External Validity of a Trial Comprised of Elderly Patients With Hormone Receptor–Positive Breast Cancer

Willemien van de Water, Mandy Kiderlen, Esther Bastiaannet, Sabine Siesling, Rudi G.J. Westendorp, Cornelis J.H. van de Velde, Johan W.R. Nortier, Caroline Seynaeve, Anton J.M. de Craen, Gerrit-Jan Liefers

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Abstract

Background: Inclusion in trials is selective, and thus results may not be generalizable to the general population. The aim of this study was to investigate the external validity of randomized clinical trial outcomes for elderly breast cancer patients.
Methods: We compared characteristics and outcomes of breast cancer patients (n = 1325) who participated in a randomized clinical trial (Tamoxifen Exemestane Adjuvant Multinational trial) with unselected breast cancer patients of corresponding age from the general population (n = 1056). Dutch patients aged 65 years or older at diagnosis of hormone receptor–positive breast cancer without distant metastases, with either nodal involvement, a tumor greater than 3cm, or a 1 to 3cm histological grade III tumor, who completed local therapy were included. Analyses were stratified by age (65–74 years; ≥75 years). Primary outcome was overall mortality. Multivariable Cox proportional hazards models were used to assess the association between covariables and overall mortality. All statistical tests were two-sided.
Results: Irrespective of age, patients who participated in the trial had fewer comorbid diseases, a higher socioeconomic status, and smaller tumors (all P < .001). In patients aged 65 to 74 years, those who participated in the trial had a similar overall mortality to patients from the general population (multivariable hazard ratio [HR] = 1.08; 95% confidence interval [CI] = 0.73 to 1.60). Alternatively, in patients aged 75 years or older, those who participated in the trial had a lower overall mortality (multivariable HR = 0.72; 95% CI = 0.55 to 0.95; P = .02) than patients in the general population.
Conclusions: Breast cancer trial participants aged 75 years or older do not represent elderly breast cancer patients of corresponding age from the general population, which hampers the external validity of a trial.
Original languageEnglish
Article numberdju051
JournalJournal of the National Cancer Institute
Volume106
Issue number4
DOIs
Publication statusPublished - 2014

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Hormones
Breast Neoplasms
exemestane
Mortality
Population
Randomized Controlled Trials
Confidence Intervals
Neoplasms
Tamoxifen
Proportional Hazards Models
Social Class
Neoplasm Metastasis

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van de Water, W., Kiderlen, M., Bastiaannet, E., Siesling, S., Westendorp, R. G. J., van de Velde, C. J. H., ... Liefers, G-J. (2014). External Validity of a Trial Comprised of Elderly Patients With Hormone Receptor–Positive Breast Cancer. Journal of the National Cancer Institute, 106(4), [dju051]. https://doi.org/10.1093/jnci/dju051
van de Water, Willemien ; Kiderlen, Mandy ; Bastiaannet, Esther ; Siesling, Sabine ; Westendorp, Rudi G.J. ; van de Velde, Cornelis J.H. ; Nortier, Johan W.R. ; Seynaeve, Caroline ; de Craen, Anton J.M. ; Liefers, Gerrit-Jan. / External Validity of a Trial Comprised of Elderly Patients With Hormone Receptor–Positive Breast Cancer. In: Journal of the National Cancer Institute. 2014 ; Vol. 106, No. 4.
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title = "External Validity of a Trial Comprised of Elderly Patients With Hormone Receptor–Positive Breast Cancer",
abstract = "Background: Inclusion in trials is selective, and thus results may not be generalizable to the general population. The aim of this study was to investigate the external validity of randomized clinical trial outcomes for elderly breast cancer patients.Methods: We compared characteristics and outcomes of breast cancer patients (n = 1325) who participated in a randomized clinical trial (Tamoxifen Exemestane Adjuvant Multinational trial) with unselected breast cancer patients of corresponding age from the general population (n = 1056). Dutch patients aged 65 years or older at diagnosis of hormone receptor–positive breast cancer without distant metastases, with either nodal involvement, a tumor greater than 3cm, or a 1 to 3cm histological grade III tumor, who completed local therapy were included. Analyses were stratified by age (65–74 years; ≥75 years). Primary outcome was overall mortality. Multivariable Cox proportional hazards models were used to assess the association between covariables and overall mortality. All statistical tests were two-sided.Results: Irrespective of age, patients who participated in the trial had fewer comorbid diseases, a higher socioeconomic status, and smaller tumors (all P < .001). In patients aged 65 to 74 years, those who participated in the trial had a similar overall mortality to patients from the general population (multivariable hazard ratio [HR] = 1.08; 95{\%} confidence interval [CI] = 0.73 to 1.60). Alternatively, in patients aged 75 years or older, those who participated in the trial had a lower overall mortality (multivariable HR = 0.72; 95{\%} CI = 0.55 to 0.95; P = .02) than patients in the general population.Conclusions: Breast cancer trial participants aged 75 years or older do not represent elderly breast cancer patients of corresponding age from the general population, which hampers the external validity of a trial.",
author = "{van de Water}, Willemien and Mandy Kiderlen and Esther Bastiaannet and Sabine Siesling and Westendorp, {Rudi G.J.} and {van de Velde}, {Cornelis J.H.} and Nortier, {Johan W.R.} and Caroline Seynaeve and {de Craen}, {Anton J.M.} and Gerrit-Jan Liefers",
year = "2014",
doi = "10.1093/jnci/dju051",
language = "English",
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van de Water, W, Kiderlen, M, Bastiaannet, E, Siesling, S, Westendorp, RGJ, van de Velde, CJH, Nortier, JWR, Seynaeve, C, de Craen, AJM & Liefers, G-J 2014, 'External Validity of a Trial Comprised of Elderly Patients With Hormone Receptor–Positive Breast Cancer' Journal of the National Cancer Institute, vol. 106, no. 4, dju051. https://doi.org/10.1093/jnci/dju051

External Validity of a Trial Comprised of Elderly Patients With Hormone Receptor–Positive Breast Cancer. / van de Water, Willemien; Kiderlen, Mandy; Bastiaannet, Esther; Siesling, Sabine; Westendorp, Rudi G.J.; van de Velde, Cornelis J.H.; Nortier, Johan W.R.; Seynaeve, Caroline; de Craen, Anton J.M.; Liefers, Gerrit-Jan.

In: Journal of the National Cancer Institute, Vol. 106, No. 4, dju051, 2014.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - External Validity of a Trial Comprised of Elderly Patients With Hormone Receptor–Positive Breast Cancer

AU - van de Water, Willemien

AU - Kiderlen, Mandy

AU - Bastiaannet, Esther

AU - Siesling, Sabine

AU - Westendorp, Rudi G.J.

AU - van de Velde, Cornelis J.H.

AU - Nortier, Johan W.R.

AU - Seynaeve, Caroline

AU - de Craen, Anton J.M.

AU - Liefers, Gerrit-Jan

PY - 2014

Y1 - 2014

N2 - Background: Inclusion in trials is selective, and thus results may not be generalizable to the general population. The aim of this study was to investigate the external validity of randomized clinical trial outcomes for elderly breast cancer patients.Methods: We compared characteristics and outcomes of breast cancer patients (n = 1325) who participated in a randomized clinical trial (Tamoxifen Exemestane Adjuvant Multinational trial) with unselected breast cancer patients of corresponding age from the general population (n = 1056). Dutch patients aged 65 years or older at diagnosis of hormone receptor–positive breast cancer without distant metastases, with either nodal involvement, a tumor greater than 3cm, or a 1 to 3cm histological grade III tumor, who completed local therapy were included. Analyses were stratified by age (65–74 years; ≥75 years). Primary outcome was overall mortality. Multivariable Cox proportional hazards models were used to assess the association between covariables and overall mortality. All statistical tests were two-sided.Results: Irrespective of age, patients who participated in the trial had fewer comorbid diseases, a higher socioeconomic status, and smaller tumors (all P < .001). In patients aged 65 to 74 years, those who participated in the trial had a similar overall mortality to patients from the general population (multivariable hazard ratio [HR] = 1.08; 95% confidence interval [CI] = 0.73 to 1.60). Alternatively, in patients aged 75 years or older, those who participated in the trial had a lower overall mortality (multivariable HR = 0.72; 95% CI = 0.55 to 0.95; P = .02) than patients in the general population.Conclusions: Breast cancer trial participants aged 75 years or older do not represent elderly breast cancer patients of corresponding age from the general population, which hampers the external validity of a trial.

AB - Background: Inclusion in trials is selective, and thus results may not be generalizable to the general population. The aim of this study was to investigate the external validity of randomized clinical trial outcomes for elderly breast cancer patients.Methods: We compared characteristics and outcomes of breast cancer patients (n = 1325) who participated in a randomized clinical trial (Tamoxifen Exemestane Adjuvant Multinational trial) with unselected breast cancer patients of corresponding age from the general population (n = 1056). Dutch patients aged 65 years or older at diagnosis of hormone receptor–positive breast cancer without distant metastases, with either nodal involvement, a tumor greater than 3cm, or a 1 to 3cm histological grade III tumor, who completed local therapy were included. Analyses were stratified by age (65–74 years; ≥75 years). Primary outcome was overall mortality. Multivariable Cox proportional hazards models were used to assess the association between covariables and overall mortality. All statistical tests were two-sided.Results: Irrespective of age, patients who participated in the trial had fewer comorbid diseases, a higher socioeconomic status, and smaller tumors (all P < .001). In patients aged 65 to 74 years, those who participated in the trial had a similar overall mortality to patients from the general population (multivariable hazard ratio [HR] = 1.08; 95% confidence interval [CI] = 0.73 to 1.60). Alternatively, in patients aged 75 years or older, those who participated in the trial had a lower overall mortality (multivariable HR = 0.72; 95% CI = 0.55 to 0.95; P = .02) than patients in the general population.Conclusions: Breast cancer trial participants aged 75 years or older do not represent elderly breast cancer patients of corresponding age from the general population, which hampers the external validity of a trial.

U2 - 10.1093/jnci/dju051

DO - 10.1093/jnci/dju051

M3 - Article

VL - 106

JO - Journal of the National Cancer Institute

JF - Journal of the National Cancer Institute

SN - 0027-8874

IS - 4

M1 - dju051

ER -