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1 )

“Tratamiento médico del cáncer en el año 2019”

Organiza:

6 , 7 y 8 d e f e b r e r o 2 0 1 9

NH Collection Eurobuilding

M A D R I D

www.revisionesencancer.com

C O O R D I N A D O R E S C I E N T Í F I C O S :

Eduardo Díaz-Rubio

Enrique Aranda Aguilar

Enrique Grande Pulido

Ana Lluch Hernández

Pedro Pérez Segura

Mariano Provencio Pulla

¿Son todos los test genómicos iguales?

Comparison of the Performance of 6 Prognostic Signatures

for Estrogen Receptor–Positive Breast Cancer

A Secondary Analysis of a Randomized Clinical Trial

IvanaSestak,PhD;RichardBuus,PhD;JackCuzick,PhD;PeterDubsky,MD;RalfKronenwett,MD;

CarstenDenkert,MD;SeanFerree,PhD;DennisSgroi,MD;CatherineSchnabel,PhD;

FrederickL.Baehner,MD;ElizabethMallon,PhD;MitchDowsett,PhD

IMPORTANCE

Multiple molecular signatures are available for managing estrogen receptor

(ER)–positive breast cancer but with little direct comparative information to guide the

patient’s choice.

OBJECTIVE

To conduct a within-patient comparison of the prognostic value of 6 multigene

signatures in women with early ER-positive breast cancer who received endocrine therapy for

5 years.

DESIGN, SETTING, AND PARTICIPANTS

This retrospective biomarker analysis included 774

postmenopausal women with ER-positive

ERBB2

(formerly

HER2

)–negative breast cancer.

This analysis was performed as a preplanned secondary study of data from the Anastrozole or

Tamoxifen Alone or Combined randomized clinical trial comparing 5-year treatment with

anastrozole vs tamoxifen with 10-year follow-up data. The signatures included the Oncotype

Dx recurrence score, PAM50-based Prosigna risk of recurrence (ROR), Breast Cancer Index

(BCI), EndoPredict (EPclin), Clinical Treatment Score, and 4-marker immunohistochemical

score. Data were collected from January 2009, through April 2015.

MAIN OUTCOMES AND MEASURES

The primary objective was to compare the prognostic value

of these signatures in addition to the Clinical Treatment Score (nodal status, tumor size,

grade, age, and endocrine treatment) for distant recurrence for 0 to 10 years and 5 to 10

years after diagnosis. Likelihood ratio (LR) statistics were used with the χ

2

test and C indexes

to assess the prognostic value of each signature.

RESULTS

In this study of 774 postmenopausal women with ER-positive,

ERBB2

-negative

disease (mean [SD] age, 64.1 [8.1] years), 591 (mean [SD] age, 63.4 [7.9] years) had

node-negative disease. The signatures providing the most prognostic information were the

ROR (hazard ratio [HR], 2.56; 95% CI, 1.96-3.35), followed by the BCI (HR, 2.46; 95% CI,

1.88-3.23) and EPclin (HR, 2.14; 95% CI, 1.71-2.68). Each provided significantly more

information than the Clinical Treatment Score (HR, 1.99; 95% CI, 1.58-2.50), the recurrence

score (HR, 1.69; 95% CI, 1.40-2.03), and the 4-marker immunohistochemical score (HR, 1.95;

95% CI, 1.55-2.45). Substantially less information was provided by all 6 molecular tests for the

183 patients with 1 to 3 positive nodes, but the BCI (ΔLR χ

2

= 9.2) and EPclin (ΔLR χ

2

= 7.4)

provided more additional prognostic information than the other signatures.

CONCLUSIONS AND RELEVANCE

For women with node-negative disease, the ROR, BCI, and

EPclin were significantly more prognostic for overall and late distant recurrence. For women

with 1 to 3 positive nodes, limited independent information was available from any test.

These data might help oncologists and patients to choose the most appropriate test when

considering chemotherapy use and/or extended endocrine therapy.

TRIAL REGISTRATION

isrctn.com

Identifier:

ISRCTN18233230

Supplementalcontent

AuthorAffiliations:

Author

affiliationsarelistedattheendofthis

article.

CorrespondingAuthor:

Ivana

Research

JAMA Oncology |

Original Investigation

and includes information on tumor size. The TransATAC co- groups. To compare the prognostic

Table 1. Univariate HRs and C Indexes for All Prognostic Signatures According to Nodal Status

During Years 0 to 10

Gene

Signature

Patient Group

No e-Negative Disease

(n = 591)

Node-Positive Disease

(n = 227)

HR (95% CI)

a

C Index (95% CI)

HR (95% CI)

a

C Index (95% CI)

CTS

1.99 (1.58-2.50)

0.721 (0.668-0.774)

1.63 (1.20-2.21)

0.640 (0.554-0.726)

IHC4

1.95 (1.55-2.45)

0.725 (0.665-0.785)

1.33 (0.99-1.78)

0.601 (0.511-0.690)

RS

1.69 (1.40-2.03)

0.667 (0.585-0.750)

1.39 (1.05-1.85)

0.603 (0.513-0.693)

BCI

2.46 (1.88-3.23)

0.762 (0.704-0.820)

1.67 (1.21-2.29)

0.652 (0.566-0.739)

ROR

2.56 (1.96-3.35)

0.764 (0.707-0.821)

1.58 (1.16-2.15)

0.636 (0.552-0.719)

EPclin

2.14 (1.71-2.68)

0.765 (0.716-0.814)

1.69 (1.29-2.22)

0.671 (0.590-0.752)

Abb

Inde

EPcl

HR,

imm

ROR

RS, r

a

All

Prognostic Signatures for Estrogen Receptor–Positive Breast Cancer