Triple-negative breast cancer (TNBC) is a distinct molecular subtype, representing 10% to 15% of all breast cancers [1]. Its particular biological profile, characterized by the absence of hormone receptor expression and HER2 overexpression, confers aggressive clinical behavior and a generally less favorable prognosis than other subtypes [2]. TNBC is distinguished by a high risk of early relapse, with a peak recurrence within the first 3 years after diagnosis, and a preferential metastatic tropism towards viscera and the central nervous system [3].

Despite recent therapeutic advances, notably the advent of immunotherapy and antibody-drug conjugates, conventional chemotherapy remains the cornerstone of treatment in many clinical contexts, particularly in resource-limited countries [4]. Pathological complete response (pCR) after neoadjuvant chemotherapy has emerged as a major prognostic factor, with crucial implications for relapse-free survival [5]. However, not all TNBCs respond equally to treatment, and identifying predictors of relapse remains an essential clinical challenge.

Several clinical, pathological, and biological parameters have been proposed as potential prognostic markers. Tumor-infiltrating lymphocytes (TILs) have emerged as a promising biomarker, reflecting the interaction between the immune system and the tumor [6]. Similarly, the Ki-67 proliferation index, nodal status, and stage at diagnosis continue to provide valuable prognostic information [7]. More recently, the recognition of the HER2-low subgroup has introduced a new dimension in TNBC classification, with potential therapeutic implications [8].

In this context, we present the results of a retrospective study conducted at the medical oncology department of Hassan II University Hospital in Fez, aiming to identify predictive factors for relapse in a cohort of 130 patients with localized TNBC. Our work is part of ongoing research to optimize risk stratification and personalize therapeutic strategies for this complex clinical entity.

We conducted a single-center retrospective study including 130 patients with localized triple-negative breast cancer treated at the Department of Medical Oncology, CHU Hassan II in Fez between January 2016 and December 2021. Inclusion criteria were: age ≥ 18 years, histologically confirmed diagnosis of localized TNBC, and eligibility for curative treatment with a minimum follow-up of 3 years.

Data were collected from medical records using a standardized collection form and analyzed using Excel software. The studied parameters included: age, menopausal status, TNM stage, lymph node status, Ki-67 proliferation index, tumor-infiltrating lymphocytes (TILs) level, HER2-low status, and pathological complete response (pCR) after neoadjuvant chemotherapy. Statistical analyses used Chi-square test or Fisher’s exact test for qualitative variables, with a significance threshold set at p < 0.05.

HER2-low status: Was defined as a HER2 immunohistochemistry (IHC) score of 1+, or 2+ with a negative in-situ hybridization (FISH/SISH) test, in accordance with the ASCO/CAP guidelines and recent clinical trial criteria [8].

TILs: Stromal TILs were evaluated on standard hematoxylin and eosin (H&E)-stained tumor sections from diagnostic biopsies, the percentage of stromal area occupied by mononuclear inflammatory cells (lymphocytes and plasma cells) was quantified. For the purpose of statistical analysis, TILs levels were categorized as “low” (<50%) or “high” (≥50%). This cut-off is supported by literature linking high stromal TILs to improved outcomes in TNBC.

Ki-67proliferation index: Based on the distribution within our cohort and literature thresholds indicating very high proliferative activity, we used a cut-off of >80% to define the “high Ki-67” group.

pCR: Was defined as the absence of residual invasive carcinoma in both the breast and axillary lymph nodes (ypT0/Tis ypN0) following neoadjuvant chemotherapy.

Our study included 130 patients with localized triple-negative breast cancer. The median age was 49 years [range: 29 - 88 years], with 47.5% of patients being postmenopausal. The overall 3-year relapse rate was 23%.

The majority of patients (85%) had a good general status (OMS 1). Stage distribution showed a predominance of advanced stages: stage I (17%), stage II (40%), and stage III (43%). Regarding treatment, 84.6% of patients received neoadjuvant chemotherapy, with a pathological complete response (pCR) rate of 25.45%.

Histopathological analysis showed that 38% of tumors had a Ki67 > 80%, 11.5% had HER2-low status, and 32% had a TILs level ≥ 50%.

Univariate analysis identified several factors significantly associated with relapse: lymph node involvement (p = 0.000271), advanced stage (p = 0.003), Ki67 > 80% (p < 0.001), absence of pCR (p < 0.001), and low TILs level (p = 0.012). In contrast, HER2-low status (p = 0.45), age (p = 0.32), and menopausal status (p = 0.28) were not associated with relapse risk.

Multivariate analysis confirmed as independent poor prognostic factors the absence of pCR (HR = 4.2; 95% CI 2.8 - 6.3), lymph node involvement (HR = 3.1; 95% CI 1.9 - 5.0), and high Ki67 (HR = 2.8; 95% CI 1.7 - 4.5). The 3-year overall survival was 78%, reaching 100% in patients with pCR versus 68% in its absence (p < 0.001), and was significantly better in cases of high TILs (89% vs 72%, p = 0.015).

Among the patients who experienced a relapse (n = 28), 75% (n = 21) presented with multisite metastases. The most frequent sites of metastasis were the liver (43% of relapsed patients), the brain (27%), and bones (23%).

Our single-center retrospective study, including 130 patients with localized triple-negative breast cancer (TNBC) treated between 2016 and 2021, provides valuable insight into prognostic factors in a “real-world” clinical practice setting in Morocco. The overall 3-year relapse rate of 23% in our cohort is at the lower end of the range reported in the literature, typically between 25% and 35% for this particularly aggressive histological subtype [3]. This relative underestimation could be explained by the specific characteristics of our population and the rigorous follow-up ensured in our center.

The limitations of our study include its retrospective design, its single-center nature, and the modest size of some subgroups. The evaluation of TILs in routine practice, without centralized review, also constitutes a limitation. These elements must be considered when interpreting our results.

In conclusion, our study conducted in real-world practice confirms the prognostic value of response to chemotherapy, nodal status, proliferation index, and TILs in localized TNBC. It contributes to the characterization of the HER2-low subgroup and documents for the first time in detail the particularities of TNBC in a Moroccan population. The integration of these parameters into a personalized approach should improve risk stratification and optimize the management of these patients in our regional context.