Abstract P4-07-28: Early relapse and predictors of relapse-free survival in neoadjuvant chemotherapy-treated breast cancer patients
Authors: Martin Natalie , Pasztorova Julia , Hibell Isabella , Wheatley Duncan 
Published: March 2022

RationaleNeoadjuvant chemotherapy (NAC) for the treatment of early and locally advanced breast cancer is shown to cause effective tumour shrinkage, allowing breast conserving surgery. However, rates of recurrence remain high following surgical excision of NAC-treated breast tumours. We investigated relapse-free survival (RFS) in NAC-treated breast cancer patients; the primary aim of this study was to estimate probability of early relapse (&lt;5 years) and identify possible predictor variables. MethodsWe retrospectively reviewed NAC-treated breast cancer patients diagnosed between January 2013 and August 2018 at the Royal Cornwall Hospital, UK. Patients met inclusion criteria with &gt;3 cycles of NAC, surgery and follow-up &gt;1 year. Demographic, histopathological and surgical data were collected including age, TNM classification, tumour histology, breast cancer immunohistochemical marker receptor status (ER, PR, HER2), NAC dose, adjuvant radiotherapy, type of breast and nodal surgery, pathologic response to NAC, number of positive lymph nodes (LN) at surgical removal and lymph node ratio (LNR). Tumour histology was categorised by inflammatory versus non-inflammatory. TNM classification was used for tumour staging. TNM nodal classification was categorised as N0 or N1 according to axillary LN cytology. LN classification data was missing for patients with inconclusive LN status at diagnosis. LNR was calculated as the ratio of positive LN to total number of LN removed at surgery. NAC response was categorised as pathologic complete (pCR) or incomplete (no-pCR). Kaplan-Meier method was used to compare survival functions for categorical variables. The Cox proportional hazards model was used at univariate and multivariate analysis for predictor variables that satisfied the proportional hazards assumption, to calculate hazard ratios for RFS. p-values &lt;0.05 were taken as statistically significant. Results165 of 190 women were eligible for analysis. Median (IQR) age at diagnosis was 51.7 years (45.5-60.3). 68 patients (41.2%) achieved pCR following NAC and 147 (89.1%) received adjuvant RT. 30 relapses (18.2%) were recorded during follow-up, of which 24 (80%) were distant metastases. The Kaplan-Meier survival function estimated a 25% (95% CI, 17-36) probability of relapse by year five post-surgery. At univariate Cox analysis, RFS was associated with fewer positive LN (p = 0.001), lower LNR (p &lt; 0.001) and TNM node classification N0 at diagnosis (p &lt; 0.001). Table 1 below shows the results of multivariate Cox proportional hazards regression. Small sample size might conceal statistical significance of some covariates.

ConclusionsOver 1 in 4 NAC-treated breast cancer patients relapsed within 5 years of surgery, usually with distant metastases. At univariate analysis, relapse-free survival (RFS) was individually associated with decreased LNR, fewer positive LN and TNM node classification N0. LNR remained a significant predictor of RFS at multivariate analysis with risk of relapse for a LNR of 1, 9-fold higher than a LNR of 0. Age, tumour histology, HER2 receptor status, TNM tumour classification, NAC dose and response to NAC had no significant association with RFS in this sample size.

Risk FactorSubjectsHazard Ratio (95% CI)p-valueAge1651.042 (0.998 - 1.088)0.064Tumour histology (inflammatory = 1, other = 0)1651.268 (0.302 - 5.331)0.746HER2 receptor status (HER2+ = 1, HER2- = 0)1651.217 (0.357 - 4.150)0.754TNM tumour classification (T3-4 = 1, T1-2 = 0)1650.852 (0.298 - 2.442)0.766TNM node classification (N1 = 1, N0 = 0)1021.684 (0.428 - 6.622)0.455NAC dose (full dose = 1, reduced dose = 0)1651.091 (0.393 - 3.028)0.866NAC response in breast (pCR = 1, no-pCR = 0)1650.696 (0.199 - 2.442)0.572Lymph node ratio1649.426 (2.061 - 43.099)0.004

Citation Format: Natalie Martin, Julia Pasztorova, Isabella Hibell, Duncan Wheatley. Early relapse and predictors of relapse-free survival in neoadjuvant chemotherapy-treated breast cancer patients [abstract]. In: Proceedings of the 2021 San Antonio Breast Cancer Symposium; 2021 Dec 7-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2022;82(4 Suppl):Abstract nr P4-07-28.