Dr. Weeks’ Comment: Triple negative breast cancer (TNBC) strikes fear in hearts of ladies worldwide because it implies that 3 commonly available targets for chemotherapy drugs (estrogen receptors, progesterone receptors and Her2Nu receptors) are not available to help fight their cancer. The conclusion is that therapy is more limited and therefore the prognosis is more guarded if you are “triple negative”. Accordingly, much research is focused on TNBC in hopes of being helpful to these ladies. The research that follows (see below) describes the utility of our old friend Metformin/Glucophage, the cheap safe and effective off-patent blood sugar lowering agent which I have encouraged all my patients who are dealing with cancer to use for the past 3 years. If you know a person dealing with cancer who is NOT on Metformin, please search this website for the term “metformin” and share those articles with the relevant oncologist.
As for treatment options for TNBC, research on a fermented soy extract Haelan 951, suggests that by increasing adiol which stimulates the critical estrogen receptor Beta (a beneficial anti-cancer hormone receptor) while reducing estrogen receptor alpha (the carcinogenic). As regards the tyrosine kinase human epidermal growth factor receptor 2 (HER-2), a dangerous gene expression, Haelan 951 helps repair the DNA which is involved in cell differential and also reduces inflammatory cytokines thereby reducing angiogenesis. Haelan 951 also increases the function of the P53 tumor suppressor gene which should mix with the cancer DNA and produce tumor suppressor P21 which serves to either repair the DNA allowing for healthy cell differentiation or it terminates the cancer cell (apoptosis) – both beneficial outcomes.
“….Trials that incorporate agents such as metformin or leptin antagonists as well as other therapies that modify the insulin-leptin-adiponectin axis may prove very beneficial for prevention and treatment of TNBC…”
Thanks to Mark and Beth for sharing this article with me!
Metabolic Syndrome and Triple-Negative Breast Cancer: A New Paradigm
Cancer Genetics Program, Division of Hematology/Oncology, Department of Medicine and Robert H. Lurie Comprehensive Cancer Center, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA
Received 25 July 2011; Accepted 15 August 2011
Abstract
Triple-negative breast cancers (TNBCs) are aggressive tumors with poor prognosis compared to other breast cancer subtypes. The evidence linking TNBC with the metabolic syndrome, which consists of central obesity, insulin resistance, impaired glucose tolerance, dyslipidemia, and hypertension, has emerged from clinical studies and experiments using cell lines and mouse models. Epidemiological studies have associated abdominal obesity with increased incidence of TNBC. Additionally, insulin resistance, dyslipidemia, and hypertension are associated with increased incidence of breast cancer across all subtypes. The insulin-leptin-adiponectin axis has been implicated mechanistically in breast cancer tumorigenesis. Specifically, increased leptin and decreased adiponectin levels disrupt homeostatic signaling pathways involved in cell proliferation, survival, cell-cycle regulation, and angiogenesis. Insulin, insulin-like growth factor I (IGF-I), and epidermal growth factor receptor (EGFR) may mediate interactions between these two hormones. Further research will facilitate the development of targeted therapeutics and programs to modify lifestyle factors to modulate the insulin-leptin-adiponectin axis for TNBC.
1. Introduction
Triple-negative breast cancers (TNBCs) lack expression of the steroid receptors estrogen (ER) and progesterone (PR) and the tyrosine kinase human epidermal growth factor receptor 2 (HER-2). Therefore, TNBCs are a diagnosis of exclusion, typically characterized by upregulation of cytokeratins 5, 14, and 17 and elevation of the epidermal growth factor receptor (EGFR) [1–3]. Studies estimate that approximately 15-20% of breast cancers meet these criteria [4–6]. Compared to other breast cancer subtypes, TNBCs are typically aggressive, invasive (ductal, medullary, or metaplastic), grade III tumors with high rates of mitotic division, of which approximately half contain a high rate of p53 mutations [7]. For these reasons, they account for a disproportionately high percentage of metastases, distant recurrence, and death among patients with breast cancer. Metastases in TNBCs are most common to visceral organs including liver, lungs, and central nervous system. As a diagnosis of exclusion, TNBC overlaps considerably with basal-like breast cancer (BLBC) although differences between the two subtypes exist, especially at a genetic level. Other molecular subtypes defined by gene expression patterns include luminal A, luminal B, HER-2-enriched group, and claudin-low, all of which may include TNBCs to some extent [8, 9]. TNCBs are most common among premenopausal women, especially those of African American descent [4–6, 10]. In addition, TNBCs are common among patients with BRCA1 mutations [11, 12].
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