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Risks of second non-breast primaries following breast cancer in women: a systematic review and meta-analysis

Risks of second non-breast primaries following breast cancer in women: a systematic review and meta-analysis
Risks of second non-breast primaries following breast cancer in women: a systematic review and meta-analysis

Background: Second primary cancer incidence is rising among breast cancer survivors. We examined the risks of non-breast second primaries, in combination and at specific cancer sites, through a systematic review and meta-analysis. Methods: We conducted a systematic search of PubMed, Embase, and Web of Science, seeking studies published by March 2022. We included studies that reported standardized incidence ratios (SIRs), with associated standard errors, assessing the combined risk of second non-breast primaries following breast cancer. We performed meta-analyses of combined second primary risks, stratifying by age, follow-up duration, and geographic region. We also assessed second primary risks at several specific sites, stratifying by age. The inverse variance method with DerSimonian–Laird estimators was used in all meta-analyses, assuming a random-effects model. Associated biases and study quality were evaluated using the Newcastle–Ottawa scale. Results: One prospective and twenty-seven retrospective cohort studies were identified. SIRs for second non-breast primaries combined ranged from 0.84 to 1.84. The summary SIR estimate was 1.24 (95% CI 1.14–1.36, I 2: 99%). This varied by age: the estimate was 1.59 (95% CI 1.36–1.85) when breast cancer was diagnosed before age 50, which was significantly higher than in women first diagnosed at 50 or over (SIR: 1.13, 95% CI 1.01–1.36, p for difference: < 0.001). SPC risks were also significantly higher when based on Asian, rather than European, registries (Asia—SIR: 1.47, 95% CI 1.29–1.67. Europe—SIR: 1.16, 95% CI 1.04–1.28). There were significantly increased risks of second thyroid (SIR: 1.89, 95% CI 1.49–2.38), corpus uteri (SIR: 1.84, 95% CI 1.53–2.23), ovary (SIR: 1.53, 95% CI 1.35–1.73), kidney (SIR: 1.43, 95% CI 1.17–1.73), oesophagus (SIR: 1.39, 95% CI 1.26–1.55), skin (melanoma) (SIR: 1.34, 95% CI 1.18–1.52), blood (leukaemia) (SIR: 1.30, 95% CI 1.17–1.45), lung (SIR: 1.25, 95% CI 1.03–1.51), stomach (SIR: 1.23, 95% CI 1.12–1.36) and bladder (SIR: 1.15, 95% CI 1.05–1.26) primaries. Conclusions: Breast cancer survivors are at significantly increased risk of second primaries at many sites. Risks are higher for those diagnosed with breast cancer before age 50 and in Asian breast cancer survivors compared to European breast cancer survivors. This study is limited by a lack of data on potentially confounding variables. The conclusions may inform clinical management decisions following breast cancer, although specific clinical recommendations lie outside the scope of this review.

Breast neoplasms, Epidemiology, Incidence, Meta-analysis, Multiple cancer, Multiple primary, Risk, Second cancer, Second primary, Systematic review
1465-5411
Allen, Isaac
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Hassan, Hend
f6df8c3f-7aca-4f59-9bce-87f557b0cbeb
Sofianopoulou, Eleni
58f9ab8c-87e5-4b7a-ad3b-4f85b89d2dad
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Turnbull, Clare
63408861-754b-4f55-a010-29d1bea914e2
Tischkowitz, Marc
1e7750c2-91a5-4079-a1f0-f59a1f42405b
Pharaoh, Paul
caae4a17-e31c-4479-9a81-66cfd2c646ce
Antoniou, Antonis C.
65739e70-823d-4acd-b99a-12c7b5521f34
Allen, Isaac
6268ab30-a744-4c41-8ea5-51fdaf383a99
Hassan, Hend
f6df8c3f-7aca-4f59-9bce-87f557b0cbeb
Sofianopoulou, Eleni
58f9ab8c-87e5-4b7a-ad3b-4f85b89d2dad
Eccles, Diana
5b59bc73-11c9-4cf0-a9d5-7a8e523eee23
Turnbull, Clare
63408861-754b-4f55-a010-29d1bea914e2
Tischkowitz, Marc
1e7750c2-91a5-4079-a1f0-f59a1f42405b
Pharaoh, Paul
caae4a17-e31c-4479-9a81-66cfd2c646ce
Antoniou, Antonis C.
65739e70-823d-4acd-b99a-12c7b5521f34

Allen, Isaac, Hassan, Hend, Sofianopoulou, Eleni, Eccles, Diana, Turnbull, Clare, Tischkowitz, Marc, Pharaoh, Paul and Antoniou, Antonis C. (2023) Risks of second non-breast primaries following breast cancer in women: a systematic review and meta-analysis. Breast Cancer Research, 25 (1), [18]. (doi:10.1186/s13058-023-01610-x).

Record type: Article

Abstract

Background: Second primary cancer incidence is rising among breast cancer survivors. We examined the risks of non-breast second primaries, in combination and at specific cancer sites, through a systematic review and meta-analysis. Methods: We conducted a systematic search of PubMed, Embase, and Web of Science, seeking studies published by March 2022. We included studies that reported standardized incidence ratios (SIRs), with associated standard errors, assessing the combined risk of second non-breast primaries following breast cancer. We performed meta-analyses of combined second primary risks, stratifying by age, follow-up duration, and geographic region. We also assessed second primary risks at several specific sites, stratifying by age. The inverse variance method with DerSimonian–Laird estimators was used in all meta-analyses, assuming a random-effects model. Associated biases and study quality were evaluated using the Newcastle–Ottawa scale. Results: One prospective and twenty-seven retrospective cohort studies were identified. SIRs for second non-breast primaries combined ranged from 0.84 to 1.84. The summary SIR estimate was 1.24 (95% CI 1.14–1.36, I 2: 99%). This varied by age: the estimate was 1.59 (95% CI 1.36–1.85) when breast cancer was diagnosed before age 50, which was significantly higher than in women first diagnosed at 50 or over (SIR: 1.13, 95% CI 1.01–1.36, p for difference: < 0.001). SPC risks were also significantly higher when based on Asian, rather than European, registries (Asia—SIR: 1.47, 95% CI 1.29–1.67. Europe—SIR: 1.16, 95% CI 1.04–1.28). There were significantly increased risks of second thyroid (SIR: 1.89, 95% CI 1.49–2.38), corpus uteri (SIR: 1.84, 95% CI 1.53–2.23), ovary (SIR: 1.53, 95% CI 1.35–1.73), kidney (SIR: 1.43, 95% CI 1.17–1.73), oesophagus (SIR: 1.39, 95% CI 1.26–1.55), skin (melanoma) (SIR: 1.34, 95% CI 1.18–1.52), blood (leukaemia) (SIR: 1.30, 95% CI 1.17–1.45), lung (SIR: 1.25, 95% CI 1.03–1.51), stomach (SIR: 1.23, 95% CI 1.12–1.36) and bladder (SIR: 1.15, 95% CI 1.05–1.26) primaries. Conclusions: Breast cancer survivors are at significantly increased risk of second primaries at many sites. Risks are higher for those diagnosed with breast cancer before age 50 and in Asian breast cancer survivors compared to European breast cancer survivors. This study is limited by a lack of data on potentially confounding variables. The conclusions may inform clinical management decisions following breast cancer, although specific clinical recommendations lie outside the scope of this review.

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Accepted/In Press date: 25 January 2023
e-pub ahead of print date: 10 February 2023
Published date: 10 February 2023
Additional Information: Funding Information: The authors acknowledge all involved in the CanGene-CanVar research programme (CRUK Catalyst Award CanGene-CanVar (C61296/A27223)). MT was supported by the NIHR Cambridge Biomedical Research Centre (BRC-1215-20014). Funding Information: This work was funded by the CRUK Catalyst Award CanGene-CanVar (C61296/A27223). Each person who contributed to the collection, analysis, and interpretation of data and in writing, editing, and giving feedback at the draft phase of this manuscript was funded by this grant. Publisher Copyright: © 2023, The Author(s).
Keywords: Breast neoplasms, Epidemiology, Incidence, Meta-analysis, Multiple cancer, Multiple primary, Risk, Second cancer, Second primary, Systematic review

Identifiers

Local EPrints ID: 474947
URI: http://eprints.soton.ac.uk/id/eprint/474947
ISSN: 1465-5411
PURE UUID: 2d0bf930-95c0-4967-a376-716720193abf
ORCID for Diana Eccles: ORCID iD orcid.org/0000-0002-9935-3169

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Date deposited: 07 Mar 2023 17:41
Last modified: 17 Mar 2024 02:36

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Contributors

Author: Isaac Allen
Author: Hend Hassan
Author: Eleni Sofianopoulou
Author: Diana Eccles ORCID iD
Author: Clare Turnbull
Author: Marc Tischkowitz
Author: Paul Pharaoh
Author: Antonis C. Antoniou

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