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. 2023 May 3;25(1):50.
doi: 10.1186/s13058-023-01647-y.

Risk of second primary cancer among women in the Kaiser Permanente Breast Cancer Survivors Cohort

Cody Ramin  1   2 , Lene H S Veiga  3 , Jacqueline B Vo  3 , Rochelle E Curtis  3 , Clara Bodelon  3 , Erin J Aiello Bowles  4 , Diana S M Buist  4   5 , Sheila Weinmann  6 , Heather Spencer Feigelson  5   7 , Gretchen L Gierach  3 , Amy Berrington de Gonzalez  3   8
Affiliations

Risk of second primary cancer among women in the Kaiser Permanente Breast Cancer Survivors Cohort

Cody Ramin et al. Breast Cancer Res. .

Abstract

Background: Breast cancer survivors are living longer due to early detection and advances in treatment and are at increased risk for second primary cancers. Comprehensive evaluation of second cancer risk among patients treated in recent decades is lacking.

Methods: We identified 16,004 females diagnosed with a first primary stage I-III breast cancer between 1990 and 2016 (followed through 2017) and survived ≥ 1 year at Kaiser Permanente (KP) Colorado, Northwest, and Washington. Second cancer was defined as an invasive primary cancer diagnosed ≥ 12 months after the first primary breast cancer. Second cancer risk was evaluated for all cancers (excluding ipsilateral breast cancer) using standardized incidence ratios (SIRs), and a competing risk approach for cumulative incidence and hazard ratios (HRs) adjusted for KP center, treatment, age, and year of first cancer diagnosis.

Results: Over a median follow-up of 6.2 years, 1,562 women developed second cancer. Breast cancer survivors had a 70% higher risk of any cancer (95%CI = 1.62-1.79) and 45% higher risk of non-breast cancer (95%CI = 1.37-1.54) compared with the general population. SIRs were highest for malignancies of the peritoneum (SIR = 3.44, 95%CI = 1.65-6.33), soft tissue (SIR = 3.32, 95%CI = 2.51-4.30), contralateral breast (SIR = 3.10, 95%CI = 2.82-3.40), and acute myeloid leukemia (SIR = 2.11, 95%CI = 1.18-3.48)/myelodysplastic syndrome (SIR = 3.25, 95%CI = 1.89-5.20). Women also had elevated risks for oral, colon, pancreas, lung, and uterine corpus cancer, melanoma, and non-Hodgkin lymphoma (SIR range = 1.31-1.97). Radiotherapy was associated with increased risk for all second cancers (HR = 1.13, 95%CI = 1.01-1.25) and soft tissue sarcoma (HR = 2.36, 95%CI = 1.17-4.78), chemotherapy with decreased risk for all second cancers (HR = 0.87, 95%CI = 0.78-0.98) and increased myelodysplastic syndrome risk (HR = 3.01, 95%CI = 1.01-8.94), and endocrine therapy with lower contralateral breast cancer risk (HR = 0.48, 95%CI = 0.38-0.60). Approximately 1 in 9 women who survived ≥ 1 year developed second cancer, 1 in 13 developed second non-breast cancer, and 1 in 30 developed contralateral breast cancer by 10 years. Trends in cumulative incidence declined for contralateral breast cancer but not for second non-breast cancers.

Conclusions: Elevated risks of second cancer among breast cancer survivors treated in recent decades suggests that heightened surveillance is warranted and continued efforts to reduce second cancers are needed.

Keywords: Breast cancer; Cancer survivorship; Chemotherapy; Endocrine therapy; Radiotherapy; Second cancers; Second non-breast cancers.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Cumulative incidence of second primary cancer among 16,004 women diagnosed with a first primary unilateral invasive breast cancer between 1990 to 2016 and followed through 2017
Fig. 2
Fig. 2
Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for second primary cancer according to characteristics of the first breast cancer among 16,004 women diagnosed with a first primary unilateral invasive breast cancer between 1990 to 2016 and followed through 2017. Abbreviations: SIRs–Standardized incidence ratios, CI–Confidence interval, O–Observed, E–Expected, ER–Estrogen receptor. Note: Second primary cancer excludes second ipsilateral breast cancer. aP-values to test for heterogeneity between SIRs. bNo/unknown receipt of radiotherapy is combined due to potential under ascertainment of radiotherapy in registry data (no radiotherapy: n = 5,302; unknown radiotherapy: n = 64). cRestricted to women diagnosed with a first ER-positive breast cancer (n = 12,746)
Fig. 3
Fig. 3
Standardized incidence ratios (SIRs) and 95% confidence intervals (CIs) for selected site-specific second primary cancers among 16,004 women diagnosed with a first primary unilateral invasive breast cancer between 1990 to 2016 and followed through 2017. Abbreviations: SIRs–Standardized incidence ratios, CIs–Confidence intervals, O–Observed, E–Expected. aCancer sites with ≥ 10 cases are presented unless specified a priori as a site of interest. bWomen with bilateral mastectomies were excluded (n = 1,042). cLeukemia subtypes not presented include acute lymphocytic leukemia (n = 2), chronic myeloid leukemia (n = 6), other leukemia (n = 2). dAnalyses for myelodysplastic syndrome are restricted to 2001–2017 since SEER did not systematically ascertain this outcome prior to this date
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