Abstract
Breast cancer (BC) is the most commonly diagnosed cancer among women globally, with significant regional variations in its molecular subtypes, clinical presentation, and management. Despite advancements in oncology, limited data exist on the molecular and clinical characteristics of BC in Libya. This study aims to analyze the prevalence of molecular subtypes, clinicopathological features, and treatment patterns among Libyan women with BC at Tobruk Medical Center. This retrospective observational study included BC patients diagnosed between January 2019 and December 2020 at Tobruk Medical Center. Demographic, clinical, pathological, and treatment-related data were extracted from medical records. Molecular subtyping was based on immunohistochemical assessment of estrogen receptor, progesterone receptor, human epidermal growth factor receptor 2 (HER2), and Ki-67. Statistical analyses were performed using SPSS version 28 (IBM Corp., Armonk). Among 115 patients analyzed, the median age at diagnosis was 46 years. Invasive ductal carcinoma accounted for 89.6% of cases, with grade II tumors being the most common (69.6%). Luminal B was the predominant molecular subtype (67.8%), followed by luminal A (14.8%), HER2-enriched (10.4%), and triple-negative BC (7.0%). Advanced-stage diagnoses (stage III and IV) were observed in 57.4% of cases. Hormone receptor positivity was detected in 82.6%, and HER2 positivity in 25.2% of cases. This study highlights the high prevalence of advanced-stage BC and the predominance of the aggressive luminal B subtype in Libya. Targeted early detection programs and improved treatment access are urgently needed to address these challenges.
Keywords: breast cancer, early detection, Libya, molecular subtypes, retrospective study
1. Introduction
Breast cancer (BC) is the most commonly diagnosed malignancy among women worldwide and remains a leading cause of cancer-related mortality. It accounts for approximately 11.7% of all new cancer cases globally and contributes to 6.9% of cancer-related deaths.[1] In Libya, BC represents a major public health concern; according to GLOBOCAN 2022, it is the most frequently diagnosed cancer among women, accounting for 28.5% of all female cancer cases, and the third leading cause of cancer-related mortality, responsible for 8.7% of cancer deaths.[2] The global burden of BC is projected to increase substantially, with more than 3 million new cases and nearly 1 million deaths annually expected by 2040, driven largely by population growth and aging.[3]
Although high-income countries report the highest age-standardized incidence rates of BC, more than half of all new cases occur in low- and middle-income countries, where the disease burden is amplified by limited healthcare resources and delayed diagnosis.[4] Rapid socioeconomic transitions in these regions, including increasing life expectancy, rising obesity rates, and changes in reproductive and lifestyle patterns, are expected to further increase BC incidence in the coming decades.[5]
BC is a biologically heterogeneous disease, comprising distinct molecular subtypes that differ in clinical behavior, treatment response, and prognosis.[6] Based on hormone receptor and human epidermal growth factor receptor 2 (HER2) status, BC is commonly classified into 4 molecular subtypes: luminal A, luminal B, HER2-enriched, and triple-negative breast cancer (TNBC).[7] Luminal subtypes are generally associated with more favorable outcomes, while HER2-enriched and TNBC subtypes tend to exhibit more aggressive clinical behavior and poorer prognosis.
Despite advances in molecular characterization and early detection strategies globally, data on BC molecular subtypes in low- and middle-income countries, including Libya, remain scarce. In Libya, the absence of organized national screening programs, limited access to specialized diagnostic services, and delays in presentation contribute to a high proportion of advanced-stage diagnoses. Furthermore, existing studies are limited in scope and do not adequately describe the distribution of molecular subtypes or their associations with clinicopathological features across different regions of the country.[2]
Therefore, this study aims to address these gaps by analyzing the prevalence of BC molecular subtypes among Libyan women treated at Tobruk Medical Center (TMC) in eastern Libya. We further investigate the associations between molecular subtypes and key clinicopathological factors, including age at diagnosis, disease stage, lymph node involvement, tumor grade, and hormone receptor status, to provide region-specific evidence that may inform clinical practice and public health planning.
2. Materials and methods
2.1. Study design
This retrospective, single-center study was conducted at the Medical Oncology Department of TMC, Tobruk, Eastern Libya. The study included BC cases diagnosed and managed between January 1, 2019, and December 31, 2020. This period was selected because complete clinicopathological and immunohistochemical (IHC) data were consistently available and verifiable for this timeframe. Data retrieval and verification for later years were limited due to administrative constraints, retrospective record availability, and disruptions related to the COVID-19 pandemic. No major changes in immunohistochemical testing protocols or core treatment modalities for BC were implemented at TMC during or immediately after the study period; however, access to certain targeted therapies and diagnostic resources has remained variable over time.
2.2. Ethical approval
The study protocol was reviewed and approved by the Research Ethics Committee of Tobruk University (approval ID: 009.H.25.2). Given the retrospective nature of the study and the use of anonymized medical records, the requirement for informed consent was waived by the Institutional Review Board. All procedures were conducted in accordance with the Declaration of Helsinki, and patient confidentiality was strictly maintained.
2.3. Study population
During the study period, 458 cancer patients were registered at TMC, of whom 145 were histopathologically diagnosed with BC (144 females and 1 male). Thirty cases were excluded due to incomplete or missing essential clinical or pathological data. The final analytical cohort consisted of 115 patients. As this was a retrospective study, a formal sample size calculation was not performed; instead, all eligible cases meeting the inclusion criteria within the defined timeframe were included.
2.4. Data collection
Clinical and pathological data were extracted retrospectively from patient medical records and oncology registries at TMC. Collected variables included demographic characteristics (age at diagnosis, sex, marital status, residence, and family history of BC), tumor-related factors (laterality, histological subtype, tumor size, tumor grade, lymph node involvement, and presence of distant metastasis at diagnosis), and treatment modalities (surgery, chemotherapy, radiotherapy, hormonal therapy, and targeted therapy).
Pathological diagnosis and tumor grading were based on histopathological examination of biopsy or surgical specimens. Tumor staging at diagnosis was determined using the 8th edition of the American Joint Committee on Cancer TNM staging system.
2.5. Immunohistochemistry and molecular subtyping
Immunohistochemical analysis for estrogen receptor (ER), progesterone receptor (PR), HER2, and the Ki-67 proliferation index was performed in the pathology laboratory of TMC as part of routine clinical care. All IHC slides were interpreted by trained pathologists following standardized institutional reporting practices. HER2 testing and scoring were conducted in accordance with the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) guidelines applicable at the time of diagnosis. ER and PR status were reported as positive or negative based on nuclear staining of tumor cells.
The Ki-67 proliferation index was recorded as the percentage of positively stained tumor nuclei and categorized as follows:
Low: <10%
Moderate: 10% to 20%
High: >20%
Based on IHC results, BC cases were classified into molecular subtypes using established surrogate definitions:
Luminal A: ER-positive and/or PR-positive, HER2-negative, and low Ki-67
Luminal B (HER2-negative): ER-positive and/or PR-positive, HER2-negative, with moderate or high Ki-67
Luminal B (HER2-positive): ER-positive and/or PR-positive, HER2-positive, regardless of Ki-67 level
HER2-enriched: ER-negative, PR-negative, and HER2-positive
TNBC: ER-negative, PR-negative, and HER2-negative
2.6. Handling of missing data
Missing data were present for several variables, most notably family history of BC. Missing values were not imputed. Analyses were conducted using complete-case analysis for each variable, and variables with substantial missingness were interpreted descriptively. The potential for bias resulting from missing data was considered when interpreting study findings.
2.7. Statistical analysis
Statistical analyses were performed using IBM SPSS Statistics for Windows, Version 28 (IBM Corp., Armonk). Continuous variables were assessed for normality using the Shapiro–Wilk test and summarized as means with standard deviations for normally distributed data or medians with interquartile ranges for non-normally distributed data. Categorical variables were expressed as frequencies and percentages. Comparisons between molecular subtypes and clinicopathological variables were conducted using the chi-square test. Fisher’s exact test was applied when expected cell counts were small. For continuous variables, 1-way analysis of variance was used for normally distributed data, while the Kruskal–Wallis test was applied for non-parametric data. Because this analysis was primarily descriptive and exploratory, we did not apply formal corrections for multiple hypothesis testing; therefore, statistically significant findings should be interpreted cautiously and in the context of the overall pattern of results. A 2-sided P-value < .05 was considered statistically significant.
3. Results
3.1. Patient demographics and clinical characteristics
A total of 115 BC patients diagnosed and treated at TMC between January 2019 and December 2020 were included in the analysis (Table 1). The cohort consisted predominantly of women (99.1%), with 1 male patient (0.9%). Most patients were married (87.0%), and the median age at diagnosis was 46 years (interquartile range: 41–52 years). The majority of patients resided in Albutnan (47.0%) and Derna (29.6%) regions.
Table 1.
Descriptive data of breast cancer patients at Tobruk Medical Center (n = 115).
| Characteristic | Level | Frequency (%) |
|---|---|---|
| Sex | Female | 114 (99.1) |
| Male | 1 (0.9) | |
| Marital status | Married | 100 (87.0) |
| Single | 5 (4.3) | |
| Unknown | 10 (8.7) | |
| Family history of breast cancer | No | 5 (4.3) |
| Unknown | 95 (82.6) | |
| Yes | 15 (13.0) | |
| Residence | Albutnan (Tobruk) | 54 (47.0) |
| Aljabal Alakhdar | 22 (19.1) | |
| Almarj | 3 (2.6) | |
| Benghazi | 1 (0.9) | |
| Derna | 34 (29.6) | |
| Igdabya and Alwahat | 1 (0.9) | |
| Age at diagnosis (median [IQR]) | 46.00 [41.00, 52.00] | |
| Weight (mean ± SD) | 74.92 ± 16.70 | |
| Height (mean ± SD) | 157.30 ± 5.55 | |
| Laterality | Bilateral | 5 (4.3) |
| Left | 56 (48.7) | |
| Right | 53 (46.1) | |
| Unknown | 1 (0.9) | |
| Method of diagnosis | Fine needle aspiration (FNA) | 19 (16.5) |
| Incisional biopsy | 6 (5.2) | |
| Lumpectomy | 55 (47.8) | |
| Mastectomy | 9 (7.8) | |
| Tru-cut needle biopsy (TCNB) | 25 (21.7) | |
| Unknown | 1 (0.9) | |
| Type of histology | Ductal Carcinoma In Situ (DCIS) | 1 (0.9) |
| Invasive ductal carcinoma | 103 (89.6) | |
| Invasive lobular carcinoma | 3 (2.6) | |
| Medullary carcinoma | 2 (1.7) | |
| Metaplastic carcinoma | 1 (0.9) | |
| Mixed invasive ductal and lobular | 1 (0.9) | |
| Mucinous carcinoma | 1 (0.9) | |
| Papillary carcinoma | 2 (1.7) | |
| Unknown | 1 (0.9) | |
| Tumor size | T1 | 4 (3.5) |
| T2 | 55 (47.8) | |
| T3 | 39 (33.9) | |
| T4 | 14 (12.2) | |
| Unknown | 3 (2.6) | |
| Regional lymph node infiltration | No | 30 (26.1) |
| Yes | 76 (66.1) | |
| Unknown | 9 (7.8) | |
| Tumor grade | Grade I | 4 (3.5) |
| Grade II | 80 (69.6) | |
| Grade III | 27 (23.5) | |
| Unknown | 4 (3.5) | |
| Hormone receptor status | Positive | 95 (82.6) |
| Negative | 20 (17.4) | |
| HER2 status | Positive | 29 (25.2) |
| Negative | 86 (74.8) | |
| Ki-67 proliferation index | High | 60 (52.2) |
| Moderate | 38 (33.0) | |
| Low | 17 (14.8) | |
| Molecular subtypes | HER2-enriched | 12 (10.4) |
| Luminal A | 17 (14.8) | |
| Luminal B | 78 (67.8) | |
| Triple-negative breast cancer (TNBC) | 8 (7.0) | |
| Stage of cancer at diagnosis | Stage 0 (in situ) | 1 (0.9) |
| Stage I | 2 (1.7) | |
| Stage IIA | 17 (14.8) | |
| Stage IIB | 26 (22.6) | |
| Stage III | 43 (37.4) | |
| Stage IV | 23 (20.0) | |
| Unknown | 3 (2.6) | |
| Metastasis at diagnosis | Yes | 25 (21.7) |
| No | 89 (77.4) | |
| Unknown | 1 (0.9) | |
| Treatment received | Surgical resection | 98 (85.2) |
| Chemotherapy | 102 (88.7) | |
| Radiotherapy | 68 (59.1) | |
| Hormonal therapy | 90 (78.3) | |
| Targeted therapy | 31 (27.0) | |
| Type of surgery | Breast-conserving surgery (BCS) | 23 (20.0) |
| Modified radical mastectomy (MRM) | 72 (62.6) | |
| None | 20 (17.4) | |
BC = breast cancer, BCS = breast-conserving surgery, DCIS = ductal carcinoma in situ, FNA = fine needle aspiration, IQR = interquartile range, MRM = modified radical mastectomy, NBC = triple-negative breast cancer, SD = standard deviation, TCNB = tru-cut needle biopsy, THER2 = human epidermal growth factor receptor 2.
Left breast involvement was slightly more common (48.7%). Invasive ductal carcinoma was the predominant histological type (89.6%), with T2 tumors (47.8%) and grade II tumors (69.6%) being the most frequently observed. Regional lymph node infiltration was present in 66.1% of cases. Hormone receptor positivity was high at 82.6%, and HER2 positivity was observed in 25.2% of patients. Molecular subtypes were dominated by luminal B (67.8%), followed by luminal A (14.8%), HER2-enriched (10.4%), and TNBC (7.0%). Most patients were diagnosed at advanced stages, with 37.4% in stage III and 20.0% in stage IV. Surgical resection was performed in 85.2% of cases, 88.7% received chemotherapy, 59.1% received radiotherapy, and 78.3% underwent hormonal therapy. Modified radical mastectomy (62.6%) was the most common surgical approach.
3.2. Molecular subtypes and treatment characteristics
The classification of patients by molecular subtype revealed significant differences in clinical and treatment characteristics (Table 2). Luminal B was the most common subtype (67.8%), followed by luminal A (14.8%), HER2-enriched (10.4%), and TNBC (7.0%). Among HER2-enriched patients, stage IIIA was the most frequent stage (66.7%), while TNBC cases were most commonly diagnosed at stage IIB (37.5%). Metastasis at diagnosis was most prevalent in luminal B (26.9%) and least common in HER2-enriched (8.3%). Surgical resection was performed in the majority of cases across all subtypes, including 83.3% of HER2-enriched and 87.5% of TNBC patients. Targeted therapy was most common in HER2-enriched patients (83.3%), compared to other subtypes. Modified radical mastectomy was the predominant surgical method across subtypes, particularly in HER2-enriched (75.0%) and TNBC (75.0%) patients.
Table 2.
Classification of breast cancer patients according to molecular subtypes.
| Characteristic | HER2-enriched (n = 12) | Luminal A (n = 17) | Luminal B (n = 78) | TNBC (n = 8) | P-value |
|---|---|---|---|---|---|
| Sex (%) | .92 | ||||
| Female | 12 (100.0) | 17 (100.0) | 77 (98.7) | 8 (100.0) | |
| Male | 0 (0.0) | 0 (0.0) | 1 (1.3) | 0 (0.0) | |
| Marital status (%) | .2 | ||||
| Married | 11 (91.7) | 17 (100.0) | 67 (85.9) | 5 (62.5) | |
| Single | 1 (8.3) | 0 (0.0) | 3 (3.8) | 1 (12.5) | |
| Unknown | 0 (0.0) | 0 (0.0) | 8 (10.3) | 2 (25.0) | |
| Family history of breast cancer (%) | .75 | ||||
| No | 1 (8.3) | 0 (0.0) | 4 (5.1) | 0 (0.0) | |
| Unknown | 9 (75.0) | 14 (82.4) | 64 (82.1) | 8 (100.0) | |
| Yes | 2 (16.7) | 3 (17.6) | 10 (12.8) | 0 (0.0) | |
| Residence (%) | .32 | ||||
| Albutnan (Tobruk) | 5 (41.7) | 9 (52.9) | 36 (46.2) | 4 (50.0) | |
| Aljabal Alakhdar | 3 (25.0) | 6 (35.3) | 11 (14.1) | 2 (25.0) | |
| Derna | 3 (25.0) | 2 (11.8) | 27 (34.6) | 2 (25.0) | |
| Age at diagnosis (median [IQR]) | 48.50 [41.00, 60.50] | 50.00 [46.00, 53.00] | 44.50 [39.00, 51.00] | 46.50 [44.50, 58.25] | .120 |
| Laterality (%) | .8 | ||||
| Bilateral | 1 (8.3) | 0 (0.0) | 4 (5.1) | 0 (0.0) | |
| Left | 6 (50.0) | 8 (47.1) | 40 (51.3) | 2 (25.0) | |
| Right | 5 (41.7) | 9 (52.9) | 33 (42.3) | 6 (75.0) | |
| Method of diagnosis (%) | .02 | ||||
| FNA | 2 (16.7) | 4 (23.5) | 12 (15.4) | 1 (12.5) | |
| Lumpectomy | 3 (25.0) | 8 (47.1) | 40 (51.3) | 4 (50.0) | |
| Mastectomy | 1 (8.3) | 0 (0.0) | 8 (10.3) | 0 (0.0) | |
| Type of histology (%) | .399 | ||||
| Invasive ductal carcinoma | 12 (100.0) | 16 (94.1) | 69 (88.5) | 6 (75.0) | |
| Medullary carcinoma | 0 (0.0) | 0 (0.0) | 1 (1.3) | 1 (12.5) | |
| Tumor size (%) | .620 | ||||
| T1 | 1 (8.3) | 1 (5.9) | 2 (2.6) | 0 (0.0) | |
| T2 | 5 (41.7) | 10 (58.8) | 39 (50.0) | 1 (12.5) | |
| T3 | 5 (41.7) | 5 (29.4) | 24 (30.8) | 5 (62.5) | |
| Hormone receptor status (%) | <.001 | ||||
| Positive | 0 (0.0) | 17 (100.0) | 78 (100.0) | 0 (0.0) | |
| Negative | 12 (100.0) | 0 (0.0) | 0 (0.0) | 8 (100.0) | |
| HER2 status (%) | <.001 | ||||
| Positive | 12 (100.0) | 0 (0.0) | 17 (21.8) | 0 (0.0) | |
| Negative | 0 (0.0) | 17 (100.0) | 61 (78.2) | 8 (100.0) | |
| Ki-67 (%) | <.001 | ||||
| High | 8 (66.7) | 0 (0.0) | 44 (56.4) | 8 (100.0) | |
| Low | 0 (0.0) | 17 (100.0) | 0 (0.0) | 0 (0.0) | |
| Stage of cancer at diagnosis (%) | .020 | ||||
| Stage I | 1 (8.3) | 0 (0.0) | 1 (1.3) | 0 (0.0) | |
| Stage IIA | 1 (8.3) | 6 (35.3) | 10 (12.8) | 0 (0.0) | |
| Stage IIB | 0 (0.0) | 6 (35.3) | 17 (21.8) | 3 (37.5) | |
| Stage III | 9 (75) | 4 (23.5) | 28 (35.9) | 2 (25) | |
| Stage IV | 1 (8.3) | 1 (5.9) | 19 (24.4) | 2 (25.0) | |
| Unknown | 0 (0.0) | 0 (0.0) | 2 (2.6) | 1 (12.5) | |
| Metastasis at diagnosis (%) | .009* | ||||
| No | 11 (91.7) | 15 (88.2) | 57 (73.1) | 6 (75.0) | |
| Unknown | 0 (0.0) | 0 (0.0) | 0 (0.0) | 1 (12.5) | |
| Yes | 1 (8.3) | 2 (11.8) | 21 (26.9) | 1 (12.5) | |
| Surgical resection of primary tumor (%) | .29 | ||||
| No | 1 (8.3) | 0 (0.0) | 13 (16.7) | 1 (12.5) | |
| Unknown | 1 (8.3) | 0 (0.0) | 1 (1.3) | 0 (0.0) | |
| Yes | 10 (83.3) | 17 (100.0) | 64 (82.1) | 7 (87.5) | |
| Chemotherapy (%) | 0.68 | ||||
| No | 1 (8.3) | 3 (17.6) | 6 (7.7) | 0 (0.0) | |
| Unknown | 0 (0.0) | 0 (0.0) | 3 (3.8) | 0 (0.0) | |
| Yes | 11 (91.7) | 14 (82.4) | 69 (88.5) | 8 (100.0) | |
| Radiotherapy (%) | .38 | ||||
| No | 2 (16.7) | 5 (29.4) | 29 (37.2) | 4 (50.0) | |
| Unknown | 2 (16.7) | 0 (0.0) | 5 (6.4) | 0 (0.0) | |
| Yes | 8 (66.7) | 12 (70.6) | 44 (56.4) | 4 (50.0) | |
| Hormonal therapy (%) | <.001* | ||||
| No | 12 (100.0) | 0 (0.0) | 3 (3.8) | 8 (100.0) | |
| Unknown | 0 (0.0) | 0 (0.0) | 2 (2.6) | 0 (0.0) | |
| Yes | 0 (0.0) | 17 (100.0) | 73 (93.6) | 0 (0.0) | |
| Targeted therapy (%) | <.001* | ||||
| No | 1 (8.3) | 16 (94.1) | 56 (71.8) | 8 (100.0) | |
| Unknown | 1 (8.3) | 0 (0.0) | 2 (2.6) | 0 (0.0) | |
| Yes | 10 (83.3) | 1 (5.9) | 20 (25.6) | 0 (0.0) | |
| Type of surgery (%) | .26 | ||||
| Breast-conserving surgery (BCS) | 1 (8.3) | 3 (17.6) | 18 (23.1) | 1 (12.5) | |
| Modified radical mastectomy (MRM) | 9 (75.0) | 14 (82.4) | 43 (55.1) | 6 (75.0) | |
| No | 2 (16.7) | 0 (0.0) | 17 (21.8) | 1 (12.5) | |
Values are presented as number (%) unless otherwise indicated.
BCS = breast-conserving surgery, FNA = fine needle aspiration, HER2 = human epidermal growth factor receptor 2, IQR = interquartile range, MRM = modified radical mastectctomy, TNBC = triple-negative breast cancer.
P-value < .05 was considered statistically significant.
3.3. Tumor grade and stage distribution across molecular subtypes
The distribution of tumor grades across molecular subtypes is shown in Figure 1. Grade II tumors were the most frequent across all subtypes, particularly among luminal A and luminal B tumors. In contrast, grade III tumors were more commonly observed in HER2-enriched and TNBC subtypes.
Figure 1.
Distribution of tumor grades across molecular subtypes of breast cancer among patients treated at Tobruk Medical Center.
The distribution of cancer stage across molecular subtypes is presented in Figure 2. Early-stage disease (stage I and IIA) was more frequently observed in luminal A tumors, whereas stage III and IV disease predominated in luminal B, HER2-enriched, and TNBC subtypes.
Figure 2.
Distribution of cancer stages at diagnosis across molecular subtypes of breast cancer.
4. Discussion
This study provides a comprehensive overview of the demographic, clinicopathological, and molecular characteristics of BC patients treated at TMC in eastern Libya. The findings reveal a pattern characterized by younger age at diagnosis, predominance of invasive ductal carcinoma, a high proportion of intermediate- to high-grade tumors, and a substantial burden of advanced-stage disease. Collectively, these results highlight ongoing challenges in early detection and timely management of BC in this setting.
The median age at diagnosis in this cohort was 46 years, which is younger than the median age reported in high-income countries, where BC is typically diagnosed after the age of 50.[8] This observation is consistent with reports from Saudi Arabia and Egypt, suggesting a regional trend toward earlier onset of BC in Middle Eastern and North African populations.[9,10] Possible explanations include differences in population age structure, genetic susceptibility, reproductive patterns, and limited implementation of routine screening programs, which may lead to diagnosis only after symptom onset.
Histopathologically, invasive ductal carcinoma was the dominant subtype, accounting for nearly 90% of cases, in line with findings from neighboring countries and global data.[9-11] The predominance of grade II tumors and the high frequency of T2–T3 lesions, together with lymph node involvement in over two-thirds of patients, indicate that many patients present with locally advanced disease. These findings underscore persistent barriers to early diagnosis, including limited access to diagnostic imaging, delays in referral, geographic challenges, and socioeconomic and cultural factors that may discourage early presentation. Similar challenges have been reported across resource-limited settings, emphasizing the importance of resource-stratified approaches to BC care, such as those proposed by the Breast Health Global Initiative.[12]
Regarding molecular subtypes, luminal B was the most prevalent subtype in this cohort, accounting for more than two-thirds of cases. This distribution contrasts with reports from Saudi Arabia and India, where luminal A is more commonly observed,[9,11] but aligns with recent Libyan data identifying luminal B as the dominant subtype.[2,8] The predominance of luminal B tumors is clinically relevant, as this subtype is associated with higher proliferation rates and a less favorable prognosis compared with luminal A. Variations in molecular subtype distribution may reflect differences in tumor biology, environmental exposures, genetic background, or the use of immunohistochemical surrogate definitions rather than gene expression profiling.
TNBC accounted for a small proportion of cases in our cohort (7.0%). This frequency appears lower than that reported in some studies from neighboring countries and other low- and middle-income countrie settings.[11,13] However, the number of TNBC cases in our dataset was limited (n = 8), which reduces the precision of subtype-specific estimates and limits strong conclusions regarding its population-level prevalence. Despite its relatively low proportion in this series, TNBC remains clinically important because it is often associated with aggressive behavior and lacks hormone receptor or HER2 targets, making treatment options more restricted and outcomes potentially poorer.[14]
Hormone receptor positivity was observed in 82.6% of cases, which is higher than the rates reported in Indian (56.4%) and Egyptian (77%) studies.[10,11] This finding suggests that a substantial proportion of Libyan patients may benefit from endocrine therapy, highlighting the importance of reliable hormone receptor testing. HER2 positivity was detected in approximately 1-quarter of cases, and HER2-enriched tumors accounted for 10.4% of the cohort. Although HER2-positive BCs are associated with aggressive disease, the availability of targeted therapies has significantly improved outcomes in recent years, emphasizing the clinical value of accurate HER2 assessment.[15-17]
More than half of the patients in this study were diagnosed at stage III or IV, reflecting a high burden of advanced disease. This proportion exceeds that reported in some neighboring regions, such as Upper Egypt, where earlier-stage diagnoses are more common[18] Similar patterns of late presentation have been reported in other Libyan studies,[2] suggesting systemic challenges related to healthcare access, limited screening infrastructure, and low public awareness. The relatively low proportion of early-stage diagnoses in this cohort reinforces the urgent need for interventions aimed at earlier detection.
Tumor grade and stage varied across molecular subtypes, with higher-grade and more advanced-stage disease observed more frequently in HER2-enriched and TNBC subtypes, while luminal A tumors were more often diagnosed at earlier stages. These findings are consistent with global literature and reflect the distinct biological behavior of BC subtypes and their implications for prognosis and management.[8,19]
Treatment patterns in this cohort were generally consistent with international practice, with high utilization of surgery and systemic therapy.[20] The predominance of modified radical mastectomy reflects the advanced stage at presentation, similar to patterns reported in other resource-limited settings.[11,18] High rates of chemotherapy use further reflect the late-stage and higher-risk disease profile of this population. The use of hormonal and targeted therapies corresponded appropriately with receptor status, underscoring the clinical relevance of molecular classification in guiding treatment decisions.
Overall, these findings highlight the urgent need to strengthen BC control strategies in Libya. Public health interventions should prioritize increasing awareness, reducing diagnostic delays, and improving access to diagnostic and treatment services. Evidence from other countries demonstrates the effectiveness of social media–based awareness campaigns, community education programs, and school-based health education in promoting early detection and timely care.[21,22,23] Adapting such interventions to the Libyan context, alongside the development of resource-stratified screening and diagnostic guidelines, could substantially improve BC outcomes.[24]
5. Limitations
This study has several limitations that should be considered when interpreting the findings. First, the retrospective and single-center design limits the ability to establish causal relationships and may reduce the generalizability of the results to other regions of Libya or to broader populations. Patterns of presentation, diagnosis, and treatment at TMC may not fully reflect practices in other healthcare settings across the country. Second, molecular subtype classification was based on immunohistochemical surrogate markers rather than gene expression profiling. Although immunohistochemistry is widely used in routine clinical practice, this approach may result in misclassification, particularly in differentiating luminal A from luminal B tumors, and may not fully capture the underlying biological heterogeneity of BC.
Third, several variables had substantial missing data, most notably family history of BC. Missing data were not imputed, and analyses were performed using complete-case approaches, which may introduce bias and limit the interpretation of associations involving these variables. Fourth, treatment-related data were collected retrospectively from medical records and may not fully reflect treatment adherence, completion, dose intensity, or variations in treatment timing. Additionally, access to certain therapies, particularly targeted treatments, may have varied over time due to resource constraints.
Fifth, the study period (2019–2020) predates recent developments in BC diagnosis and treatment. Although no major changes in immunohistochemical testing protocols were implemented at the study center during or immediately after this period, evolving diagnostic capabilities, treatment availability, and healthcare delivery systems may limit the direct applicability of these findings to current clinical practice. Finally, the relatively small sample size, particularly for certain molecular subtypes such as TNBC, limits statistical power and requires that subgroup analyses be interpreted with caution. Larger, multicenter, and prospective studies incorporating molecular profiling and survival outcomes are needed to validate and extend these findings.
6. Conclusion
This study describes the clinical and molecular characteristics of BC among women treated at a tertiary center in eastern Libya, demonstrating a predominance of luminal B tumors and a high proportion of advanced-stage disease at diagnosis. These findings reflect persistent challenges related to delayed presentation, limited access to healthcare services, and the absence of organized screening programs. The high prevalence of hormone receptor–positive and HER2-positive tumors indicates that a substantial proportion of patients may benefit from endocrine and targeted therapies when these treatments are accessible. Strengthening public awareness, improving early detection strategies, and implementing resource-stratified screening and diagnostic approaches are essential to reducing late-stage presentation and improving outcomes. Overall, this study provides region-specific evidence that may support the development of targeted BC control strategies in Libya.
Acknowledgments
We thank the reviewer for the constructive feedback, which helped us further improve the clarity and originality of the manuscript.
Author contributions
Conceptualization: Zinelabedin Mohamed.
Data curation: Zinelabedin Mohamed.
Software: Zinelabedin Mohamed, Mohamed Baklola.
Supervision: Alqasim Abdulkarim, Ahmed R. Abdullah, Mohammed Al-Azab, Mohamed Baklola.
Validation: Alqasim Abdulkarim, Ahmed R. Abdullah, Mohammed Al-Azab, Mohamed Baklola.
Visualization: Mohamed Baklola.
Writing – original draft: Zinelabedin Mohamed, Alqasim Abdulkarim, Ahmed R. Abdullah, Mohammed Al-Azab, Mohamed Baklola.
Writing – review & editing: Zinelabedin Mohamed, Alqasim Abdulkarim, Ahmed R. Abdullah, Mohammed Al-Azab, Mohamed Baklola.
Abbreviations:
- BC
- breast cancer
- ER
- estrogen receptor
- HER2
- human epidermal growth factor receptor 2
- IHC
- immunohistochemistry
- PR
- progesterone receptor
- TMC
- Tobruk Medical Center
- TNBC
- triple-negative breast cancer
This study was approved by the Research Ethics Committee of Tobruk University (approval ID: 009.H.25.2). As this study is retrospective in nature, the need for informed consent was waived by the Institutional Review Board (IRB) in accordance with relevant guidelines and regulations. The study was conducted in compliance with the Declaration of Helsinki and ensured the confidentiality and anonymity of patient data.
The authors have no funding and conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
How to cite this article: Mohamed Z, Abdulkarim A, Abdullah AR, Al-Azab M, Baklola M. Molecular subtypes of breast cancer in Libyan women and their clinicopathological associations: A retrospective observational study from eastern Libya. Medicine 2026;105:13(e48215).
Contributor Information
Zinelabedin Mohamed, Email: Zen_Zen47@yahoo.com.
Alqasim Abdulkarim, Email: gasim1988@gmail.com.
Ahmed R. Abdullah, Email: ahmed.hamouda@azhar.edu.eg.
Mohamed Baklola, Email: Mohamedbaklola2000@gmail.com.
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