Abstract
IntroductionSeveral authors have underscored a strong relation between the molecular subtypes and the axillary status of breast cancer patients. The aim of our work was to decipher the interaction between this classification and the probability of a positive sentinel node biopsy.Materials and MethodsOur dataset consisted of a total number of 2654 early-stage breast cancer patients. Patients treated at first by conservative breast surgery plus sentinel node biopsies were selected. A multivariate logistic regression model was trained and validated. Interaction covariate between ER and HER2 markers was a forced input of this model. The performance of the multivariate model in the training and the two validation sets was analyzed in terms of discrimination and calibration. Probability of axillary metastasis was detailed for each molecular subtype.ResultsThe interaction covariate between ER and HER2 status was a stronger predictor (p = 0.0031) of positive sentinel node biopsy than the ER status by itself (p = 0.016). A multivariate model to determine the probability of sentinel node positivity was defined with the following variables; tumour size, lympho-vascular invasion, molecular subtypes and age at diagnosis. This model showed similar results in terms of discrimination (AUC = 0.72/0.73/0.72) and calibration (HL p = 0.28/0.05/0.11) in the training and validation sets. The interaction between molecular subtypes, tumour size and sentinel nodes status was approximated.DiscussionWe showed that biologically-driven analyses are able to build new models with higher performance in terms of breast cancer axillary status prediction. The molecular subtype classification strongly interacts with the axillary and distant metastasis process.
Highlights
Several authors have underscored a strong relation between the molecular subtypes and the axillary status of breast cancer patients
We showed that biologically-driven analyses are able to build new models with higher performance in terms of breast cancer axillary status prediction
The aim of our work was to decipher the relation between the molecular subtype classification as defined by a combination of estrogen receptor status (ER) and HER2 status evaluated by immuno-histochemistry (IHC) and confirmed by FISH in case of IHC-HER2 2+ and the probability of a positive sentinel node biopsy
Summary
Several authors have underscored a strong relation between the molecular subtypes and the axillary status of breast cancer patients. Gene expression profiling of invasive breast carcinoma has resulted in highlighting three main categories of breast cancer with very specific features [luminal-like, basal-like, HER2-like][1]. Several authors have underscored a strong relation between the molecular subtypes classification and the axillary status of breast cancer patients [9,10,11,12,13,14,15,16]. As the nodal status is the most robust and the strongest factor correlated to overall survival in breast cancer patients, and is one of the major determinants in therapeutic decisions, axillary staging (either by sentinel node biopsy or axillary lymph node dissection) is a mandatory step in breast cancer management. Tumour grade, tumour location, presence of lymphatic/vascular invasion, high MIB-1 index, age at diagnosis, S phase, estrogen receptor status (ER), progesteron receptor status (PR), HER2 status are independent variables identified in these studies [17,18,19,20,21,22,23,24,25]
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