Non-sentinel lymph node metastasis prediction in breast cancer with metastatic sentinel lymph node: impact of molecular subtypes classification.
BACKGROUND
To decipher the interaction between the molecular subtype classification and the probability of a non-sentinel node metastasis in breast cancer patients with a metastatic sentinel lymph-node, we applied two validated predictors (Tenon Score and MSKCC Nomogram) on two large independent datasets.


METHODS
Our datasets consisted of 656 and 574 early-stage breast cancer patients with a metastatic sentinel lymph-node biopsy treated at first by surgery. We applied both predictors on the whole dataset and on each molecular immune-phenotype subgroups. The performances of the two predictors were analyzed in terms of discrimination and calibration. Probability of non-sentinel lymph node metastasis was detailed for each molecular subtype.


RESULTS
Similar results were obtained with both predictors. We showed that the performance in terms of discrimination was as expected in ER Positive HER2 negative subgroup in both datasets (MSKCC AUC Dataset 1 = 0.73 [0.69-0.78], MSKCC AUC Dataset 2 = 0.71 (0.65-0.76), Tenon Score AUC Dataset 1 = 0.7 (0.65-0.75), Tenon Score AUC Dataset 2 = 0.72 (0.66-0.76)). Probability of non-sentinel node metastatic involvement was slightly under-estimated. Contradictory results were obtained in other subgroups (ER negative HER2 negative, HER2 positive subgroups) in both datasets probably due to a small sample size issue. We showed that merging the two datasets shifted the performance close to the ER positive HER2 negative subgroup.


CONCLUSIONS
We showed that validated predictors like the Tenon Score or the MSKCC nomogram built on heterogeneous population of breast cancer performed equally on the different subgroups analyzed. Our present study re-enforce the idea that performing subgroup analysis of such predictors within less than 200 samples subgroup is at major risk of misleading conclusions.
Department of Surgery, Institut Curie, Paris, France. Fabien.reyal@curie.net
Fabien
F
Reyal
Catherine
C
Belichard
Roman
R
Rouzier
Emmanuel
E
de Gournay
Claire
C
Senechal
Francois-Clement
FC
Bidard
Jean-Yves
JY
Pierga
Paul
P
Cottu
Florence
F
Lerebours
Youlia
Y
Kirova
Jean-Guillaume
JG
Feron
Virginie
V
Fourchotte
Anne
A
Vincent-Salomon
Jean-Marc
JM
Guinebretiere
Brigitte
B
Sigal-Zafrani
Xavier
X
Sastre-Garau
Yann
Y
De Rycke
Charles
C
Coutant
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000378:metabolism*; D005260:Female; D006801:Humans; D008207:Lymphatic Metastasis; D008875:Middle Aged; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D021701:Sentinel Lymph Node Biopsy
D018719:Erb-b2 Receptor Tyrosine Kinases; C508053:ERBB2 protein, human