D. N. Carr3, N. Vera3, J. Mullinax1, D. Korz1, W. Sun1, M. Lee1, S. Hoover1, W. Fulp2, G. Acs4, C. Laronga1 1Moffitt Cancer Center And Research Institute,Breast Program,Tampa, FL, USA 2Moffitt Cancer Center And Research Institute,Biostatistics,Tampa, FL, USA 3University Of South Florida College Of Medicine,Tampa, FL, USA 4Women’s Pathology Consultants, Ruffolo Hooper & Associates,Tampa, FL, USA
Introduction: Adjuvant treatment planning for early stage, estrogen receptor (ER) positive invasive breast cancer has been historically based on menopausal status. The Recurrence Score (RS) from the 21-gene breast cancer assay (ODX) is predictive of distant recurrence in this population, but is rarely applied to younger, premenopausal patients (pts). To evaluate the validity of this historical bias, we sought to evaluate the relationship between menopausal status and the recurrence score derived from the Oncotype DX assay.
Methods: An IRB-approved retrospective review was conducted of invasive breast cancer pts with known RS. Eligibility for performance of the ODX was based on NCCN guidelines or physician discretion. Data collected included demographics, clinical-pathologic variables, surgery type, adjuvant treatment and outcomes. Menopausal status was documented at time of ODX. Perimenopausal women were classified with premenopausal for statistical analyses. Comparisons on RS were made by menopausal status (premenopausal vs. postmenopausal) using general linear regression model and the exact Wilcoxon Rank Sum Test.
Results: 607 pts with invasive breast cancer and a RS were identified. Menopausal status was available for 600 pts (166 premenopausal, 434 postmenopausal) comprising our study population. Median age for the entire population was 58yrs (range: 27-84); 47yrs for premenopausal and 62yrs for postmenopausal. Median invasive tumor size was 1.5 cm for both cohorts. No significant differences were seen between cohorts for overall survival, metastatic disease rate, histologic grade, lymphovascular invasion (LVI), nodal status, stage, adjuvant chemotherapy, or endocrine therapy use. Mastectomy rate was higher in the premenopausal group (53.8%), compared to postmenopausal (41.9%) (p=0.0001), and thus receipt of breast irradiation was lower in premenopausal women. Despite the higher mastectomy rate in premenopausal women, a higher local-regional recurrence rate (3% vs. 0.7%; p=0.0384) was observed. Degree of ER expression was lower in premenopausal women (95%) than postmenopausal (100%) (p<0.0001). Median RS was the same (16) for both premenopausal (range: 0-62) and postmenopausal (range: 0-63) women. Tumor size, nodal status, and stage did not affect RS. Menopausal status as a categorical variable was not predictive of RS (p value = 0.7731). Factors predicting higher RS included higher mitotic rates (p<0.0001), higher nuclear grade (p<0.0001), decreased tubule formation (p=0.0001), presence of LVI (p=0.002), high grade (p<0.0001), and lower expression levels of ER/PR (p<0.0001).
Conclusion: Menopausal status has limited predictive power for distant breast cancer recurrence. We have shown that RS across the spectrum of menopausal status is well distributed in this cohort of women. Therefore, menopausal status alone should not preclude recommendations for performance of ODX in ER-positive, early stage breast cancer.