Effect of Ki-67 assessment in the distribution of breast cancer subtypes: Evaluation in a cohort of Latin American patients

Abstract

Breast cancer (BC) is a heterogeneous disease composed of four main subtypes with distinct clinical and epidemiological features. Although several reports have described the distribution of BC subtypes in Latin America, the majority of them have not included the cellular marker, Ki-67, in the immunohistochemical (IHC) panel. The aim of the present study was to describe the distribution of BC subtypes in a cohort of Latin American women using an IHC panel with Ki-67. A prospective cohort of 580 patients in three centers of Peru (the Hospital Nacional Edgardo Rebagliatti Martins, the Hospital Nacional Guillermo Almenara Irigoyen, the Hospital Nacional Alberto Sabogal, Lima) and one in Uruguay (Instituto Nacional del Cáncer, Montevideo) were evaluated. BC phenotypes were classified according to an IHC panel: Estrogen receptor (ER), progesterone receptor (PgR), HER2 and Ki-67. Silver in situ hybridization was used when the HER2 status, as determined by IHC, was equivocal. The associations between the BC phenotypes and their clinicopathological features were evaluated. ER was positive in 65% of the cases (n=377), and PgR in 50% (n=203). In total, 79.1% (n=459) were HER2-negative, 19.8% (n=115) were HER2-positive and 1% (n=6) had an equivocal status. With respect to Ki-67, 44.7% of the patients exhibited staining in >14% of the tumor cells (n=259). The distribution of subtypes was as follows: Luminal A, 31.9% (n=183); luminal B, 35% (n=201); HER2, 12.1% (n=70); and triple-negative, 20.9% (n=120). When Ki-67 was not included in the panel, the frequency of luminal A was 41.1% and luminal B, 25.8% (9.2% of the cases were misclassified). Ki-67 was most highly expressed in triple-negative and HER2 tumors. Inclusion of Ki-67 in the IHC panel to assign subtypes revealed a higher frequency of luminal B tumors than was reported previously for Latin American women with BC, whereas the distribution of triple-negative and HER2 tumors were similar to that previously reported. In conclusion, these results demonstrated that excluding Ki-67 from the panel of IHC markers may lead to an underestimation of the rates of luminal B tumors.

Perfil histológico e imuno-histoquímico das pacientes com câncer de mama operadas no Hospital Santa Casa de Curitiba no período de 2014 e 2015

“…Analisando o perfil imuno-histoquímico dos casos apresentados, o mais prevalente foi o Luminal A conforme dados encontrados na literatura (22,30,33) . Porém o triplo negativo se apresentou mais prevalente do que o Luminal B (30,33) , divergindo do nosso estudo onde o Luminal B aparece mais prevalente que o triplo negativo corroborando com o trabalho de Yábar et al (2017) (34) .…”

Barriers in Latin America for the management of locally advanced breast cancer

“…Another distinctive feature of BC presentation in LATAM is that young women comprise a large proportion of diagnosed cases. In addition, there is a higher prevalence of triple-negative BC (≈20%) compared with other regions of the world, which leads to the larger burden of aggressive tumours [66, 70].…”

Precision medicine for locally advanced breast cancer: frontiers and challenges in Latin America

“…One typical feature of LATAM patients is a high prevalence of triple-negative breast cancer (up to 21.3%) in contrast to Caucasian populations (around 9%) [82, 86]. Subtypes identification is performed mainly by IHC in the clinical routine.…”

“…Heterogeneity seen in luminal tumours could be attributed to the difficulty to discriminate luminal A from luminal B cases, where Ki-67 staining plays a major role. Yabar et al [86] evaluating a mixed cohort of patients from Peru and Uruguay, found that distribution of luminal A tumours change from 41.1% to 31.9% after the inclusion of Ki-67 in the IHC panel to determine the breast cancer subtypes. Inclusion of Ki-67 in the IHC panel to evaluate recently diagnosed breast tumours is relatively new and therefore in the coming years, reports about the distribution of breast cancer subtypes in LATAM will be more accurate and less heterogeneous.…”