Breast Cancer Characteristics in Young Women Under 50 Years Old in Mankweng Hospital, South Africa

Background: Breast cancer is a diverse disorder, commonly occurs in elderly women in Europe and America. However, in Africa, it happens often among younger women. Main aim of the study is to have better understand the characteristics of breast cancer in women under 50 years and to identify any differences exist between HIV positive and negative groups of breast cancer patients.

Method: Retrospective descriptive quantitative study intended to analyse the profile of women under 50 years old with breast cancers who attended Breast Oncology Clinic, Mankweng Hospital from July 2020 to December 2021.

Results: Total 109 breast cancer patients evaluated. Mean age in HIV negative 40.6 and HIV positive 39 years. HIV status: HIV Positive 28(25.7%). HIV Negative 81(74.3%). HIV positive group: Molecular subtype: Luminal A:5(24%), Luminal B:8(38%), HER2+ overexpression:3(14%), Triple negative:5(24%). Stage: Early stage 6(21%), late stage 22(79%). HIV negative group: Molecular subtype: Luminal A:16(22%), Luminal B:41(58%), HER2+ overexpression:7(10%), Triple negative:7(10%). Stage: Early stage 16(20%), late stage 65(80%).

Conclusion: Majority of breast cancer patients presented in advance stage in both HIV positive and negative group. Mean age of HIV positive slightly younger than HIV negative (39-year vs 40.6 years). Triple negative molecular subtype was proportionately more in HIV-positive group in compared to HIV-negative patients. Initiative of Routine breast cancer screening should take place on this population of women under 40-year age.

Introduction

Breast cancer is a diverse disorder involving several subgroups of cellular compositions, molecular variations as well as clinical behaviour [1]. Phenotypically identical breast tumours, which are histologically similar, can present with a wide range of clinical outcomes and responses to therapy due to the presence or absence of hormone receptors and human epithelial growth factor 2 (HER2/neu) [2], [3]. Breast cancer is the most commonly diagnosed cancer in women an incidence of 2.3 million, comprising 11.6% of all cancer cases in 2022 [4]. Breast cancer usually occurs among elderly women, particularly in Europe and America. However, in Africa, it often happens among young women, and the prognosis of breast cancer in young women is worse than breast cancer in older patients [5]. In Limpopo province, South Africa over 38% of breast cancer cases occurred in younger women under 50 years of age [6] and the majority (76%) of breast cancer patients presented with a late stage [7]. In one of the studies in Nigeria, the average age of women with breast cancer was 49 years [8]. Vanderpuye et al. (2017) cited that the age range of women with breast cancer in Kenya and Tanzania was 35 to 45 years [9]. Bhatia et al. [10] mentioned that HIV-infected patients presented at a younger age in comparison to HIV uninfected persons. Similarly, in a study from Tygerberg Academic Hospital, South Africa (SA), Langenhoven et al. [11] stated that breast cancer with HIV was younger than those without HIV and found an average age at presentation without HIV was 56 years in comparison to the patients with HIV which was 42 years. However, a few more literature from Sub-Saharan Africa (SSA) reported that patients with breast cancer usually present at a younger age, and there is no association between breast cancer and HIV infection [12]–[14]. HIV prevalence is 19.5% among the young adult population (15–49 years old) in South Africa [15]. Lifetime, there is a risk of developing cancer increases in HIV patients when compared with HIV-negative patients [16], [17].

There has been no study done discretely on the profile of breast cancer in the younger group of patients in Limpopo province. The main objective of the study is to have a better understanding of the characteristics of breast cancer in young women under 50 years, and the other objective is to identify any differences that exist between the HIV-positive and negative groups of breast cancer patients in Limpopo province.

Method

Study Design and Population

This is a retrospective descriptive quantitative study designed to analyse the profile of younger women under 50 years old with breast cancer who attended the Breast Oncology Clinic, Mankweng Hospital, from July 2020 to December 2021. Patients under 50 years old who had confirmed histological breast cancers were included in this study. Patients 50 and above and cases in which HIV (human immunodeficiency virus) status were not known have been excluded.

Data Collection

Mankweng Breast Cancer Clinic register was used to get patients’ initial data, and the patients’ relevant records were assessed to collect detailed information. Data collection sheets comprised of women’s age, histological type of breast cancer, grading, estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki67 index, molecular subtype, stage of cancer, and HIV status. Stages at presentation were grouped into early (0, I & II) and late (III & IV) stages. Breast cancer is categorized into four molecular subtypes, determined by the status of three therapeutic receptors (ER, PR, and HER2) based on Immunohistochemistry. These subtypes are luminal A (ER+/PR+/HER2-/low Ki-67), luminal B (ER+/PR+/HER2-/+/high Ki-67), HER2 overexpression (ER-/PR-/HER2+), and triple-negative Breast cancer (ER-/PR-/HER2-) or basal-like [3], [5]. In some histology results, estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2, Ki67 index and grading were not reported or not done because biopsy samples seemed insufficient. The grading and molecular subtype analysis were accomplished only on patients where the grading and immunochemistry results were reflected in the histology report. The data collected was transferred to an Excel spreadsheet.

Statistical Analysis

The statistical software package SPSS v29 was used for data analysis. The patient demographics were summarised using descriptive statistics. Categorical variables were expressed as proportions and frequency. Association between categorical variables was done using a Chi-square test. A p-value of less than 0.05 was considered statistically significant.

Ethical Statement

The database document was protected with only the researcher having the password.

Results

A total of 109 breast cancer patients met the inclusion criteria for analysis in the present study. The age range of the participants was 20 to 49 years, with a mean age of 40.2 years. The mean age of the HIV-negative group was 40.6 years (ranging from 20 to 49 years), and the mean age of the HIV-positive group was 39 years (ranging from 30 to 49 years). Regarding HIV status, 28 patients (25.7%) were HIV positive, while 81 patients (74.3%) were HIV negative. In terms of disease stage, 22 patients (20%) were diagnosed at an early stage, and 87 patients (80%) were diagnosed at a late stage. Detailed results are provided in Table I.

Table I. Descriptive Summary of Breast Cancer Patients Under 50 Years Old

Description	HIV positive	HIV negative	Total
HIV status	28 (25.7%)	81 (74.3%)	109 (100%)
Mean age (Range)	39 (30–49)	40.6 (20–49)
Stage
Early-Stage	6 (21%)	16 (20%)	22 (20%)
Late-stage	22 (79%)	65 (80%)	87 (80%)
Total	28 (100%)	81 (100%)	109 (100%)
Histology type
Invasive ductal carcinoma (no special type)	28	81	109
Grade
Grade 1	5 (25%)	2 (3%)	7 (8%)
Grade 2	6 (30%)	42 (61%)	48 (54%)
Grade 3	9 (45%)	25 (36%)	34 (38%)
Total	20	69	89
Molecular subtype
L-A	5 (24%)	16 (22%)	21 (23%)
L-B	8 (38%)	41 (58%)	49 (53%)
HER2+	3 (14%)	7 (10%)	10 (11%)
Triple negative	5 (24%)	7 (10%)	12 (13%)
Total	21	71	92

In the HIV-positive group, the most predominant molecular subtype was Luminal B, accounting for 8 patients (38%), followed by Luminal A with 5 patients (24%), Triple Negative with 5 patients (24%), and HER2+ overexpression with 3 patients (14%). Regarding grading, grade 3 was the most common, observed in 9 patients (45%), followed by grade 2 in 6 patients (30%), and grade 1 in 5 patients (25%). In terms of stage, 6 patients (21%) were diagnosed at an early stage, while 22 patients (79%) were diagnosed at a late stage.

In the HIV-negative group, Luminal B was also the most predominant molecular subtype, observed in 41 patients (58%), followed by Luminal A in 16 patients (22%), Triple Negative in 7 patients (10%), and HER2+ overexpression, which was the least common, seen in 7 patients (10%). For grading, grade 2 was the most common, observed in 42 patients (61%), followed by grade 3 in 25 patients (26%), and grade 1 in 2 patients (3%). Regarding disease stage, 16 patients (20%) were diagnosed at an early stage, while 65 patients (80%) were diagnosed at a late stage.

Discussion

In this study, 109 breast cancer patients were evaluated, of which 28 (25.7%) were HIV-positive and 81 (74.3%) were HIV-negative. The age range of investigated patients was 20–49 years. When related to HIV status, statistically, there was no significant age difference found between HIV-positive and negative group patients. However, HIV-positive group patients were younger than HIV-negative group. The mean age of the HIV-positive group was 39 years, and the HIV-negative group was 40.6 years. Other literature mentioned that the average age of breast cancer patients is 49 years [8]. Reddy et al. [18] mentioned that HIV-positive patients with breast cancer were younger than HIV-negative patients in a study done in Kwa-Zulu Natal, South Africa. Across the globe, a few other studies also confirmed that breast cancers occur in younger women among HIV-positive patients in comparison to their HIV-negative counterparts [10], [19], [20]. However, a few more literature from Sub-Saharan Africa (SSA) reported that there is no association between breast cancer and HIV infection [12]–[14].

Regarding the histological type of breast cancer in this study, all patients, both HIV-positive and HIV-negative patients, had Invasive ductal carcinoma (no special type). In many sub-Saharan Africa, Invasive Ductal carcinoma (IDC) is more common. Kohler et al. [21] reported that IDC was Malawi’s most common (86%) histological type. Another Nigerian study cited approximately 89% of invasive ductal carcinoma of no special type [5]. A similar trend was found among the women in Limpopo, South Africa, as shown in a previous study [6].

Concerning tumour biology with grading, most patients had grade 2 nearly 54% and grade 3 was 38%. A previous study from Limpopo revealed that most of the patients had the disease at grade 2 (61%) followed by Grade 3 (29%) [22]. However, when categorised discretely with HIV status, grade 3 was more in HIV-positive patients at 45% and grade 2 was 30%. In HIV-negative group patients, grade 3 was 36%, and grade 2 was nearly 61% (Fig. 1). It implied that HIV-positive group patients had more aggressive tumour biology than HIV-negative patients. Layton and Castillo [17] stated that breast cancer occurs at approximately the same incidence in HIV-positive patients as compared to HIV-negative patients. However, when breast cancer occurs in HIV-positive patients, the malignancy tends to be poorly differentiated [17]. Some other studies also indicated that breast cancers among HIV-positive patients, in comparison to their HIV-negative counterparts, showed a more aggressive appearance in tumour biology [19], [21]. On the contrary, another study from Johannesburg, South Africa, mentioned that HIV does not affect stages, grades, tumour sub-types, and survival of patients with breast cancer [12].

Fig. 1. Grading in HIV negative and positive patients’ group.

With regards to molecular classification in this study, the Luminal B Molecular subtype type was more frequent at 53%, Luminal A at 23%, Triple negative at 13%, and HER 2 overexpression at 11%. However, across the globe, there are variations of incidences of molecular subtypes that do occur in different populations [1], [23]–[25]. Luminal A cancers grow slowly and have the best prognosis. Luminal B cancers grow faster than luminal A cancers, and their prognosis is slightly worse, and both Luminal A and Luminal B respond to hormonal therapy. HER2-overexpression cancers usually grow faster than luminal subtype cancers and have a worse prognosis. However, they are often successfully treated with targeted therapies such as trastuzumab, pertuzumab, and lapatinib. Triple-negative breast cancer is a poor prognosis [26]–[29].

Another observation in this study regarding molecular subtype when related to HIV status is that triple-negative molecular subtype had a higher prevalence than other molecular subtypes in HIV-positive group patients (24%) compared to HIV-negative patients (10%). Luminal B was predominant in both HIV-positive and negative group patients (Fig. 2).

Fig. 2. Molecular subtype in HIV-negative and HIV-positive group.

Triple negative (TN) breast cancer was found on 12 patients in this study and grade 3 had higher prevalence in triple molecular subtype (92%) in compared to other grades (Fig. 3). Triple negative patients are more aggressive appearing in tumour biology. Sheppard et al. [29] mentioned that triple negative disease patients usually present in the advanced stage. In this study the average age of triple negative patients was found less in comparison to others molecular subtype. Mean age in triple negative was 37.6 and other molecular subtype was 41.2 years. Interestingly, when the age of triple negative patients compared with HIV status, Triple negative with HIV positive group patients were younger. Age of triple negative with HIV positive group patients was found 35 years while in HIV negative group patients 39 year.

Fig. 3. Molecular subtype vs. Grading. Grade 1–Green, Grade 2–Blue; Grade 3–Orange colour.

In this study, there were no significant associations found between the stage and HIV status. Majority presented in advance stage in both HIV positive and negative groups (Fig. 4). Most of the patients who presented in this study with advanced stage were Triple negative, Luminal B and HER2/neu amplification. Advanced stage in presentation are generally common problems in low- and middle-income countries [30] and in many sub-Saharan Africa [12], [14].

Fig. 4. Stage in HIV Negative & Positive group (stage 1-Green, stage 2-Blue, Stage 3-Orange, stage 4-Grey colour).

Breast cancer in young women encounters many challenges, diagnostic delays, and limited awareness in many countries [5]. A study from Soweto, Johannesburg, showed that lack of breast cancer knowledge and awareness and as well as health care service ineffectiveness were associated with an advanced stage at diagnosis [31]. Rayne et al. [32] stated low levels of education was a major factor delaying diagnosis. Another study from rural KwaZulu-Natal found, lack of understanding of the severity of breast cancer responsible for presenting late [33]. Previous study from Limpopo province, South Africa found the most common reasons for delaying, deficit of knowledge about breast cancer and its symptoms [7].

Breast cancer screening programs for the general population normally do not include women under the age of 40, which contributing to diagnostic delays [5]. Growth rate of breast cancer in younger women is much faster than in older women [34], [35]. Early diagnosis of breast cancer is a crucial factor for efficient management which reduce the suffering of the patients and improve survival. Costa et al. [5] encouraged for increasing awareness and educational programs to identify signs and symptoms in young women and to develop clear diagnostic guidelines, and screening strategies. The breast cancer policy 2017 of Department of Health, South Africa urged direct access to a dedicated breast cancer clinic to reduce delays in presentation and improve time to diagnosis and care [36]. Lince-Deroche et al. [37] also advocated for women of younger age for routine screening. The findings of the present study support the need to include women of younger age for regular screening. As mean age of breast cancer diagnosis among the younger group of women in Limpopo province is 40 years, hence it is strongly advisable to start breast cancer screening under 40-year-old.

Limitations of the Research

The present study was retrospective, and information was not available in few cases. Some patients did not have complete histology results with Immunohistochemistry.

Conclusion

Majority of breast cancer patients presented in advance stage in both HIV positive and negative group. Mean age of HIV positive slightly younger than HIV negative (39-year vs. 40.6 years). Triple negative molecular subtype was proportionately more in HIV-positive group patients in compared to HIV-negative patients.

Recommendations

Initiative of Routine breast cancer screening should take place on this population of women under 40 years of age. Further studies are indicated to elucidate the genetics, environmental influences of breast cancer in young women.