Lifetime Estrogen Exposure and Survival Outcomes in Female Patients With Advanced Solid Cancer — ASN Events
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Lifetime Estrogen Exposure and Survival Outcomes in Female Patients With Advanced Solid Cancer (#502)

Jwa Hoon JHK Kim 1 , Sang Hyun SHC Cho 1 , Jong Youn JYM Moon 2
  1. Korea University College of Medicine, Korea University Anam Hospital, Seoul, SEOUL, South Korea
  2. Gill Medical Center, Seoul

Background

Sex-related differences in advanced solid cancer (ASC) incidence suggest a protective role of estrogen in carcinogenesis. We investigated the association between lifetime estrogen exposure and clinical outcomes in females with ASC.

Methods

We conducted a retrospective cohort study of females diagnosed with ASC between 2022 and 2025. Female reproductive history, including age at menarche, age at natural menopause, hormone replacement therapy (HRT), and oral contraceptive (OC) use, was collected at diagnosis. A Lifetime Estrogen Exposure (LEE) score was constructed by integrating reproductive lifespan (age at menopause minus age at menarche), HRT use, and OC use, with higher scores indicating greater cumulative endogenous and exogenous estrogen exposure. Patients were categorized into low-, and high-LEE groups. The primary outcome was overall survival (OS). Multivariable Cox proportional hazards models adjusted for age, body mass index, tumor stage, treatment modality, smoking status, diabetes, and hypertension were used to assess the association between LEE and survival outcomes.

Results

Among 350 females included in the analysis, the median age was 68 years and the median follow-up was 23 months. Patients with lower LEE scores were older, more frequently postmenopausal, and had shorter reproductive lifespans. During follow-up, the low-LEE group demonstrated significantly poorer OS compared with the high-LEE group (median OS, 15.7 vs. 21.2 months; P=0.03). After multivariable adjustment, low lifetime estrogen exposure remained independently associated with inferior OS (adjusted HR 1.4, 95% CI 1.1–1.9, P=0.04). The prognostic impact of LEE was consistent across age, tumor stage, and menopausal status.

Conclusion

Lower lifetime estrogen exposure was independently associated with poorer survival in females with ASC. These findings suggest that female reproductive history may capture biologically relevant hormonal influences on cancer progression and could serve as a novel prognostic marker. Further studies are warranted to elucidate the mechanisms linking estrogen exposure to tumor biology and survival.