Breast cancer lacking expression of genes of progesterone receptor, estrogen receptor and Her2/neu, is termed as triple negative breast cancer. Most of the triple negative breast cancer tumors are basal like and most of basal like tumors are triple negative tumors.
Basal like tumors consist of cells having features similar to the basal cells that lined the mammary duct. Around 15-20 % of breast cancer is basal like or triple negative and occurs more frequently in African American women of younger age groups. Most of the BRCA1 gene breast cancers are both basal like and triple negative.
Characterization of Triple Negative Breast Cancer
Triple negative breast cancers (TNBC) are heterogeneous group of cancers. Majority of the triple negative breast cancers are more aggressive kinds with poor prognosis in initial five years as compared to other hormone receptor positive cancer forms.
Risk of relapse in triple negative breast cancers is much higher in the initial 3 to 5 years but drops down significantly after that.
Though, many of TNBC are high grade lesions, but few of these are low grade or moderate lesions, demonstrating much lower rate of lymph node metastasis. Therefore, diagnosis of triple negative breast cancer not necessarily means spread of cancer.
Risk Factors For Triple Negative Breast Cancer
A strong link has been found between obesity and the elevated risk of postmenopausal breast cancer. A strong association of estrogen and adipose tissue is known to contribute to this higher risk. On the other hand, greater physical activity is shown to decrease the risk for triple negative breast cancer.
Risk for triple negative breast cancer increases 2.5 folds in women using oral contraceptives (OCs) for a duration of more than one year, compared to those who used them for lesser than a year or never.
In women with age 40 or below, who used OCs for more than 1 year, the increased risk was found to be 4.2 times higher. There was no risk observed for women using OCs and falling in age group of 41 to 45 years. Both duration of oral contraceptive use and the age group, play a significant role in elevating the risk of TNBC.
Various Forms of Triple Negative Breast Cancer
Many of the TNBC show over expression of EFGR (epidermal growth factor receptor), whereas other show high expression of trans-membrane glycoprotein NMB (GPNMB). Histological examination characterizes TNBC into adenoid cystic type or secretory carcinoma (the less aggressive types), grade 3 invasive ductal carcinomas, medullary cancers and very aggressive metastatic forms of cancers.
Medullary TNBC is frequently seen linked to BRCA1, in younger women. Rare types of triple negative breast cancer are squamous and apocrine carcinoma form. In most of the cases, inflammatory breast cancer is also found to be triple negative cancer.
Triple negative breast cancer patients undergoing chemotherapy to shrink the tumor before surgery, usually show multiple genetic mutations within their cancerous cells.
Treatment For Triple Negative Breast Cancer
Since the cancer is hormone receptor negative and Her2neu negative, it cannot be treated with hormonal therapies. Hence, the standard treatment remains a surgery performed with adjuvant radiotherapy and chemotherapy.
A variation form called neo-adjuvant chemotherapy is also performed these days to treat triple negative breast cancer. This facilitates an increased rate of breast conserving surgeries and on evaluation of chemotherapeutic response, gives important information about the patient’s responsiveness to chemotherapy treatment.
Triple negative breast cancers are usually quite susceptible to chemotherapy, but in certain cases, early response may not correlate with an overall survival rate. Hence, it becomes complicated to find an optimal chemotherapy. Addition of taxane to chemotherapy is known to improve the treatment outcomes substantially. BRCA1 related TNBCs are particularly more susceptible to chemotherapy that includes taxanes and platinum based agents.
Use of Novel Trio Drugs
Recent advancement in treatment of TNBCs includes a cocktail of Entinostat (blocks the enzyme unfolding DNA), All Trans Retinoic acid (ATRA) and protein of RARß gene. Entinostat provides access of genes to regulatory molecules and reactivates the RARß (retinoic acid receptor beta) gene.
ATRA drug is related to vitamin A that binds to protein synthesized by RARß. Together, RARß gene and ATRA drug puts a brake on cancerous cell growth.
Disease free survival from triple negative breast cancer is a short lived scenario in women as the disease does not respond to hormonal drugs and may become resistant to chemotherapy. More research studies are performed to fine tune this fearsome cancer’s properties and bring out a more sensitive and long term treatment for triple negative breast cancer patients.
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