Identifying the window of aggressive postpartum breast cancer based on the 21-gene Oncotype DX® test in women with HR+, HER2-negative breast cancer.

Postpartum breast cancer (PPBC) is associated with worse outcomes in young women with breast cancer and demonstrates distinct transcriptomic features, yet a temporal definition based on gene expression has not been established. We conducted a single-institution retrospective cohort study to evaluate the impact of postpartum status on the 21-gene Oncotype DX Recurrence Score® (RS) in hormone receptor-positive, HER2-negative young women with breast cancer. Among 385 patients, 153 were nulliparous, 62 were more than 10 years postpartum, and 170 were within 10 years postpartum. Diagnosis within one year of childbirth was associated with a 13.2-point higher RS compared with nulliparous patients (p < 0.001). Defining PPBC as within 3 years postpartum was associated with increased odds of RS category shift (OR 2.83, p = 0.001). In the context of contemporary adjuvant treatment, with patients diagnosed within three years postpartum more likely to receive chemotherapy, ovarian function suppression, and CDK4/6 inhibitors, differences in IDFS associated with time since last childbirth did not result in significantly worse IDFS within the follow-up period (89.0% in patients with PPBC up to 3 years vs. 93.7% in all other patients p = 0.39). These findings indicate that tumors diagnosed within the first year postpartum have significantly elevated RS, and that the period of most aggressive PPBC, as reflected by gene expression profiles, may arise in the more recently postpartum period, in the first 0-3 years postpartum.