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Page 2 of 11 Nguyen et al. J Transl Genet Genom 2018;2:19 I http://dx.doi.org/10.20517/jtgg.2018.20

was a third-line or a fourth-line treatment, the time to progression was longer than that observed with previous lines
of chemotherapy. When we explored the 19 chemotherapy regimens given to these women and their corresponding
xenograft models, there was a strong correlation between ΔSUV max (maximum standard uptake value) on positron
emission tomography-computed tomography and the corresponding coefficients of inhibition obtained in mice.

Conclusion: The combination of gene expression profiling and individual xenografts is a promising method and could be
proposed as a personalized therapeutic resort for women with metastatic TNBCs.

Keywords: Patient-derived xenografts, triple negative metastatic breast cancer, personalized treatment

INTRODUCTION
Triple negative breast cancer (TNBC) is the most severe subtype of breast cancer, occurring in younger
women and associated with poor prognosis even when treated at a localized stage. TNBCs lack any detectable
expression of estrogen receptor, progesterone receptor, or human epithelial growth factor receptor 2 (HER2)
amplification. Treatment of metastatic TNBC is still challenging daily clinical practice, mainly because of a
lack of targeted therapies.

At the end of the 19th century, Beatson opened the way to hormone therapy and personalized medicine in
[1]
oncology with the first successful “surgical castration” in a young pre-menopausal woman with metastatic
breast cancer. In the late 1990s, an anti-HER2 monoclonal antibody, trastuzumab, was approved for the
treatment of HER2 overexpressing metastatic breast cancer . To date, 48 targeted therapies have been
[2]
approved for the treatment of various types of metastatic cancers .
[3]
High-speed whole-genome sequencing technologies have led to the identification of numerous potential
molecular targets. In 2000, a first molecular classification of breast cancer individualized four subtypes:
luminal A, luminal B, HER2-enriched, and basal-like (BL) , most BL subtypes corresponding to triple-
[4-6]
negative breast cancers . In 2011, TNBCs were classified into 6 molecular subtypes including BL1, BL2,
[7,8]
immunomodulatory, mesenchymal-like, mesenchymal stem-like, and luminal androgen receptor (LAR) .
[9]
According to this classification, BL1 tumors are likely to be more sensitive to cisplatin and DNA repair
inhibitors, BL2 tumors to anti-epidermal growth factor receptor (EGFR) therapies, and LAR tumors to
androgen inhibitors [10-12] .

Patient-derived xenografts (PDXs) are rediscovered pre-clinical pharmacological models. They enable
limited available quantities of human cancer tissue to be amplified. In addition, PDX models efficiently
reflect the characteristics of the original cancer, including tumor heterogeneity and metastatic potential [13-15] .
As a result, there is an excellent correlation between the anti-tumor activity of a given drug in a xenograft
model, and the anti-tumor effect of the same drug in the corresponding patient [16-19] .

In this pilot study, we combined individual PDXs and whole-genome analyses to personalize the resort
treatment for women with metastatic TNBCs.

METHODS
Patients with metastatic TNBC and gene expression profiling
Five women with metastatic TNBC participated in this study. For each patient, five tumor samples were
obtained during an imagery-guided biopsy, at the time of metastatic disease, before any medical treatment.
Informed written consent was obtained from the patients. The Clinical Research Board Ethics Committee
(Comité de Protection des Personnes) approved this study (CPP Ile-de-France N°13218). Among these five
tumor samples, (1) two were formaldehyde-fixed and paraffin-embedded for histological analyses; (2) two