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.&lt;ref name = dent01&gt;&lt;/ref&gt;&lt;ref name = medscape/&gt; It is diagnosed more frequently in younger women,&lt;ref name = dent01/&gt;&lt;ref name = medscape/&gt; women with BRCA1 mutations,&lt;ref name = dent01/&gt; and those belonging to African-American&lt;ref name = dent01/&gt;&lt;ref name = medscape/&gt;&lt;ref name = nci/&gt; and Hispanic&lt;ref name = medscape/&gt;&lt;ref name = nci/&gt; ethnic groups, and those having a recent birth.&lt;ref name = "Trivers KF"&gt;&lt;/ref&gt;

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).&lt;ref name = "Basu S"&gt;&lt;/ref&gt; 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.

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.&lt;ref name = dent01/&gt;

"Triple-negative" breast cancer cells do not express any of these receptors.&lt;ref name = dent01/&gt; This means they are generally unresponsive to such standard receptor-mediated treatments. However, other forms of chemotherapy can still generate positive outcomes.&lt;ref name = "de giorgi"&gt;&lt;/ref&gt; Some reports even suggest they are more susceptible to non-receptor mediated therapies than other tumours.&lt;ref name = "Brenton"&gt;&lt;/ref&gt;

Although triple-negative breast cancer can be treated with chemotherapy, early relapse and metastasis (spread to other tissues) is common.

A recent convergence of clinical and epidemiologic evidence has linked hyperinsulinemia, insulin resistance, and diabetes to poor breast cancer outcomes.&lt;ref name = "Goodwin PJ"&gt;&lt;/ref&gt; The widely-used diabetes drug metformin holds promise for the treatment of triple-negative breast cancer.&lt;ref name = "Basu S"&gt;&lt;/ref&gt; 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).&lt;ref name = "Basu S"&gt;&lt;/ref&gt;

Clinical trials
A number of new strategies are currently being tested in clinical trials,&lt;ref&gt;&lt;/ref&gt; including the PARP inhibitor BSI 201.&lt;ref&gt;http://www.medpagetoday.com/MeetingCoverage/SABCS/17496 "SABCS: PARP Inhibitor Data Called 'Spectacular'" Dec 2009&lt;/ref&gt;

Distribution
According to Cancer Research UK, triple-negative breast cancer account for approximately 15% of all breast cancer cases.&lt;ref name=CRUK&gt;&lt;/ref&gt;

Younger women fall into the high risk group for this subtype of breast cancer.&lt;ref name = medscape/&gt; Additionally, it is found to disproportionally affect African American and Hispanic women,&lt;ref name = nci&gt;&lt;/ref&gt; with African Americans facing worse prognosis than other ethnic groups.&lt;ref name = medscape&gt;&lt;/ref&gt;

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.&lt;ref&gt;&lt;/ref&gt; 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 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.