Rapid Extensive Recurrence of Triple Negative Breast Cancer: Are Both Therapy and Cancer Biology the Culprit?

Abstract

Triple negative breast cancer (TNBC) comprises 17-20% of all breast cancers and is one of the most common breast cancers. The lack of therapy and failure of existing therapy has been a challenge for clinicians. Doxorubicin (DOX) is the first-line therapy, however, it has significant limitations. Rapid extensive recurrence with metastasis in any cancer has been a challenge for surgeons and medical oncologists. The challenge can be due to failure of therapy, drug resistance, or epigenetic changes. Here, we are discussing a stage I breast cancer patient, operated and treated with appropriate chemotherapy with complete response, which recurred in less than 8 months and metastasized to bone, liver and other organs. We are also presenting lab data of the IL-6 secretions on exposure to DOX in one of the most commonly used TNBC cell lines MDA-MB-231. Breast cancer cell line MDA-MB-231 upon exposure to DOX shows an increase in IL-6 levels more than the already elevated IL-6 levels. This might be a reason for early recurrence. We concluded that patients with TNBC might benefit from a standard DOX treatment regimen with an inflammation-blocking agent.

Identification of Specific miRNA Signature in Paired Sera and Tissue Samples of Indian Women with Triple Negative Breast Cancer

“…Of several subtypes of breast cancer, the most aggressive form is characterised by absence of estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth receptor 2 (HER2) and designated as triple negative breast cancer (TNBC) [ 3 ]. The drug resistance and recurrence rate of TNBCs is very high and it accounts for 10–24% of all breast cancers [ 4 – 6 ]. Most alarmingly and unlike in US and Europe, TNBC is highly prevalent in Indian women at premenopausal stage (<35 year) when they are in the prime time of their reproductive life.…”

Prevention and treatment of anthracycline-induced cardiotoxicity: A bibliometric analysis of the years 2000–2023

“… Inflammation: Cardiotoxicity caused by DOX involves many factors, and the activation of pro-inflammatory mediators is one of the mechanisms leading to cardiomyocyte injury [ 34 ]. Studies have shown that the levels of inflammatory factors such as tumor necrosis factor-alpha (TNF-α), interleukin-1beta (IL-1β) and interleukin-6 (IL-6) in DOX-administered rats were significantly increased [ [35] , [36] , [37] ]. DOX exposure stimulates the release of ROS and increases oxidative stress, thereby enhancing the expression of NF-κB in myocardial tissue, initiating an inflammatory cascade, and promoting the release of TNF-α and IL's [ 38 , 39 ].…”

Alamandine significantly reduces doxorubicin-induced cardiotoxicity in rats

“…11 Several studies have shown that DOX therapy increases inflammation and IL-6 levels. 12,13 Evidence indicates that the extrinsic and intrinsic pathways of apoptosis are associated with DOXinduced cardiotoxicity. Caspase-3 plays a central role in the execution of apoptosis.…”