% (p = 0.011). In the Cox model, lower stage [stage I: HzR = 0.08 (0.07, 0.10), stage II: 0.29 (0.25, 0.33)], more recent diagnosis years [1999–2004: HzR = 0.60 (0.51, 0.70), 2005–2011: HzR = 0.44 (0.38, 0.52)], HR+ [HzR = 0.62 (0.53, 0.72)], and age 40+ [HzR = 0.81 (0.67, 0.98)] had decreased rMBC risk. Compared to HR+/HER2− BC, triple-negative BC had increased rMBC risk [HzR = 2.02 (1.61, 2.53)] but HER2+ subtypes did not. HR−, age 70+, > 1, or visceral metastases and stage III disease were associated with worse DDSS. DDSS did not improve over time.ConclusionrMBC incidence declined over time with decreased HER2-positive distant recurrence, a shift to more triple-negative BC and consistently poor distant disease survival.

Sentinel Lymph Node Biopsy Use Among Melanoma Patients 75 Years of Age and Older.

While SLN biopsy is recommended for melanoma ≥1 mm in depth, its use among the elderly population is more controversial. We reviewed our experience at the University of Michigan with melanoma patients ≥75 years of age. A total of 952 melanoma patients ≥75 years of age from 1996 to 2011 were identified from our institutional review board-approved database. In addition to clinicopathologic features and outcome data, comorbidity data were collected to calculate the Charlson comorbidity index (CCI). Univariate and multivariate Cox regression analysis was performed to characterize predictors of outcome. Kaplan-Meier analysis was used to generate survival curves. Among 553 clinically node-negative patients with melanoma ≥1 mm in Breslow thickness, 213 had wide excision alone, whereas 340 had excision and SLN biopsy, with 83 (24 %) having a positive SLN. SLN biopsy was less likely with older age (p < 0.0001) and H&N location (p = 0.007), but not CCI. SLN involvement was associated with female gender [odds ratio (OR) 2.15, p = 0.009], Breslow thickness [OR 1.23/mm increase, p = 0.004], and satellitosis (OR 4.43, p = 0.004). Distant disease-specific survival was negatively associated with male gender (OR 1.5, p = 0.007), increasing age (OR 1.05/year, p < 0.001), increasing Breslow thickness (OR 1.07/year, p = 0.013), ulceration (OR 1.51, p = 0.004), a positive SLN (OR 2.61, p < 0.001), and not having a SLN biopsy (OR 1.72, p < 0.001). CCI did not predict worse disease-free or melanoma-specific survival. WLE and SLN biopsy was not only strongly prognostic, but compared with WLE alone was associated with improved outcome, even after factoring for age and comorbidities. If otherwise healthy, SLN biopsy should be strongly considered for this population.