Triple-negative breast cancer

Triple-negative breast cancer (sometimes abbreviated TNBC) refers to any breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR) and HER2/neu. This makes it more difficult to treat since most hormone therapies target one of the three receptors, so triple-negative cancers often require combination therapies. Triple negative is sometimes used as a surrogate term for basal-like; however, more detailed classification may provide better guidance for treatment and better estimates for prognosis. Triple-negative breast cancer (sometimes abbreviated TNBC) refers to any breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR) and HER2/neu. This makes it more difficult to treat since most hormone therapies target one of the three receptors, so triple-negative cancers often require combination therapies. Triple negative is sometimes used as a surrogate term for basal-like; however, more detailed classification may provide better guidance for treatment and better estimates for prognosis. Triple-negative breast cancers comprise a very heterogeneous group of cancers. There is conflicting information over prognosis for the various subtypes, but it appears that the Nottingham prognostic index is valid and hence general prognosis is rather similar with other breast cancer of same stage, except that more aggressive treatment is required. Some types of triple-negative breast cancer are known to be more aggressive, with poor prognosis, while other types have very similar or better prognosis than hormone receptor positive breast cancers. Among breast cancer patients, 15-20% of women have been diagnosed as triple-negative, while the majority of TNBC patients have been found to be young women or women with a mutation in the BRCA1 gene. Pooled data of all triple-negative subtypes suggests that, with optimal treatment, 20-year survival rates are very close to those of hormone positive cancer. Triple-negative breast cancers have a relapse pattern that is very different from hormone-positive breast cancers: the risk of relapse is much higher for the first 3–5 years, but drops sharply and substantially below that of hormone-positive breast cancers afterwards. This relapse pattern has been recognized for all types of triple-negative cancers for which sufficient data exist, although the absolute relapse and survival rates differ across subtypes. One known cause of triple negative breast cancer is germline mutations. These are alterations within the heritable lineage that is being passed down to the offspring. 15% of TNBC can be traced back to germline mutations that are within the BRCA1 and BRCA2 genes (Song 2014). Due to their high disposition for cancers of the breast, ovaries, pancreas, and prostate, the BRCA1 and BRCA2 genes were identified as high risk for triple-negative (Pruss 2014). Changes or mutations in 19p13.1 and MDM4 loci have also been associated with triple negative breast cancer, but not other forms of breast cancer. Thus, triple negative tumors may be distinguished from other breast cancer subtypes by a unique pattern of common and rare germline alterations (Kristen 2013). Triple-negative breast cancers (TNBC) are sometimes classified into 'basal-type' and other cancers; however, there is no standard classification scheme. Basal type cancers are frequently defined by cytokeratin 5/6 and EGFR staining. However, no clear criteria or cutoff values have been standardized yet. About 75% of basal-type breast cancers are triple negative. Some TNBC overexpress epidermal growth factor receptor (EGFR) or transmembrane glycoprotein NMB (GPNMB). Upon histologic examination, triple-negative breast tumors mostly fall into the categories of secretory cell carcinoma or adenoid cystic types (both considered less aggressive); medullary cancers and grade 3 invasive ductal carcinomas with no specific subtype; and highly aggressive metastatic cancers. Medullary TNBC in younger women are frequently BRCA1-related. Rare forms of triple-negative breast cancer are apocrine and squamous carcinoma. Inflammatory breast cancer is also frequently triple negative. Many proteins such as Caveolin 1/2, Survivin are researched as possible classification or prognostic factors.