Introduction
Clinicopathological parameters
0-5 years
|
5-10 years
| |||
---|---|---|---|---|
(number of all recurrences = 83)
|
(number of all recurrences = 107)
| |||
Univariate
|
Multivariate
|
Univariate
|
Multivariate
| |
LR-χ2
| LR-χ2a
| LR-χ2
| LR-χ2a
| |
(P value) | (P value) | (P value) | (P value) | |
Nodal status (negative versus positive) | 17.24 | 7.60 | 30.80 | 18.99 |
(<0.0001) | (0.006) | (<0.0001) | (<0.0001) | |
Tumor size (≤2 versus >2 cm) | 28.95 | 10.96 | 25.40 | 13.03 |
(<0.0001) | (0.0009) | (<0.0001) | (0.0003) | |
Grade (well/moderate versus poor) | 21.88 | 5.22 | 1.74 | - |
(<0.0001) | (0.02) | (0.2) | ||
ER10
| 12.17 | 5.51 | 1.65 | - |
(0.004) | (0.02) | (0.2) | ||
PgR10
| 18.81 | 6.46 | 1.45 | - |
(<0.0001) | (0.01) | (0.2) | ||
Ki67 | 17.90 | 6.52 | 9.04 | 2.14 |
(<0.0001) | (0.01) | (0.003) | (0.1) | |
HER2 (negative versus positive) | 15.45 | 3.18 | 0.04 | - |
(<0.0001) | (0.07) | (0.8) |
Cancer-related genes
Molecular scores
Score
|
Abbreviation
|
Details
|
Reference
|
---|---|---|---|
MammaPrint | MammaPrint | 70 gene-based expression profile using DNA microarray. Fresh frozen material is used to perform analysis. | |
Genomic Grade Index | GGI | 97 gene-based assay using DNA micro array. Fresh frozen material is used to perform the analysis. | |
Oncotype Dx Recurrence Score | RS | 21 gene-based expression profile score using qRT-PCR (16 cancer genes, 5 housekeeping genes). FFPE blocks used to extract RNA. | [25] |
Immunohistochemical Score 4 | IHC4 | Includes information on estrogen receptor (ER), progesterone receptor (PgR), Ki67, and HER2. Score developed on transATAC data. FFPE blocks used to extract RNA to perform IHC for ER, PgR, Ki67, and HER2. | [31] |
Prosina Risk of Recurrence Score | ROR | 50 gene-based expression profile score using qRT-PCR. FFPE blocks used to extract RNA to perform analysis on nCounter system. | [34] |
Breast Cancer Index | BCI | Multi-gene assay using qRT-PCR. Combination of two biomarkers HOXB13/IL17BR (H/I) and molecular grade index (MGI). FFPE blocks used to extract RNA to perform analysis. | |
EndoPredict | EPclin | 12 gene-based expression profile score using qRT-PCR (8 cancer genes, 4 housekeeping genes). FFPE blocks used to extract RNA to perform analysis. | [41] |
Current genetic tests for the prediction of recurrence
MammaPrint
Genomic grade index
Oncotype DX recurrence score
Prosigna PAM50 risk of recurrence
Breast cancer index
EndoPredict
Novel predictors
Trial
|
Study design
|
Reference
|
---|---|---|
STIC CTC METABREAST | 1,000 hormone receptor-positive, metastatic breast cancer patients randomly assigned to either standard arm or CTC-driven arm, which dictates whether hormone therapy (5 CTCs <7.5 mL) or to chemotherapy (5 CTCs ≥7.5 mL) is administered. Trial aims to show non-inferiority of the CTC arm versus standard arm for progression-free survival. | [54] |
SWOG 0500 | Screening patients with metastatic disease and more than 5 CTCs (n = 610) and randomization between continuation of first-line therapy (CTC response, <5 CTC/7.5 mL) and switch to another chemotherapy regime (no CTC response, ≥5 CTCs/7.5 mL) (n = 120). Primary endpoint is improvement in overall survival in the CTC-driven arm. | [55] |
CirCe01 | 304 women with metastatic disease starting with third-line chemotherapy will be randomly assigned between a CTC-driven arm and standard care arm. Patients in the CTC-driven arm change chemotherapy regimens according to their CTC counts during treatment. Primary endpoint is overall survival. | [56] |
Treat CTC | Patients with HER2-negative breast cancer having completed chemotherapy and primary surgery and with at least 1 CTC/15 mL will be randomly assigned to an observation arm or to receive trastuzamab. Primary endpoint is detection rate of CTCs after 18 weeks between the two arms. | NCT01548677 |
DETECT III | Around 300 patients with metastatic and HER2-negative disease with detectable at least one HER2-positive CTC/7.5 mL will be randomly assigned to receive standard care (endocrine or chemotherapy or both) versus standard care plus lapatinib. Primary endpoint is progression-free survival. | NCT01619111 |