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

Abstract Background Lead 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). Methods An 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. Results 39% 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. Conclusion We 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.

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Breast Cancer Distant Recurrence Lead Time Interval by Detection Method in an Institutional Cohort

10.21203/rs.3.rs-31572/v3 ◽

2020 ◽

Author(s):

Henry G. Kaplan ◽

Judith Malmgren ◽

Mary K. Atwood

Keyword(s):

Breast Cancer ◽

Lead Time ◽

Detection Method ◽

Distant Recurrence ◽

Stage I ◽

Time Interval ◽

Disease Specific Survival ◽

Distant Disease ◽

Disease Free ◽

Disease Specific

Abstract Background: Lead 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). Methods: An 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.Results: 39% 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.Conclusion: We 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.

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Lead Time Bias as a Factor in Mammography Detected Invasive Breast Cancer Survival in an Institutional Cohort

10.21203/rs.3.rs-31572/v1 ◽

2020 ◽

Author(s):

Henry G. Kaplan ◽

Judith Malmgren ◽

Mary K. Atwood

Keyword(s):

Breast Cancer ◽

Lead Time ◽

Cancer Survival ◽

Detection Method ◽

Distant Recurrence ◽

Breast Cancer Survival ◽

Stage I ◽

Time Interval ◽

Distant Disease ◽

Lead Time Bias

Abstract Background: Lead time, the interval between screen detection and when a disease would have become clinically evident, is commonly cited to explain longer survival times in mammography detected breast cancer cases (BC). Methods: An 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. Results: 39% 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.Conclusion: We observed breast cancer survival differential lead time to be a function of stage at diagnosis and tumor characteristics with marginal contribution of detection method. Patient and mammography detected breast cancer time to distant recurrence did not differ stratified by stage indicating survival difference is more likely related to early diagnosis than lead time bias. Lead time bias associated with breast cancer detection method appears to have marginal influence on survival in the current diagnostic and treatment era.

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Lead Time Bias as a Factor in Mammography Detected Invasive Breast Cancer Survival in an Institutional Cohort

10.21203/rs.3.rs-31572/v2 ◽

2020 ◽

Author(s):

Henry G. Kaplan ◽

Judith Malmgren ◽

Mary K. Atwood

Keyword(s):

Breast Cancer ◽

Lead Time ◽

Cancer Survival ◽

Detection Method ◽

Distant Recurrence ◽

Breast Cancer Survival ◽

Stage I ◽

Time Interval ◽

Distant Disease ◽

Lead Time Bias

Abstract Background: Lead 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). Methods: An 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. Results: 39% 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.Conclusion: We observed breast cancer survival differential lead time to be a function of stage at diagnosis and tumor characteristics with marginal contribution of detection method. Patient and mammography detected breast cancer time to distant recurrence did not differ stratified by stage indicating survival difference is more likely related to early diagnosis than lead time bias. Lead time bias associated with breast cancer detection method appears to have marginal influence on survival in the current diagnostic and treatment era.

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

10.1158/1538-7445.sabcs18-p1-03-01 ◽

2019 ◽

Author(s):

HG Kaplan ◽

JA Malmgren ◽

MK Atwood

Keyword(s):

Breast Cancer ◽

Early Detection ◽

Invasive Breast Cancer ◽

Lead Time ◽

Clinical Presentation ◽

Distant Disease ◽

Breast Cancer Early Detection ◽

Lead Time Bias ◽

Cancer Early Detection ◽

Disease Free

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Longer Time Intervals from Diagnosis to Surgical Treatment in Breast Cancer: Associated Factors and Survival Impact

The American Surgeon ◽

10.1177/000313481808400124 ◽

2018 ◽

Vol 84 (1) ◽

pp. 63-70 ◽

Cited By ~ 1

Author(s):

Margaret Mariella ◽

Charles W. Kimbrough ◽

Kelly M. Mcmasters ◽

Nicolas Ajkay

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Adjuvant Chemotherapy ◽

Time Interval ◽

Recurrence Free Survival ◽

Disease Specific Survival ◽

Free Survival ◽

Factors Associated ◽

The Impact ◽

Disease Specific

Time interval (TI) from breast cancer diagnosis to definitive surgery is increasing, but the impact on outcomes is not well understood. TI longer than 30 days is associated with a greater chance of delay of chemotherapy, which may impact survival. We sought to identify factors associated with longer TI and the influence on outcome measures. Methods: We examined TI for stage 0-III breast cancer patients treated between 2006 and 2015 at a university-based cancer center. Univariate and multivariate analyses were used to study factors associated with TI <30, 30 to 60, and >60 days. Kaplan–Meier plots were used to examine the effect of different TI on overall survival, disease-specific survival, and recurrence-free survival. Results: 1589 patients were included with a median follow-up of 47 months. Median TI was 32 days. Median TI increased in patients from 2011 to 2015 compared with those from 2006 to 2010 (35 vs 30 days, P < 0.001). On multivariate analysis, mastectomy (with or without reconstruction), MRI use, and increasing age were independent predictors of TI >30 days. There were no significant differences in overall survival, disease-specific survival, or recurrence-free survival. There was no association between TI >30 days and a subsequent delay >60 days to adjuvant chemotherapy (OR 1.04, 95% CI 0.72–1.52). Conclusions: TI has increased in the last five years. Patient characteristics, tumor biology, and stage do not influence TI, whereas age, mastectomy, and MRI use were all associated with longer TI. Longer TI does not appear to significantly delay adjuvant chemotherapy or influence short-term outcomes.

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Bioinformatics Analysis of Expression and Alterations of BARD1 in Breast Cancer

Technology in Cancer Research & Treatment ◽

10.1177/1533033819892260 ◽

2019 ◽

Vol 18 ◽

pp. 153303381989226

Author(s):

Yong-Zi Chen ◽

Duo Zuo ◽

Hai-Ling Ren ◽

Sai-Jun Fan ◽

Guoguang Ying

Keyword(s):

Breast Cancer ◽

Confidence Interval ◽

Bioinformatics Analysis ◽

Disease Free Survival ◽

Hazard Ratio ◽

Disease Specific Survival ◽

Free Survival ◽

Distant Metastasis Free Survival ◽

Disease Free ◽

Disease Specific

Background: Breast cancer is one of the most common malignant tumor type in women worldwide. BARD1 could impact function of BRCA1 as its interaction partner. In the current study, we aimed to investigate the prognostic role of BARD1 expression as well as its alterations in breast cancer using different online tools. Methods: We performed a bioinformatics analysis for BARD1 in patients with breast cancer using several online databases, including Oncomine, bc-GenExMiner, PrognoScan, Search Tool for the Retrieval of Interacting Genes, Cytoscape, and cBioPortal. Results: We found that BARD1 was highly expressed in basal-like, HER2-E, and luminal B compared with normal-like subtype. Forest plot showed that BARD1 overexpression was correlated with worse distant metastasis-free survival (hazard ratio: 2.72, 95% confidence interval: 1.02-2.21; P = .0448), disease-specific survival (hazard ratio: 2.65, 95% confidence interval: 1.37-5.12; P = .0037), and disease-free survival (hazard ratio: 1.98, 95% confidence interval: 1.22-3.24; P = .0062) but positively correlated with overall survival (hazard ratio: 0.66, 95% confidence interval: 0.50-0.85; P = .0017). Multivariate analysis indicated that BARD1 expression was significantly associated with distant metastasis-free survival (hazard ratio: 4.60, 95% confidence interval: 1.22-17.28; P = .0239) whereas marginally significant for disease-free survival (hazard ratio: 1.00, 95% confidence interval: 1.00-1.01, P = .0630) and disease-specific survival (hazard ratio: 1.96, 95% confidence interval: 0.97-3.96; P = .0602). Meanwhile, alterations in BARD1 interaction network were associated with worse overall survival instead of BARD1 alteration alone. Conclusions: Bioinformatics analysis revealed that BARD1 may be a predictive biomarker for prognosis of breast cancer. However, future research is required to validate our findings.

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113P Impact of local recurrence on disease-specific survival in breast cancer patients who underwent breast-conserving surgery

Annals of Oncology ◽

10.1016/j.annonc.2020.03.216 ◽

2020 ◽

Vol 31 ◽

pp. S54

Author(s):

D.G. Tiezzi ◽

L. de Mattos ◽

L.F. Orlandini ◽

F.J. Candido Dos Reis ◽

H.H. Carrara ◽

...

Keyword(s):

Breast Cancer ◽

Local Recurrence ◽

Cancer Patients ◽

Breast Conserving Surgery ◽

Disease Specific Survival ◽

Breast Cancer Patients ◽

Disease Specific

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Genomic Profile of Early Stage Node-Negative Luminal Breast Cancer Associated with Short Disease-Specific Survival

Annals of Oncology ◽

10.1093/annonc/mdu327.31 ◽

2014 ◽

Vol 25 ◽

pp. iv95

Author(s):

A. Durigova ◽

P. Tsantoulis ◽

R. Lyle ◽

C. Borel ◽

G. Fioretta ◽

...

Keyword(s):

Breast Cancer ◽

Early Stage ◽

Luminal Breast Cancer ◽

Genomic Profile ◽

Disease Specific Survival ◽

Node Negative ◽

Disease Specific

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Survival in Early Breast Cancer Patients Is Favorably Influenced by a Natural Humoral Immune Response to Polymorphic Epithelial Mucin

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.3.574 ◽

2000 ◽

Vol 18 (3) ◽

pp. 574-574 ◽

Cited By ~ 153

Author(s):

S. von Mensdorff-Pouilly ◽

A.A. Verstraeten ◽

P. Kenemans ◽

F.G. M. Snijdewint ◽

A. Kok ◽

...

Keyword(s):

Breast Cancer ◽

Cancer Patients ◽

Early Breast Cancer ◽

Humoral Response ◽

Disease Specific Survival ◽

Breast Cancer Patients ◽

Antibody Levels ◽

Pretreatment Serum ◽

Test Result ◽

Disease Specific

PURPOSE: Polymorphic epithelial mucin (PEM or MUC1) is being studied as a vaccine substrate for the immunotherapy of patients with adenocarcinoma. The present study analyzes the incidence of naturally occurring MUC1 antibodies in early breast cancer patients and relates the presence of these antibodies in pretreatment serum to outcome of disease.MATERIALS AND METHODS: We measured immunoglobulin G (IgG) and immunoglobulin M (IgM) antibodies to MUC1 with an enzyme-linked immunoassay (PEM.CIg), which uses a MUC1 triple-tandem repeat peptide conjugated to bovine serum albumin, in pretreatment serum samples obtained from 154 breast cancer patients (52 with stage I disease and 102 with stage II) and 302 controls. The median disease-specific survival time of breast cancer patients was 74 months (range, 15 to 118 months). A positive test result was defined as MUC1 IgG or IgM antibody levels equal to or greater than the corresponding rounded-up median results obtained in the total breast cancer population.RESULTS: A positive test result for both MUC1 IgG and IgM antibodies in pretreatment serum was associated with a significant benefit in disease-specific survival in stage I and II (P = .0116) breast cancer patients. Positive IgG and IgM MUC1 antibody levels had significant additional prognostic value to stage (P = .0437) in multivariate analysis. Disease-free survival probability did not differ significantly. However, stage II patients who tested positive for MUC1 IgG and IgM antibody and who relapsed had predominantly local recurrences or contralateral disease, as opposed to recurrences at distant sites in the patients with a negative humoral response (P = .026).CONCLUSION: Early breast cancer patients with a natural humoral response to MUC1 have a higher probability of freedom from distant failure and a better disease-specific survival. MUC1 antibodies may control hematogenic tumor dissemination and outgrowth by aiding the destruction of circulating or seeded MUC1-expressing tumor cells. Vaccination of breast cancer patients with MUC1-derived (glyco)peptides in an adjuvant setting may favorably influence the outcome of disease.

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