BN107 Effective Against Hormone-Negative Cancers

From a news release from Bionovo on the use of the mTOR Inhibitor, BN107, in cases of estrogen-negative breast cancer:

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.

A Triple-Negative Breast Cancer Diet

What to eat to reduce your risk of recurrence of triple-negative and other forms of hormone-negative breast cancer.

So, the doc has scared the wind (or whatever) out of you, told you that your cancer—triple-negative, or some form of hormone-negative—is highly aggressive yet has fewer treatment options than hormone-positive. Been there, done that. Tamoxifen or aromatase inhibitors offer no benefit. What now?

After researching this disease for the three and a half years since my diagnosis, I have learned a great deal about how diet reacts to hormone-negative forms of cancer. Below is the diet that I follow. So far, so good. I am past the magic three-year mark and I feel darn good. Elsewhere in this blog are specific posts that offer research details on each of these dietary choices.

Fruits and vegetables. This is a huge key. Aim for five servings a day. My approach:

• A breakfast smoothie with blueberries (antioxidants), flaxseeds (cancer-fighting fighting fiber)), bananas, black cherry (more antioxidant) juice, and yogurt (bone-building and cancer-fighting calcium). I figure this gives me 2.5 servings of fruits and one serving of calcium.

• Juiced veggies every evening. This includes 3-4 carrots, 1-2 leaves of kale, 1/8 cabbage, 1 bunch parsley, 1 stalk celery, ¼ apple, ¼ lemon. My super-juicing husband uses a Champion juicer, which takes the pulp out and leaves only the juice. This gives me 2- 3 servings of veggies and is heavy on cancer-fighting cruciferous vegetables—kale and cabbage. The lemon, apple, and celery really help the taste.

• Spinach, broccoli, asparagus, green beans, romaine and other dark greens throughout the day as side dishes. I have found that it is true that the more you eat something, the more you will like it. I used to only tolerate broccoli if it came smothered in cheese. Now I eat it raw and unadorned.

Low fat

I avoid fried foods, use healthy fats such as olive oil instead of butter and cream, and go mainly vegetarian. I use oil and vinegar on my salad, lemon oil on veggies, and olive or flax oil on my whole grain bread. For treats, I have nuts, air-popped popcorn, whole grain crackers, and low-fat cheese.

COMPLEX CARBS

I limit my processed carbohydrates—sugar, white bread and pasta—and eat 1-2 servings of whole grains a day. Look for the word “whole” on the label. Multigrain breads are not whole grain unless they include whole wheat, rice, oats, or other grains, so watch out for trick labels. A good serving of whole grains will have 3 grams of fiber per serving.

Vitamins and Minerals

I try to get as many of my goodies in my diet, but I find I need some supplements to assure I get everything I need. I take:

• 1000-2000 IU of vitamin D. It would be great to get this through the sun, but I live in Iowa, so that’s not going to happen for a good portion of the year.

• Folic acid—800 mg daily. This is especially important if I have alcohol.

• Calcium—1200 mg. I figure I get at least half of this with yogurt and cheese during the day, so I take 600 mg daily in supplement form. Make sure you take a calcium supplement with magnesium, as this helps calcium enter the system and keeps calcium from causing constipation.

• Omega 3 fatty acids. I take this in the form of fish oil, 450-500 mg per day of combined EPA/DHA.

• A multi-vitamin, to assure I get enough vitamin A, B, C, and E, plus minerals.

ORGANICS

I buy organic milk and cheese to avoid the added hormones and antibiotics in conventional dairy products even though my disease was hormone-negative. Why mess with unnatural additives?I buy organic versions of the Environmental Working Group's Dirty Dozen —a list of fruits and vegetables that are high in pesticides, when I can. I seldom eat meat.

Calorie limits

I am 5’9”, so I can have 1500-1800 or so calories a day. I also exercise at least 30 minutes six days a week, so I can occasionally afford a few more calories without gaining weight.

ALCOHOL

Even though research shows that alcohol is most dangerous for hormone-positive disease, I choose not to take a chance. I have my beloved martini once or twice a week. I have wine, perhaps, on a third day.

CAFFEINE

I drink decaf tea and coffee, and keep the coffee to a cup a day, as even decaf has caffeine.

Choose your partner well

My husband is a great cook and he has his eye out for my health. He makes my juice every day, finds yummy low-fat recipes, and keeps the fridge full of healthy foods. I am a lucky woman.

For more information on a cancer-fighting diet, check out my book, Surviving Triple-Negative Breast Cancer.  You can get a free signed copy just by donating $25 to this site.  Click the Donate button on the right to donate through PayPal.   You'll then get an email from me asking how you want your book signed and where you want it sent.  Thanks!  And hugs.

Nationwide Trial of Ixempra Looking for Participants in Memphis

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.

New Brochure About TNBC

Living Beyond Breast Cancer has a new brochure on triple-negative breast cancer. You can download it as a free PDF from their site.

Christmas 09

From our home to yours. Wishing you the blessings of the season: family, friends, love, hope, faith, and goodwill.

Pat and Joe

Breast Cancer DNA Mapped: Triple Negative Has Unique DNA Sequence

From a news release from the Wellcome Trust Sanger Institute:

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."

Source:
Stephens PJ et al. (2009) Complex landscapes of somatic rearrangement in human breast cancer genomes. Nature.

Teresa Heinz Kerry Speaks Out About Her Breast Cancer

A mammogram found the cancer, says Heinz Kerry. In an essay in the Pittsburgh Post-Gazette, she talks about the cancer that had been diagnosed right before the proposed change in mammogram guidelines. Her prognosis, she says, "is good."

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.

Who Benefits from Taxanes?

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.

Some findings:

•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.

Retinoblastoma protein (pRb) associated with better prognosis for TNBC

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.

Is Thermography A Valid Diagnostic Tool for Breast Cancer?

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:

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.

BSI-201 phase 3 study in progress for metastatic triple-negative breast cancer

From a Sanofi-aventis news release:

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.

Soy May Benefit Women with Estrogen-Negative Breast Cancer

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.

PARP Inhibitor BSI-201 Improves Survival for Metastatic Triple Negative

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.

TNBC Tumors Respond to Bone-Loss Drugs

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.”

 

 

Fish Oil Improves Overall Survival for Breast Cancer with Visceral Metastases

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

Second Anniversary of this Blog

I posted my first essay on this blog two years ago, December 6, 2007. It was a cheeky piece, "Pat's Breast Is Here," about how so many medical folks saw me as a disembodied breast while I went through treatment. Since then, I have added 175 posts; learned an extraordinary amount; racked up almost 39,000 page views; and connected with lovely readers from all over the world.

The blog has become a part of me, a focus of my life, and a beautiful reward. I am saddened to see the search terms readers use to get to me: The most popular is a variation of "triple negative survival statistics." Readers often frame that question in terms such as "Can you survive triple negative?" The answer, of course, is yes. Triple negative is not an automatic death sentence, and I have posted the stats here to prove that--the great majority of women with the disease survive.

I sit here with a sinus infection feeling sorry for myself . And then I get perspective. I am more than three-years disease-free of hormone-negative, and most cases recur in the first three years. My readers remind me also that my case was not that big of a deal.

So happy anniversary to this blog, and thanks to all of you who have connected with me, and whose emails I look forward to--Deb, Ghazala, Noreen, Victoria, Marousa, Rose, Anhila, Doris, Kimberly, Susan, Carol, Julie, Susan, Nancy, Penny, Chelsea.... What a beautiful international list.

Metabolic syndrome tied to triple negative breast cancer

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.

Cleveland Hospital Testing Vaccine for Triple Negative

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."

Information from a news release from University Hospitals. Check here for details on the clinical trial. NOTE: They are no longer enrolling participants; this was dated in September.

Breastcancer.org Survey: Most Breast Cancers Discovered By Mammograms

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%.

Natural Sources of Cancer-Fighting Vitamin D

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.

Can you take too many vitamins?

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.

Vitamin D and Breast Cancer: An Overview

Studies of the benefits of vitamin D have been controversial, with some showing significant benefits and other showing none, and most not differentiating between hormone receptor types. The difference often is in the study design. Research on serum vitamin D—the form that circulates in the blood—often find more cancer-fighting evidence. Those that study vitamin D intake are less convincing. This could be because our bodies use vitamin D differently, depending on a variety of factors: age, diet, activity level, and even genetics. Also, serum vitamin D might come from the most natural of all sources—the sun or our diets—whereas vitamin D intake often measures artificial forms. Still, even researchers who study the serum form advocate supplements, especially for people in northern latitudes who do not have the benefit of regular sunny days.

Triple Negative and Vitamin D

A case study of 91 breast cancer patients in Whittier, California found that those with triple-negative were more likely to be deficient in serum vitamin D—doctors measured a form called 25 (OH)D. Fifteen of the patients were triple-negative, and the majority of those—87 percent—had lower levels of the vitamin than other cancer patients, with the remaining 13 percent being borderline low. This ties in with other research on triple negative and on vitamin D, the researchers write: “African American women have the highest breast cancer specific mortality rates, the lowest serum levels of 25(OH)D, and the highest incidence of aggressive triple-negative or basal-like tumors.”

A specific form of active vitamin D3 known as Gemini 0097 substantially reduced the development of both ER- and ER+ breast cancer in rats, according to research done at Rutgers University. Scientists injected rats with breast cancers then treated them with Gemini 0097. The vitamin D slowed the growth of ER-positive by 60 percent and ER-negative by 50 percent. As with all studies in animals, more research needs to be done to determine the effects of Gemini 0097 on human cancers. One benefit so far is that Gemini 0097 is less toxic than other forms of synthetic vitamin D and does not lead to an overload of calcium, the vitamin’s most common side-effect.

Research Reviews on Vitamin D and Breast Cancer

Several research reviews support the benefits of vitamin D. According to a 2009 review done by scientists at the University of California, San Diego, low levels of serum Vitamin D are connected to a variety of cancers, including breast, colon, ovarian, renal, pancreatic, and aggressive forms of prostate, and other cancers. Researchers projected that raising our intake of vitamin D would prevent 58,000 new cases of breast cancer each year; 2,000 mg a day, they say, can increase serum levels to a healthier range without other risks.

In a 2006 review, scientists cited numerous studies that link both calcium and vitamin D to breast cancer risk for premenopausal and well as postmenopausal women. And in a third review, in 2007, researchers noted that 2000 IU a day of Vitamin D3 can reduce the risk of breast cancer by 50 percent.

Research on 16,818 participants in the Third National Health and Nutrition Examination Survey (NHANES III) determined that women with higher levels of serum vitamin D (over 25 ng/mL) had only about one fourth the mortality rate from breast cancer as those with lower amounts. Survey participants were 17 years or older at enrollment and were followed from 1988–1994 through 2000.

Research on Vitamin D Supplements and Breast Cancer

Yet a long-term study—seven years—of postmenopausal women as part of the Women’s Health Initiative found no relationship between Vitamin D and breast cancer. Researchers gave women 1000 mg of elemental calcium with 400 IU of vitamin D3 daily. Those women had no lower risk of breast cancer than those receiving a placebo.

And research using data from the Cancer Prevention Study-II Nutrition Study also found no association between postmenopausal breast cancer risk and levels of Vitamin D, regardless of hormone receptor status, body mass index, postmenopausal hormone therapy, weight gain, season of the year, or calcium intake. However, researchers did note that:

• the source of Vitamin D might be important, with women who get the vitamin through their diet—in fortified milk or fish, for example—having higher levels circulating in their bodies. Also, dietary Vitamin D is strongly correlated with calcium, which may be effective in fighting breast cancer.

• Women living at northern latitudes—above 37° —get less Vitamin D from the sun and were more likely to have breast cancer than those in southern latitudes.

What the research says on breast self-exams

The recommendations by the U.S. Preventive Services Task Force to forego breast self-exams (BSE) was based on research on the effectiveness of the exams. I found three studies, but the newest was in 2003. I continue to search for newer studies.

The studies below show no benefit, but have some flaws. In the Russian study, women did not follow through with the exams, so testing the BSEs effectiveness was compromised. And the Chinese study showed an equal number of cancers in the group that learned self-exams and the group that didn’t. This doesn’t address the issue of whether some of the cancers in the group that learned BSEs were found early enough to be treated.

The studies:

In a clinical tiral in St. Petersburg, Russia, 122,471 women between 40 and 64 were trained to perform BSE. One problem: many of these women did not actually practice self exams after they were taught how; after 5 years, only 55.8 percent of the women practiced BSE at least 5 times per year. After 9 years, the group that was taught self exams and the group that was not taught them had the same mortality rate from breast cancer, with no difference in the stage of breast cancers diagnosed. Self-exams did lead to a higher rate of biopsies for benign lumps. This was published in the journal Vopr Onkol in 1999.

In a randomized trial in Shanghai, China, 267,040 women ages 31-64 were taught BSE and were regularly reminded to practice the technique. Most women followed through during the study period and learned the BSE well. After about 10 years, the group that was taught self-exams and the group that was not taught them had the same breast cancer mortality rate, also with little evidence that BSEs led women to find their cancers earlier. The group that learned self-exams and the group that didn’t found the same number of cancers each year of the study. In addition, the number of cancers that had spread to the lymph nodes was similar in each group. Again, self-exams had more benign lumps than the control group did. This was published in the Journal of the National Cancer Institute in 2002.

A third study the Russian and the Chinese trials together and, likewise, found no benefits to breast self-exams. The review found twice as many biopsies with benign results in the groups taught self-exams compared to the groups who were not taught self-exams. This was published by the Cochrane Collaboration in 2003.

Sources:

Semiglazov VF, Moiseenko VM, Manikhas AG, et al. [Interim results of a prospective randomized study of self-examination for early detection of breast cancer (Russia/St.Petersburg/WHO)]. Vopr Onkol 1999;45:265-71.


Thomas DB, Gao DL, Ray RM, et al. Randomized trial of breast self-examination in Shanghai: Final Results. J Natl Cancer Inst 2002;94(19):1445-57.

Kosters JP and Gotszsche PC. Regular self-examination or clinical examination for early detection of breast cancer (Review). John Wiley & Sons Ltd. (for The Cochrane Collaboration) 2008.

What do the New Mammography Guidelines Really Say?

You’ve read about them and heard about them and talked about them to your office colleagues. But what are the new standards presented b the U.S. Preventive Services Task Force ( USPSTF)?

The guidelines are published in the Annals of Internal Medicine and you can read the entire manuscript there.

Some highlights of the paper. The recommendations are simple. They are:

The USPSTF recommends biennial screening mammography for women between the ages of 50 and 74 years.

The USPSTF concludes that the current evidence is insufficient to assess the additional benefits and harms of screening mammography in women 75 years or older.

The USPSTF concludes that the current evidence is insufficient to assess the additional benefits and harms of clinical breast examination beyond screening mammography in women 40 years or older.

The USPSTF recommends against clinicians teaching women how to perform breast self-examination.

The USPSTF concludes that the current evidence is insufficient to assess additional benefits and harms of either digital mammography or magnetic resonance imaging instead of film mammography as screening modalities for breast cancer.

Task force members maintain that research supports mammogram screening for women over 50, but not for women 40-49:

There is convincing evidence that screening with film mammography reduces breast cancer mortality, with a greater absolute reduction for women aged 50 to 74 years than for women aged 40 to 49 years. The strongest evidence for the greatest benefit is among women aged 60 to 69 years.

Notice that they mention film mammography. That is an outdated method. Digital mammograms are offered at most—if not all—breast cancer centers. They are more precise and more effective in finding cancers in younger women. In reference to digital mammos, task force members say, in research-ese, that evidence is lacking.

As for breast self exams, the write:

Adequate evidence suggests that teaching BSE does not reduce breast cancer mortality.

I am looking for research on self-exams. My question: Are they studied all that much? If no absolute evidence exists, is that because the subject has not been adequately studied? I will post what I find.

The task force also worried about the harm caused by mammograms and self-exams, although they say these harms are small or moderate.

All in all, not that convincing a case, and a seriously confusing presentation. Shame on them for taking women’s health concerns so lightly that they didn’t think this through better.