Abstract P3-03-17: The Impact of Cardiovascular Disease Risk on Cancer Progression among Female Breast Cancer Survivors: A Longitudinal Study within The Boss Cohort
Authors: Feng Xinyi , Deng Zhengyi , McCollough Michelle , May Betty , Selznick Erica , Connor Avonne , Armstrong Deborah K. , Visvanathan Kala 
Published: March 2023

Abstract
Background Among breast cancer (BC) survivors, cardiovascular disease (CVD) is one of the most common comorbidities contributing to mortality. Data on to what extent CVD risk impacts disease progression and second cancers in younger women is limited. We conducted a prospective cohort study to examine whether CVD risk is associated with disease recurrence or new primary cancer among female BC survivors enrolled in a cohort of women with a family history of BC. Methods The study included 301 females with a first primary diagnosis of BC in the Breast and Ovarian Surveillance Service (BOSS) Cohort, after excluding those who had a history of recurrence or second primary cancer prior to enrollment (N=125), a diagnosis of ductal carcinoma in situ (DCIS) (N=66), and with missing CVD risk factors (N=3). A risk score based on 7 CVD risk factors (age 65 or older, diabetes, hypertension, high cholesterol, body mass index (BMI), smoking status, and physical activity) was assessed at baseline and updated 4 and 8 years after enrollment. Each risk factor was given a score (0, 1, or 2) and was summed and categorized into low (score=0 or 1), intermediate (score=2 or 3), and high (score &gt;3) risk. The primary outcome was either BC progression or all second primary cancers. Analyses limited to BC progression and second BC only were also conducted. Outcomes were ascertained through active follow-up and confirmed by pathology records. Kaplan-Meier graphs and two different Cox regression models were used to compare risk groups: model 1 adjusted for participants’ age, race, BMI, time from diagnosis, education, tumor stage, and estrogen receptor (ER) status; model 2 included further adjustment of cancer treatments (chemotherapy, hormone therapy, radiation), statin use, baby aspirin use, and specifically cardiotoxic treatments. For subgroup analyses, a more parsimonious model was used including age, race, BMI, education, cancer treatments, and cardiotoxic treatment. Results Participants’ mean age of BC diagnosis was 47.4 years and the median follow-up time was 11.5 years. The incidence rate of recurrence or any second cancer was 21 cases per 1000 person-years. At baseline, there were 168, 130, and 84 survivors in the low, intermediate, and high CVD risk groups respectively, and their use of statins increased from 12.7%, 34.5% to 52.7%. In the multivariable model, BC survivors with an intermediate CVD risk score had a 2.23 times greater risk of recurrence or second primary cancer as compared to those with a low CVD risk score (95% CI=1.20- 4.17). After further adjusting for cancer and CVD treatment in model 2, the HR was attenuated but still significant to 2.01 (95% CI = 1.20- 4.17. Interestingly, the association was attenuated and non-significant in the high-risk group (model 2: HR=1.37, 95% CI = 0.54- 3.45). The positive association between intermediate CVD risk score and recurrence or second cancer was also observed among subgroups of BC survivors including those who were postmenopausal (HR = 2.23, 95% CI = 1.01-4.93), with ER-positive BC (HR=2.07, 95% CI=1.08-3.99), regional disease (HR = 2.74, 95% CI = 1.06-7.04), diagnosed 5 years or greater (HR = 4.85, 95% CI = 1.14-20.66). There was a significant interaction between intermediated CVD risk and diagnosis time of 5 years (P interaction = 0.033). Restricting the outcome to disease progression and second BC alone led to similar results. The HR comparing the intermediate risk group and low risk group was 2.65 (95% CI = 1.27-5.55) in model 1 and decreased to 2.28 (95% CI = 1.06-4.89) in model 2. Conclusion There was a significant association between CVD risk and subsequent cancer progression in female breast cancer survivors, particularly among long-term BC survivors. The non-significant results among the women with high CVD risk scores may reflect the fact that a greater proportion of these women compared to women in the intermediate group reported taking cardiac treatments that can favorably impact cancer progression.
Citation Format: Xinyi Feng, Zhengyi Deng, Michelle McCollough, Betty May, Erica Selznick, Avonne Connor, Deborah K. Armstrong, Kala Visvanathan. The Impact of Cardiovascular Disease Risk on Cancer Progression among Female Breast Cancer Survivors: A Longitudinal Study within The Boss Cohort [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P3-03-17.