Abstract P2-11-02: Subsequent breast cancer among women with HER2+ disease in a large integrated healthcare system
Authors: Haque Reina , Chen Lie H , Kwan Karen , Oestreicher Nina , Chlebowski Rowan T. , Lalla Deepa 
Published: March 2022

BACKGROUND: Women with breast cancer are living longer, including those with risk factors like HER2+ tumors or diagnosed at later stages, but a dearth of information exists on patients’ outcomes beyond clinical trials. We aimed to describe the risk of subsequent breast cancer (recurrence, second primary breast cancer, breast cancer-specific death) in women with HER2+ disease in a large community health plan. METHODS: We assembled a cohort of 3550 women (≥18 years) with HER2+ breast cancer (Stages I-III) during 2009-2017 whom were Kaiser Permanente Southern California members and followed them through December 2018. Subjects were identified from the plan’s NCI-SEER tumor registry. Data elements were captured from the tumor registry, pathology reports, and electronic health records. Hormone receptor (HR, ER and/or PR+), and HER2 status were assessed by immunohistochemistry or FISH. Subsequent breast cancer (SBC) events were identified from pathology report review (2/3 of cohort) or a validated computerized algorithm (1/3 of cohort without pathology reports). We computed SBC rates by trastuzumab use, HR status and tumor size and followed women from the index date to the date of SBC, disenrollment, death, or end of study in December 2018, whichever occurred first. Multivariable Cox proportional hazards regression was used to estimated adjusted hazard ratios (HR) and 95% confidence intervals. RESULTS: Of the 3550 women, the median age at diagnosis was 57 years. The cohort comprised 46% White; 13% Black; 16% Asian/Pacific Islander; and 24% Hispanic. 83% had stage I-II disease and 68% were HR+. Among these women, 81% received adjuvant trastuzumab; 3% other chemotherapy only and 16% neither. Less than 20 women used neoadjuvant trastuzumab. The cohort was followed a mean of 4.1 years (IQR: 1.5-6.3), with a maximum of 10 years. In the trastuzumab treated group, the cumulative 1-, 3-, 5-, and 10-year SBC risk were: 9.8%, 24.6%, 27.8%, and 30.4%, respectively. The mean time to SBC was 2.0 years (IQR: 0.9-2.5). SBC rate was lower in women who had trastuzumab (73.5/1,000 PY) therapy than those who did not (90.8/1,000 PY), corresponding to 22% reduced risk (adjusted HR=0.78, 95% CI: 0.66-0.91) (Table 1). Compared to women diagnosed at stage I, those with stage II-III disease were 1.19 times (adj HR=1.19, 95% CI: 1.01-1.40) more likely to develop SBC. Tumor size≥2cm was associated with a 23% greater risk of SBC (adj HR=1.23, 95% CI: 1.00-1.51) versus tumors&lt;2cm. The multivariable analyses included these covariates: trastuzumab use; diagnosis age and year; stage; race/ethnicity; geocoded income; ER/PR; surgery type; other adjuvant therapy (endocrine, radiation, chemotherapy); lymph node status; histology; BMI; comorbidity; neoadjuvant trastuzumab, and other chemotherapy. CONCLUSION: This population-based study using one of the most comprehensive electronic medical records in California, we observed that the cumulative SBC risk persists, and was 30.4% at 10 years in women with HER2+ breast cancer treated with trastuzumab. Further, the SBC risk was greater in those with higher stages, large tumors (≥2 cm) and lymph node positive, even after accounting for trastuzumab use.

Table. Multivariable HRs (95% CI) for subsequent breast-cancer in women with HER2+ invasive diseaseTotal Women*SBCSBC rates per 1,000 woman-yearsCrude modelMultivariable modelNNHR (95% CI)HR (95% CI)All Women 3550110176.5 TrastuzumabNo67522790.81.00 (ref)1.00 (ref)Yes287587473.50.86 (0.74-0.99)0.78 (0.66-0.91) Stage at dxI147138862.31.00 (ref)1.00 (ref)II-III207971387.31.45 (1.28-1.65)1.19 (1.01-1.40) Tumor sizeTumors&lt;2 cm53012657.11.00 (ref)1.00 (ref)Tumors≥2 cm291094380.11.51 (1.25-1.83)1.23 (1.00-1.51) Lymph NodesPositive (ref)117043387.11.00 (ref)1.00 (ref)Negative206254363.90.69 (0.61-0.79)0.75 (0.65-0.88)*Some variables do not sum to N=3550 due to missing

Citation Format: Reina Haque, Lie H Chen, Karen Kwan, Nina Oestreicher, Rowan T. Chlebowski, Deepa Lalla. Subsequent breast cancer among women with HER2+ disease in a large integrated healthcare system [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P2-11-02.