Abstract PO2-01-11: Demographic, Lifestyle, and Clinical Factors Associated with Early vs. Late Recurrence among Women with Early-Stage Estrogen Receptor-Positive Breast Cancer in the Prospective Pathways Study
Authors: Chua Alfredo , Sheng Haiyang , Gandhi Shipra , Kwan Marilyn , Ergas Isaac , Roh Janise , Laurant Cecile , Khoury Thaer , Gomez Scarlett , Ambrosone Christine , Kushi Lawrence , Yao Song 
Published: May 2024

Abstract
Background: Although women diagnosed with early-stage estrogen receptor (ER)-positive breast cancer generally have a favorable prognosis, they face a lingering risk of late recurrence that can occur years to decades after diagnosis. Relatively little is known about the demographic, lifestyle, or clinical factors associated with the risk of late recurrence, or whether the associations differ between early vs. late recurrence.
Methods: We performed a comprehensive analysis of factors related to early vs. late recurrence in early-stage ER-positive breast cancer in the Pathways Study, an established prospective cohort of women diagnosed with invasive breast cancer at Kaiser Permanente Northern California (KPNC) between 2006 and 2013. Recurrences were identified through monthly searches of the KPNC Cancer Registry, follow-up interviews with participants, and confirmation with electronic medical records. For this analysis, 2,473 women with stage I-IIB, ER-positive breast cancer were included, with ascertainment of recurrence and death through December 31, 2021. Univariate analysis and multivariable Cox regression models were used to examine the factors associated with early (&lt; 5 years since diagnosis) and late (≥ 5 years since diagnosis) recurrence.
Results: The median age of diagnosis was 57 (± 10) years, with 35% diagnosed before menopause. While 64% of patients self-reported as White, 16% identified as Asian, 6% Black, 12% Hispanic, and 2% other ethnicity. After a median 13.3 (range: 0.6-16.8) years of follow up, a total of 341 (13.8%) recurrences occurred, with 158 before and 181 at or after 5 years from diagnosis. Approximately a third of recurrences were local or regional and the other two thirds were distant. In univariate analysis, increasing stage and tumor grade were associated with higher risk of both early and late recurrence (p&lt; 0.05). Progesterone receptor (PR) negativity was associated with only early (hazard ratio [HR]=1.49, 95% confidence interval [CI] 1.06-2.09) but not late recurrence (HR=0.90, 95% CI 0.63-1.28). In unadjusted models, receiving lumpectomy (vs. mastectomy), chemotherapy, radiation therapy, or endocrine therapy were associated with lower risk of both early and late recurrence. Among the demographic and lifestyle factors examined, postmenopausal status at diagnosis was associated with lower risk of early (HR=0.69, 95% CI 0.51-0.96) but not late recurrence (HR=1.00, 95% CI 0.73-1.36). No association was found with body mass index, socioeconomic measures (education, income, employment, marital status), smoking, alcohol intake, or physical activity assessed at the time close to diagnosis. Notably, minoritized racial/ethnic groups all had higher risk of early recurrence than White women (Asian: HR=1.76, 95% CI 1.16-2.66; Black: HR=2.33, 95% CI 1.38-3.93; Hispanic: HR=1.80, 95% CI 1.15-2.82), but no association was found with late recurrence (Asian: HR=0.99, 95% CI 0.65-1.51; Black: HR=0.80, 95% CI 0.41-1.58; Hispanic: HR=0.80, 95% CI 0.48-1.33). In multivariable Cox models adjusted for age, cancer stage, grade, PR status, surgery, radiation therapy, chemotherapy, and endocrine therapy, the trend of higher risk of early recurrence among minoritized racial/ethnic groups remained, although the association remained significant only in Black women (HR=1.89, 95% CI 1.08-3.31).
Conclusion: Most histopathological features and cancer treatment modality had similar impact on early vs. late recurrence among women with early-stage ER-positive breast cancer, although PR negativity might be an adverse risk factor for early recurrence only. The findings of higher risk of early but not late recurrence among Asian, Black, and Hispanic relative to White women provide some novel data on the racial/ethnic disparities of prognosis for ER-positive breast cancer and may warrant further investigation.
Citation Format: Alfredo Chua, Haiyang Sheng, Shipra Gandhi, Marilyn Kwan, Isaac Ergas, Janise Roh, Cecile Laurant, Thaer Khoury, Scarlett Gomez, Christine Ambrosone, Lawrence Kushi, Song Yao. Demographic, Lifestyle, and Clinical Factors Associated with Early vs. Late Recurrence among Women with Early-Stage Estrogen Receptor-Positive Breast Cancer in the Prospective Pathways Study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO2-01-11.