Dados do Resumo

Título

Clinicopathological profile of invasive breast tumors with undetermined HER2 immunohistochemistry

Introdução

Human Epidermal Growth Factor 2 (HER2) amplification and overexpression are found in 15-20% of breast cancers. Currently, immunohistochemistry (IHQ) and in situ hybridization (ISH) are the methods of choice for screening HER2 status. HER2 2+ cases (equivocal) require ISH testing to classify tumors as HER2 amplified or HER2 non-amplified. Although accurate, ISH is a very expensive and inaccessible test for smaller cancer centers, and the diagnosis of mutated/amplified HER2 is very important for the use of specific anti-HER2 medications.

Objetivo

To compare the HER2-amplified and HER2-unamplified groups and then determine whether there are distinct clinical-pathological features associated with each group that could guide therapy without the need for further ISH testing.

Métodos

This is a cross-sectional study, based on departmental data from cases treated at the A.C. Camargo Cancer Center between 2020 and 2023. With the help of electronic medical records, we screened patients with invasive breast cancer whose immunohistochemistry resulted in HER 2+/equivocal. Out of 2546 exams, we identified 215 patients who met the inclusion criteria. The clinical-pathological characteristics were entered into the institutional REDCap®️ system. Summary measures of position and dispersion (such as mean, median, standard deviation, minimum and maximum values) and absolute and relative frequencies (%) will be used for qualitative variables. The significance level adopted will be 5.0%. Ethical approval nº3561/24.

Resultados

Of the 2546 patients evaluated, 215 were HER2 2+ equivocal (8.4%). The median age was 54.5 years. Around 54.0% were postmenopausal. A palpable lesion was the complaint for 30.7% and 48.8% had findings on mammography. Invasive ductal carcinoma was present in 81.9% of the sample, and histological grade 2 was the most prevalent (59.5%). Around 90.0% were luminal. Initial disease was 77.2%, and locally advanced, 19.5%. Neoadjuvant chemotherapy was given in 27.4% of cases. Of the HER 2+ cases, 177 were HER2 non-amplified (82.3%) and 17.7%  were HER2 amplified. A higher rate of premenopausal women (34.2%) was observed in the HER2-amplified group (versus 20.3%). The HER2 amplified group was found to be associated with more aggressive nuclear and histological grade tumors. There was more early disease in the ISH negative group and more advanced disease in the ISH amplified group (p=0.065).  There was also a higher rate of birth control pills (BCP) in the HER2 amplified group (63.2%) [p<0,05].

Conclusões

The overall HER2+ rate was 8.4% (literature incidence 10-15%). The incidence of amplified HER2 of 17.7% is, however, within the expected range (15-20%). Of the clinical variables studied, there were no variables that could suggest the result of ISH without the need to do so. There was a higher prevalence of amplified ISH in groups with more advanced disease and higher histological grades. Furthermore, an association is suggested between the amplified group and the use of contraceptives.

Palavras Chave

Breast cancer; imunohistochemistry; HER2