Triple-negative breast cancer
Triple-negative breast cancer refers to a specific subtype of breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR) or Her2/neu. This subtype of breast cancer is clinically characterised as more aggressive and less responsive to standard treatment and associated poorer overall patient prognosis.<ref name = dent01>Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK et al (2007-08-01). "Triple-Negative Breast Cancer: Clinical Features and Patterns of Recurrence". Clinical Cancer Research (American Association for Cancer Research) 13 (15 Pt 1): 4429–4434. doi:10.1158/1078-0432.CCR-06-3045. PMID 17671126. http://clincancerres.aacrjournals.org/cgi/content/full/13/15/4429. Retrieved 2008-10-13. </ref><ref name = medscape/> It is diagnosed more frequently in younger women,<ref name = dent01/><ref name = medscape/> women with BRCA1 mutations,<ref name = dent01/> and those belonging to African-American<ref name = dent01/><ref name = medscape/><ref name = nci/> and Hispanic<ref name = medscape/><ref name = nci/> ethnic groups, and those having a recent birth.<ref name = "Trivers KF">Trivers KF, Lund MJ, Porter PL, Liff JM, Flagg EW, Coates RJ, Eley JW (2009). "The epidemiology of triple-negative breast cancer, including race". Cancer Causes Control 20 (7): 1071–1082. doi:10.1007/s10552-009-9331-1. PMID 19343511. http://www.ncbi.nlm.nih.gov/pubmed/19343511. </ref>
Triple-negative breast cancers have, on average, significantly higher fluorine-18 fluorodeoxyglucose (FDG) uptake (measured by the SUVmax values) compared with uptake in ER+/PR+/HER2- tumors using fluorine-18 fluorodeoxyglucose-positron emission tomography (FDG-PET).<ref name = "Basu S">Basu S, Chen W, Tchou J, Mavi A, Cermik T, Czerniecki B, Schnall M, Alavi A (2008). "Comparison of triple-negative and estrogen receptor-positive/progesterone receptor-positive/HER2-negative breast carcinoma using quantitative fluorine-18 fluorodeoxyglucose/positron emission tomography imaging parameters: a potentially useful method for disease characterization". Cancer 112 (5): 995–1000. doi:10.1002/cncr.23226. PMID 18098228. http://www3.interscience.wiley.com/journal/117870430/abstracthttp://annonc.oxfordjournals.org/cgi/content/full/18/1/202. </ref> It is speculated that enhanced glycolysis in these tumors is probably related to their aggressive biology.
Triple-negative breast cancers are themselves a subgroup of "basal-type" breast cancers. As triple-negative breast cancers make up the overwhelming majority of this subgroup, what limited data that is available typically deals with triple-negative breast cancers.
Breast cancers are classified by whether or not they express the genes for estrogen receptor, progesterone receptor or Her2/neu. These three receptors are known to help the cancer develop, and the most successful breast cancer treatments are hormone-based drugs that directly target these receptors. It is important to know what subtype the cancer is before commencing treatment as different drugs target different receptors.<ref name = dent01/>
"Triple-negative" breast cancer cells do not express any of these receptors.<ref name = dent01/> This means they are generally unresponsive to such standard receptor-mediated treatments. However, other forms of chemotherapy can still generate positive outcomes.<ref name = "de giorgi">De Giorgi U, Rosti G, Frassineti L, Kopf B, Giovannini N, Zumaglini F & Marangolo M (2006-09-13). "High-dose chemotherapy for triple negative breast cancer". Annals of Oncology (European Society for Medical Oncology) 18 (1): 202–203. doi:10.1093/annonc/mdl306. PMID 16971660. http://annonc.oxfordjournals.org/cgi/content/full/18/1/202. Retrieved 2008-10-13. </ref> Some reports even suggest they are more susceptible to non-receptor mediated therapies than other tumours.<ref name = "Brenton">Brenton JD, Carey LA, Ahmed AA & Caldas C (2005-10-10). "Molecular Classification and Molecular Forecasting of Breast Cancer: Ready for Clinical Application?". Journal of Clinical Oncology (American Society of Clinical Oncology) 23 (29): 7350–7360. doi:10.1200/JCO.2005.03.3845. PMID 16145060. http://jco.ascopubs.org/cgi/content/full/23/29/7350?ijkey=c85c0a9d79694e155ef5ab04293aae36a191b86b. Retrieved 2008-10-13. "Given its triple-negative receptor status (ER, PR, and HER2), basal-like breast cancer is not amenable to conventional targeted therapies for breast cancer such as endocrine therapy or trastuzumab, leaving only chemotherapy in the therapeutic armamentarium. Despite their poor prognosis, basal-like breast cancers are sensitive to conventional chemotherapy.". </ref>
A recent convergence of clinical and epidemiologic evidence has linked hyperinsulinemia, insulin resistance, and diabetes to poor breast cancer outcomes.<ref name = "Goodwin PJ">Goodwin PJ, Ligibel JA, Stambolic V (2009). "Metformin in breast cancer: time for action". American Society of Clinical Oncology 27 (20): 3271–3273. doi:10.1200/JCO.2009.22.1630. PMID 19487373. http://jco.ascopubs.org/cgi/content/short/27/20/3271. </ref> The widely-used diabetes drug metformin holds promise for the treatment of triple-negative breast cancer.<ref name = "Basu S">Jiralerspong S, Gonzalez-Angulo AM, Hung MC (2009). [Expression error: Missing operand for > "Expanding the arsenal: metformin for the treatment of triple-negative breast cancer?"]. Cell Cycle 8 (13): 2031–40. PMID 19440038. </ref> In addition metformin may influence cancer cells through indirect (insulin-mediated) effects, or it may directly affect cell proliferation and apoptosis of cancer cells. Epidemiologic and preclinical lab studies indicate that metformin has anti-tumor effects, via at least two mechanisms, both involving activation of the AMP-activated protein kinase (AMPK).<ref name = "Basu S">Jiralerspong S, Gonzalez-Angulo AM, Hung MC (2009). [Expression error: Missing operand for > "Expanding the arsenal: metformin for the treatment of triple-negative breast cancer?"]. Cell Cycle 8 (13): 2031–2040. PMID 19440038. </ref>
A number of new strategies are currently being tested in clinical trials,<ref>Anders C (2008). "Understanding and Treating Triple-Negative Breast Cancer". Oncology 22 (11). http://www.cancernetwork.com/display/article/10165/1340727. </ref> including the PARP inhibitor BSI 201.<ref>http://www.medpagetoday.com/MeetingCoverage/SABCS/17496 "SABCS: PARP Inhibitor Data Called 'Spectacular'" Dec 2009</ref>
According to Cancer Research UK, triple-negative breast cancer account for approximately 15% of all breast cancer cases.<ref name=CRUK>"Triple negative breast cancer". Cancer Research UK. 2007. http://www.cancerhelp.org.uk/help/default.asp?page=26093. Retrieved 2008-10-13. </ref>
Younger women fall into the high risk group for this subtype of breast cancer.<ref name = medscape/> Additionally, it is found to disproportionally affect African American and Hispanic women,<ref name = nci>Reynolds, Sharon (2007-07-24). "Spotlight: Triple-Negative Breast Cancer Disproportionately Affects African American and Hispanic Women". National Cancer Institute. http://www.cancer.gov/ncicancerbulletin/NCI_Cancer_Bulletin_072407/page7. Retrieved 2008-10-13. </ref> with African Americans facing worse prognosis than other ethnic groups.<ref name = medscape>Chustecka, Zosia (2007-03-19). "Survival Disadvantage Seen for Triple-Negative Breast Cancer". Medscape Medical News. http://www.medscape.com/viewarticle/554234. Retrieved 2008-10-13. </ref>
In 2009, a case-control study of 187 triple-negative breast cancer patients by the Fred Hutchinson Cancer Research Center described a 2.5 increased risk for triple-negative breast cancer in women who used oral contraceptives (OCs) for more than one year compared to women who used OCs for less than one year or never.<ref>Dolle JM, Daling JR, White E, Brinton LA, Doody DR, Porter PL, Malone KE (2009). "Risk Factors for Triple-Negative Breast Cancer in Women Under the Age of 45 Years". Cancer Epidemiology, Biomarkers & Prevention 18 (4): 1157–1166. doi:10.1158/1055-9965.EPI-08-1005. PMID 19336554. PMC 2754710. http://cebp.aacrjournals.org/content/18/4/1157. </ref> Interestingly, the increased risk for triple-negative breast cancer was 4.2 among women 40 years of age or younger who used OCs for more than one year, while there was no increased risk for women between the ages of 41 and 45. Also, as duration of OC use increased, triple-negative breast cancer risk increased.
With a view towards finding better treatment options for this disease, The Triple Negative Breast Cancer Foundation, together with Susan G. Komen for the Cure convened the Triple Negative Breast Cancer Symposium in December 2007. The Symposium brought together over 30 leading doctors, researchers and scientists from around the world for a think tank aimed at exploring the most promising research leads in the area of triple negative breast cancer.
- The Official Triple Negative Breast Cancer Foundation Site
- Triple Negative Breast Cancer Discussion Forum
- Information about Triple Negative Breast Cancer
- Susan G. Komen for the Cure
- Breast Cancer Network of Strength- Information about Triple Negative Breast Cancer
- The Collaboration of Scientists for Critical Research in Biomedicine