Abstract 5912: A postpartum breast cancer diagnosis is an independent risk factor for metastasis
Authors: Zhang Zhenzhen , Bassale Solange , Jindal Sonali , Guinto Emily , Fraser Alison , Mori Tomi , Smith Ken R. , Schedin Pepper 
Published: June 2022

Abstract
Introduction: A diagnosis of breast cancer after childbirth increases risk for metastasis and death in patients diagnosed at ≤45 years of age [1]. Data to delineate if a postpartum diagnosis is an independent risk factor for breast cancer metastasis remain limited. Here, we addressed this question using early-onset cases available from the Utah Population Database.
Methods: This population-based study includes 2,970 women with stage I-III breast cancer, diagnosed at ≤45 years of age between 1996 and 2017. The primary exposures are nulliparity or time between last childbirth and diagnosis of breast cancer. Primary outcomes are distant metastasis and breast cancer-specific death. The Cox proportional hazard model was used to investigate associations between exposures and outcomes adjusting for diagnosis year, age, tumor stage and estrogen receptor (ER) status. Stratified analyses were conducted.
Results: Reproductive histories of the breast cancer patients were grouped as nulliparous (n=860), and parous: diagnosed 0-&lt;5 years (n=614), 5-&lt;10 years (n=615) and ≥10 years (n=881) since last childbirth. Through multivariate analyses, we find a breast cancer diagnosis within 5 years postpartum associates with elevated risk for metastasis [(HR)(95%CI)]=1.5(1.2-2.0)] and breast cancer-specific death [HR(95%CI)=1.5(1.1-2.1)] compared to nulliparous cases. Further, for stage I or II cancers that classically have good prognoses, a postpartum diagnosis (0-&lt;5 years) is a dominant feature of increased risk for metastasis [HR(95% CI)]=[1.9 (1.2-2.8)], particularly liver metastasis, and a 2 fold increase in probability of death [HR(95% CI)]=[2.0 (1.2-3.2)]. For women diagnosed with poor prognostic ER- breast cancer, the probability of dying in 0-&lt;5 yrs postpartum group is also ~2 fold compared to nulliparous cases [HR(95% CI)]=[2.3 (1.3-4.1)]. ER+ cases diagnosed 0-&lt;5 yrs postpartum trended towards poor outcomes with marginal significance. Unexpectedly, the proportion of patients progressing to metastasis was the same for ER+ and ER- disease, at 13.2% and 13.5% respectively, with ~3 fold more deaths in women diagnosed with ER+ breast cancer due to increased incidence. Further, we find increased liver metastasis in ER+ patients diagnosed &lt;5 years postpartum, with a full 46% of women who progressed to metastasis having liver as first site of metastasis.
Conclusion: This study shows a postpartum diagnosis as an independent risk factor for breast cancer progression and implicates a birth-interval-associated liver biology in the increased liver metastasis observed in this study. Irrespective of ER status, clinical consideration of time between last completed pregnancy and breast cancer diagnosis will increase accuracy of prognosis in young-onset breast cancer patients.
1.Nichols, H.B., et al., Breast Cancer Risk After Recent Childbirth: A Pooled Analysis of 15 Prospective Studies. Ann Intern Med, 2018.
Citation Format: Zhenzhen Zhang, Solange Bassale, Sonali Jindal, Emily Guinto, Alison Fraser, Tomi Mori, Ken R. Smith, Pepper Schedin. A postpartum breast cancer diagnosis is an independent risk factor for metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5912.