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Chemotherapy effectiveness in trial-underrepresented groups with early breast cancer: A retrospective cohort study

Chemotherapy effectiveness in trial-underrepresented groups with early breast cancer: A retrospective cohort study
Chemotherapy effectiveness in trial-underrepresented groups with early breast cancer: A retrospective cohort study

BACKGROUND: Adjuvant chemotherapy in early stage breast cancer has been shown to reduce mortality in a large meta-analysis of over 100 randomised trials. However, these trials largely excluded patients aged 70 years and over or with higher levels of comorbidity. There is therefore uncertainty about whether the effectiveness of adjuvant chemotherapy generalises to these groups, hindering patient and clinician decision-making. This study utilises administrative healthcare data-real world data (RWD)-and econometric methods for causal analysis to estimate treatment effectiveness in these trial-underrepresented groups. METHODS AND FINDINGS: Women with early breast cancer aged 70 years and over and those under 70 years with a high level of comorbidity were identified and their records extracted from Scottish Cancer Registry (2001-2015) data linked to other routine health records. A high level of comorbidity was defined as scoring 1 or more on the Charlson comorbidity index, being in the top decile of inpatient stays, and/or having 5 or more visits to specific outpatient clinics, all within the 5 years preceding breast cancer diagnosis. Propensity score matching (PSM) and instrumental variable (IV) analysis, previously identified as feasible and valid in this setting, were used in conjunction with Cox regression to estimate hazard ratios for death from breast cancer and death from all causes. The analysis adjusts for age, clinical prognostic factors, and socioeconomic deprivation; the IV method may also adjust for unmeasured confounding factors. Cohorts of 9,653 and 7,965 were identified for women aged 70 years and over and those with high comorbidity, respectively. In the ≥70/high comorbidity cohorts, median follow-up was 5.17/6.53 years and there were 1,935/740 deaths from breast cancer. For women aged 70 years and over, the PSM-estimated HR was 0.73 (95% CI 0.64-0.95), while for women with high comorbidity it was 0.67 (95% CI 0.51-0.86). This translates to a mean predicted benefit in terms of overall survival at 10 years of approximately3% (percentage points) and 4%, respectively. A limitation of this analysis is that use of observational data means uncertainty remains both from sampling uncertainty and from potential bias from residual confounding. CONCLUSIONS: The results of this study, as RWD, should be interpreted with caution and in the context of existing and emerging randomised data. The relative effectiveness of adjuvant chemotherapy in reducing mortality in patients with early stage breast cancer appears to be generalisable to the selected trial-underrepresented groups.

1549-1277
Gray, Ewan
640f76cd-997b-4a8d-8690-081ffdcd7d01
Marti, Joachim
55e9017a-66c0-4f11-9d38-97cbccac95f4
Wyatt, Jeremy C.
8361be5a-fca9-4acf-b3d2-7ce04126f468
Brewster, David H.
0ee02f74-62c5-480c-9956-2cf86b4abeb2
Hall, Peter S.
d45f9300-0dd4-4ad7-bd9d-f23873f80616
SATURNE advisory group
Gray, Ewan
640f76cd-997b-4a8d-8690-081ffdcd7d01
Marti, Joachim
55e9017a-66c0-4f11-9d38-97cbccac95f4
Wyatt, Jeremy C.
8361be5a-fca9-4acf-b3d2-7ce04126f468
Brewster, David H.
0ee02f74-62c5-480c-9956-2cf86b4abeb2
Hall, Peter S.
d45f9300-0dd4-4ad7-bd9d-f23873f80616

Gray, Ewan, Marti, Joachim, Wyatt, Jeremy C., Brewster, David H. and Hall, Peter S. , SATURNE advisory group (2019) Chemotherapy effectiveness in trial-underrepresented groups with early breast cancer: A retrospective cohort study. PLoS Medicine, 16 (12), [e1003006]. (doi:10.1371/journal.pmed.1003006).

Record type: Article

Abstract

BACKGROUND: Adjuvant chemotherapy in early stage breast cancer has been shown to reduce mortality in a large meta-analysis of over 100 randomised trials. However, these trials largely excluded patients aged 70 years and over or with higher levels of comorbidity. There is therefore uncertainty about whether the effectiveness of adjuvant chemotherapy generalises to these groups, hindering patient and clinician decision-making. This study utilises administrative healthcare data-real world data (RWD)-and econometric methods for causal analysis to estimate treatment effectiveness in these trial-underrepresented groups. METHODS AND FINDINGS: Women with early breast cancer aged 70 years and over and those under 70 years with a high level of comorbidity were identified and their records extracted from Scottish Cancer Registry (2001-2015) data linked to other routine health records. A high level of comorbidity was defined as scoring 1 or more on the Charlson comorbidity index, being in the top decile of inpatient stays, and/or having 5 or more visits to specific outpatient clinics, all within the 5 years preceding breast cancer diagnosis. Propensity score matching (PSM) and instrumental variable (IV) analysis, previously identified as feasible and valid in this setting, were used in conjunction with Cox regression to estimate hazard ratios for death from breast cancer and death from all causes. The analysis adjusts for age, clinical prognostic factors, and socioeconomic deprivation; the IV method may also adjust for unmeasured confounding factors. Cohorts of 9,653 and 7,965 were identified for women aged 70 years and over and those with high comorbidity, respectively. In the ≥70/high comorbidity cohorts, median follow-up was 5.17/6.53 years and there were 1,935/740 deaths from breast cancer. For women aged 70 years and over, the PSM-estimated HR was 0.73 (95% CI 0.64-0.95), while for women with high comorbidity it was 0.67 (95% CI 0.51-0.86). This translates to a mean predicted benefit in terms of overall survival at 10 years of approximately3% (percentage points) and 4%, respectively. A limitation of this analysis is that use of observational data means uncertainty remains both from sampling uncertainty and from potential bias from residual confounding. CONCLUSIONS: The results of this study, as RWD, should be interpreted with caution and in the context of existing and emerging randomised data. The relative effectiveness of adjuvant chemotherapy in reducing mortality in patients with early stage breast cancer appears to be generalisable to the selected trial-underrepresented groups.

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Accepted/In Press date: 26 November 2019
e-pub ahead of print date: 31 December 2019
Published date: December 2019

Identifiers

Local EPrints ID: 437201
URI: http://eprints.soton.ac.uk/id/eprint/437201
ISSN: 1549-1277
PURE UUID: 3fb0d928-1017-43a2-8807-8675da1e9a2e
ORCID for Jeremy C. Wyatt: ORCID iD orcid.org/0000-0001-7008-1473

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Date deposited: 21 Jan 2020 17:36
Last modified: 26 Nov 2021 03:05

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Contributors

Author: Ewan Gray
Author: Joachim Marti
Author: Jeremy C. Wyatt ORCID iD
Author: David H. Brewster
Author: Peter S. Hall
Corporate Author: SATURNE advisory group

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