RAMB - JULHO 2017

rias

VEA

566

ssoc

ras

2017; 63(7):566-574

ORIGINAL ARTICLE

Assessment of HER-2 status in invasive breast cancer in Brazil

ictor

duardo

rrua

rias

, H

elenice

obbi

, S

érgio

ssamu

oshii

, C

ristovam

capulatempo

, A

lexandre

olim

inicius

uval

ilva

, D

iego

chôa

, C

laudio

ettler

, F

ernando

ugusto

oares

Reference Center for Women’s Health, Hospital Pérola Byington, São Paulo, SP, Brazil

Department of Pathologic Anatomy, Faculdade de Medicina da Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil

Pathology Division, Hospital Erasto Gaertner and Pontifícia Universidade Católica do Paraná, Curitiba, PR, Brazil

Department of Pathology and Center for Research in Molecular Oncology, Hospital de Câncer de Barretos, Barretos, SP, Brazil

Hospital Napoleão Laureano, Universidade Federal da Paraíba, João Pessoa, PB, Brazil

Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, RS, Brazil

Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil

Pathology Service, Irmandade da Santa Casa de Porto Alegre, Porto Alegre, RS, Brazil

Department of Pathologic Anatomy, A.C. Camargo Cancer Center, São Paulo, SP, Brazil

ummary

Study conducted at the Department

of Pathologic Anatomy, A.C. Camargo

Cancer Center, São Paulo, SP, Brazil

Article received:

12/15/2016

Accepted for publication:

2/5/2017

*Correspondence:

Departamento de Anatomia Patológica,

A.C. Camargo Cancer Center

Address: R. Prof. Antônio Prudente, 211

São Paulo, SP – Brazil

Postal code: 01509-010

fasoares@icloud.com http://dx.doi.org/10.1590/1806-9282.63.07.566

Objective:

To characterize the frequency of HER-2-positive breast cancer in Brazil.

Method:

In this prospective observational study, we first ascertained the HER-2 status

of invasive breast cancer specimens by automated immunohistochemistry (IHC).

For specimens classified as 2+ by IHC, we performed in situ hybridization (ISH).

Results:

From February, 2011 to December, 2012, 1,495 breast specimens were

registered, and 1,310 samples collected at 24 centers were analyzed. Median patient

age was 54 years, and the majority of samples were obtained from segmental (46.9%)

or radical mastectomy (34.4%). The predominant histological type was invasive

breast carcinoma of no special type (85%), 64.3% had tubule formation (grade 3),

and estrogen/progesterone receptors (ER/PR) were positive in 77.4/67.8% of the

specimens analyzed, respectively. Using IHC, we found a negative HER-2 status (0

or 1+) in 72.2% of specimens, and 3+ in 18.5%; the 9.3% scored as 2+ were further

analyzed by ISH, of which 15.7% were positive (thus, 20.0% of samples were HER-2-‑positive by either method). We found no association between HER-2 scores and

menopausal status or histological type. Tumors classified as 3+ came from younger

patients, and had higher histological grade and less frequent expression of ER/PR.

In the North region of Brazil, 34.7% of samples were 3+, with lower frequencies in

the other four regions of the country.

Conclusion:

Our findings provide estimates for the frequency of HER-2 positivity

in Brazil and raise the hypothesis that biological differences may underlie the

different distribution of breast-cancer phenotypes among different Brazilian regions.

Keywords:

breast neoplasms, immunohistochemistry, in situ hybridization,

erbB2, trastuzumab, HER-2.

ntroduction

Breast cancer, which affects one out of eight US women

during their lifetime,

is the second most common tumor

worldwide, with an estimated 1.67 million new cases and

522 thousand deaths in 2012.

In Brazil, breast cancer is

the most common tumor among women, affecting almost

60,000 patients in 2014.

Currently, breast cancer is con-

sidered a group of different diseases on the basis of mo-

lecular subtypes, with this classification bearing relevant

prognostic and predictive implications.

Between 15 and

20% of breast tumors display

HER-2

gene amplification

or overexpression of the HER-2 protein,

5-7

a transmem-

brane tyrosine kinase receptor involved in cell proliferation

and migration that confers worse prognosis, with faster

disease progression and decreased survival, compared

with HER-2-negative tumors.

One of the most important

advances in breast cancer therapy has been the introduc-

tion of trastuzumab and other HER-2-targeting antibod-

ies, which increase the survival of patients with meta-

static disease,

9-11

and reduce the risk of relapse in early