**10. Discussion**

A group of patients without the expression of any of the receptors qualifying for hormone therapy or targeted therapy against HER2 constitutes an important clinical problem in breast cancer treatment. Therefore, it seems important to undertake studies aimed at determining histopathological and immunohistochemical characteristics of this invasive group of triplenegative breast cancer (TNBC). Triple-negative breast cancer is most commonly found in patients less than 50 years of age [49, 50]. Our study also found that TNBC is most common among women before 50 years of age (mean age 47.8).

In our study, histopathological subtyping of 111 patients with identified TNBC yielded the following results: 89.1% of IDC-NST and 10.9% of other special types of cancers. Infiltrating ductal carcinoma of no special type (IDC-NST) was the predominant histopathological type. Similar results were obtained by other researchers, e.g., Nofech-Mozes et al. [51], Williams et al. [52], Atik et al. [53], Rao et al. [54], Osman et al. [55], Sood et al. [56] and Tawfik et al. [57] (92%, 91%, 27%, 88%, 85.7%, 80.56% and 81.9%), who found that IDC-NST is the dominant histological type in a group of triple-negative breast cancers. Given the histological grade of malignancy, the largest group of triple-negative breast cancers encompassed tumors given G2 and G3 grade. Statistical analysis showed no significant correlation between histological grade (G1–G3) and triple-negative tumor morphology (*p* > 0.05). The following authors obtained similar results: Atik et al. [53] assessing 75% of cancers in TNBC group as G3, Carey et al. [58], who found that in the TNBC group most cases are G3 cancers (26%). In a study on 16 cases of TNBC, Dabbs et al. [59] found that all tested tumors showed high degree of histological malignancy. Choi et al. [60] obtained similar results, stating that in a group of triple-negative cancers 63.1% were G3 tumors. Research by Zhou et al. [61] also showed that triple-negative G2 (51.6%) and G3 (45.2%) cancers were most numerous. Osman et al. [55] confirmed in their study that G3 carcinomas (61.9%) comprised the largest group of triple-negative tumors, while Sood et al. [56] pointed to G2 (47.22%) and G3 (38.89%) as most common tumors.

There are conflicting reports on the prevalence of lymph node metastases at the time of diagnosis among patients with TNBC. In our study we found that women without metastases to regional lymph nodes (pN0) comprised the largest group of all investigated patients with invasive triple-negative breast cancer (56.7%); no statistically significant relationship between lymph node status and histological type of TNBC-IC (*p* > 0.05) was noted. Lymph node status among patients with TNBC was reported as follows: 19.81%—N1, 19.81%— N2, 3.6%—N3. The study also showed no association between tumor size and presence of lymph node metastasis in patients with TNBC, which stood in contradiction to the findings of Thike et al. [62] who had demonstrated a relationship between tumor size and presence of nodal metastases. In studies by Rao et al. [54] lymph node metastases were found in 37 of 50 patients with TNBC (74% of cases), and TNBC was associated with higher rates of node-positive cases, which was in agreement with the findings of Carey Rakha et al. [58] and Rakha et al. [63].

In our study 30.9% of all tumors showed central necrosis. In TNBC more commonly than in non-TNBC the presence of necrosis was observed (36%; 19.6%). Yehia et al. [64] in their study divided breast cancers into three subgroups (TNBC, HER2+ and ER+/PR+). 15.3% of all tumors showed central fibrosis and tumor necrosis, which differed significantly among the three groups (*p* = 0.019). TNBC had the highest values among all groups even after adjusting the results for age. Respectively necrosis was observed in 25.8% TNBC, 9.4% HER2+ and 10.9% ER+/PR+ of cancers [64]. 62 TNBC, 64 HER2+, and 64 hormone-receptors positive breast cancers were evaluated also for HIF-1α expression. HIF-1α was expressed in 35.5% TNBC, 45.3% HER2+ and 25.0% ER+/PR+ (*p* = 0.055). In our study HIF-1α expression was observed in 43.2% TNBC and 35.3% non-TNBC.

**10. Discussion**

92 Breast Cancer and Surgery

HIF-1α (\*statistically significant result *p* < 0.05).

among women before 50 years of age (mean age 47.8).

**Clinicopathological features of TNBC HIF-1 α expression**

Histological grade G1 0 3 0.134

Tumor stage pT1 16 22 0.021\*

Nodal stage pN1 30 20 0.821

**Negative (<10%)**

G2 35 23 G3 28 22

pT2 46 23 pT3 1 2 pT4 0 1

pN2 25 21 pN3 8 7

**Positive (>10%)**

**p-value**

A group of patients without the expression of any of the receptors qualifying for hormone therapy or targeted therapy against HER2 constitutes an important clinical problem in breast cancer treatment. Therefore, it seems important to undertake studies aimed at determining histopathological and immunohistochemical characteristics of this invasive group of triplenegative breast cancer (TNBC). Triple-negative breast cancer is most commonly found in patients less than 50 years of age [49, 50]. Our study also found that TNBC is most common

**Table 3.** Clinicopathological features of TNBC and their relationship to expression of novel breast cancer marker -

In our study, histopathological subtyping of 111 patients with identified TNBC yielded the following results: 89.1% of IDC-NST and 10.9% of other special types of cancers. Infiltrating ductal carcinoma of no special type (IDC-NST) was the predominant histopathological type. Similar results were obtained by other researchers, e.g., Nofech-Mozes et al. [51], Williams et al. [52], Atik et al. [53], Rao et al. [54], Osman et al. [55], Sood et al. [56] and Tawfik et al. [57] (92%, 91%, 27%, 88%, 85.7%, 80.56% and 81.9%), who found that IDC-NST is the dominant histological type in a group of triple-negative breast cancers. Given the histological grade of malignancy, the largest group of triple-negative breast cancers encompassed tumors given G2 and G3 grade. Statistical analysis showed no significant correlation between histological grade (G1–G3) and triple-negative tumor morphology (*p* > 0.05). The following authors obtained similar results: Atik et al. [53] assessing 75% of cancers in TNBC group as G3, Carey et al. [58], who found that in the TNBC group most cases are G3 cancers (26%). In a study on 16 cases Due to the fact that TNBC subtype frequently show morphologic evidence of hypoxia (central fibrosis and necrosis) [40, 41] an augmented expression of HIF-1α in tumors with a triplenegative phenotype was anticipated. In fact, this had been elegantly demonstrated through the preferential expression of HIF-1α in peri-necrotic tumor cells in TNBC and BRCA1 mutated breast cancers [42].

HIF-1α overexpression is an indicator of poor prognosis and significant survival time reduction in patients suffering from breast cancer [45]. HIF-1 upregulates transcription of angiogenic genes like EPO and vascular endothelial growth factor (VEGF), which induce sprouting of new vessels and in result they increase the risk of metastasis because they boost surface of contact between tumor cells and vasculature. HIF-1 induces transcription of cytoprotective proteins in malignant cells in hypoxic conditions. HIF-1α predicts poor prognosis breast cancer [46, 47].
