BACKGROUND: With increasing survival after cancer diagnoses, second primary cancers (SPCs) are becoming more prevalent. We investigated the incidence and site of non-breast SPC risks following male breast cancer (BC). METHODS: PubMed, Embase and Web of Science were systematically searched for studies reporting standardised incidence ratios (SIRs) for SPCs published by March 2022. Meta-analyses used the generic inverse-variance method, assuming a random-effects model. We evaluated SIRs for overall SPCs, site-specific risks, by age at BC onset, time since BC onset and geographic region. We assessed study quality using routine techniques. RESULTS: Eight population-based retrospective cohort studies were identified. SIRs ranged from 1.05 to 2.17. The summary SIR estimate was 1.27 (95% CI: 1.03-1.56, I 2 : 86%), and there were increased colorectal (SIR: 1.29, 95% CI: 1.03-1.61), pancreatic (SIR: 1.64, 95% CI: 1.05-2.55) and thyroid (SIR: 5.58, 95% CI: 1.04-30.05) SPC risks. When an outlying study was excluded, the summary SIR for men diagnosed with BC before age 50 was 1.50 (95% CI: 1.21-1.85), significantly higher than men diagnosed at older ages (SIR: 1.14, 95% CI: 0.98-1.33). CONCLUSIONS: Male BC survivors are at elevated risks of developing second primary colorectal, pancreatic and thyroid cancers. The estimates may assist their clinical management and guide decisions on genetic testing.
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, I2: 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.
Background: Second primary cancer (SPC) incidence is rising among breast cancer (BC) survivors, but these risks remain unclear. We estimated SPC risks for male and female BC survivors using large-scale electronic health record data from a linkage of National Cancer Registration and Analysis Service data and Hospital Episode Statistics surgical records in England. Material and Methods: We used a retrospective cohort study design comprising 763,578 female and 4,795 male BC survivors first diagnosed with BC between 1995-2018. We calculated overall and site-specific SPC standardized incidence ratios (SIRs) by comparing observed and expected SPC counts for 19 cancer sites. Study participants were followed from one year after the first BC diagnosis until either a SPC diagnosis (excluding ipsilateral breast and non-melanoma skin cancers), death, migration, relevant surgical procedures, or the end of 2019. Expected SPC counts were calculated using year-, age- and sex-specific cancer incidence rates in the general English population. We stratified the SIRs by age group, sex, and cancer site. We estimated Kaplan-Meier absolute risks of site-specific SPCs and assessed the influence of age at first BC diagnosis using Cox proportional hazards models. Results: There were 68,550 and 720 incident SPCs among female and male BC survivors, respectively. There was a significant increased risk of all SPCs combined for female BC survivors (SIR: 1.19, 95%CI: 1.18-1.20). There were significant increased risks for SPC at all sites combined, all non-breast sites combined, and at 12 further specific sites for females and at 2 specific sites for males. Among females, the increase was greatest for contralateral breast (SIR: 1.82, 95%CI: 1.79-1.85) and uterine cancers (SIR: 1.80, 95%CI: 1.76-1.85). The risk at all sites combined was higher for women first diagnosed with BC before age 50 (SIR: 1.89, 95%CI: 1.85-1.92) compared to women diagnosed with BC at age 50 or over (SIR: 1.11, 95%CI: 1.10-1.12). The largest associations were observed for contralateral breast (SIR: 3.19, 95%CI: 3.11-3.29) and uterine (SIR: 1.77, 95%CI: 1.73-1.82) SPCs in the younger and older age groups, respectively. Increasing age at first female BC diagnosis was associated with decreasing CBC absolute risks, but significantly increased absolute risks of all other SPCs. Male BC survivors were at increased risk of contralateral breast (SIR: 42.39, 95%CI: 28.39-60.89) and prostate (SIR: 1.29, 95%CI: 1.13-1.46) SPCs. Conclusions: This is the largest study to date to assess SPC risks following BC in either men or women. SPC risks were significantly increased, both in combination and at specific sites. These findings could help guide clinical management, such as screening recommendations, for BC survivors. Further analysis is underway to investigate the effects of chemotherapy, radiotherapy, hormonal therapy, comorbidities, or germline BC susceptibility. Citation Format: Isaac Allen, Tameera Rahman, Andrew Bacon, Craig Knott, Sophie Jose, Sally Vernon, Hend Hassan, Catherine Huntley, Lucy Loong, Yvonne Walburga, Katrina Lavelle, Eva Morris, Steven Hardy, Beth Torr, Diana Eccles, Clare Turnbull, Marc Tischkowitz, Paul Pharoah, Antonis C. Antoniou. Second primary cancer risks for female and male breast cancer survivors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3057.
BackgroundSecond 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. MethodsWe 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. ResultsOne 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, I2: 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), uterus (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. ConclusionsBreast 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 could inform clinical management decisions following breast cancer.
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