Friday, January 31, 2014

Melatonin May Slow TNBC Tumor Growth

I take 10 mg of melatonin every night and have done so since my diagnosis almost eight years ago.  I do it because of previous research on cancer in general.  It also helps me sleep.  This research encourages me to continue.    
Melatonin may help slow the growth of triple-negative negative breast cancer tumors, according to   research from the Henry Ford Hospital in Detroit and Foundation for Research Support of the State of São Paulo. 
According to the study, melatonin may inhibit tumor growth and cell production and block the formation of new blood vessels.  The research, which was done in the lab on mice, was published online in the journal PLoS One
Melatonin is a hormone that regulates the body's sleep and awake cycles and is available in inexpensive supplements.  
According to the American Cancer Society, low levels of melatonin have been linked to cancer.  Other research has tied it the seasonal occurrence of breast cancer.
To determine the effectiveness of melatonin on triple-negative breast cancer tumor growth,  mice implanted with TNBC tumors were randomly assigned to either the melatonin or control groups. The melatonin group received treatment each night for 21 days; concentrated melatonin was administered one hour before room lighting was switched off. Melatonin administered prior to sleep is believed to be more effective because tissues are most sensitive to the hormone at this time.
Those treated showed significantly smaller tumors after 21 days while the mean tumor volume increased significantly in the control group. And, there was less vascular growth in the tumors of the treated group. Results were also replicated in cell models.
Researchers warn that this is an early stage trial, and more basic research is needed on this topic before clinical trials with humans can be planned—Information from Henry Ford Health Systems
SOURCE: Bruna Victorasso Jardim-Perassi, Ali S. Arbab, Lívia Carvalho Ferreira, Thaiz Ferraz Borin, Nadimpalli R. S. Varma, A. S. M. Iskander, Adarsh Shankar, Meser M. Ali, Debora Aparecida Pires de Campos Zuccari. Effect of Melatonin on Tumor Growth and Angiogenesis in Xenograft Model of Breast Cancer. PLoS ONE, 2014; 9 (1): e85311 DOI: 10.1371/journal.pone.0085311

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

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Thursday, January 30, 2014

Breast Abnormalities May Be Early Warning of Cancer

Contrary to existing understanding, long-term follow-up of patients with two types of breast tissue abnormalities suggests that both types of abnormalities have the same potential to progress to breast cancer, according to a study published in Cancer Prevention Researcha journal of the American Association for Cancer Research. Findings from this study could improve clinical management of patients with breast tissue abnormalities.

This study challenges current understanding that atypical ductal hyperplasia (ADH), a type of breast tissue abnormality, leads to breast cancer in the same breast while atypical lobular hyperplasia (ALH), another type of breast tissue abnormality, may not be a direct precursor of breast cancer, but may indicate equal risk of breast cancer across both breasts.

“Ours is the first report with sufficient numbers of both types of atypia and long-term follow-up for breast cancers that compared the side of breast that had atypia with the side of breast in which cancer arose and the timeframe when the cancers developed,” said Lynn C. Hartmann, M.D., professor of oncology at the Mayo Clinic in Rochester, Minn. “We showed that even though the two types of atypia look different histologically, they behave quite similarly in terms of what happens to patients.

“More than a million American women have a breast biopsy with benign findings every year, and about 10 percent of these biopsies reveal atypical hyperplasia, a premalignant finding with a proliferation of abnormal cells, which have some but not all the features of a breast cancer,” she added. “There are two types of atypical hyperplasia based on their microscopic appearance—ADH and ALH—and it has been thought that they behave differently.

“Most have considered ADH a direct precursor to breast cancer, arguing that it requires complete surgical excision while others have maintained that ALH serves as an indicator of heightened and equal risk of breast cancer across both breasts and does not need complete surgical removal,” explained Hartmann. “Moreover, some experts have argued that women with atypia develop ‘better risk’ breast cancers, meaning low-grade cancers with a good prognosis.”

Hartmann and colleagues identified 698 women from the Mayo Benign Breast Disease Cohort who had biopsy-confirmed atypia; 330 of them had ADH, 327 had ALH, and 32 had both. The investigators followed these women for an average of 12.5 years, and 143 of them developed breast cancer.

The investigators found that the ratio of breast cancer in the same breast in which the atypia was detected versus in the opposite breast was the same, 2:1, for both ADH and ALH.

A similar number of women with either ADH or ALH developed breast cancer in the same breast within five years of diagnosis, which led the authors to suggest that, like ADH, ALH may also be a precursor in addition to being a risk indicator.

Contrary to current understanding that ALH might mostly lead to the development of lobular cancer, this study found that ALH predominantly resulted in ductal cancer of the breast, which is a similar outcome as with ADH. Both ADH and ALH resulted in invasive ductal cancers, of which 69 percent were of intermediate or high grade. About 25 percent of them had spread to the lymph nodes. The pattern of cancers in these patients resembled those seen in the general population.

“If a woman has a breast biopsy and if it shows atypia, it might be wise for her to be seen at a breast center for recommendations about surveillance and preventive therapy options,” said Hartmann. “We hope these data will further help clinicians make informed decisions for breast atypia management strategies.”  
—News release from the American Association for Cancer Research.

For help planning a cancer-fighting diet and overall lifestyle, check out my book, Surviving Triple-Negative Breast Cancer.

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Saturday, January 25, 2014

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!

Saturday, January 18, 2014

Phase 3 Trial of Veliparib and Carboplatin for Early Stage TNBC Announced

AbbVie, a global, research-based biopharmaceutical company formed in 2013 following separation from Abbott, announced the initiation of a Phase 3 clinical trial evaluating the safety and efficacy of its investigational compound, veliparib (ABT-888) when added to carboplatin, a chemotherapy, in women with early-stage, triple-negative breast cancer.  The three-arm trial will compare the addition of veliparib plus carboplatin or placebo plus carboplatin to standard neoadjuvant chemotherapy. 
"This new Phase 3 trial is an important step in potentially providing women with early-stage triple-negative breast cancer with a new treatment option for use in conjunction with surgical therapy," said Scott Brun MD, Vice President, Pharmaceutical Development, AbbVie. "While therapies exist to treat many forms of breast cancer, there is still a significant need for effective, targeted therapies for women with early-stage triple-negative breast cancer, which tends to be an aggressive, faster growing form of breast cancer."  [Pat's note:  Some forms are aggressive, but not all.  I wish experts would not make such blanket statements. Research needs to show us which ones are fast growing and which are not. Again, most women survive TNBC, especially those with early stage.]
The randomized, placebo-controlled, double-blind, Phase 3 trial will recruit approximately 620 patients who will be randomized to one of three arms of the trial. The primary efficacy outcome of the trial is pathological complete response (pCR), which is achieved when there is no evidence of residual, invasive cancer in the breast tissue and lymph node tissue, following treatment. The secondary outcome of the trial will determine the rate of eligibility for breast conservation after therapy. Other pre-specified outcome measures include event-free survival (EFS), overall survival (OS), and complete response rate (CRR). The safety of veliparib will also be evaluated in the trial.
More information on the trial is available at (NCT02032277). The trial will be conducted in collaboration with cooperative groups: Alliance Oncology, German Breast Group (GBG), German Gynecological Oncology Working Group-Breast (AGO-B), National Surgical Adjuvant Breast and Bowel Project (NSABP), and U.S. Oncology Research.
About Veliparib (ABT-888) Veliparib (ABT-888) is an investigational oral poly (adenosine diphosphate [ADP]–ribose) polymerase (PARP) inhibitor being evaluated in multiple tumor types. PARP is a naturally occurring enzyme in the body that repairs damage to DNA, and contributes to chemotherapy resistance in cancer cells. Discovered and developed by AbbVie researchers, veliparib is being developed to increase the effectiveness of common DNA-damaging therapies like chemotherapy or radiation. Veliparib is currently being studied in more than a dozen cancers and tumor types, including Phase 2 studies in a variety of cancers, including breast, ovarian, and non-small cell lung cancers.
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Researchers think TNBC metastasizes differently than other breast cancers

A team of researchers from the Cleveland Clinic and Case Western Reserve School of Medicine have identified critical complex mechanisms involved in the metastasis of triple negative breast cancers (TNBC). The discovery of this critical interaction of mechanisms could be used to develop new life saving treatments to kill metastatic tumors in TNBC.
“In previous findings published over the past 10 years, our teams have described key mechanisms in these critical proteins,” said Khalid Sossey-Alaoui, PhD, Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic.  A key component in the metastatic potential of TNBC tumors is that they spread through tissues outside the breast very quickly. "The two proteins that we studied, WAVE3 and TGF-β, when together, promote tumor aggressiveness.” [Pat's note:  And that means that not all TNBC tumors are aggressive; this may help determine which are and which aren't.]
“We found important biological implications,” said William Schiemann, PhD, an associate professor, Division of General Medical Sciences-Oncology, Case Western Reserve School of Medicine, and co-leader of the Breast Cancer Program at the Case Comprehensive Cancer Center. “For the first time, we uncovered an interplay between the two proteins that can inhibit or suppress TNBC – a discovery that has the potential to inhibit proliferations of the tumor.”
The next step in the research process is to find a way to deliver inhibitors to the tumor. Using nanoparticles, the Sossey-Alaoui, Schiemann team hope to deliver therapies directly to the site of the tumor and reverse the disease. Their goal is to move this basic research into clinical trials in the next three years.
“This finding helps to uncover the complex cascade of events that lead to metastasis, ” said Stanton Gerson, MD, director of the Case Comprehensive Cancer Center and director of the Seidman Cancer Center at UH Case Medical Center. “These studies are part of a broad initiative in breast cancer research through numerous collaborative efforts at the Case Comprehensive Cancer Center. Using a team science approach is the most efficient and productive way to have an impact in cancer.”
Metastasis is a complex, multi-stage process in which primary tumor cells invade the surrounding cells, tissues and organs, integrate into blood vessels, and survive and move throughout the body. Metastasis of primary mammary tumors accounts for the vast majority of deaths of breast cancer patients. The five-year survival rate for patients with breast cancer drops precipitously from 98% for individuals with localized disease to 23% for those with metastatic disease.
Research support was provided in part by the National Institutes of Health to W.P.S. (CA129359) and E.F.P. (HL073311 and HL HL096062), and by the Department of Defense to K.S.-A. (BC073783) and to M.A.T.(BC093128). Additional support was provided to W.P.S. and K.S.-A. by pilot funds from the Case Comprehensive Cancer Center (P30 CA043703).
This study appeared in the print addition of Breast Cancer Research and Treatment on November 7, 2013. In addition to K. Sossey-Alaoui and W. P. Schiemann, co-authors on the paper include: M. A. Taylor, M. K. Wendt, Case Comprehensive Cancer Center; G. Davuluri, E. F. Plow, Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic; J. G. Parvani, Department of Pathology, Case Western Reserve University.
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Wednesday, January 8, 2014

Reduce Your Risk of Cancer: Eat Healthy, Stay Active, Limit Alcohol, Don't Smoke

Postmenopausal women whose behaviors were consistent with the Nutrition and Physical Activity Cancer Prevention Guidelines put forth by the American Cancer Society (ACS) had lower risk for cancer incidence, and cancer-related and cancer-unrelated death, according to a study published in Cancer Prevention Researcha journal of the American Association for Cancer Research.

“Postmenopausal women who have greater adherence to cancer prevention guidelines demonstrate a 17 percent lower risk for cancer incidence, 20 percent lower risk for cancer-related death, and 27 percent lower risk for death from all causes,” said Cynthia Thomson, Ph.D., R.D., professor of public health at the Mel and Enid Zuckerman College of Public Health at the University of Arizona in Tucson. “We found that the association was stronger for Asian, African-American, and Hispanic women, compared with non-Hispanic white women. It is possible that different ethnic groups may have differential disease course with varied response to environmental and/or behavioral exposures.

The message is simple and clear: If you want to reduce your risk for cancer, even later in life, eat a healthy diet, be active daily, avoid or limit alcohol, and don’t smoke,” she said. “Our results support the ACS guidelines for cancer prevention. Certainly, efforts to identify complementary factors that can reduce risk further should be supported as well, because diet and activity alone do not account for the majority of risk,” Thomson added.

The ACS guidelines for cancer prevention include four behavior-associated measures: body weight, physical activity, diet, and alcohol consumption. Each component is assigned a numerical score in an effort to quantify diet and physical activity into a single indicator of cancer-preventive behavior. The guidelines are reviewed, updated, and published about every five years, explained Thomson.

Thomson and colleagues analyzed data available from 65,838 postmenopausal women age 50-79, enrolled in the Women’s Health Initiative (WHI) Observational Study between 1993 and 1998 at 40 clinical centers across the United States. This is the largest study of postmenopausal women in the United States, according to her.
Behaviors least consistent with the recommendations got a score of zero, and behaviors that met the criteria got scores of one or two depending on the level of adherence to the guidelines, and the scores were added to get the final score for an individual.

The researchers found that a majority of the women had final scores between three and six, with less than 1 percent resorting to behaviors that gave them a score of eight (the maximum score).
Participants were followed for an average of 8.3 years, and during this period, 8,632 cancers were diagnosed and 2,356 deaths due to cancer were recorded.

Compared with those who had the lowest scores (zero to two), those who had the highest scores (seven or eight) had 22 percent lower risk for breast cancer and 52 percent lower risk for colorectal cancer, in addition to having lower risk for all cancers combined, and for death related and unrelated to cancer. - NEWS RELEASE FROM THE AMERICAN ASSOCIATION FOR CANCER RESEARCH.

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Monday, January 6, 2014

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.

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.

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 23rd 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!