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'{{Multiple issues | globalize=October 2010 | expand=October 2008 }} '''Triple-negative breast cancer''' refers to any [[breast cancer]] that does not [[genetic expression|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 [[wikt:prognosis|prognosis]].<ref name = dent01>{{cite journal |author= Dent R, Trudeau M, Pritchard KI, Hanna WM, Kahn HK ''et al'' |date= 2007-08-01 |title= Triple-Negative Breast Cancer: Clinical Features and Patterns of Recurrence |journal=[[Clinical Cancer Research]] |volume= 13 |pages= 4429–4434 |publisher= American Association for Cancer Research |doi= 10.1158/1078-0432.CCR-06-3045 |url= http://clincancerres.aacrjournals.org/cgi/content/full/13/15/4429 |accessdate= 2008-10-13 |pmid= 17671126 |issue= 15 Pt 1}}</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">{{cite journal |author=Trivers KF, Lund MJ, Porter PL, Liff JM, Flagg EW, Coates RJ, Eley JW |date=2009 |title=The epidemiology of triple-negative breast cancer, including race |journal=Cancer Causes Control |volume=20 |issue=7 |pages=1071–1082 |url=http://www.ncbi.nlm.nih.gov/pubmed/19343511 |doi=10.1007/s10552-009-9331-1 |pmid=19343511}}</ref> It has a poor prognosis (due to lack of a [[targeted therapy]]) but the [[PARP inhibitor]] [[BSI 201]] is now giving very promising results in clinical trials.<ref name=Dec2009/> A novel, targeted antibody-drug conjugate, CDX-011, has also shown very encouraging results in recent clinical trials. ==Characteristics== Triple-negative breast according to caj 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. Triple-negative breast cancers (TNBC) do not have any of three frequent causes (ER+, PR+, HER2+) so they include those of any other cause. "[N]ine out of ten women with triple negative breast cancer also had faulty [[BRCA1]]"<ref name=UTNBC>{{cite web |url=http://scienceblog.cancerresearchuk.org/2010/05/10/understanding-triple-negative-breast-cancer/ |title=Understanding triple negative breast cancer – 53BP1 and the BRCA1 connection }}</ref>. "[M]ost samples of triple negative cancers had very low levels of [[53BP1]]"<ref name=UTNBC/> (making them less sensitive to [[radiotherapy)]]. Most TNBC over expresses [[EGFR]].<ref>Feb 2009 Breast Cancer Watch</ref> <ref name=Anders2008>{{cite web |url=http://www.cancernetwork.com/display/article/10165/1340727 |title=Understanding and Treating Triple-Negative Breast Cancer |Author=Anders |Year=2008 }}</ref> ===Future diagnostic possibility=== 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 2008">{{cite journal |author=Basu S, Chen W, Tchou J, Mavi A, Cermik T, Czerniecki B, Schnall M, Alavi A |date=2008 |title=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 |journal=Cancer |volume=112 |issue=5 |pages=995–1000 |doi=10.1002/cncr.23226 |url=http://www3.interscience.wiley.com/journal/117870430/abstract |pmid=18098228}}</ref> It is speculated that enhanced glycolysis in these tumors is probably related to their aggressive biology. ==Treatment== 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">{{cite journal |author= De Giorgi U, Rosti G, Frassineti L, Kopf B, Giovannini N, Zumaglini F & Marangolo M |date= 2006-09-13 |title= High-dose chemotherapy for triple negative breast cancer |journal= [[Annals of Oncology]] |volume= 18 |issue =1 |pages= 202–203 |publisher= European Society for Medical Oncology |doi= 10.1093/annonc/mdl306 |url= http://annonc.oxfordjournals.org/cgi/content/full/18/1/202 |accessdate= 2008-10-13 |pmid= 16971660}}</ref> Some reports even suggest they are more susceptible to non-receptor mediated therapies than other tumours.<ref name = "Brenton">{{cite journal |quote=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. |author= Brenton JD, Carey LA, Ahmed AA & Caldas C |date= 2005-10-10 |title= Molecular Classification and Molecular Forecasting of Breast Cancer: Ready for Clinical Application? |journal= [[Journal of Clinical Oncology]] |volume= 23 |issue =29 |pages= 7350–7360 |publisher= American Society of Clinical Oncology |doi= 10.1200/JCO.2005.03.3845 |url= http://jco.ascopubs.org/cgi/content/full/23/29/7350?ijkey=c85c0a9d79694e155ef5ab04293aae36a191b86b |accessdate= 2008-10-13 |pmid=16145060}}</ref> Although triple-negative breast cancer can be treated with [[chemotherapy]], early relapse and [[metastasis]] (spread to other tissues) is common. ===Research=== By 2009 a convergence of clinical and epidemiologic evidence linked hyperinsulinemia, insulin resistance, and diabetes to poor breast cancer outcomes.<ref name = "Goodwin PJ">{{cite journal |author=Goodwin PJ, Ligibel JA, Stambolic V |date=2009 |title=Metformin in breast cancer: time for action |journal=American Society of Clinical Oncology |volume=27 |issue=20 |pages=3271–3273 |doi=10.1200/JCO.2009.22.1630 |url=http://jco.ascopubs.org/cgi/content/short/27/20/3271 |pmid=19487373}}</ref> The widely-used diabetes drug [[metformin]] holds promise for the treatment of triple-negative breast cancer.<ref name = Jiralerspong>{{cite journal |author=Jiralerspong S, Gonzalez-Angulo AM, Hung MC |date=2009 |title=Expanding the arsenal: metformin for the treatment of triple-negative breast cancer? |journal=Cell Cycle |volume=8 |issue=13 |pages=2031–40 |doi= |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). ===Clinical trials=== A number of new strategies are currently being tested in clinical trials,<ref>{{cite journal |author= Anders C |title= Understanding and Treating Triple-Negative Breast Cancer|journal=Oncology |volume=22 |issue=11 |year=2008 |url=http://www.cancernetwork.com/display/article/10165/1340727}}</ref> including the [[PARP inhibitor]] [[BSI 201]]<ref name=Dec2009>http://www.medpagetoday.com/MeetingCoverage/SABCS/17496 "SABCS: PARP Inhibitor Data Called 'Spectacular'" Dec 2009</ref>, and [[NK012]]<ref>{{cite web |url=http://clinicaltrials.gov/ct2/show/NCT00951054 |title=A Study of NK012 in Patients With Advanced, Metastatic Triple Negative Breast Cancer }}</ref>. ==Distribution== According to [[Cancer Research UK]], triple-negative breast cancer account for approximately 15% of all breast cancer cases.<ref name=CRUK>{{cite web |url=http://www.cancerhelp.org.uk/help/default.asp?page=26093 |title=Triple negative breast cancer |accessdate=2008-10-13 |year=2007 |publisher=Cancer Research UK}}</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>{{cite web | url = http://www.cancer.gov/ncicancerbulletin/NCI_Cancer_Bulletin_072407/page7 | title = Spotlight: Triple-Negative Breast Cancer Disproportionately Affects African American and Hispanic Women | accessdate = 2008-10-13| last = Reynolds | first = Sharon | date = 2007-07-24 | publisher = National Cancer Institute}}</ref> with African Americans facing worse prognosis than other ethnic groups.<ref name = medscape>{{cite web | url = http://www.medscape.com/viewarticle/554234 | title = Survival Disadvantage Seen for Triple-Negative Breast Cancer | accessdate=2008-10-13 | last= Chustecka | first= Zosia | date= 2007-03-19 | publisher= Medscape Medical News}}</ref> ===Oral contraceptive a risk factor=== 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>{{cite journal |title=Risk Factors for Triple-Negative Breast Cancer in Women Under the Age of 45 Years |journal=[[Cancer Epidemiology, Biomarkers & Prevention]] |year=2009 |volume=18 |issue=4 |pages=1157–1166 |doi=10.1158/1055-9965.EPI-08-1005 |pmid=19336554 |url=http://cebp.aacrjournals.org/content/18/4/1157 |author=Dolle JM, Daling JR, White E, Brinton LA, Doody DR, Porter PL, Malone KE |pmc=2754710}}</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. ==Research== 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|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.{{Citation needed|date=October 2008}} ==See also== [[The Triple Negative Breast Cancer Foundation]] == References == {{reflist}} ==External links== *[http://www.tnbcfoundation.org/ The Official Triple Negative Breast Cancer Foundation Site] *[http://forum.tnbcfoundation.org/search_form.asp Triple Negative Breast Cancer Discussion Forum] *[http://www.cancerhelp.org.uk/help/default.asp?page=26093/ Information about Triple Negative Breast Cancer] *[http://ww5.komen.org/BreastCancer/SubtypesofBreastCancer.html#TripleNegative Susan G. Komen for the Cure - Subtypes of breast cancer] *[http://www.networkofstrength.org/information/diagnosis/hrc/triple.php Breast Cancer Network of Strength - Information about Triple Negative Breast Cancer] *[http://www.lbbc.org/data/media/LBBCunderstandtriplenegative.pdf Living Beyond Breast Cancer's Guide to Understanding Triple-Negative Breast Cancer] *[http://www.nosurrenderbreastcancerhelp.org/breastcancer101/TNBC/TNBC.html No Surrender Breast Cancer Foundation - Review of TNBC treatments] :*[http://bcwatchdigest.evidencewatch.com/ Breast Cancer Watch ] (Click on "triple negative" at top for Feb 2009 review with links to references) *[http://www.nosurrenderbreastcancerhelp.org/breastcancer101/TNBC/Hope%20for%20TNBC.html No Surrender Breast Cancer Foundation - PARP inhibitors] *[http://clinicaltrials.gov/ct2/results?term=triple+negative Current clinical trials for TNBC] *[http://clinicaltrials.gov/ct2/results?term=triple+negative+breast+cancer&recr=&rslt=&type=&cond=&intr=&outc=&lead=&spons=&id=&state1=&cntry1=&state2=&cntry2=&state3=&cntry3=&locn=&gndr=&phase=2&phase=3&rcv_s=&rcv_e=&lup_s=&lup_e= Phase III or IV trials for TNBC] *[http://www.cscrb.org The Collaboration of Scientists for Critical Research in Biomedicine] Just shows pics of fund raising event. [[Category:Breast cancer]]'