Cancer Res Treat.  2023 Apr;55(2):580-591. 10.4143/crt.2022.410.

Epidemiology of Second Non-breast Primary Cancers among Survivors of Breast Cancer: A Korean Population–Based Study by the SMARTSHIP Group

• Kim H
• Kim SS
• Lee JS
• Yoon JS
• Youn HJ
• Shin H
• Lee JE
• Lee SK
• Chung IY
• Jung SY
• Choi YJ
• Cho J
• Woo SU
• Korean Breast Cancer Society

• KMID: 2541245
• DOI: http://doi.org/10.4143/crt.2022.410

Abstract

Purpose
This study aimed to evaluate the incidence and prognosis of second non-breast primary cancer (SNBPC) among Korean survivors of breast cancer.
Materials and Methods
Data from the Korean National Health Insurance Service were searched to identify women who received curative surgery for initial breast cancer (IBC) between 2003 and 2008 (n=64,340). Among them, patients with the following characteristics were excluded: other cancer diagnosis before IBC (n=10,866), radiotherapy before IBC (n=349), absence of data on sex or age (n=371), or male (n=248). Accordingly, data of 52,506 women until December 2017 were analyzed. SNBPC was defined as a newly diagnosed SNBPC that occurred 5 years or more after IBC diagnosis.
Results
The median follow-up time of all patients was 12.13 years. SNBPC was developed in 3,084 (5.87%) women after a median of 7.61 years following IBC diagnosis. The 10-year incidence of SNBPC was 5.78% (95% confidence interval [CI], 5.56 to 6.00). Higher SNBPC incidence was found in survivors with the following factors: old age at IBC diagnosis, low household income, and receiving combined chemotherapy with endocrine therapy, whereas receiving radiotherapy was related to a lower incidence of SNBPC (hazard ratio, 0.89; p < 0.01). Among the patients with SNBPC, the 5-year survival rate was 62.28% (95% CI, 65.53 to 69.02).
Conclusion
Approximately 5% of breast cancer survivors developed SNBPC within 10 years after IBC diagnosis. The risk of SNBPC was associated with patient’s age at IBC diagnosis, income level, and a receipt of systemic treatments.

Keyword

Breast neoplasms; Cancer survivors; Neoplasms; Second primary; Epidemiology; Incidence; Risk factors

Figure

• 

  Fig. 1 Flowchart of the study. The second non-breast primary cancer (SNBPC) was defined as newly diagnosed non-breast primary cancer that occurred 5 years or more after an initial breast cancer diagnosis. a)Data on mortality were available until December 2018.

Reference

References

1. Sung H, Ferlay J, Siegel RL, Laversanne M, Soerjomataram I, Jemal A, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021; 71:209–49.

2. Hong S, Won YJ, Park YR, Jung KW, Kong HJ, Lee ES, et al. Cancer statistics in Korea: incidence, mortality, survival, and Prevalence in 2017. Cancer Res Treat. 2020; 52:335–50.

3. Ministry of Health and Welfare. Central Cancer Registry. The national cancer registry statistics in 2019 [Internet]. Sejong: Ministry of Health and Welfare;c2020. [cited 2020 May 10]. Available from: http://www.mohw.go.kr .

4. Kang SY, Lee SB, Kim YS, Kim Z, Kim HY, Kim HJ, et al. Breast cancer statistics in Korea, 2018. J Breast Cancer. 2021; 24:123–37.

5. Moore HC. Breast cancer survivorship. Semin Oncol. 2020; 47:222–8.

6. Lin CY, Chen SH, Huang CC, Weng SF, Lee ST, Guo HR, et al. Risk of secondary cancers in women with breast cancer and the influence of radiotherapy: a national cohort study in Taiwan. Medicine (Baltimore). 2016; 95:e5556.

7. Grantzau T, Mellemkjaer L, Overgaard J. Second primary cancers after adjuvant radiotherapy in early breast cancer patients: a national population based study under the Danish Breast Cancer Cooperative Group (DBCG). Radiother Oncol. 2013; 106:42–9.

8. Silverman BG, Lipshitz I, Keinan-Boker L. Second primary cancers after primary breast cancer diagnosis in Israeli women, 1992 to 2006. J Glob Oncol. 2017; 3:135–42.

9. Zhang W, Becciolini A, Biggeri A, Pacini P, Muirhead CR. Second malignancies in breast cancer patients following radiotherapy: a study in Florence, Italy. Breast Cancer Res. 2011; 13:R38.

10. Kirova YM, Gambotti L, De Rycke Y, Vilcoq JR, Asselain B, Fourquet A. Risk of second malignancies after adjuvant radiotherapy for breast cancer: a large-scale, single-institution review. Int J Radiat Oncol Biol Phys. 2007; 68:359–63.

11. Molina-Montes E, Requena M, Sanchez-Cantalejo E, Fernandez MF, Arroyo-Morales M, Espin J, et al. Risk of second cancers cancer after a first primary breast cancer: a systematic review and meta-analysis. Gynecol Oncol. 2015; 136:158–71.

12. Grantzau T, Overgaard J. Risk of second non-breast cancer after radiotherapy for breast cancer: a systematic review and meta-analysis of 762,468 patients. Radiother Oncol. 2015; 114:56–65.

13. Li D, Weng S, Zhong C, Tang X, Zhu N, Cheng Y, et al. Risk of second primary cancers among long-term survivors of breast cancer. Front Oncol. 2019; 9:1426.

14. Sung H, Freedman RA, Siegel RL, Hyun N, DeSantis CE, Ruddy KJ, et al. Risks of subsequent primary cancers among breast cancer survivors according to hormone receptor status. Cancer. 2021; 127:3310–24.

15. Kim S, Kim MS, You SH, Jung SY. Conducting and reporting a clinical research using Korean Healthcare Claims Database. Korean J Fam Med. 2020; 41:146–52.

16. Jabagi MJ, Vey N, Goncalves A, Le Tri T, Zureik M, Dray-Spira R. Risk of secondary hematologic malignancies associated with breast cancer chemotherapy and G-CSF support: a nationwide population-based cohort. Int J Cancer. 2021; 148:375–84.

17. Roychoudhuri R, Evans H, Robinson D, Moller H. Radiation-induced malignancies following radiotherapy for breast cancer. Br J Cancer. 2004; 91:868–72.

18. Schaapveld M, Visser O, Louwman MJ, de Vries EG, Willemse PH, Otter R, et al. Risk of new primary nonbreast cancers after breast cancer treatment: a Dutch population-based study. J Clin Oncol. 2008; 26:1239–46.

19. Molina-Montes E, Pollan M, Payer T, Molina E, Davila-Arias C, Sanchez MJ. Risk of second primary cancer among women with breast cancer: a population-based study in Granada (Spain). Gynecol Oncol. 2013; 130:340–5.

20. Fiorino C, Guckemberger M, Schwarz M, van der Heide UA, Heijmen B. Technology-driven research for radiotherapy innovation. Mol Oncol. 2020; 14:1500–13.

21. Ahn E. Introducing big data analysis using data from National Health Insurance Service. Korean J Anesthesiol. 2020; 73:205–11.

22. Park S. Medical service utilization and out-of-pocket spending among near-poor National Health Insurance members in South Korea. BMC Health Serv Res. 2021; 21:886.