Friday, December 30, 2011

How Things Look Five Years Past Diagnosis

I am 2,055 days past diagnosis. That’s five years, 7 months and 16 days. I remember those first few days dragging on, each one seeming to last a year or so, as I looked longingly into the future to a time when my risk of recurrence would drop down to a level at which I could breathe easily.

I finished surgery, chemo, radiation. The first full year. The second. Then the days started to move quicker and quicker. And then, one day, I was three years past diagnosis, the point at which the risk of recurrence drops dramatically for triple-negative breast cancer. Then it was five years. And now cancer is history.

I had turned 60 a few months before my diagnosis and had made the dreadful joke that it was better than the alternative. Not so funny when I was faced with the prospect of that alterative.

I never actually thought I was going to die soon. But being diagnosed was the first time I faced the fact that I honestly and truly would eventually breathe my last breath. And I began to think that cancer might be what would cause my death. Not perhaps in a month or a year, but sometime. That is a sobering, life-changing, scary thought.

Now that I am so far on the other side, that point I looked at with such yearning when I was diagnosed, I have been reflecting on how it feels.

Darn good, folks. Darn good.

I am a different person now—certainly more thankful of things, more introspective, more contemplative, less judgmental. I matured into a deeper me through this experience, and I like that.

Sure, I can still be snarky, cynical, and impatient. I didn’t turn into Mother Theresa, just maybe a lower intern on her staff.

The longer I go past cancer, the less likely I am to see every symptom as a recurrence. I had a nasty pain in the back of my head the other day and Googled it. Sure enough, at some point, brain cancer came up—usually a recurrence of breast cancer, according to one site. (www.scarethepantsoffyou.com). Did I stiffen with anxiety, as I used to at such prospects? No, I moved on. I did not have brain cancer then any more than I had it with a headache two years or three years or five years ago. I knew that. The difference now was that I also felt it. I felt like I was OK.

I have loosened my dietary restraints a tad and am letting myself eat a bit more fat, but only occasionally. I still try hard to eat well. And I keep up my exercise. Lately I have been doing a workout through Beachbody.com. After about nine months I am still at the “getting started” level, but I can keep up, I get a workout, and my weight has dropped a tad. I wish the workout were called something more befitting of somebody with my obvious high class and finesse, but it is what it is. I do have to watch how I explain what I am doing. “I am working on my Beach Body” really makes people do a double take at the grandma they see before them.

My day is filled with meaningful activities—time with family and friends, yoga, meditation, spiritual activities, discussion groups. I spend time almost every day in email chats with somebody who is going through the cancer journey, and I hope I can help. I love that I have the chance to try.

I retired from full-time work about a year after my diagnosis. And, while I miss that regular salary, I love being able to do what is meaningful to me, to spend a good amount of time each day taking care of myself and others. That doesn’t pay all that well in dollars and cents, but it sure has a solid emotional and spiritual reward.

I drink a lot less. I still enjoy a martini every now and then and, actually, enjoy it more because it is an event, not an everyday thing, a needed soother after a stressful day. And I notice that I sleep much better when I do not drink.

I have been blessed with 2,055 days after diagnosis with no recurrence. I remain thankful for every day. I hope that does not change.

Friday, December 23, 2011

Breathe: Health in, Cancer out

Deep breathing can help calm us in almost all instances. Yoga exercises emphasize the importance of deep, cleaning breaths. If you've been recently diagnosed or are going through treatment, see if this technique might help soothe you:

On a long inhale, say "health in."
On a long exhale, say "cancer out."

Repeat as long as you want. I usually did this for about 10 repetitions a time and, if I were really focusing well, I honestly could envision good, clean white air going in, and the evil cancer going out. I still occasionally do this, five years later.

Now, I seldom mention cancer, I just repeat "health in" on the inhale, and simply relax on the exhale.
Breathe......

Sunday, December 11, 2011

How to Manage Holiday Stress + Breast Cancer Stress

It’s the most wonderful time of the year, croons Andy Williams over the store’s loud speaker. Really? I think. I’m sure the retailer wants me to agree with Andy, which might mean I’ll toss some more goodies into my cart. But I am not convinced. Buying stuff does not equal happiness, nor does piped-in music mean all is wonderful. I leave the store empty handed and head to the lake for a walk.

My post-cancer self is sort of like that—she finds less appeal in acquiring stuff and is much more eager to spend time in nature, getting exercise and some psychological balance. I like this change—I wish I had made it without having to go through surgery, chemo, radiation, and fearing for my life. I’ve learned that contentment is not for sale at the mall or on the Internet, but discontent surely is. And it is all ramped up during the holidays.

In most cases, the holidays can’t stand up to their own hype. We, in general, expect too much of the season—family togetherness, a beautiful snowy landscape, peace, joy, exquisite decorations, and fancy cookies. Our own living, breathing Hallmark card—a pretty tall order under the best of circumstances. But when you’re dealing with breast cancer, the season of forced glee can be a heavy burden.

The sadness of what a diagnosis means, the fear for our future, worry about our kids, anxiety about what treatment will do to our bodies, terror about whether or not we can beat this disease, anger that we got sick in the first place—it can be a pretty potent stew of emotions on any given day. And we’re often simply sick and tired and not physically up to our usual, let alone somebody else’s expectation of holiday-level wonderful.

My first post-diagnosis Christmas came when my hair was a thin layer of fuzz and my energy was stuck at slug level. I was still at the point where I resented every woman I saw who did not have breast cancer, so I was a little raw physically and emotionally. The only thing I really wanted that year was normalcy, which I tried to achieve by making myself at least look somewhat like the old me. I was tired of wearing wigs, so I opted for a snazzy silk scarf for a family celebration at our home. Hair equaled ordinary to me, so I wanted to show off my new stubby growth. But, for the life of me, I cannot tie a scarf like a grown-up, so that little number kept falling down my forehead or slipping lopsidedly over one ear and then another. I looked like a drunken pirate. I considered ducking into my bedroom and throwing on a wig. But, ultimately I decided that this is the way I looked at this point in my life, and my family loved me despite that fact. Or, maybe, even because of it.

This should be a season of love, a time for you to rebuild your health, which may be the only gift your family and friends want. Some thoughts on making the season more enjoyable for you:

Manage Expectations. What do you need from the holidays this year? Rest? Peace and quiet? Or lots of company? Talk this over with friends and family and determine what you can and can’t do—and realize it’s OK for this year to be different. I found that decorating the house perked me up, but I still left quite a few ornaments in the basement because I simply ran out of energy. Nobody noticed.

Avoid Holiday Pitfalls. Caffeine and alcohol can take us even farther into the doldrums. Both are plentiful during the holidays and both are harmful for our physical recovery. I generally follow a diet heavy on complex carbs—grains, vegetable, and fruits—supported with cheese, yogurt, fish, and shellfish. I use the Mediterranean diet as a model, but reduce the amount of wine it suggests because of the link between breast cancer and alcohol.

Keep Active. Walk, do yoga, swim, dance—anything that keeps your body active can help calm your mind. If you feel sadness descending, or you are getting anxious, get up and do whatever you can handle: walk to the mailbox, put on a yoga DVD, or hang up the Christmas wreath. Any activity will do. A friend of mine started taking piano lessons during treatment, bought herself an inexpensive keyboard, and hit the ivories when she started feeling low. She now plays pretty darn well.

Enjoy Nature. Spending time outdoors can increase your energy and reduce your anxiety. I actually enjoy bundling up in a warm coat, hat, scarf, mittens, a boots, and going out into the wintry air. Too much hot inside air can be stifling. Fresh air is invigorating for body and mind.

Honor Your Emotions. I was sad and angry that first year, grieving my former life. Pretending otherwise would have been denying my own reality. Bottled emotions, like liquor, get stronger with age. And denying them just gives them more power over you. Your body, mind and spirit have been through a huge change, especially if you have already started treatment, and that can turn your emotions inside out. Check BCO’s overview of treatment side effects, which includes anxiety, depression, and fatigue.

Talk it Out. If the holidays are making you especially low, find a wise friend, counselor, minister, or anybody you can trust and sit down and talk about how you feel. Sometimes simply expressing yourself is the first step toward feeling better.

Know the Difference Between Sadness and Depression. Sadness is not a sign of weakness. It is a sign you are human. Yet, if you are so sad you don’t feel like doing anything or seeing anybody, and if it’s not getting any better, you might be depressed. Check BCO’s analysis of the difference between sadness and depression. Depression requires professional help. But before you take any additional medications, check with your oncologist, to make sure those drugs will not interfere with your treatment, especially if you are on tamoxifen.

Laugh. Watch funny movies, hang around friends who make you laugh, do anything that can tickly your funny bone. Even try laughter yoga. The act of laughing itself can reduce stress. I come from a funny family in oh so many ways, but mainly we just enjoy laughing. I know that helped my recovery greatly. And if you’re going to look like a drunken pirate in your Christmas pictures, you sure should be able to chuckle about it.

Thursday, December 8, 2011

News from San Antonio: Do TNBC Women Not Exist?

Broadcast and print media have been heralding breakthroughs in breast cancer research at the San Antonio Breast Cancer Symposium this week. The Oncotype DX test can help determine treatment for women with DCIS, they say. Yay! BUT: The Oncotype DX test only works with hormone-postive disease, not hormone-negative, including triple-negative.

Strike one for a breakthrough for the TNBC women.

And zoledronic acid (Zometa) increases breast cancer survivorship. Yay! Oh, wait, that's for hormone-positive disease.

Strike two for TNBC women.

If we get one more strike, are we out?

This would be less frustrating if media reports would clarify that these advances apply to some types of breast cancer but not all. Lumping all of our lumps together is just confusing, frustrating, and wrong. We get our hopes up, only to spend hours looking for the research and finding that it does not include TNBC benefits.

OK, that's all. Just a little rant here.

Breast Cancer and the Environment: Report from the Institute of Medicine

The study below, as far as I can tell, did not differentiate between estrogen-positive and estrogen-negative disease. (The effects of hormone replacement therapy, for example, are largely restricted to hormone-positive disease.) Still, researchers are taking environmental issues seriously and Susan G. Komen for the Cure has announced it will be promoting further research. And even if there is no explicit link to hormone-negative, who wants to get hormone-positive? Plus, living healthy is good for your entire body, not just your breasts.


WASHINGTON — Women may be able to reduce their risk for breast cancer by avoiding unnecessary medical radiation, forgoing use of combination estrogen-progestin menopausal hormone therapy if possible, limiting alcohol consumption, maintaining a healthy weight, exercising regularly, and avoiding tobacco use, says a new report from the Institute of Medicine. These preventive steps focus on the environmental risk factors for which there is consistent scientific evidence of an association with breast cancer.

The evidence also indicates a possible, though currently less clear, link to increased risk for breast cancer from exposure to benzene, 1,3-butadiene, and ethylene oxide, which are chemicals found in some workplace settings and in gasoline fumes, vehicle exhaust, and tobacco smoke. Avoiding personal use of hair dyes and non-ionizing radiation emitted by mobile devices and other technologies likely will not impact a woman's risk for breast cancer, as multiple studies have found no connection to the disease.


Because of insufficient or contradictory evidence, the scientific jury is still out on whether many chemicals of concern, including bisphenol A (BPA), pesticides, ingredients in cosmetics and dietary supplements, and other substances alter the risk for breast cancer, the report says. Women may choose to minimize their exposure to some chemicals, but the committee found the research inadequate to draw conclusions about the potential benefit of such actions. Chemical ingredients in cosmetics, dietary supplements, and other products undergo only very limited testing before they are put on the market, and the committee noted the value of efforts to help consumers become more aware of this issue.


The steps identified in the report have the potential to reduce risk for breast cancer among women in general, but the committee cautioned that the evidence on how much risk reduction any of these steps offers is inconclusive. Whether it is small or significant, the impact on individuals will vary considerably because women are exposed to a range of substances throughout their lives; in addition, biological, physical, and genetic factors influence their individual chances for developing the disease.


The report's conclusions are the result of a detailed review of scientific research on environmental factors that may affect breast cancer risk. The committee also explored challenges to studying possible links between environmental exposures and breast cancer and recommends future research directions. Areas where there is provocative but as yet inconclusive evidence and that warrant priority attention include overnight shift work and accompanying disruptions of the sleep cycle; chemicals that mutate genes, alter gene expression, or affect hormones such as estrogen; and gene-environment interactions. More research needs to be conducted on the effects of exposures throughout the entire life span, including at specific stages of breast development, and on the cumulative effects of exposures at different life stages or multiple exposures that occur together, the report emphasizes. Most research has focused on adults and on exposures occurring within a few years prior to a diagnosis, but recent studies have shown the importance of exposures at various life stages, such as childhood, adolescence, pregnancy, and menopause.


In many cases, more information also needs to be gathered to determine whether preventive steps can be taken and how they can be most effective. For example, we do not yet know when weight loss is most likely to be beneficial in reducing postmenopausal cancer risk.


"Breast cancer develops over many years, so we need better ways to study exposures throughout women's lives, including when they are very young," said committee chair Irva Hertz-Picciotto, professor, department of public health sciences, and chief, division of environmental and occupational health, School of Medicine, University of California, Davis. "We also need improved methods to test for agents that may be contributing to breast cancer risk and to explore the effects of combined exposures."


The study was sponsored by Susan G. Komen for the Cure. Established in 1970 under the charter of the National Academy of Sciences, the Institute of Medicine provides independent, objective, evidence-based advice to policymakers, health professionals, the private sector, and the public. The National Academy of Sciences, National Academy of Engineering, Institute of Medicine, and National Research Council make up the National Academies. For more information, visit http://national-academies.org or http://iom.edu.

Test to Show Whether Chemo Works not Effective for TNBC

CHICAGO, IL, Nov 29, 2011 (MARKETWIRE via COMTEX) -- Presented yesterday at the RSNA 2011 annual meeting, researchers from The University of Texas MD Anderson Cancer Center showed that using Positron Emission Mammography (PEM) to measure PEM values (PUV) from baseline may indicate whether neoadjuvant chemotherapy is effective. PEM is positioned to benefit this patient population as it may help identify when a chemotherapeutic regimen is not working. PEM also has the potential to play a role in initial staging of breast cancer in patients at high risk for multifocal or multicentric disease who desire breast conservation therapy as an alternative to breast MRI.

"It is conceivable that PEM values may be an early indicator of efficacy to targeted therapy for breast cancer patients," stated Dr. Wei Yang, Vice Chair of Radiology at MD Anderson Cancer Center. "Breast cancer, as we understand it today, is currently being treated on the basis of molecular features of the patient's tumor. A knowledge of the range of the molecular and functional imaging features of tumors will hopefully help confirm current molecular phenotypes, serve as a tool for the prediction of response and hopefully help to develop a schema that incorporates imaging, molecular phenotypes and predictive biomarkers that will translate into better clinical trials for diagnosis, treatment and prevention."

PEM is the breast application of the Naviscan high-resolution PET scanner showing the location as well as the metabolic phase of a lesion. It is the only FDA-cleared 3D Molecular Breast Imaging (MBI) device on the market. The metabolic view assists physicians in making optimal care decisions by providing an ability to distinguish between benign and malignant lesions, what researchers term "specificity."

The goal of the study was to report the utility of PEM to evaluate pathologic and clinical response to targeted therapy for breast cancer patients treated on two neoadjuvant clinical trials, phase II lapatinib for HER 2 overexpressing inflammatory breast cancer (IBC) and phase 1b dasatanib for triple negative breast cancer (TNBC). All patients underwent PEM in conjunction with mammography and ultrasound. Lapatinib patients also underwent dynamic contrast-enhanced MRI. PEM was performed prior to treatment and repeated at day 21 after run-in with the chemotherapeutic agent and imaging results were correlated either with subsequent pathological response for the lapatinib study or clinical response by RECIST criteria for the dasatinib study.

Results showed that PEM values decreased from baseline in the effective chemotherapeutic regimen, lapatinib. However there was not substantial change in the ineffective dasantinib regimen.

About Naviscan, Inc.

Naviscan, founded in 1995, develops and markets compact, high-resolution PET scanners intended to provide organ-specific molecular imaging and guide radiological and surgical procedures. The Naviscan PET scanner is currently installed and available in breast and imaging centers throughout the U.S. and is globally distributed in 34 countries. The Company is headquartered in San Diego, California and is the first to obtain FDA-clearance and CE Mark for a high-resolution PET scanner designed to image small body parts and for breast biopsy image guidance.

Diabetes drug Metformin prevents spread of hormone-negative cancer cells

FROM A NEW RELEASE FROM THE KIMMEL CANCER CENTER:

IMAGE: This is Michael P. Lisanti, M.D., Ph.D., Professor and Chair of Stem Cell Biology & Regenerative Medicine at Thomas Jefferson University.

Click here for more information.

PHILADELPHIA -- Researchers at the Kimmel Cancer Center at Jefferson have identified cancer cell mitochondria as the unsuspecting powerhouse and "Achilles' heel" of tumor growth, opening up the door for new therapeutic targets in breast cancer and other tumor types.

Reporting in the online Dec.1 issue of Cell Cycle, Michael P. Lisanti, M.D., Ph.D., Professor and Chair of Stem Cell Biology & Regenerative Medicine at Thomas Jefferson University, and colleagues provide the first in vivo evidence that breast cancer cells perform enhanced mitochondrial oxidative phosphorylation (OXPHOS) to produce high amounts of energy.

"We and others have now shown that cancer is a 'parasitic disease' that steals energy from the host -- your body," Dr. Lisanti said, "but this is the first time we've shown in human breast tissue that cancer cell mitochondria are calling the shots and could ultimately be manipulated in our favor."

Mitochondria are the energy-producing power-plants in normal cells. However, cancer cells have amplified this energy-producing mechanism, with at least five times as much energy-producing capacity, compared with normal cells. Simply put, mitochondria are the powerhouse of cancer cells and they fuel tumor growth and metastasis.

The research presented in the study further supports the idea that blocking this activity with a mitochondrial inhibitor -- for instance, an off-patent generic drug used to treat diabetes known as Metformin -- can reverse tumor growth and chemotherapy resistance. This new concept could radically change how we treat cancer patients, and stimulate new metabolic strategies for cancer prevention and therapy.

Investigating the Powerhouse

Whether cancer cells have functional mitochondria has been a hotly debated topic for the past 85 years. It was argued that cancer cells don't use mitochondria, but instead use glycolysis exclusively; this is known as the Warburg Effect. But researchers at the Jefferson's KCC have shown that this inefficient method of producing energy actually takes place in the surrounding host stromal cells, rather then in epithelial cancer cells. This process then provides abundant mitochondrial fuel for cancer cells. They've coined this the "Reverse Warburg Effect," the opposite or reverse of the existing paradigm.

To study mitochondria's role directly, the researchers, including co-author and collaborator Federica Sotgia, Assistant Professor in the Department of Cancer Biology, looked at mitochondrial function using COX activity staining in human breast cancer samples. Previously, this simple stain was only applied to muscle tissue, a mitochondrial-rich tissue.

Researchers found that human breast cancer epithelial cells showed amplified levels of mitochondrial activity. In contrast, adjacent stromal tissues showed little or no mitochondrial oxidative capacity, consistent with the new paradigm. These findings were further validated using a computer-based informatics approach with gene profiles from over 2,000 human breast cancer samples.

It is now clear that cancer cell mitochondria play a key role in "parasitic" energy transfer between normal fibroblasts and cancer cells, fueling tumor growth and metastasis.

"We have presented new evidence that cancer cell mitochondria are at the heart of tumor cell growth and metastasis," Dr. Lisanti said. "Metabolically, the drug Metformin prevents cancer cells from using their mitochondria, induces glycolysis and lactate production, and shifts cancer cells toward the conventional 'Warburg Effect'. This effectively starves the cancer cells to death".

Personalized Treatment

Although COX mitochondrial activity staining had never been applied to cancer tissues, it could now be used routinely to distinguish cancer cells from normal cells, and to establish negative margins during cancer surgery. And this is a very cost-effective test, since it has been used routinely for muscle-tissue for over 50 years, but not for cancer diagnosis.

What's more, it appears that upregulation of mitochondrial activity is a common feature of human breast cancer cells, and is associated with both estrogen receptor positive (ER+) and negative (ER-) disease. Outcome analysis indicated that this mitochondrial gene signature is also associated with an increased risk of tumor cell metastasis, particularly in ER-negative (ER-) patients.

"Mitochondria are the 'Achilles' heel' of tumor cells," Dr. Lisanti said. "And we believe that targeting mitochondrial metabolism has broad implications for both cancer diagnostics and therapeutics, and could be exploited in the pursuit of personalized cancer medicine."

More TNBC treatment tools on the horizon? Whole-genome sequencing

PHOENIX, Ariz. -- Initial results from an ongoing clinical trial, the first designed to examine the utility of whole-genome sequencing for triple negative breast cancer, were reported today during the CRTC-AACR San Antonio Breast Cancer Symposium.

The results indicate activation of targets not previously associated with triple negative disease and could point toward new treatment strategies. Based on mutations uncovered by sequencing, physicians recommended the women enter treatment protocols for either existing drugs or new agents being evaluated in pharma-sponsored clinical trials.

Triple negative breast tumors, which make up nearly 20 percent of breast cancers, do not respond to treatment with targeted therapies such as Herceptin® (trastuzumab).

Of eleven tumors sequenced to date, each was genomically unique, but commonalities were observed. Some patients displayed amplified genes in the RAS pathway; one patient had amplification of the BRAF oncogene, as well as activation of a growth pathway known as the MEK/AKT pathway. This patient displayed an impressive response to a MEK/AKT inhibitor currently in a phase I clinical study.

"Those results are quite striking considering that these are women with advanced disease," said Joyce O'Shaughnessy, M.D., who presented the data. "If MEK/AKT activation is found to be present in a substantial fraction of triple negative patients, inhibitors of this pathway could prove a significant tool in fighting this disease."

Dr. O'Shaughnessy is medical director and co-chair of the Breast Cancer Research Committee, US Oncology Research; a practicing oncologist with Texas Oncology; and the Celebrating Women Chair of Breast Cancer Research at Baylor Charles A. Sammons Cancer Center.

"This is among the largest studies of a single tumor type in which whole genome sequencing is being used to identify potential options for targeted treatment," said John Carpten, Ph.D., director of the Integrated Cancer Genomics Division at the Translational Genomics Research Institute (TGen). "As the field of genomic medicine matures, this study is sure to provide key early insights into how sequencing can best be utilized in the clinic."

The study, titled "Next Generation Sequencing Reveals Co-Activating Events in the MAPK and PI3K/AKT Pathways in Metastatic Triple Negative Breast Cancers," is sponsored by the Translational Genomics Research Institute (TGen) and US Oncology Research with support from Life Technologies Corporation. Whole-genome sequencing of tumors and normal tissue was performed on Life Technologies' Applied Biosystems SOLiD™ platform, and results were validated in a CLIA-certified laboratory.

About Baylor Health Care System

Baylor Health Care System is a not-for-profit, faith-based supporting organization providing services to a network of acute care hospitals and related health care entities that provide patient care, medical education, research and community service. Baylor recorded more than 2.6 million patient encounters, $3.8 billion in total operating revenue, $4.4 billion in total assets and $513.5 million in community benefit in fiscal year 2010. Baylor's network of more than 300 access points includes 27 owned/operated/ ventured/affiliated hospitals, 23 joint ventured ambulatory surgical centers, 50 satellite outpatient locations, four senior centers and 156 HealthTexas Provider Network physician clinics.

About Texas Oncology

Texas Oncology delivers high-quality cancer care with leading-edge technology and advanced treatment and therapy options available to help patients achieve "More breakthroughs. More victories."® in their fights against cancer. Texas Oncology, a pioneer in community-based cancer care, is an independent oncology practice with sites of service throughout Texas and southeastern Oklahoma. Texas Breast Specialists and Texas Urology Specialists, which focus on all areas of breast and urologic care, are a part of Texas Oncology.

Texas Oncology patients have the opportunity to take part in some of the most promising clinical trials in the nation for a broad range of cancers. Texas Oncology participates in innovative clinical trials from Phase I through Phase IV through US Oncology Research, which has helped to develop 43 FDA approved cancer therapies.

Texas Oncology is united in healing with The US Oncology Network, one of the nation's largest community-based cancer treatment and research networks focused on advancing cancer care in America. As an affiliate of The US Oncology Network, Texas Oncology is united with more than 1,000 physicians and 10,000 cancer professionals nationwide. The US Oncology Network is supported by McKesson Specialty Health.

For more information, visit http://www.TexasOncology.com or call 1-888-864-I-CAN (4226).

About TGen

The Translational Genomics Research Institute (TGen) is a Phoenix, Arizona-based non-profit organization dedicated to conducting groundbreaking research for life changing results. Research at TGen is focused on helping patients with diseases such as cancer, neurological disorders and diabetes. TGen is on the cutting edge of translational research where investigators are able to unravel the genetic components of common and complex diseases. Working with collaborators in the scientific and medical communities, TGen believes it can make a substantial contribution to the efficiency and effectiveness of the translational process. TGen is affiliated with the Van Andel Research Institute in Grand Rapids, Michigan. For more information, visit: http://www.tgen.org.

About US Oncology Research

McKesson Specialty Health conducts clinical trials through US Oncology Research, which draws from a network of experienced investigators and dedicated clinical staff who specialize in Phase I through Phase IV oncology clinical trials. US Oncology Research serves more than 90 sites in over 250 locations managing more than 200 active trials at any given time. Physicians in the research network have enrolled more than 50,000 patients in over 1,200 trials since inception in 1992 and have contributed to the development of 43 cancer therapies approved by the FDA. For more information call 800-482-6700, option 4 or visit http://www.usoncology.com/oncologists.

Phase 2 Clinical Trial Shows Ganetespib Effective in TNBC

A News Release from Synta Pharmaceuticals Corp.

LEXINGTON, Mass., Dec 08, 2011 (BUSINESS WIRE) -- Ganetespib, a potent, second generation Hsp90 inhibitor, has demonstrated clinical activity in heavily pre-treated patients with HER2-positive and triple negative metastatic breast cancer according to Phase 2 clinical trial results presented by researchers from Memorial Sloan-Kettering Cancer Center at the San Antonio Breast Cancer Symposium (SABCS).

"The single agent ganetespib results presented today further validates Hsp90 as a target for treating HER2-positive breast cancer and suggest Hsp90 inhibition may be an important new approach to treating triple negative breast cancer," said Shanu Modi, M.D., Memorial Sloan-Kettering Cancer Center, the principal investigator on this study. "15% (2/13) of the patients with the HER2 gene amplification experienced a partial response in this trial and an additional 46% (6/13) achieved stable disease. These encouraging results for Hsp90 inhibition in HER2 positive disease are consistent with results from an earlier Phase 2 study of 17-AAG, a first generation Hsp90 inhibitor, in which 22% (6/27) achieved partial response and an additional 37% (10/27) achieved stable disease(1). While in the prior study 17-AAG was given in combination with trastuzumab, in the current study ganetespib was given as a monotherapy. Together, these studies present compelling evidence that Hsp90 inhibition is effective in HER2-positive breast cancer."

"We were also encouraged by evidence of clinical activity in one of three evaluable triple negative breast cancer patients, who experienced significant tumor shrinkage following three doses of ganetespib," continued Dr. Modi. "Triple-negative breast cancer represents a difficult-to-treat disease, for which no targeted therapies are currently approved."

All HER2-positive patients on the ganetespib Phase 2 trial had progressed following treatment with trastuzumab (Herceptin(R)).

"We are excited to continue development with this compound in a Phase 1/2 combination trial," continued Dr. Modi. "This new trial will evaluate ganetespib in combination with paclitaxel and trastuzumab in HER2-positive breast cancer, and ganetespib in combination with paclitaxel in triple negative breast cancer. "Ganetespib has demonstrated synergy with taxanes in pre-clinical studies and is currently being studied in a Phase 2b/3 trial in combination with docetaxel in non-small cell lung cancer. The Phase 1/2 trial in breast cancer will be initiated in 2012.

"The evidence of single agent activity shown today is supported by earlier ganetespib clinical results, including a confirmed, objective response in the triple-negative breast cancer patient enrolled in our Phase 1 trial," said Iman El-Hariry, M.D., Ph.D., Vice President, Clinical Research, Synta. "Importantly, ganetespib was well-tolerated in this trial Phase 2 trial with Grade 1 and 2 diarrhea and fatigue being the most commonly reported adverse events. This is consistent with the safety profile seen in over 450 patients treated to date across a wide range of cancers. The activity reported today combined with a favorable safety profile supports advancing both the MSKCC combination trial as well as additional proof-of-concept trials of ganetespib in HER2-positive and triple negative breast cancer."

A total of 22 patients were enrolled in the trial reported today. Of the 13 HER2+ patients, all of whom were refractory to treatment with trastuzumab, 2/13 (15%) showed a partial response, and an additional 6/13 (46%) showed stable disease as their best response.

About HER2-positive Breast Cancer

HER2-positive breast cancer is a subtype of breast cancer that tests positive for over-expression of a protein called human epidermal growth factor receptor 2 (HER2), which promotes the growth and progression of cancer cells. In about 1 of every 5 breast cancers, the cancer cells make an excess ("over-expression") of HER2 due to a gene mutation.

About Triple-negative Breast Cancer

Triple-negative breast cancer is a subtype of breast cancer that tests negative for expression of estrogen and progesterone receptors (ER/PR) and HER2 protein. It is characterized by its aggressive behavior, distinct patterns of metastasis, and lack of approved targeted therapies.

1. Shanu Modi, Alison Stopeck, Hannah Linden, David Solit, Sarat Chandarlapaty, Neal Rosen, Gabriella D'Andrea, Maura Dickler, Mary E. Moynahan, Steven Sugarman, Weining Ma, Sujata Patil, Larry Norton, Alison L. Hannah, Clifford Hudis: HSP90 Inhibition is Effective in Breast Cancer: A Phase 2 Trial of Tanespimycin (17AAG) plus Trastuzumab in Patients with HER2-Positive Metastatic Breast Cancer Progressing on Trastuzumab. Clin Cancer Res, May 10, 2011. 2. Baselga J, Tripathy D, Mendelsohn J, Baughman S, Benz CC, Dantis L, Sklarin NT, Seidman AD, Hudis CA, Moore J, Rosen PP, Twaddell T, Henderson IC, Norton L: Phase II study of weekly intravenous recombinant humanized anti-p185HER2 monoclonal antibody in patients with HER2/neu-overexpressing metastatic breast cancer. J Clin Oncol 1996, 14:737-744. 3. Cobleigh MA, Vogel CL, Tripathy D, Robert NJ, Scholl S, Fehrenbacher L, Wolter JM, Paton V, Shak S, Lieberman G, Slamon DJ: Multinational study of the efficacy and safety of humanized anti-HER2 monoclonal antibody in women who have HER2-overexpressing metastatic breast cancer that has progressed after chemotherapy for metastatic disease. J Clin Oncol 1999, 17:2639-2648.

About Hsp90

Hsp90 is a chaperone protein required for the proper folding and activation of cellular proteins, particularly kinases. Many of these "client proteins" of Hsp90 -- such as ALK, AKT, BCR-ABL, BRAF, KIT, MET, EGFR, FLT3, HER2, PDGFRA, VEGFR -- have been shown to be critical to cancer cell growth, proliferation, and survival and are the targets of clinically validated cancer drugs. In preclinical studies, inhibiting Hsp90 causes the degradation of multiple client proteins and leads to cancer cell death.

About Ganetespib

Ganetespib (formerly STA-9090) is a potent, synthetic, small-molecule inhibitor of heat shock protein 90 (Hsp90). Hsp90 is a molecular chaperone required for the proper folding and activation of many cancer-promoting proteins, and is recognized as a key facilitator of cancer cell growth and survival. In preclinical experiments, ganetespib has shown activity in multiple tumor models both as a single agent and in combination with certain widely used cancer agents. Ganetespib is currently being evaluated in a broad range of cancer clinical trials, including the global Phase 2b/3 GALAXY trial in non-small cell lung cancer. In these trials, ganetespib has shown anti-tumor activity in heavily pretreated patients with lung cancer, breast cancer, and other tumor types and has been well tolerated with no evidence of severe liver or common ocular toxicities seen with other Hsp90 inhibitors. The most common adverse event seen to date has been diarrhea, which has been manageable with standard supportive care. Information on clinical trials with ganetespib can be found at www.clinicaltrials.gov .

About Synta Pharmaceuticals

Synta Pharmaceuticals Corp. is a biopharmaceutical company focused on discovering, developing, and commercializing small molecule drugs to extend and enhance the lives of patients with severe medical conditions, including cancer and chronic inflammatory diseases. Synta has a unique chemical compound library, an integrated discovery engine, and a diverse pipeline of clinical- and preclinical-stage drug candidates with distinct mechanisms of action and novel chemical structures. All Synta drug candidates were invented by Synta scientists using our compound library and discovery capabilities. For more information, please visit www.syntapharma.com .

Safe Harbor Statement

This media release may contain forward-looking statements about Synta Pharmaceuticals Corp. Such forward-looking statements can be identified by the use of forward-looking terminology such as "will", "would", "should", "expects", "anticipates", "intends", "plans", "believes", "may", "estimates", "predicts", "projects", or similar expressions intended to identify forward-looking statements. Such statements, including statements relating to the timing, developments and progress of our clinical and preclinical programs, particularly the timing of initiation of the Phase 1/2 trial of ganetespib in breast cancer, reflect our current views with respect to future events and are based on assumptions and subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied by such forward-looking statements, including those described in "Risk Factors" of our Form 10-K for the year ended December 31, 2010 as filed with the Securities and Exchange Commission. Synta undertakes no obligation to publicly update forward-looking statements, whether because of new information, future events or otherwise, except as required by law.