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. 2022 Aug;17(4):349-355.
doi: 10.1159/000522057. Epub 2022 Jan 19.

Risk and Survival of Third Primary Cancers in a Population-Based Cohort of Breast Cancer Patients

Samantha Morais  1   2   3 , Elisabete Gonçalves  1   2 , Filipa Fontes  1   2   3   4 , Jéssica Rodrigues  4   5 , Rita Calisto  4   5 , Maria José Bento  4   5   6 , Nuno Lunet  1   2   3
Affiliations

Risk and Survival of Third Primary Cancers in a Population-Based Cohort of Breast Cancer Patients

Samantha Morais et al. Breast Care (Basel). 2022 Aug.

Abstract

Introduction: The growing number of women diagnosed with breast cancer (BCa) together with high survival has resulted in an increasing population of survivors at risk of subsequent primary cancers. This study aimed to estimate the long-term risk and survival of third primary cancers (TPCs) among females with a first primary BCa.

Methods: Breast first primary cancers (FPCs) from the Portuguese North Region Cancer Registry, diagnosed between 2000 and 2010 (n = 15,981), were followed for a TPC (December 31, 2015) and death from any cause (June 30, 2021). The cumulative incidence of and mortality among TPCs were estimated. To compare survival, female patients with a TPC were matched (1:1, by age group, years between FPC and second primary cancer [SPC] diagnosis, and SPC location) to FPC + SPC patients without a TPC.

Results: Overall, 67 (0.4% of FPCs and 5.4% of SPCs) TPCs were diagnosed. The most common TPC sites were digestive, breast, and female genital organs. Among all FPCs, the 15-year cumulative incidence (95% confidence interval [CI]) of a TPC was 0.69% (0.47-0.90%) and among SPCs, 7.21% (4.99-9.43%). The 15-year cumulative mortality of TPCs and matched patients was 70.0% and 51.5%, respectively. For TPCs, compared to matched SPC only patients, the age-adjusted hazard ratio (95% CI) for death was 2.86 (1.61-5.07).

Discussion/conclusion: The most common TPC sites were digestive, breast, and female genital organs, with a 15-year cumulative incidence of 0.69% among FPCs. TPCs had a worse long-term survival compared to patients with an SPC only.

Keywords: Breast neoplasms; Epidemiology; Mortality; Multiple primary neoplasms; Registries.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

Figures

Fig. 1
Fig. 1
Distribution of TPCsa among SPCsb in female breast FPC patients. FPC, first primary cancer; ICD-10, International Statistical Classification of Diseases and Related Health Problems 10th Revision; SPC, second primary cancer; TPC, third primary cancer. a Digestive organs (C15–C26); respiratory and intrathoracic organs (C30–C39); breast (C50); female genital organs (C51–C58); urinary tract (C64–C68); thyroid and other endocrine glands (C73–C75); lymphoid, hematopoietic, and related tissues (C81–C96); and others: lip, oral cavity and pharynx (C1–C14), skin melanoma (C43), mesothelial and soft tissue (C45–C49), ill-defined, secondary, or unspecified sites (C76–C80) defined according to the ICD-10 [13]. b Digestive organs (C15–C26), respiratory and intrathoracic organs (C30–C39), breast (C50), female genital organs (C51–C58), others: skin melanoma (C43), urinary tract (C64–C68), eye (C69), brain and other parts of the central nervous system (C70–C72), lymphoid, hematopoietic, and related tissue (C81–C96), uncertain or unknown behavior (D37–D48) defined according to the ICD-10 [13].
Fig. 2
Fig. 2
Cumulative incidence of TPCs, among female breast FPCs (a) and SPCs (b) following a breast FPC, considering the competing event of death. FPC, first primary cancer; SPC, second primary cancer; TPC, third primary cancer. Note that a different scale is used for the two graphs.
Fig. 3
Fig. 3
Observed cumulative all-cause mortalitya of female breast FPCs with an SPC, and with and without a TPC. FPC, first primary cancer; SPC, second primary cancer; TPC, third primary cancer. a Calculated using 1 − Kaplan-Meier [16].
See this image and copyright information in PMC

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