KHRONOS Project: Is time to surgery really important in the treatment of early breast cancer?
Authors: Navarro Lucia , Cejas Javier , Camús Juan Adrián , Rangel Natalia , Perez-Bartivas Luis , Ponferrada David , García Cesteros Natalia , Teso Martín Beatriz , Cardeña Cristina , Sánchez-Miranda Daniel , Ruiz Estela , Armenta Ana , Rodrigo Paula , Atance Victor , Ruiz Irene , De La Haba Juan , Rioja Pilar , Alvarez Marina , Palacios Amalia , Aranda Enrique 
Published: July 2024

e12598

Background: Recent studies suggest that delaying surgery in early breast cancer (BC) longer than 8 weeks(w) has a worse overall survival compared to those who undergo surgery between 0-4 w. Because BC has developmental heterogeneity over time, the aim of our study is to demonstrate that time from diagnosis to primary surgery is not the most important factor and focus on the value of biology in BC development. Methods: Descriptive, observational and retrospective study in our centre with patients (pts) diagnosed with early stage BC from 2015-2022 without radiological lymph node involvement, whose first therapeutic strategy was surgery. We used chi-square test to analyse the association between categorical variables using SPSS statistical software. Results: 927 pts were included, of which 75.3% (696) maintained pre-surgical staging (N0), while 24.7% (228) changed from N0 to N+ after surgery, with 157 cases having exclusive sentinel lymph node involvement. 98 pts (11.1%) underwent axillary emptying. The histological characteristics were 789 cases (84.9%) ductal while 126 cases (13.6%) were lobular carcinoma. Tumor grades were distributed as follows: G1 (296 cases), G2 (419 cases), and G3 (205 cases). Hormone receptor expression was ER+ (51 cases), ++ (45), +++ (755), and PR + (77), ++ (134), +++ (537). HER2 expression in 516 cases were negative, HER2+ (195), ++ (151), +++ or FISH+ (56). Regarding surgery, 71.8% underwent breast conservative surgery while 28.2% underwent mastectomy. 583 pts were operated below 8w (62.9%), and in 344 (37.1%) time to surgery were > 8w. 583 pts were operated <8w (62.9%), 134 transitioned from N0 to N+ post-surgery, while 448 maintained negative nodal after surgery. In 344 (37.1%) time to surgery were > 8w, 94 pts went from radiologically N0 to nodal involvement after surgery; however, 248 maintained negative nodal status. Although there was a tendency for pts who underwent surgery beyond 8 w to have a greater change in nodal involvement, the differences were not statistically significant (p=0.129). When we performed a stratified analysis by subgroups, in terms of tumour grade, we observed that among pts with G3 tumours operated on >8w, 37.8% had gone from N0 to N+ vs. 23.8% of the group operated <8w, with statistically significant differences, p=0.034. No statistically significant differences were found stratifying by hormone receptors, HER2 or Ki67. Conclusions: In our study we do not find that delay from diagnosis to surgery in BC ≥ 8w worsens lymph node staging. However, we observe that changes in nodal staging occur (transitioning from N0 to N+ in early BC) in poorly differentiated tumors (G3). Therefore, due to BC developmental heterogeneity over time, we believe tumour biology is more important than time to surgery, this may be useful for prioritising pts with these characteristics on the surgical waiting list. Further studies including other biological factors are needed to confirm it.