Risks of second primary cancers among 584,965 female and male breast cancer survivors in England: a 25-year retrospective cohort study

Abstract

Background: second primary cancers (SPCs) after breast cancer (BC) present an increasing public health burden, with little existing research on socio-demographic, tumour, and treatment effects. We addressed this in the largest BC survivor cohort to date, using a novel linkage of National Disease Registration Service datasets.

Methods: the cohort included 581,403 female and 3562 male BC survivors diagnosed between 1995-2019. We estimated standardized incidence ratios (SIRs) for combined and site-specific SPCs using incidences for England, overall and by age at BC and socioeconomic status. We estimated incidences and Kaplan-Meier cumulative risks stratified by age at BC, and assessed risk variation by socio-demographic, tumour, and treatment characteristics using Cox regression.

Findings: both genders were at elevated contralateral breast (SIR:2.02 (95%CI:1.99-2.06) females; 55.4 (35.5-82.4) males) and non-breast (1.10 (1.09-1.11) females, 1.10 (1.00-1.20) males) SPC risks. Non-breast SPC risks were higher for females younger at BC diagnosis (SIR:1.34 (1.31-1.38) <50y, 1.07 (1.06-1.09) >=50y) and more socioeconomically deprived (SIR:1.00 (0.98-1.02) least deprived quintile, 1.34 (1.30-1.37) most).

Interpretations: enhanced SPC surveillance may benefit BC survivors, although specific recommendations require more detailed multifactorial risk and cost-benefit analyses. The associations between deprivation and SPC risks could provide clinical management insights.

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Identifiers

ORCID for Diana Eccles: orcid.org/0000-0002-9935-3169

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