Top Five Advances in TNBC Research in 2013


Patricia Prijatel

Last year was a lively one for research on triple-negative breast cancer. Below is my list of the year's top studies -- all pointing toward understanding what makes TNBC tick, which will ultimately lead to treatment and a reduction in the risk of recurrence. Remember, though, that the road from research to clinical practice can be long and rocky, so most of these treatments won't be immediately available. Still, this list points to a rich reservoir of inquiry and information -- which is good news for those of us on the TNBC Road and for those who follow us. 1. New Treatment Regimens Include Existing Drugs

Bisphosphonates such as Zometa and Reclast reduced the risk of bone metastases following breast cancer in post-menopausal women by 34 percent in research presented at the 2013 San Antonio Breast Cancer Symposium. And they reduced the risk of death in that same group by 17 percent, regardless of receptor status, node involvement or previous chemotherapy.

• Adding the chemotherapy drug carboplatin to standard treatment improved outcomes for women with triple-negative breast cancer in two studies presented at the 2013 San Antonio Breast Cancer Symposium. Both measured pathological complete response (pCR), which is recognized as a positive marker for overall survival. The second study also showed improved outcomes using bevacizumab (Avastin).

• Triple-negative breast cancers may be vulnerable to drugs like bortezomib (Velcade), which is used in multiple myeloma, according to a paper in Cancer Cell. In lab tests, researchers selectively "turned off" genes in triple-negative tumor cells. When turned off, the cells die.

• Tumor-infiltrating lymphocytes may become an additional factor in determining which types of triple-negative breast cancer respond best to chemotherapy. Seventy-five percent of tumors with the highest levels of lymphocytes -- researchers call this lymphocyte predominate breast cancer (LPBC) - had a pathological complete response to doxorubicin and taxane plus carboplatin when compared to non-LPBC tumors. The results came from the GeparSixto trial (GBG 66) in Germany.

• The diabetes drug metformin can effectively reduce breast cancer risk that is associated with insulin resistance and was directly correlated with Ki67 status, according to research in the British Journal of Cancer. TNBC has shown links to insulin resistance in previous studies, and many TNBC tumors are positive for Ki67.2. New Drugs May Be On The Horizon

• An anti-copper drug compound that disables the ability of bone marrow cells from setting up a "home" in organs to receive and nurture migrating cancer tumor cells has shown benefit for metastatic triple-negative breast cancer. Results of a phase 2clinical trial reported in the Annals of Oncology show that patients who are copper depleted show a significantly reduced risk of relapse. In fact, only two of 11 study participants with a history of advanced triple-negative breast cancer relapsed within 10 months after using the anti-copper drug, tetrathiomolybdate (TM).

• A protein called Numb may promote the death of cancer cells by binding to and stabilizing the tumor suppressor protein p53, which is implicated in many cases of triple-negative breast cancer, according to research published in the May 23rd issue of Molecular Cell. When Numb is reduced by the Set8 enzyme, it will no longer protect p53.3. Genetic Research Is Leading Toward Better Definition of TNBC

• Beyond its most basic definition -- negative for receptors for estrogen, progesterone and Her2/neu -- triple-negative breast cancer has unique genetic characteristics. Research published in the journal Cancer Research outlined some of TNBC's genetic associations.

• In a study published in the journal Breast Cancer Research, scientists discovered that basal-like breast cancers with the BRCA1 mutation--many of them TNBC--grow differently than other cancers. In fact, the way they grow predicts the prognosis of the tumor.

• Cancer Scientists at Weill Cornell Medical College have discovered the molecular switch that allows triple-negative breast cancer cells to grow the amoeba-like protrusions they need to crawl away from a primary tumor and metastasize throughout the body. Their findings, published in Cancer Cell, suggest a novel approach for developing agents to treat cancer once it has spread.

• Researchers at St. Louis University have uncovered a pathway responsible for the loss of 53BP1 in TNBC tumors related to the BRCA1 mutation. Loss of BRCA1, they discovered, increases the expression of the protease cathepsin L (CTSL), which causes the degradation of 53BP1. Cells that have lost both BRCA1 and 53BP1 have the ability to repair DNA and proliferate. That means the protease helps cancer cells with faulty BRCA1 survive -- it is a defined bad guy in TNBC growth. 4. Technological Advances Improve Imaging, Diagnosis, and Treatment

• An optical imaging technique that measures metabolic activity in cancer cells can accurately differentiate breast cancer subtypes, and it can detect responses to treatment as early as two days after therapy administration, according to a study published in Cancer Research, a journal of the American Association for Cancer Research.

• UCLA researchers have developed a potential new treatment for TNBC that uses nanoscale, diamond-like particles called nanodiamonds. Byproducts of conventional mining and refining operations, nanodiamonds can form clusters following drug binding and have the ability to precisely deliver cancer drugs to tumors, significantly improving the drugs' desired effect. 5. Lifestyle Changes Continue to Show Promise

• Researchers from Fox Chase Cancer Center have found that omega-3 fatty acids slow or stop the proliferation of triple-negative breast cancer cells more effectively than cells from luminal types of the disease. The omega-3s worked against all types of cancerous cells, but the effect was observed to be stronger in triple-negative cell lines, reducing proliferation by as much as 90 percent.

• Young women who eat excess amounts of saturated fats during their teenage years increase their risk of basal-like breast cancer, according to a study published in Breast Cancer Research. Many basal-like tumors are also triple-negative.Patricia Prijatel is a TNBC survivor, advocate and writer. This post is an excerpt from "Top Triple-Negative Breast Cancer Research: 2013," published on Patricia's blog, Positives About Negative. Read more about TNBC in Patricia's book, Surviving Triple-Negative Breast Cancer, available from Oxford University Press.

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