Recurrence Score Elevated in Breast Cancers Diagnosed Within 3 Years Postpartum

Breast cancers diagnosed within 3 years of childbirth were associated with significantly higher 21-gene recurrence score (RS) results than cancers in nulliparous women, according to a single-institution retrospective cohort study published in npj Breast Cancer.¹ The findings suggest that the period of greatest molecular aggressiveness in postpartum breast cancer (PPBC) may be narrower than the 5- to 10-year windows used in prior definitions.

Researchers at the University of California, Los Angeles analyzed Oncotype DX Recurrence Score results, generated using the 21-gene assay, from 385 women aged 45 years or younger with hormone receptor-positive (HR+), HER2-negative breast cancer. Compared with 153 nulliparous patients, women diagnosed within 1 year postpartum had a mean RS 13.2 points higher (95% CI, 8.15-18.01; P <.001). When PPBC was redefined as diagnosis within 3 years postpartum (n = 47), the mean RS difference compared with nulliparous patients was 6.44 points (95% CI, 3.37-9.52; P <.001), and the odds of falling into a higher RS risk category were nearly 3 times greater (OR, 2.83; 95% CI, 1.51-5.34; P =.001). Patients diagnosed within 3 years postpartum also had significantly higher odds of higher pathologic tumor grade (OR, 2.35; P =.009) compared with nulliparous patients.

Despite the molecular differences, these did not translate into significantly worse 4-year invasive disease-free survival (IDFS) during the study's follow-up period: 89.0% in patients with PPBC within 3 years vs 93.7% in all other patients (log-rank P =.39). The authors noted that patients diagnosed within 3 years postpartum received chemotherapy, ovarian function suppression, and CDK4/6 inhibitors more often than other groups, though these treatment differences did not reach statistical significance, and this more intensive treatment approach may have offset the higher molecular risk reflected by RS.

An unexpected finding emerged in patients diagnosed more than 10 years postpartum, who had a significantly increased hazard of invasive disease recurrence compared with nulliparous patients (HR, 4.45; 95% CI, 1.24-15.90; P =.022). The authors cautioned that this subgroup had few recurrence events and wide confidence intervals and noted a higher proportion of stage III disease in this group, so the finding should be interpreted cautiously pending validation in larger cohorts.

Study Design and Limitations

This was a retrospective cohort study, not a randomized or prospective trial, conducted at a single academic center using patients who underwent RS testing between 2015 and 2024; parity data were obtained through retrospective chart review, and 15% of otherwise eligible patients were excluded for incomplete reproductive history documentation. The cohort likely represents an intermediate-risk population, since patients with very high-risk disease (for whom testing may be considered unnecessary) or very low-risk disease (for whom testing may be foregone) could be underrepresented. Outcome analyses were limited by a relatively short median follow-up of 48.6 months and a small number of recurrence events (29 total), which is a particular limitation given that HR+, HER2-negative breast cancer carries a risk of late recurrence extending beyond a decade. No correction for multiple testing was applied.

The authors noted that an ongoing trial, OFSET (NCT05879926), is examining whether chemotherapy benefit in premenopausal, node-positive patients derives from cytotoxic effects or treatment-induced ovarian suppression—a question with direct relevance to interpreting RS-guided treatment decisions in this younger population.² They called for larger, multi-institutional studies and more systematic collection of reproductive history data, including time since last childbirth, in future breast cancer trials.¹

REFERENCES

1. Zhang S, Queen KJ, Duggirala N, et al. Identifying the window of aggressive postpartum breast cancer based on the 21-gene Oncotype DX test in women with HR+, HER2-negative breast cancer. npj Breast Cancer. 2026. doi:10.1038/s41523-026-01002-2

2. Evaluating the Addition of Adjuvant Chemotherapy to Ovarian Function Suppression Plus Endocrine Therapy in Premenopausal Patients With pN0-1, ER-Positive/​HER2-Negative Breast Cancer and an Oncotype Recurrence Score Less Than or Equal to 25 (OFSET). ClinicalTrials.gov. Updated July 2, 2026. Accessed July 10, 2026. https://clinicaltrials.gov/study/NCT05879926