Background
Breast cancer is the most frequent malignant tumor and the most common cause of cancer-related death among women in the developed countries [
1,
2]. Breast cancer is increasing in the developing countries, including Ivory Coast, where it ranks at the first cancer in women after cervical cancer [
3]. Breast cancer is a hormone-dependent disease, and thus, resulting from the mitogenic effects of estrogen and progesterone [
4,
5]. The positivity of the ER is generally more than 70% in women with breast cancer than that of PgR, 50% [
6,
7]. The ER/PgR status is essential for clinical and therapeutic care of the breast cancer patients [
8,
9]. The ER has well-established prognostic and predictive values [
9,
10], while the PgR has a controversial additional predictive value [
11,
12]. The presence or not of ER and PgR helps determine a possible relapse of breast cancer [
9]. The hormonal receptor status allows to distinguish four subgroups of breast cancers: ER+PgR+, ER+PgR-, ER-PgR+, and ER-PgR- [
8,
13,
14]. This classification helps to decide hormonal treatment for ER/PgR positive patients and chemotherapy for the ER/PgR negative patients [
9,
15]. Although the immunohistochemical evaluation of ER and PgR is a routine clinical practice in the diagnosis and treatment of breast cancer management worldwide, the clinical utility of ER and PgR testing in breast cancer is currently performed since June 2013 in Ivory Coast. Moreover, very few studies have been done on small sample size (22 patients) to assess the hormonal receptor status of breast cancer in Ivory Coast [
16]. The current research is essential to update the immunohistochemical activity of ER/PgR in primary breast cancers. Herein, the aim of this study was to evaluate the expression of ER and PgR, their distribution, and their correlation with classic clinicopathologic prognostic parameters (age, menopausal status, histologic type, and grade) to enhance the breast cancer patients’ medical care. The present study will contribute to classify patients into different subgroups based on their hormonal receptor status in order to determine the better treatment strategies for women with breast cancer in Ivory Coast.
Discussion
For decades, samples of patients diagnosed with invasive breast carcinomas were sent to laboratories equipped with immunohistochemical techniques in the developed countries for ER and PgR examination. The Roche-Hoffman Laboratory in Ivory Coast, in collaboration with the Ivorian Health Ministry, has recently offered a Unit of Immunohistochemistry to the Central Laboratory to investigate the ER/PgR status of breast cancer patients for an efficient medical support. This study aimed at determining the hormonal receptor status to better characterize breast cancer subtypes and to assess the association of the hormonal receptor with age, menopausal status, histologic type, and tumor grade.
In the present study, several significant observations have been identified. The mean age of all patients at the diagnostic was 48 years, indicating that breast cancer appears early, before the menopause. This finding is similar to several studies conducted in Africa [
16,
19‐
22] and in the Middle East [
23]. However, the mean age of our patients is different from that of the developed countries [
2,
6,
24], where breast cancer commonly occurs at the advanced age or at the postmenopausal period. The early occurrence of breast cancer in women in Ivory Coast could be due to the relative short life expectancy (54 years), the multiparity, and the early age at first childbirth. Parkin et al. found that the multiparity increased the risk of breast cancer before 45 years in a study in Zimbabwe [
25]. Moreover, the multiparity [
26,
27] and the early age at first childbirth [
28] were the main risk factors for breast cancer in black American women. These observations may explain the high incidence of the breast cancer in premenopausal patients in our study.
In this study, IDC NOS associated with tumor grade 2 was predominant. These results are in agreement with data of other studies [
7,
29], suggesting that clinical prognostic factors of breast cancer are worse in the African women, including Ivorian women. In contrast, the histologic type and the tumor grade have insufficient prognostic and predictive implications with limited clinical utility [
30]. Therefore, it is valuable to detect ER and PgR status immunohistochemically in the current study to evaluate the survival of patients and to select their treatment.
The proportion of patients expressing ER is superior to those of PgR+. The same finding was reported by different authors in Europe, [
29,
31,
32], in the USA [
7,
8], and in Africa [
21,
33]. In addition, ER+PgR+ and ER-PgR- were the most frequent subtypes in the current study. Our remarks corroborate with results of several studies [
8,
13,
27,
33], suggesting that ER+PgR+ patients should be considered for hormonal therapy, and ER-PgR- patients should benefit from chemotherapy. Previously, a large number of breast cancer women underwent a systematic hormonal treatment in a blind manner in Ivory Coast. However, 38% of the study patients may not suitable for hormonal therapy, tamoxifen, since they do not express ER and PgR. As a result, they will not benefit from hormonal therapy, and the chemotherapy remains the only systematic treatment [
9,
34,
35]. In this study, ER+PgR+ patients would more favorably respond to hormonal therapy than ER+PgR- and ER-PgR+ patients [
9,
14,
36]. Additionally, ER+PgR+ patients, receiving hormonal therapy, have the advantage of avoiding a tumor relapse leading to a good long-term survival [
9].
The high rate of ER-PgR- in our study is a remarkable finding and is approximately comparable with results reported by Seshie et al. in Ghana [
37], Galukande et al. in Uganda [
38], Adeniji et al. in Nigeria [
39], and Palmer et al. in black American women [
27]. Palmer et al. identified that the ER-PgR- subtype is greatly aggressive and resistant to hormonal therapy whose incidence is increased in the black American population. This high rate is related to the multiparity [
27] and the early age at first childbirth [
28]. Further studies should be done to determine the inherent reasons of the large frequency of ER-PgR- patients in Ivory Coast. Additionally, the increased proportion of ER-PgR- subtype could be explained by a deficiency of the preanalytical factors, particularly the fixation quality, investigated by Werner et al. [
40] and Goldstein et al. [
41]. Hence, a multidisciplinary collaboration between oncologists, radiologists, and pathologists is required to have sampled breast tissues fixed within the allotted time (6–18 h) to preserve hormonal receptor epitopes [
40,
41].
In this current study, the ER-PgR+ subtype, accounting for 6%, is identical to that reported by Osborne et al. [
8] and Hefti et al. [
13]; however, differ from that of Nadji et al. [
7] and Inwald et al. [
32], who listed 0% and 0.8% respectively. Hefti et al. [
13] have recently found that ER-PgR+ group does not represent a subtype of biologically distinct or clinically important cancer, and therefore, should be regarded as a false negative. This artifact subtype results from an inappropriate fixation leading to the loss of epitopes of paraffin-embedded breast tissue blocks [
7,
40,
41].
Despite the unquestionable contribution of ER and PgR testing for a better therapeutic implication, it appears necessary to examine the correlation between ER/PgR status with standard clinicopathologic parameters of primary invasive carcinomas in 302 patients. There was a significant association between the age of the patients and the ER/PgR subgroups. The ER/PgR status has no significant influence on the menopausal status. Our results are consistent with findings of Elwood and Godolphin. Both authors revealed in an analysis of multiple regression study of age and menopausal status in 735 patients that the mean age was significantly associated with the ER/PgR, while there was no significant link between the ER/PgR and the menopausal status [
6]. In the past, tamoxifen was given based on the menopausal status of patients in Ivory Coast because postmenopausal patients appeared to be ER+PgR+ and would better respond to tamoxifen than premenopausal patients. As a result, our data pinpoint that hormonal therapy should be given regardless of the menopausal status.
A correlation was found between the ER/PgR and the tumor grade, which corroborates with the literature data [
6,
7]. In contrast, there was not significant association between ER/PgR status and the histologic type. This result differs from finding of numerous studies [
6,
7,
34]. Nadji et al. observed that ER status predicted some histologic types in breast cancer, and thereby, a lack of such correlation in our study should suspect a technical problem [
7]. In our study, this technical problem may be resulted from the morphologic diagnostic errors or the handling issue of preanalytical factors of breast samples, such as the duration and the type of fixation.
Acknowledgements
The authors thank the Roche-Hoffman Laboratory and the Ministry of Health for implementing the first Unit of Immunohistochemistry at the Central Laboratory in Abidjan, Ivory Coast. The authors also thank Mr. Koffi Arthur and Ms. Gnenaho Pamela for performing the immunohistochemical technique.