Prognostic Implications of MALAT1 and BACH1 Expression and Their Correlation with CTCs and Mo-MDSCs in Triple Negative Breast Cancer and Surgical Management Options

Abstract

Background. Triple negative breast cancer (TNBC) is a biologically separate entity of breast cancer that cannot get benefits from targeted or endocrine therapy. Objective. To assess the expression of MALAT1 and BACH1, as well as monocyte-myeloid-derived suppressor cell (Mo-MDSC) levels and circulating tumor cell (CTC) count in TNBC to correlate these markers with the clinic-pathological criteria of TNCB patients and to evaluate their roles as predictive markers for selection of the patients that can be operated by oncoplastic conserving breast surgery. Methods. Eighty-eight TNBC were managed by modified doughnut breast oncoplastic surgery in early stages and by modified radical mastectomy for patients with late stages unsuitable for breast-conserving. All were examined for MALAT1 and BACH1 expression by immunohistochemistry and RT-PCR as well as Mo-MDSC levels and CTCs. Results. MALAT1 and BACH1 expressions are correlated with the larger size, lymph node, distance metastasis, and TNM staging ( p < 0.05 ). CTCs ≥ 5 and high MO-MDSCs were significantly more in TNBC with MALAT1 and BACH1 overexpression. The survival study proved that DFS for patients with both positive expression of MALAT1 and BACH1 was shorter than that of one positive expression, and both negative expression p ≤ 0.001 , CTCs ≥ 5 , and high Mo-MDSCs are associated with poor outcomes. No significant difference between modified round block and modified radical mastectomy techniques as regards recurrence. However, all postoperative management outcomes were significantly better in patients operated by oncoplastic conserving breast surgery. Conclusion. BACH1 and MALAT1 expressions are significantly upregulated in TNBC. They are correlated with CTCs and Mo-MDCs, and all are associated with poor outcomes. Not all TNBC patients have a bad prognosis, patients negative for one of MALAT1 and BACH1 or both, have a slightly good prognosis, and so can be managed by breast oncoplastic conserving surgery.

Obesity correlates with the immunosuppressive ILC2s‐MDSCs axis in advanced breast cancer

“…MDSCs are related to the poor prognosis of breast cancer. 23 Bergenfelz et al 24 found that compared with the healthy control group, the level of MDSCs in the peripheral blood of patients with advanced breast cancer was significantly higher. Patients with high levels of MDSCs had a higher proportion of liver metastases, bone metastases, and multiple metastases.…”

“…MDSCs are related to the poor prognosis of breast cancer 23 . Bergenfelz et al 24 found that compared with the healthy control group, the level of MDSCs in the peripheral blood of patients with advanced breast cancer was significantly higher.…”

Circulating tumor cell-blood cell crosstalk: Biology and clinical relevance

“…MDSCs interact with other immune cells, including NK cells and T lymphocytes, to regulate their function, although their mechanisms of action have not been elucidated yet (Tumino et al, 2022). In cancer patients, the amount of MDSCs found in circulation are highly increased and it has been associated with an increased number of CTCs (Elbasateeny et al, 2022;Papadaki et al, 2021). Furthermore, Sprouse et al (2019) identified CTC-MDSC clusters in patient blood and further in vitro analyses demonstrated that CTC-MDSC clusters induced a pro-tumorigenic differentiation of MDSCs resulting in a pro-survival CTC activation via ROS and the Notch signaling pathway.…”

The impact of breast‐conserving surgery and modified radical mastectomy on postoperative wound complications in patients with early breast cancer

“…4 The postoperative recurrence rate of breast cancer patients has reached about 50%, and about 60% of patients survive 5 years. 5 Radical mastectomy is one of the important means of treating breast cancer. 6 MRM is an improved form of radical mastectomy, which aims to preserve the pectoralis major muscle and pectoralis minor muscle as much as possible, while removing axillary lymph nodes.…”

“…Due to the improvement in the diagnosis level of breast cancer in women in recent years and the popularization of related prevention and treatment knowledge, the early detection rate of breast cancer has been greatly improved 4 . The postoperative recurrence rate of breast cancer patients has reached about 50%, and about 60% of patients survive 5 years 5 …”