Best Chemo For Triple Negative Breast Cancer

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Best Chemo For Triple Negative Breast Cancer

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Ethnic Disparities In The Immune Microenvironment Of Triple Negative Breast Cancer And Its Role In Therapeutic Outcomes

Department of Pharmacy, Jiangsu Cancer Hospital (Jiangsu Cancer Research Institute, Nanjing Medical University Cancer Hospital), Nanjing 210009, China

Received: 24 July 2022 / Revised: 7 October 2022 / Accepted: 10 October 2022 / Published: 12 October 2022

Triple negative breast cancer (TNBC) is characterized by high invasiveness, high metastasis and poor prognosis. More than a third of patients with TNBC have relapse or distant metastasis. Anthracycline- and taxane-based chemotherapy is the standard treatment strategy for metastatic TNBC (mTNBC). Due to the lack of expression of progesterone receptor, estrogen receptor, and human epidermal growth factor receptor 2, therapies targeting these receptors are not effective for mTNBC, thus requiring strategies to specific treatment. In recent years, the development of new chemotherapy drugs, targeted drugs, and immunotherapy drugs offers promising prospects for the treatment of mTNBC. However, as these drugs are still in development, a number of issues related to optimizing and managing the clinical use of these new options need to be addressed. Pharmacists can play an important role in drug selection, drug therapy management, adverse drug reaction management, and pharmacoeconomic evaluation. In this review, we summarize traditional treatment strategies and discuss the efficacy and safety of new agents and combination regimens for mTNBC approved in the last decade to provide management strategies for the clinical management of mTNBC from the perspective of pharmaceuticals

Chemoimmunotherapy: Still The Standard Of Care For Metastatic Triple Negative Breast Cancer

Triple-negative breast cancer (TNBC) is a particularly aggressive type of breast cancer characterized by estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor 2 (HER2) deficiency [1] . TNBC accounts for approximately 15% to 20% of all breast cancers and has a higher recurrence rate, higher metastatic potential, poorer prognosis, and poorer survival than other breast cancer subtypes. More than one-third of patients with TNBC may show distant metastases, including visceral and brain metastases, within the third year after diagnosis. In metastatic TNBC (mTNBC), the median overall survival (OS) is only 12 to 18 months [4]. Chemotherapy has been the only systemic treatment for mTNBC for many years, and standard chemotherapy regimens are usually based on anthracyclines or taxanes as first-line treatment.

Chemotherapy drugs kill tumor cells directly or inhibit the growth and reproduction of tumor cells. However, in addition to attacking tumor cells, they also affect normal cells in the body and cause serious systemic toxic side effects. This condition limits the use of chemotherapeutic drugs. Tumor heterogeneity, genetic diversity, and chemoresistance also contribute to poor response. Due to the absence of ER, PR and HER2, TNBC is insensitive to endocrine therapy and HER2-targeted therapy [4]. Thus, the treatment of mTNBC is limited by the lack of curative therapy, especially for patients who have failed anthracycline and taxane therapy. With the development of high-throughput sequencing technology, the heterogeneity and complexity of TNBC is better understood [5]. A number of new targets have been developed that may offer promising prospects for the treatment of mTNBC. These new mechanisms include antibodies to trophoblast cell surface antigen 2 (Trop-2), which disrupt the three-dimensional structure of double-stranded DNA and inhibit DNA damage repair, direct the phosphoinositide-3 kinase (PI3K) pathway and inhibit binding. from tumor cells to T cells, cell cycle regulators, etc. (Figure 1).

New chemotherapy agents, such as epothilone analogs, antibody drug conjugates (ADCs), poly (ADP-ribose) polymerase (PARP) inhibitors, programmed cell death, agents targeted and immunotherapy agents are effective for the treatment of mTNBC. 1 ligand 1 (PD-L1)/inhibitors of programmed cell death 1 (PD-1), PI3K inhibitors and androgen receptor antagonists. Agents approved for the treatment of mTNBC are shown in Figure 2 [6, 7]. A detailed analysis of therapeutic trends, biomarkers predicting efficacy of promising targets and therapeutic strategies in mTNBC, as well as experimental compounds currently effective in clinical trials are discussed in detail in other reviews [8, 9]. In addition, Lu et al. mBC has completed important clinical trials in metastatic breast cancer that have established the current standard of care for mBC to guide personalized treatment for mBC [10]. However, in clinical practice, a number of issues related to the optimization and management of the clinical use of these new options should be considered in order to improve the safety and efficacy of the treatment and the patients’ quality of life. The role of pharmacists in the clinical use of new drugs is shown in Figure 3. In this review, we have summarized traditional treatment strategies and potential combination therapy strategies from the perspective of pharmacists, aimed at the clinical management of new drugs approved for mTNBC, providing useful information on the efficacy and safety of the drugs and their clinical use. Details of the literature search strategies are described in the Supplementary Materials.

New Treatments Bring Hope For Those With Triple Negative Breast Cancer

Systemic cytotoxic chemotherapy is the mainstay of therapy in patients with mTNBC, and the best response to chemotherapy is first-line. Combination chemotherapy regimens based on anthracyclines and taxanes are preferred. Compared with monotherapy, combination chemotherapy regimens such as anthracycline, cyclophosphamide, and taxane in combination with platinum generally have better objective response rate (ORR) and progression-free survival (PFS) for patients with higher disease burden . However, they are more toxic and have a negative impact on the patient’s quality of life [11]. Cardiotoxicity is the most serious adverse reaction of anthracyclines and limits their use. Other cytotoxic drugs are available for further treatment, such as capecitabine, gemcitabine, and cisplatin, as monotherapy or combination regimens when chemotherapy is continued or when patients are intolerant to anthracyclines or taxanes. Understanding the treatment goal, prior chemotherapy regimen, disease burden, patient preference, and dose are important in selecting the appropriate treatment strategy for each patient [12].

In recent years, many studies have shown that platinum-based chemotherapy regimens can play an important role in mTNBC chemotherapy as first-line or subsequent treatment [ 13 , 14 ], but it causes worse hematological toxicity [ 15 ]. For example, the combination of cisplatin and docetaxel has been found to be superior to the capecitabine plus docetaxel regimen as first-line treatment for mTNBC with improved OS [16], and cisplatin combined with gemcitabine may be more effective than paclitaxel and gemcitabine. to be an alternative or even preferred first-line chemotherapy strategy for mTNBC patients [ 17 , 18 ]. However, the combination of platinum and the PARP inhibitor veliparib also significantly improved PFS and showed a trend toward improved OS in mTNBC patients [ 19 ]. It should be noted that in clinical practice, the risk of adverse reactions, especially hematological toxicity, may increase. In addition, effective screening of molecular markers for certain populations that may benefit from platinum-based chemotherapy regimens may be a means of improving efficacy and is the focus of current research.

In preclinical studies, epothilone analogs have been shown to have potent cytotoxic activity against multidrug-resistant cells [ 20 ]. They stimulate the polymerization of tubulin, stabilize the microtubule structure and induce cell apoptosis. Ixabepilone is the first epothilone analog approved for the treatment of mBC [21] alone or in combination with capecitabine. However, ixabepilone is expensive and discontinuation due to hematological toxicity and liver toxicity is common [22]. A new drug with promising results, utidelone, is approved in China for the second-line and advanced treatment of mBC in combination with capecitabine. Several clinical trials have shown that both are similar

Pembrolizumab Plus Chemotherapy In Advanced Triple Negative Breast Cancer

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