Breast cancer is the most frequently diagnosed cancer in females globally. However, we know relatively little about trends in males. This study describes United Kingdom (UK) secular trends in breast cancer from 2000 to 2021 for both sexes. We describe a population-based cohort study using UK primary care Clinical Practice Research Datalink (CPRD) GOLD and Aurum databases. There were 5,848,436 eligible females and 5,539,681 males aged 18+ years, with ≥ one year of prior data availability in the study period. We estimated crude breast cancer incidence rates (IR), prevalence and survival probability at one-, five- and 10-years after diagnosis using the Kaplan-Meier method. Analyses were further stratified by age. Crude IR of breast cancer from 2000 to 2021 was 194.4 per 100,000 person-years for females and 1.16 for males. Crude prevalence in 2021 was 2.1% for females and 0.009% for males. Both sexes have seen around a 2.5-fold increase in prevalence across time. Incidence increased with age for both sexes, peaking in females aged 60-69 years and males 90+ . There was a drop in incidence for females aged 70-79 years. From 2003-2019, incidence increased > twofold in younger females (aged 18-29: IR 2.12 in 2003 vs. 4.58 in 2018); decreased in females aged 50-69 years; and further declined from 2015 onwards in females aged 70-89 years. Survival probability for females after one-, five-, and ten-years after diagnosis was 95.1%, 80.2%, and 68.4%, and for males 92.9%, 69.0%, and 51.3%. Survival probability at one-year increased by 2.08% points, and survival at five years increased by 5.39% from 2000-2004 to 2015-2019 for females, particularly those aged 50-70 years. For males, there were no clear time-trends for short-term and long-term survival probability. Changes in incidence of breast cancer in females largely reflect the success of screening programmes, as rates rise and fall in synchronicity with ages of eligibility for such programmes. Overall survival from breast cancer for females has improved from 2000 to 2021, again reflecting the success of screening programmes, early diagnosis, and improvements in treatments. Male breast cancer patients have worse survival outcomes compared to females, highlighting the need to develop male-specific diagnosis and treatment strategies to improve long-term survival in line with females.

1st Department of Tuberculosis and Respiratory Diseases 1st Faculty of Medicine Charles University Katerinska 1660 32 121 08 Prague Czech Republic

Centre for Statistics in Medicine Nuffield Department of Orthopaedics Rheumatology and Musculoskeletal Sciences University of Oxford Oxford OX3 7LD UK

Department of Medical Informatics Erasmus University Medical Centre Rotterdam The Netherlands

Fundació Institut Universitari Per a La Recerca a L'Atenció Primària de Salut Jordi Gol 1 Gurina Barcelona Spain

Odysseus Data Service Cambridge MA USA

OHDSI Center at the Roux Institute Northeastern University Boston MA USA

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