Model Might Help Predict How TNBC Spreads

Cancer tumors contain a variety of traits that affect their response to treatment and their risk of metastasis.  A team of researchers has used this fact to suggest a model that can predicts how a tumor might evolve.  Their research, published in Cell Reports, emphasizes the importance of mapping the genetic traits of specific tumors.

That is, while we all might be diagnosed with triple-negative breast cancer, our tumors are unique to us.

Led by Kornelia Polyak, at Dana-­Farber Cancer Institute and Harvard Medical School, the researchers analyzed the heterogeneity of tumors from 47 patients   before and after treatment for breast cancer.  After treatment, they found:

• an increase in the number of CD44^-CD24-positive cells in luminal A, luminal B, and TNBC tumors.

• lower levels of CD44^-CD24-negative  cells.

• the cell subpopulations in Her2-positive tumors changed very little.

• the fraction of Ki67-positive cells declined in all cell types in all tumors.

The significance of this research?  In an interview in Genomeweb, Polyak explained: "Based on this knowledge, we could predict which tumor cells will likely be eliminated or slowed down by treatment and how this may change the tumor overall.This knowledge could aid the design of subsequent therapies for those who do not respond to the first line of treatment."

It's one more step toward understanding what TNBC is, rather than just what it isn't, and that is a step toward targeted treatment.  And, maybe, eventually, prevention.

Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.

Please consider a donation to Positives About Negative to keep this site going.  This work is entirely supported by readers.  Just click on the Donate button in the right of the page.  Thank you!

Top Triple-Negative Breast Cancer Research: 2013

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.

Are Common Bone Drugs the TNBC Follow-Up Treatment We’ve Been Seeking?

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.   More.

Genetic Details of Triple-Negative Breast Cancer

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 has outlined some of TNBC’s genetic associations.   Once they know what it is rather than what it isn't, they can target it.  Put a big red bull’s eye on its nasty old back.  More.

New Drug Regimens Can Lead to Improved Outcomes for Women with Stages II and III TNBC 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). More.

Lymphocytes May Signal Chemo Response in TNBC

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.  More.

High Fat Diet in Puberty Linked to Basal-Like Breast Cancer

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. More

Metformin: New Agent Against TNBC?

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, so this could be additional support for considering metformin as a treatment for TNBC.  More.

Restorative Yoga Can Help Trim Fat

Yoga’s health benefits may go beyond stress reduction – a study funded by the National Institutes of Health (NIH) found that for overweight women, restorative yoga may offer a way to actually trim subcutaneous fat.  Obesity is a risk factor for breast cancer, including TNBC. The benefits of restorative yoga – a form of the practice that emphasizes relaxation over flowing movements or challenging balance poses – compared favorably with simple stretching when tested among a group of women who were clinically obese.  More.

New Imaging Technique Can Determine Cancer Subtype and Response to 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.  More.

Existing Drugs Kill TNBC Drugs By Targeting Their Own Waste

Triple-negative breast cancers may be vulnerable to drugs that attack the proteasome, a cellular structure that acts as the cell's waste disposal, breaking down damaged or unneeded proteins, according to a new paper in Cancer Cell.  In lab tests, researchers selectively "turned off" genes in triple-negative tumor cells. When turned off, the cells die. These data suggest that triple-negative breast cancers may respond to treatment with drugs similar to bortezomib (Velcade), which is used in multiple myeloma.  More.

Protein May Be Path to Targeted TNBC Treatment

A protein called Numb (seriously) 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 23^rd issue of Molecular Cell.   When Numb is reduced by the Set8 enzyme , it will no longer protect p53.  More.

HMGA1 Turns TNBC Cells Back to More Normal and Slows Their Growth

Researchers at Johns Hopkins have identified a gene that, when repressed in tumor cells, puts a halt to cell growth and a range of processes needed for tumors to enlarge and spread to distant sites. The researchers hope that this so-called “master regulator” gene may be the key to developing a new treatment for tumors resistant to current drugs.  More.

Diamonds May Be A TNBC Girl's Best Friend

UCLA researchers  have developed a potential new treatment for triple-negative breast cancer that uses nanoscale, diamond-like particles called nanodiamonds.  Nanodiamonds are between 4 and 6 nanometers in diameter and are shaped like tiny soccer balls. Byproducts of conventional mining and refining operations, the particles can form clusters following drug binding and have the ability to precisely deliver cancer drugs to tumors, significantly improving the drugs' desired effect. In the UCLA study, the nanodiamond delivery system has been able to home in on tumor masses in mice with TNBC.  More.

Omega 3 Fatty Acids in Fish Oil May Slow Triple-Negative

Researchers from Fox Chase Cancer Center have found that omega-3 fatty acids and their metabolite products slow or stop the proliferation, or growth in the number of cells, 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. More.

SOX11 and p53 May Spell Unique Development of Triple-Negative Breast Cancer

Could you create a breast cancer tumor in mature mice by reactivating how embryonic breast cancer cells develop?  And, if you could, what would you learn?  In a study published in the journal Breast Cancer Research, scientists discovered that basal-like  breast cancers with the BRCA1 mutation—many of them triple-negative breast cancers—grow differently than other cancers.  In fact, the way they grow predicts the prognosis of the tumor. More.

Could Copper Depletion Be a Cure for Metastatic TNBC?

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 surprising benefit for metastatic triple-negative breast cancer. Results of a phase II clinical trial conducted by researchers at Weill Cornell Medical College and reported in the Annals of Oncology shows 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). More.

Scientists Map TNBC's Metastatic Path

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. More.

Protease May Help Define New Subset of TNBC—and Lead to Treatment.

Researchers at St, Louis University have  found a molecular signature that may define a particular subset of triple-negative breast cancer,  which can ultimate lead to target therapy for that group of patients.  In specific, they 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.  And, when we know who the bad guy is, we can stop looking at ways to stop him in his mean old tracks. More

Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.

Please consider a donation to Positives About Negative to keep this site going.  This work is entirely supported by readers.  Just click on the Donate button in the right of the page.  Thank you!

HMGA1 Turns TNBC Cells Back to More Normal and Slows Their Growth

From a News Release from the Johns Hopkins University School of Medicine

Researchers at Johns Hopkins have identified a gene that, when repressed in tumor cells, puts a halt to cell growth and a range of processes needed for tumors to enlarge and spread to distant sites. The researchers hope that this so-called “master regulator” gene may be the key to developing a new treatment for tumors resistant to current drugs.

“This master regulator is normally turned off in adult cells, but it is very active during embryonic development and in all highly aggressive tumors studied to date,” says Linda Resar, M.D., an associate professor of medicine, oncology and pediatrics, and affiliate in the Institute for Cell Engineering at the Johns Hopkins University School of Medicine. “Our work shows for the first time that switching this gene off in aggressive cancer cells dramatically changes their appearance and behavior.” A description of the experiments appears in the May 2 issue of the journal PLOS ONE.

Resar has been investigating genes in the master regulator’s family, known as high mobility groupor HMG genes, for two decades. In addition to their role in cancer, these genes are essential for giving stem cells their special powers, and that’s no coincidence, she says. “Many investigators consider cancer cells to be the evil twin of stem cells, because like stem cells, cancer cells must acquire special properties to enable the tumor to grow and metastasize or spread to different sites,” she explains.

In a previous study, she and her team devised techniques to block the HMGA1 gene in stem cells in order to study its role in those cells. In their prior work, they discovered that HMGA1 is essential for reprogramming adult cells, like blood or skin cells, into stem cells that share most, if not all, properties of embryonic stem cells.

In the newly reported study, the Resar team applied the same techniques to several strains of human breast cancer cells in the laboratory, including the so-called triple negative cells — those that lack hormone receptors or HER2 gene amplification. The Resar team blocked HMGA1 expression in breast cancer cells and followed their appearance and growth patterns.

"Remarkably, within a few days of blocking HMGA1 expression, they appeared rounder and much more like normal breast cells growing in culture,” says Resar. The team also found that the cells with suppressed HMGA1 grow very slowly and fail to migrate or invade new territory like their HMGA1-expressing cousins.

The team next implanted tumor cells into mice to see how the cells would behave. The tumors withHMGA1 grew and spread to other areas, such as the lungs, while those with blocked HMGA1 did not grow well in the breast tissue or spread to distant sites.

“From previous work, we know that HMGA1 turns on many different genes needed during very early development, but it’s normally turned off by the time we’re born,” says postdoctoral fellow Sandeep Shah, Ph.D., who led the study. “Flipping that master regulator back on seems to be necessary for a cancer to become highly aggressive, and now we’ve seen that flipping HMGA1 off again can reverse that aggressive behavior.”

The next step, Resar says, is to try to develop a therapy based on that principle. The team is working with other researchers at Johns Hopkins to see whether HMGA1-blocking molecules could be delivered to tumors inside nanoparticles. Another possible approach, she says, would be to block not HMGA1 itself, but one of the pathways or processes that it affects.

• Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.

• Please consider a donation to Positives About Negative to keep this site going.  This work is entirely supported by readers.  Just click on the Donate button in the right of the page.  Thank you!

Genetic Details of Triple-Negative Breast Cancer

Beyond its most basic definition—negative for receptors for estrogen, progesterone and Her2/neu—triple-negative breast cancer has unique genetic characteristics.  Research published April 1, 2013 in the journal Cancer Research has outlined some of TNBC’s genetic associations.  Researchers keep getting closer to finding what makes TNBC tick.  Once they know that, they can target it.  Put a big red bull’s eye on its nasty old back. 

Some details of the research:

• TNBC is more likely to be associated with TOX3, ESR1, RAD51L1, TERT, 19p13.1, 20q11, MDM4, 2p24.1, and FTO.

• 70 percent of those with the BRCA1 mutation who get breast cancer get TNBC.

• 16  to 23 percent of those with the BRCA2 mutation who get breast cancer get TNBC.

• Variations in the 19p13.1 locus and the MDM4 locus have been associated with TNBC, but not other forms of breast cancer, meaning that these are TNBC-specific.

• TNBC accounts for 12 to 24 percent of all breast cancers.