EMERYVILLE, Calif., Dec. 29 /PRNewswire-FirstCall/ -- Bionovo, Inc. (Nasdaq: BNVI) announced today the publication of results from its study on the anti-tumor mechanism of BN107. The results of the study, published in the International Journal of Cancer, describe the potential molecular mechanisms mediating the selective pro-apoptotic (cell death) effect induced by BN107 on estrogen receptor negative (ER-) breast cancer cells.
Despite favorable advances that treatment options have had on survival, oncologists continue to face challenges in providing safe and effective treatment options for ER- breast cancer patients. In this patient population, the PI3K/Akt/mTOR pathway is often abnormally activated which allows cancer cells to grow uncontrollably and evade death. There are two mTOR protein complexes, mTORC1 and mTORC2, both of which are essential for the control of aberrant survival signals. Agents that can inhibit mTORC1 and mTORC2 at the same time might lead to effective suppression of the Akt/mTOR pathway and result in tumor cell death. The study showed that BN107 decreases the levels of proteins present in the mTORC1 and mTORC2 complexes, resulting in their demise specifically in ER- breast cancer cells. The mTOR pathway as a target for cancer therapies has been actively pursued by many pharmaceutical companies. To the Company's knowledge, this is the first report demonstrating effective inhibition of both mTOR complexes concomitantly through a novel mechanism.
As explained by Dr. Sylvia Fong, Research Scientist at Bionovo, "The ability of BN107 to induce cancer cell death is selective. We demonstrate that breast cancer cells lacking estrogen receptors are highly sensitive to BN107. Our studies show that disruption of mTOR signaling mediated by both mTORC1 and mTORC2 complexes is most likely responsible for the anti-tumor effect of BN107. Simply put, BN107 has a unique way to target a specific sub-group of breast cancer cells that currently has no selective treatment. This is exciting."
"It is critical to develop novel and safe strategies to effectively treat the patients with ER- breast cancers. We believe BN107 will result in better selectivity to hormone independent tumors based on its unique selectivity and mechanisms of action. Currently the only available treatment for this group, constituting 40% of women diagnosed with breast cancer, is chemotherapy. BN107, an oral drug candidate, should provide a chronic treatment option with a low toxicity profile," said Dr. Isaac Cohen, Chairman and CEO of Bionovo.
Tuesday, December 29, 2009
Monday, December 28, 2009
Read more about lifestyle changes that can reduce your risk of recurrence of TNBC in my book, Surviving Triple-Negative Breast Cancer.
Sunday, December 27, 2009
The Sarah Cannon Research Institute is looking for participants for a clinical trial of the drug Ixempra, which has shown promise as a treatment for triple-negative breast cancer in previous trials. According to the Memphis Commercial Appeal, women with triple-negative who are interested in participating should contact Sandra Dodd, research administrator with the Family Cancer Center, at (901) 747-9081.
The trial is part of a nationwide trial sponsored by Bristol-Myers Squibb, maker of Ixempra. The study will continue through 2011.
Saturday, December 26, 2009
Friday, December 25, 2009
Wednesday, December 23, 2009
The first detailed search of breast cancer genomes to uncover genomic rearrangements is published today. The team characterised the ways in which the human genome is broken and put back together in 24 cases of breast cancer.
Rearrangements involve reshuffling and reorganisation of the genome and include deletions, duplications and novel juxtaposition of DNA sequences. The study shows that breast cancer samples can differ greatly in the extent to which they are subject to genomic rearrangements: some are relatively undisturbed whereas others are fractured extensively and then reassembled with more than 200 rearrangements present.
While it is known that the majority of cancer genes important in blood cancers are activated by rearrangement, the role of this process in the common adult cancers is much less clear. This new study builds on pioneering work from the team using next generation sequencing to characterise comprehensively rearrangements in adult solid tumours.
"We have looked at the level of the DNA sequence at just how splintered and reorganised the genome is in many breast cancers. We were, frankly, astounded at the number and complexity of rearrangements in some cancers." says Professor Mike Stratton of the Wellcome Trust Sanger Institute. "Just as important, the genomes were different from each other, with multiple distinctive patterns of rearrangement observed, supporting the view that breast cancer is not one, but several diseases."
The information obtained from this study will add a new dimension to tumour classification and thus refine diagnosis and treatment.
In the study, the team used next-generation DNA sequencing to produce maps of genome rearrangements in 24 breast cancer samples, which were chosen to include the major subtypes of breast cancer and also included examples of breast cancers arising in BRCA1 and BRCA2 breast cancer families.
One breast cancer showed just a single genomic rearrangement – while others showed more than 200. The study provides detailed insights into the ways that the genome in some cancers have broken and also the processes that were used by the cancer cell in gluing the broken bits of genome back together again.
"It looks as though some breast cancers have a defect in the machinery that maintains and repairs DNA and this defect is resulting in large numbers of these abnormalities," says Dr Andy Futreal of the Wellcome Trust Sanger Institute. "At the moment we do not know what the defect is or the abnormal gene underlying it, but we are seeing the result of its malfunction in the hideously untidy state of these genomes. Identifying the underlying mutated cause will be central to working out how some breast cancers develop."
The broad groups of rearrangement were associated with different subtypes of breast cancer: HER2 positive breast cancers – those that are responsive to herceptin – have similar patterns of disruption. By the same measure, triple-negative breast cancers, which don't respond to treatment with herceptin or hormones, looked similar.
The size of the DNA regions that are deleted, duplicated or removed ranges from a few hundred letters of DNA code to several millions. Most changes were rearrangements within the same chromosome, but there were also a substantial number involving the joining of two different chromosomes.
Dissecting out the complexity and the diversity of the breast cancer genomes is important for understanding how the cancers arise. Importantly, however, the apparent loss of DNA repair systems raises the possibility of new therapeutic opportunities in some breast cancers.
"It appears that in different subtypes of breast cancers, distinct mechanisms of DNA repair are impaired, leading to different types of genomic disorganisation," suggests Dr Jorge Reis-Filho, team leader from the Breakthrough Breast Cancer Research Centre at The Institute of Cancer Research.
"If we damage further an already-faulty DNA repair system using tailored therapies, one can kill tumour cells selectively, without harming normal cells. There are already some highly interesting results suggesting that breast cancers with defects in DNA repair are more sensitive to drugs that cause additional DNA damage."
Stephens PJ et al. (2009) Complex landscapes of somatic rearrangement in human breast cancer genomes. Nature.
Under ordinary circumstances, the revised mammogram guidelines recommended last month by the U.S. Preventive Services Task Force would have struck me as misguided. But these were not ordinary circumstances, at least not for me. Just before the guidelines were released, I had been diagnosed with breast cancer.
It was one of those strange accidents of timing that sometimes happen in life. I know some people dismiss these instances as meaningless coincidence. But as someone who believes God has a special if mysterious purpose for each us in this world, I have always paid special attention to them. Read the entire essay here.
I do wonder about the 2004 Democratic presidential ticket, though. First Elizabeth Edwards, now Teresa Heinz Kerry.
Receptor status is one variable, but unique genetic aspects of breast cancer tumors might provide the most guidance on which tumors are the most sensitive to chemotherapy using taxanes.
Determining who benefits from adding taxanes as part of the treatment regimen for early-stage breast cancer may mean looking more at the biology of the disease—whether it is basal or luminal, for example—rather than on the current policy of screening based on lymph-node involvement.
A review of 21 trials affecting nearly 36,000 women with early-stage breast cancer evaluated the benefits of adjuvant chemotherapy—after surgery—using taxanes versus those not using taxanes. Published in the January 2010 issue of Nature Reviews Clinical Oncology, the analysis found that many women are overtreated with chemotherapy, while some greatly benefit from aggressive treatment. How to determine which is which is complex, and the decision is even more serious given the potential toxic effects of taxanes—heart failure, leukemia, neuropathy, and weight gain—not to mention the cost.
•Taxanes provide a 5 percent improvement in disease-free survival and 3 percent improvement in overall survival regardless of the type of taxane, its schedule of administration, lymph node involvement, or hormone-receptor status. Researchers call this a “modest improvement.”
• Women under 50 with and without affected lymph nodes benefit from taxanes. Relative risk of recurrence for node-negative disease in this group was reduced by 36 percent; relative risk of recurrence for node positive disease was reduced by 37 percent.
• Women 50-69 have less of a benefit—a 23 percent reduced relative risk of recurrence for node-negative and 17 percent for node-positive.
• Hormone-receptor status does not affect the benefit significantly for women under 50. Those with estrogen-negative cancers face a relative risk reduction of 39 percent and those with ER-positive had a 44 percent relative risk of reduction.
• In women 50-69, taxanes may provide less of a benefit to women with estrogen-positive (16 percent relative risk reduction) than estrogen-negative (33 relative percent risk reduction).
• For women under 50, the relative risk of recurrence after two years remains similar to the risk after 15 years. For women 50-69, however, the risk reduction occurs in the first two years, with little or no effect after that. This may be related to estrogen-receptor status, as women with ER-negative typically face the highest risk of recurrence within two years, while those with ER-positive disease face a sustained risk—over a longer period.
• Paclitaxel at 80 mg/m2 once a week or docetaxel every 3 weeks at 100 mg/m2 is superior to paclitaxel at 175 mg/m2 every three weeks following four cycles of AC.
• Doxorubicin and paclitaxel followed by once-weekly paclitaxel is more effective than standard AC with paclitaxel every 3 weeks.
• Improvements in the pathologically-complete response rate do not always translate to improvements in disease-free survival or overall survival.
• ER status or Her2 status alone aren’t significant predictors of who will benefit from taxanes.
• Genetic factors that are still being studied may provide the most information on who benefits from taxanes, once again demonstrating that our cancers are as unique as our DNA. For example, tumors with the P glycoprotein may be taxane resistant, as are those with β-tubulin mutations. Tumors with the TP53 mutation, however, may be more sensitive to taxanes. But ER-negative tumors with high levels of Aurora-A may be taxane resistant.
In their conclusion, the researchers write:
Based upon the first-generation taxane trials, taxane-based regimens are an important addition to the armamentarium against early-stage breast cancer. However, deciding which individual patients are likely to benefit from taxanes remains a challenge. Ultimately, clarifying the role of factors that affect the efficacy of taxanes in particular subgroups of patients (defined by traditional biomarkers such as age, ER status, and HER2 expression) will require international collaboration with rigorous examination of data from individual patients in first-generation taxane trials, in a future EBCTCG meta-analysis. Validation of additional biomarkers and evaluation of novel agents in the adjuvant setting will require innovative approaches to clinical trial design. Previous trials have clearly demonstrated that defining inclusion criteria for adjuvant chemotherapy trials on the basis of anatomically defined risk factors—such as lymph-node status—rather than disease biology is inherently flawed. Future advances will require identification of the patients likely to benefit from particular therapies, prospective centralized tumor banking, and a commitment to innovative platforms for translational research, to further optimize therapy for early-stage breast cancer.
Sunday, December 20, 2009
Triple negative breast cancer tumors that lack retinoblastoma protein (pRb) are much more likely to react positively to chemotherapy than TNBC tumors with pRb. Researchers studied 53 TNBC patients; at a follow-up of 105 months (8.75 years), all were disease-free after standard chemotherapy regimens. The research was published in the Annals of Oncology in June 2009 and was conducted in Bologna, Italy.
Thermography, which uses infrared imaging to detect changes in breast cancer tissue, can be effective in screening for breast cancer, according to research published in 2008 in the American Journal of Surgery. One huge benefit of this technique is that it is less painless than mammograms and does not emit radiation. In a randomized clinical trial, researchers used digital infrared imaging thermal imagining (DITI) on 92 patients for whom a breast biopsy was recommended. Thermography was 97 percent accurate. The researchers wrote:
DITI is painless, noninvasive,does not emit harmful radiation, has no patient risk, provides immediate results, and is relatively inexpensive.Compared to magnetic resonance imaging (MRI)—an adjunctive diagnostic tool for breast malignancy gaining more popularity—DITI is considerably more affordable to both patient and provider. MRI may cost $2,000 to the patient for each examination and $2 million to own the equipment, while DITI costs less than $200 for each exam and approximately $25,000 to own the equipment.
Researchers do not recommend thermography as a replacement for mammography, but suggest that some patients might benefit from this technique:
Researchers do not recommend thermography as a replacement for mammography, but suggest that some patients might benefit from this technique:
Patients who could potentially stand to benefit from this technology are those whose diagnosis of breast cancer can be difficult, including younger women, men, patients with dense breasts, or patients with surgically altered breasts (implants, breast reduction; provided nipples are intact for orientation and asymmetry analysis). Future studies using DITI for these individual groups can help to asses this potential.
Saturday, December 12, 2009
Sanofi-aventis (EURONEXT: SAN and NYSE: SNY) and its wholly-owned subsidiary, BiPar Sciences, announced that the clinical development program in metastatic triple-negative breast cancer (mTNBC) for the investigational PARP1 inhibitor, BSI-201, progresses as planned with the Phase 3 study meeting expectations on patient accrual and trial site coverage in the United States. Study investigators have enrolled 214 of the target number of 420 patients.
BSI-201 entered a Phase 3 clinical trial in the United States in July 2009 and is being evaluated in combination with chemotherapy in patients with mTNBC, a condition defined by tumors lacking expression of estrogen, progesterone receptors and without overexpression of HER2. BSI-201 is a novel investigational targeted therapy that inhibits poly (ADP-ribose) polymerase (PARP1), an enzyme involved in DNA damage repair. Read more on Medicalnewstoday.
Women with estrogen-negative breast cancers, as well as those with estrogen-positive disease, benefit from high soy intake, according to research in China published in the Journal of the American Medical Association.
Results were based on data from the Shanghai Breast Cancer Survival Study, a large, population-based cohort study of 5,042 female breast cancer survivors aged 20 to 75 years diagnosed between March 2002 and April 2006. Women were interviewed about their diet at 18, 36, and 60 months after diagnosis. Those with the highest intake of soy had the lowest recurrence rates. No toxic effects of soy were discovered.
Soy contains folate, fiber, and calcium, all of which have been shown to be beneficial in reducing cancer.
I am still going to avoid soy, because one study isn’t enough to convince me. I will continue my diet high in folate, fiber, and calcium and get my cancer fighters there.
Sources of folate, according to the National Institutes of Health, include vegetables, grains, and the innards of animals. (Ick.) Whole grains are a good source of fiber, as are fruits, vegetables, nuts, and seeds. The best sources of calcium are dairy products.
Friday, December 11, 2009
Adding the investigational drug BSI-201, a PARP inhibitor, to gemcitabineand carboplatin chemotherapy improves survival by almost 60 percent in patients with metastatic triple-negative breast cancer (estrogen-receptor, progesterone-receptor, and HER2 negative), in comparison to chemo alone. Results of a Phase II study presented at the San Antonio Breast Cancer Symposium replicate previous findings on PARP inhibitors, which interfere with the ability of cancer cells to repair themselves, making them more vulnerable to chemotherapy.
Reference: O'Shaughnessy J, et al "Updated results of a randomized phase II study deonstrating efficacy and safety of BSI-201, a PARP inhibitor, in combination with gemcitabine/carboplatin in metastatic triple-negative breast cancer" SABCS 2009; Abstract 3122.
Bone-density drugs like Fosamax show promise in reducing triple negative breast cancer tumors, according to two studies presented at the San Antonio Breast Cancer Symposium. The findings come from data from the Women's Health Initiative and an Israeli study of postmenopausal women.
Dr. Gabriel N. Hortobagyi, who directs the breast cancer research program at the University of Texas M.D. Anderson Cancer Center, told The New York Times:
“With tamoxifen and raloxifene, we have drugs that reduce estrogen receptor-positive tumors, but we’ve never had anything worth anything that prevented estrogen receptor-negative tumors.”
The next step is a randamized clinical trial to see if the findings hold up in a controlled setting. Hortobagyi told The Times:
“These are provocative data, but certainly not compelling, and not definitive.”
Wednesday, December 9, 2009
Triple negative breast cancers that metastasize typically move to the lungs or liver, which is called visceral metastases. Now, research published in the November 2009 British Journal of Cancer demonstrates that use of docosahexaenoic acid (DHA)—found in cold water fish, fatty fish, fish oil supplements, and seaweed—along with chemotherapy can extend life for these patients, with few side effects.
The study was a clinical trial enrolling 25 women at University Hospital in Bretonneau in Tours, France on breast cancer patients with visceral metastases. Patients were given 1800 mg of DHA a day, as nine capsules a day, three at each meal. Patients were asked to limit intake of antioxidants. They started this regimen before chemotherapy and continued it throughout five months of chemo.
The median age of participants was 58; 72 percent had liver metastases and 40 per cent had three or more metastatic sites. These, then, were seriously ill patients.
Chemo consisted of FEC: cyclophosphamide and fluorouracil followed by an IV infusion of epirubicin administered every 3 weeks. (This is a common chemo regimen in Europe but not in the US.) DHA was suspended on the day of chemotherapy. Duration was at least six cycles.
Median overall survival was 22 months, with a high at 34 months. Previous studies had shown overall survival rates for FEC of 18-23 months.
Those with the longest survival had the highest DHA intake. The median time to progression was six months. The most common side effect was neuropathy, caused by the chemo.
So, this is no cause for cartwheels, as metastatic breast cancer is serious business, and the study only slowed death—it did not beat it. But this does show that a simply dietary supplement—fish oil—can improve the effects of chemotherapy. Researchers suggest that this effect comes because DHA strengthens the non-cancerous cells, giving them more oomph to fight against cancer.
Given that fish oil has many other positive effects—especially helping avoid heart problems—it seems we should incorporate it into our diets ASAP.
The irony of my writing this is that I ran out of fish oil about two weeks ago and keep forgetting to buy it. As soon as this blizzard subsides, I am heading out to replenish my supply. I do take a daily green drink that includes spirulina and seaweed, though, so I have some deep-sea goodies circulating
Tuesday, December 8, 2009
Sunday, December 6, 2009
Women diagnosed with triple negative breast cancer are much more likely to have metabolic syndrome—a combination of risk factors that can include high blood glucose, high blood pressure, abdominal obesity, low HDL, elevated cholesterol and high triglycerides—than those with other forms of breast cancer. In a study presented at the 2009 American Society of Clinical Oncology Annual Meeting and published in a special edition of the Journal of Clinical Oncology, researchers evaluated 176 patients, 86 who were triple negative and 90 who were not. Fifty-eight percent of triple negative patients had metabolic syndrome compared to only 36.7 percent of non-triple negative patients. Hypertension and BMI alone, however, were not associated with triple-negative.
Friday, December 4, 2009
Most triple negative breast cancers carry a protein called MUC-1, say researchers at
the Ireland Cancer Center of University Hospitals Case Medical Center in Cleveland., and this could lead to the development of a vaccine for early stage TNBC.
Doctors analyzed 53 triple negative tumors and found that 92 percent of them expressed MUC-1, a protein in breast cancer cells could be a target for a vaccine using the patient's immune system to target and kill cancer cells.
Researchers are now testing a vaccine to fight MUC-1 and, therefore triple negative.
If it succeeds, subsequent research would study the effects of the vaccine on relapse-free survival rates. The vaccine is given after traditional treatment of surgery, chemotherapy, and radiation.
"This vaccine trial has the potential to rev up patients' immune response to the MUC-1 protein and shut down the tumor's ability to grow," says MD, PhD, chief researcher and director of Breast Cancer Research at the Ireland Cancer Center. "Women with this aggressive triple negative breast cancer have an increased risk of recurrence and we are hoping to provide them with protection against the return of this deadly disease."
Thursday, December 3, 2009
Breastcancer.org recently conducted a survey of its members about how and when their breast cancer was discovered. Mammograms detected breast cancer in 74 percent of respondents; 52 percent were diagnosed under age 50. The survey was motivated by the new breast cancer guidelines presented last week by the US Preventive Services Task Force.
More than 3,000 readers responded. Some of the survey's findings, from information provided by breastcancer.org:
•69% of respondents had been diagnosed with breast cancer, while 5% were either awaiting a test result or at high risk.
•52% were diagnosed under age 50 (41% between the ages of 40-49).
•Among all respondents diagnosed with breast cancer, routine mammogram (49%) and Breast Self Exam (37%) were the most common tool for initial breast cancer detection. Clinical exam was reported third at only 4%.
•Among the subset of women 40-49 diagnosed with breast cancer, initial detection was reported as: routine mammography (45%), Breast Self Exam (42%), clinical exam (4%), ultrasound (2%).
•Mammography detected the breast cancer in 74% of all breast cancer respondents. Among women diagnosed 40-49, mammography detected breast cancer in 73%.
Wednesday, December 2, 2009
Multiple studies have shown that vitamin D can reduce the risk of breast cancer; vitamin D is especially important for women with triple negative breast cancer, as they have been found to be more deficient in the vitamin than other cancer patients.
Natural sources of vitamin D are more effective than supplements, with the best source being UV rays from the sun. According to the National Institutes of Health, researchers recommend five to 30 minutes of sun exposure from 10 a.m. to 3 p.m. at least twice a week to the the face, arms, legs, or back without sunscreen.
However, those of us in sun-challenged areas of the country—a line above 42 degrees latitude, or roughly above the northern border of California and Boston—don’t get enough sun between November and February. Smog, shade, and cloud cover all reduce the sun’s effectiveness elsewhere. And UV rays cannot penetrate glass, so sitting in front of a window may feel good, but if offers little vitamin D benefit.
The NIH says the average adult can tolerate up to 2000 IUs of vitamin D a day. But where do we get it if not from the sun? Some of the best sources:
Cod liver oil (1 tablespoon): 1360 IU
Sockeye Salmon (3 ounces): 794 IU
Vitamin D-fortified milk (1 cup): 115-124 IU
Vitamin D-fortified orange juice (I cup): 100 IU
One egg yolk: 25 IU
See the entire list here.
If you cannot get enough natural vitamin D, go for supplements. Studies show that vitamin D3 is as much as three times as effective as other forms of vitamin D. A form of vitamin D known as Gemini 0097 is being studied by researchers at Rutgers for benefit to both hormone-positive and hormone-negative breast cancers, reducing the former by 60 percent and the latter by 50 percent. At this point, Gemini 0097 is still in the testing stage and is not yet available to consumers.
Short answer: yes. Fat-soluble supplements, however, are more of a problem than water-soluable. A meta-analysis of existing studies (Journal of the American Medical Association, February 2007) determined that overdoses of beta carotene, vitamin A, and vitamin E—all fat-soluable—may increase mortality. The risks of vitamin C, which is water-soluble, were not clear-cut and needed more study. Complementary Prescriptions, however, takes issue with the JAMA study, saying it was flawed in focusing on research that showed dangers while not looking at research that demonstrated positive effects.
Some clarification on vitamin types:
Fat-Soluble: These include vitamins A, D, E and K, which are stored in body fat tissues. Too many of these can build up in the liver, brain and heart and may be toxic. Dangerous levels, though, are typically many times the suggested normal dose.
Water-Soluble: B-complex and vitamin C are water-soluble, which means excess amounts are eliminated from the body in the urine, making them less dangerous.
Natural Sources: Your best bet for vitamins is to get them from vegetables, fruits, fish oils, low-fat dairy products, nuts, seeds, and whole grains. You’re far less likely to overdose on carrots than on beta-carotene.
The Annie Appleseed Project has a comprehensive overview of vitamins and their sources.