Management of the Triple Negative Locally Advanced Breast Cancer

*Amir Iqbal Memon, Ikram Din Ujjan and Aisha Masroor Bhatti*

#### **Abstract**

One out of eight women is suffering from the breast cancer. 2.3 million New cases is predicted by 2023 worldwide. Triple negative breast cancer (TNBC) is having 10–15% incidence. As categorized with the lack of estrogen, progesterone and human epidermal growth factor receptor 2 neu receptor expression. Though it presents with narrow management opportunities that makes it to be the poor prognostic as well as survival rate. The management of the TNBC includes: neoadjuvant treatment then surgery and the adjuvant treatment or the surgery as the first step and then the adjuvant treatment options accordingly. The discussion are still going on to set a management protocol for the triple negative breast cancers with positive outcome and the good disease free survival. Neoadjuvant or adjuvant chemotherapy decreases the estradiol levels and thus improves the survival. The immune check points and immune modulators are under the research and the trials are still going on to treat the TNBC with the improved outcomes. It has been concluded that the management of the TNBC, still wanting the guidelines as tumor-specific targeted therapies is in trials.

**Keywords:** triple negative breast cancer (TNBC), locally advanced breast cancer (LABC), modified radical mastectomy (MRM), chemotherapy and immunotherapy

#### **1. Introduction**

Breast cancer is the leading cancer globally [1] and when it presents as TNBC, it carries the worst prognosis [2]. As the commonly diagnosed malignancy with the second cause of mortality among women with cancer [3]. Incidence of the breast cancer has been increasing from the western word to the east. It has increased the mental burden to the patients and the families of the affected individual's younger women.

TNBC is described as the lack of the hormone receptor status. As estradiol heights among TNBC patients were considered as favorable outcome [4]. Fortunately the incidence of TNBC is only 15–20% of invasive breast cancers [5], its hostile behavior, comprising prior recurrence with high proliferation and metastasis [6, 7]. International Breast Cancer Conference delivered a novel description of breast cancer molecular subtypes that are: luminal A (ER/PR+ , HER2− , Ki67+ < 20%), luminal B (ER/PR+ < 20%, HER2− , Ki67+ ≥ 20%); HER2+ B2 (ER/PR<sup>+</sup> , HER2 overexpression), HER2 overexpression (ER<sup>−</sup> , PR− , HER2+ ) and basal-like TNBC (triple negative) [1]. TNBC is so hostile that it leads to poor survival of the diagnosed cases and makes it

shorter. As the short disease free survival with the death ratio in the initial years of identification. Half of the TNBC patients usually presents with the metastatic disease.

Though molecular phenotype, of the TNBC presents without the receptors expression, proving it most difficult to manage. To control the local disease we have surgical options like modified radical mastectomy (MRM) and lumpectomy or wide local excision (WLE) in breast conserving surgery (BCS) and for the systemic disease add neo-adjuvant or adjuvant chemotherapy. As chemotherapy to these patients can be an option to regress the tumor size and the stage and make it an operable in case of locally advanced disease stage and make the survival considerably good [8].

TNBC has narrow management opportunities that makes it vulnerable. While it is usually known that TNBC that diagnosed timely in its initial stages is responding well to the chemotherapy instead of indistinct management plan. Specifically the inoperable and locally advanced TNBC has a good outcome with the Neoadjuvant therapy.

The residual TNBC lesions ultimately prone to the relapse of the disease. The metastatic disease will get benefit from the neoadjuvant course with platinum-based therapy, combination therapy of paclitaxel per week as adjuvant course will be used [9].

TNBC patients recently receiving FDA-approved regimen of chemotherapy plus immunotherapy [10]. TNBC has the specific features that leads it towards the immunotherapy [11]. As the TNBC tumor has additional tumor-infiltrating lymphocytes (TILs), which correlate to the improved responses to immune check point inhibitors (ICIs), and the high levels of tumor-infiltrating lymphocytes in TNBC proves with better-quality prognosis in initial phase of the TNBC. TNBC also has better PD-L1 expression and making it more useful for the future targeted therapies for ICIs and anti–PD-1 therapies. TNBC has an overexpression of no synonymous mutations, that provide tumor-specific neoantigens for specific T cells to support the targeted behavior towards the tumor reinforced by ICIs [6]. The trials of the immunotherapy with or without the chemotherapy is ongoing to conclude the treatment regimen for the TNBC patients. The blend of ICIs and chemotherapeutic agents has also established the primarily control towards the TNBC. Metastatic progress is more in the favor of liver, chest and brain [12].

Metastatic TNBC has an effect by the Platinum compounds that work by DNA crosslinking and are of better efficiency towards the gBRCA1/2 transformation carriers, while combination therapy with PARP inhibition with veliparib provides the better-quality survival as well [13].
