Abstract Background The Oncotype Dx Recurrence Score (RS) has been validated in TAILORx and RxPONDER as both prognostic and predictive of chemotherapy benefit in women with hormone receptor positive (HR+) breast cancer with tumor size 1-5cm and 0-3 lymph nodes involved. It is unclear whether the ability of RS to predict breast cancer outcomes varies by histologic type because a large proportion of women in these studies had invasive ductal cancer (IDC). The goal of this analysis is to compare the clinical utility of RS by histologic type at diagnosis among women treated at an NCI designated comprehensive cancer center in Detroit, with particular attention to invasive lobular histology. Methods The study population included women diagnosed between 2013 and 2022, age 18 to 79 years, with invasive, HR+, HER2 negative, AJCC stage I or II breast cancer. All women with invasive lobular carcinoma (ILC) and mixed IDC/ILC were included, with a random sample of women with IDC selected. A medical record review was conducted to supplement cancer registry data obtained from the Metropolitan Detroit Cancer Surveillance System (MDCSS). Two abstractors performed the review, with a third reviewing a random sample of charts to assess accuracy. We compared the proportion of women with low risk (RS≤25) vs high risk (RS25) stratified by histologic group using chi-square tests. Time to distant recurrence was the primary end point, with patients censored at death or last clinic visit. Results Of the 787 women identified, we included 366 for medical record review; 140 with IDC, 92 ILC, 48 mixed IDC 25 (p=0.001). There were a total of 14 distant recurrences after a mean 6.7 years of follow-up: five recurrences among women with IDC, four ILC, and five mixed IDC/ILC. Further analyses compared women with ILC or mixed vs. IDC. For women with low RS who did not receive chemotherapy, 4% (n=2/55) of women with IDC had distant recurrence compared with 9% (n=6/69) of women with ILC or mixed. Of the women with high RS who received chemotherapy, 13% (n=2/15) of women with IDC recurred compared to 100% (n=2/2) of women with ILC or mixed. Of the women with high RS who did not receive chemotherapy, 22% (n=2/9) of women with IDC recurred compared to 100% (n=1/1) of women with ILC or mixed. Conclusion High RS was significantly more common among women with IDC compared to tumors with lobular histology in this cohort of women with early-stage invasive breast cancer. There was a suggested higher rate of distant recurrence among women with lobular histology compared to those with IDC or mixed. All women with invasive lobular histology and RS 25 developed a distant recurrence, regardless of whether they received chemotherapy, however the total number was small. Longer follow-up is needed for additional evaluation of differences in the predictability of RS by histologic type among women with early-stage breast cancer. We have received a grant from the Dynami Foundation to continue this work. Citation Format: M. Mayo, H. Assad, J. J. Ruterbusch, J. Boerner, S. Karne, M. S. Simon. Distribution and prognostic significance of recurrence score by histologic sub-type among women with early-stage hormone receptor-positive invasive breast cancer abstract. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS2-12-30.
Mayo et al. (Tue,) studied this question.
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