Older Women with TNBC Benefit from Chemo

Some physicians contend that the risks of chemotherapy are greater than its benefits for older breast cancer patients; new research shows otherwise.

Women over 65 with triple-negative breast cancer with affected lymph nodes benefit from chemotherapy, according to research published in the Journal of the American Medical Association. Researchers surveyed the records of 6,487 women with lymph-node positive disease who were older than 65 and who had been treated between 1975 and 1999 with a variety of chemotherapy regimens. Their basic conclusion: Age alone should not be the determining factor in assessing treatment options.

"I believe older patients in generally good health with triple-negative disease should get the best possible chemotherapy," said researcher Hyman Muss, MD, at the Miami Breast Cancer Conference. Muss is director of geriatric oncology at the University of North Carolina's Lineberger Comprehensive Cancer Center, in Chapel Hill.

The Cancernetwork has an article on the research.

Two April Teleconferences on TNBC

The Triple Negative Foundation and Living Beyond Breast Cancer are sponsoring two teleconferences of triple-negative breast cancer.

April 12, 12-1:15 pm Eastern. Triple Negative Breast Cancer: A Medical Update, with Lisa Carey, MD. She will provide an overview and cover treatments and latest research.

April 26, 12- 1:15 pm. Triple-Negative Breast Cancer: Fear of Recurrence, with Hester Hill Schnipper, LICSW, BCD, OSW-C. She will discuss where to go and what to do once treatment ends.

Register at the TNBC Foundation or LBBC.

Journey to Spring: Understanding Disasters, Natural and Personal

Bald eagles are hanging out at the lake by us and robins are chirping outside my window. Some early trees are budding, and the sun is no longer a stranger.

The seasons are changing and spring becomes more and more of a promise.

And we need it. The earthquake, tsunami and nuclear disaster in Japan are heartbreaking and terrifying. Apparently the Japanese are better prepared for natural disasters than almost any other country on Earth. Man can seldom beat nature when nature is determined, though.

And, closer to home, bad news lurks.

I got an email from a friend yesterday telling me that her husband has Lou Gehrig’s disease. He is 64 and, while the disease is in its early stages, it is moving rapidly. He is a musician who will soon have to give up his music. They are devastated, reeling from the diagnosis, figuring out how to go on.

I just visited a friend in a nursing home. She is there temporarily, for skilled nursing as she rebuilds her strength after back surgery. She is in pain, but strives to be upbeat. When she tells me she fears she might be there for more than a month, I encourage her to take one day at a time.

Lame advice, but that is really all we have at any point. One day at a time.

So it is difficult for me to take too much pleasure in the sun streaming through my window, at the chubby robin on a nearby branch. But we must see joy in these gifts—they are the blessing of living.

Lymph node surgery may not be needed for early stage breast cancer

The current standard for all forms of breast cancer is sentinel node dissection to determine if the cancer has spread to the lymph nodes. Immediately before surgery, doctors inject dye into the tumor and trace its route. It will go first to the sentinel node. The dye highlights that node, which is removed, along with one or two surrounding nodes, which are all tested for cancer. If the cancer has spread to that node, the patient will have a full axillary lymph node dissection, or removal of all cancerous nodes.

However, according to a phase 3 clinical trial recently published in JAMA (2011), women with tumors smaller than 2 centimeters with affected lymph nodes who had surgery to remove the nodes had nearly identical survival statistics as those who did not have the nodes removed.

This was true no matter the hormone status of the tumor, so it would be true of triple-negative. Researchers clarify that this does not apply to women who are at a high risk for reoccurrence such as those with three or more positive sentinel lymph nodes, larger tumors, or those who received preoperative chemotherapy.

Five-year survival rates were were 92.5 percent for those with no additional surgery and 91.8 percent for those with axillary lymph node dissection, a difference that researchers say is not statistically significant.

Doctors say this research may be a game changer, leading to fewer removals of the lymph nodes, a surgery that can lead to lymphedema and limited range of motion.

Amednews.com and the Cancer Network have both run stories on the study.

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Journey to Spring: A Tribute To the Caregivers

“When your wife is fighting a life-threatening disease, you want to be at the top of your game,” writes Marc Silver in Breast Cancer Husband: How to Help Your Wife (And Yourself) through Diagnosis, Treatment, and Beyond.

Marc’s wife, Marsha Dale, was diagnosed with breast cancer in 2001. He was a true partner, supporting Marsha as honestly and faithfully as he could—feeling his way at every step of the process. His motto: “Shut up and listen.” To save other husbands the stress and confusion he faced, Marc, a journalist with more than 30 years experience, wrote an excellent book that was my own husband's guide.

In a blog post on caregiving on breastcancer.org, Marc writes:

I was my wife’s strategic adviser at doctor’s appointments, taking notes and reminding her of questions she wanted to ask (but never asking for her). I was her lover, reassuring her that even with a bald head, she was beautiful (and she was!). I was her supply sergeant, dashing out to find ginger candies she craved on a cold winter’s night. I was her confidant, listening to her honest emotions and fighting the urge to say, “Cheer up honey!” when all she wanted to do was talk about how much cancer sucks.

So today, I offer tribute to all the Marcs out there—the husbands, lovers, partners, children, siblings, friends, colleagues, parents, ministers—who walk with us down the breast cancer path. We all need, in some form or another, an adviser, lover, supply sergeant, and confident. And those who step up to the plate to stand by us when we need them, who hide their own fears as they try to quell ours, who strengthen us when our spirits are limp—you are a blessing. And you are blessed.

Journey to Spring: Celebrating Lives

My husband, Joe, turned 73 today and our grandson Eli turned two months. It is a day of celebration for me, for the little family Joe and I have created: our son Josh, daughter Ellen and her husband Steve, plus little Eli and his big brother Tarin.

And to think it all started when Joe and I first met at a dance in 1969 and he asked if I wanted a drink. I did not understand if he wanted to buy me one or if he was some sort of a bartender. Turns out he was president of the club that organized the dance and he was being sociable in offering me a drink on the house. I said no, but he asked me to dance anyway, and we have been dancing ever since. Sometimes we step on one another’s feet—there were a few years when we did that regularly. But now we are in step with one another quite nicely—and we actually do go out to dances where we tango and swing and do everything but the polka. I grew up with the polka, but Joe does not find its steps to make sense. So I give him that one and we sit out all oompa-oompa tunes.

Joe and I share religious and political views, like many of the same books, enjoy the same leisure activities. He makes me laugh and he makes me smile. We just got home from a walk along the river a mile from our house—it ends up being about a 4-mile loop. We both thoroughly enjoy that outing, as we do the hikes we take at our Colorado cabin. And we like to dance and, when we’re tired, watch Damages and Nurse Jackie on Netflix.

The best thing about us, though, is that we raised amazing kids. Josh and Ellen are both good people and good citizens of the country and the earth. They are smart and funny and loving. They both live more that a thousand miles from us, but they come home often and visit us in Colorado, and we visit them in Washington and Vermont. So I think they enjoy our company as well. And, you know, there is much to be said about grown kids liking to be around you. Much to be said about that.

Josh is a journalist who creates beautiful prose that is thoughtful and important. Sometimes I feel I need to take notes when I read what he has written. He has been published in The Atlantic, Time, Slate, The Nation, among other national and international magazines, newspapers, and online publications. His blog, The Bug Pit, focuses on geopolitical issues in Central Asia.

Right now Ellen keep busy with her two beautiful little boys, the dear Eli and the energetic and highly personable Tarin. She is also a talented artist—some of my favorites are fossil boxes she creates out of found art. She had a show of her work that made the New York Times, along with a sizable photo. Her husband, Steve, is a wonderful husband and father and a creative and successful entrepreneur who works at home, which allows Ellen breaks during the day to go snowshoeing and cross country skiing.

Ellen gets much of her talent for building from Joe, who makes beautiful wood creations in his basement workshop. Right now he is making amazing cutting boards.

I am in awe of these remarkable people with whom I am privileged to share my life. What a blessing. What a joy. I am thankful for all of them everyday.

Happy birthdays, honeys.

Journey to Spring: Thankfulness, Snarkiness, and Deep Breaths

In my closet, I have several sacks of the cards friends and family sent to me while I went through treatment. I still look through them and smile at all the people who offered support and showed their love. The cards are just a physical reminder of the wonderful thoughtfulness of the people in my life.

How do you thank somebody for showing you that they love you? For loving you? My response was to show them I love them as well.

In some ways, a thank-you note would have been so much easier.

Without doubt I am made better by remembering the good in people. My life is richer and my soul stronger. To be honest, though, sometimes it is darn difficult to be a good friend and family member. Love is so easy to write, so hard to practice.

It can be a personal challenge to get over my snarkiness about friends' and family members' occasional oddities and weaknesses. Sometimes people just get on my nerves. I mean, why is one friend so picky and another so unreliable and another….you get the idea.

I, of course, am perfect.

I noticed my impatience peaking this winter with my realization that as my friends are getting older they are developing some traits I could do without. And I choose strong women as friends, so I am surrounded by a certain amount of bossiness that can be wearing. I seldom am bossy in return, of course, because at that perfection I mentioned.

So, on this journey to spring, I am taking deep breaths and realizing that the picky friend was with me when I was sick and from then on, that the unreliable one was completely dependable in her love, that quirks make them interesting and I have always loved interesting people. And that they love me despite everything.

So, here I am, breathing deeply and smiling at the memories of the love that surrounded me when I was sick and that surrounds me still.

And resolving to continue giving thanks by showing my own love.

Inhale, exhale, inhale, exhale.

Let's Journey Together to Spring

Celebrations of spring have been a constant of human cultures for thousands of years. Some say Easter was named after Eostre, the great mother goddess of the Northern European Saxons. Others says it was Ostara, a Norse goddess of fertility. Both names are variations of an ancient word for spring, eastre.

Many of us have faced a hard winter, both literally and figuratively. The weather throughout the world has been brutal, with hurricanes and earthquakes, tornadoes and ice storms. The lucky among us have taken refuge in the comfort and warmth of our homes. The less fortunate have lost homes and livelihoods and lives. Still others see this weather as a gift and head to the slopes to revel in the beauty of the snow.

In winter, mother nature can be gorgeous, but she can also be foreboding, a killer.

A diagnosis of cancer is a bit like winter. It is dark, menacing, dangerous, a killer. Yet, it can challenge us to strengthen good relationships and rebuild bad ones, to give thanks for the good we have as we gird ourselves to face the bad. To see that life itself has been a gift full of beauty that we often have been too busy to appreciate fully, sometimes to even notice.

Today, most Christian churches begin the season of Lent, a time of reflection and meditation in preparation for Easter. When I was little, we always gave things up for Lent—usually candy. And on Easter we would gorge ourselves on jelly beans and chocolate eggs. As I got older, I saw the weakness of this plan—who cared about what Easter meant spiritually when you finally got to eat lots of sugar?

My adult choice was, too often, to just do nothing different in Lent, or worse, to criticize others' choices. The colleague who was giving up French fries, I thought, was making a spiritually meaningless gesture. Yet I made to effort to make a gesture at all of my own.

Like many cancer patients, I rediscovered my spiritual side on this journey to regain my health, and that was a true gift. So, as we go through this season in preparation of the rebirth of spring and as many of you go through the cancer journey, I plan to take a few minutes each day in this blog to focus on the good, to share love and caring, to celebrate life and rebirth.

And this coincides with a milestone on my passage through the land of cancer. I was diagnosed on a beautiful May morning, when the air was warm and clear, the sky azure, the blossoms sprouting, the natural world green. On May 16, 2006, that all turned grey for me as I heard the words, “Patricia, the test came back; it is positive for cancer.”

I will soon celebrate five years from that day. Those of us with hormone-negative disease get to breathe a little easier three years after diagnosis, as that is when the risk of recurrence drops significantly. Five years, though, becomes an important benchmark.

So, journey with me, with hope and love throughout the ending days of winter and help me welcome the spring with joy. Cancer-free joy, the best kind.

Antibody May Separate TNBC into Aggressive and Less Aggressive Subgroups

High levels of the antibody Ki-67 was associated with higher rates of recurrence and lower survival for triple-negative patients, according to new research. And low levels signaled a less aggressive form of the disease. Researchers say this could lead to two separate subgroups of TNBC with significantly different levels of aggressiveness and prognosis. The research, on 105 patients who received neoadjuvant (after surgery) Adriamycin and Cytoxan, was published in the journal Breast Cancer Research. Antibodies are part of the immune system.

Phase II study of entinostat and anastrozole for TNBC

From a News Release from Syndax Pharmaceuticals:

WALTHAM, Mass., March 1, 2011 -- /PRNewswire/ -- Syndax Pharmaceuticals, a clinical-stage epigenetics oncology company, announced the National Cancer Institute (NCI) will sponsor a multi-center phase 2 study of Syndax's lead product entinostat, a novel inhibitor of histone deacetylases (HDAC), and anastrozole, an aromatase inhibitor, in postmenopausal women with operable triple negative breast cancer to evaluate biomarkers and surrogates for response. The trial, to be conducted under a Cooperative Research and Development Agreement (CRADA) executed between the NCI and Syndax, will investigate whether patient tumors can be reprogrammed to express estrogen receptor and render them to be sensitive to hormonal agents. This trial is based on animal data being published in the March 1, 2011, issue of Cancer Research.

Laboratory studies by Dr. Angela Brodie, professor of pharmacology and experimental therapeutics, and Gauri J. Sabnis, Ph.D., assistant professor of pharmacology and experimental therapeutics at the University of Maryland School of Medicine, in collaboration with Saraswati Sukumar, M.S., Ph.D., professor of oncology and pathology at the Johns Hopkins University School of Medicine, provided the basis for the phase 2 clinical trial. Their work demonstrates that entinostat induces hormone sensitivity in an animal model of triple negative breast cancer and that the combination with aromatase inhibitors prevents tumor growth as well as tumor metastasis.

"In the pre-clinical study that is being published in Cancer Research we demonstrated that entinostat can induce re-expression of estrogen receptor and aromatase in triple negative breast cancer cell lines and render them sensitive to an aromatase inhibitor," said Saranya Chumsri, M.D., assistant professor of medicine at the University of Maryland School of Medicine and a medical oncologist at the University of Maryland Marlene and Stewart Greenebaum Cancer Center, principal investigator of the trial. "Moreover the combination of entinostat with an aromatase inhibitor suppressed the growth of tumors in an animal model of triple negative breast cancer. Given this promising data, we are evaluating entinostat with anastrozole in a neoadjuvant setting to see if we can extend the benefit of hormone therapy seen in patients with estrogen receptor positive breast cancer to those with triple negative disease - where cytotoxic therapy is the only treatment option."

While the mortality rate in breast cancer has decreased in the past few decades, some subsets still have poor outlooks. With the advent of targeted therapy, particularly endocrine and anti-human epidermal growth factor receptor 2 (HER2) therapies, the outcome of breast cancer has changed dramatically. Nevertheless, approximately 15 to 20 percent of breast cancers lack expression of all three constructive cell surface receptors, namely estrogen receptor (ER), progesterone receptor (PR) and HER2, hence the term "triple negative" breast cancer (TNBC). Due to an absence of ER and/or PR, these tumors typically do not respond to endocrine therapy like tamoxifen and aromatase inhibitors, which have minimal toxicities and are generally well tolerated. For that reason, the treatment option for these tumors is solely chemotherapy.

TNBC declining in white women

Hormone-negative breast cancer rates dropped for white women ages 40-49 and 60-69, according to new data from 2003 through 2007. Using the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) data, researchers noted a slight increase in hormone-positive cancers. Rates for African-American and Hispanic women showed little change. Kathleen Doheny in WebMD offers an overview of the research, which was published online in Cancer Epidemiology, Biomarkers & Prevention.

Low exercise and high BMI are risk factors for TNBC

Increasing your exercise levels and reducing your body mass index can help reduce your risk of triple-negative breast cancer, according to research using data from the Women’s Health Initiative. Researchers analyzed records of 162,000 women, 3,116 of whom had complete tumor marker data; 307, or 10 percent, of these were triple-negative.

The research was published in the March issue of Cancer Epidemiology, Biomarkers and Prevention. Michele Sullivan, of Internal Medicine News, explains the research and interviews the lead researcher, Amanda I. Phipps, Ph.D.

Of special note is that fact that weight gain between age 35 and 50 was the most risky. A body mass index above 31 and below 23.75 were also risk factors.

Multiple Childbirth linked to Triple-Negative Breast Cancer

The more times you give birth, the higher your risk of triple-negative breast cancer. In fact, women who never have given birth had a 40 percent s reduced risk of TNBC, although they do face an increased risk of hormone-positive disease. This comes in a study at the Fred Hutchinson Cancer Research Center recently published in the Journal of the National Cancer Institute. It is based on Women’s Health Initiative data on the reproductive histories of 150,000 postmenopausal women, 300 of whom ultimately developed triple-negative breast cancer.

The news release from the Hutchinson Center:

SEATTLE — Feb. 24, 2011 — Full-term pregnancy has long been associated with a reduced risk of breast cancer, but a new study finds that the more times a woman gives birth, the higher her risk of “triple-negative” breast cancer, a relatively uncommon but particularly aggressive subtype of the disease. Conversely, women who never give birth have a 40 percent lower risk of such breast cancer, which has a poorer prognosis than other types of breast cancer and doesn’t respond to hormone-blocking therapies such as tamoxifen.

These findings, from a study led by Amanda Phipps, Ph.D., a postdoctoral research associate in the Public Health Sciences Division of Fred Hutchinson Cancer Research Center, are published online ahead of the March 16 issue of the Journal of the National Cancer Institute.

“Unlike most breast cancers, triple-negative tumors don’t depend on hormonal exposures to grow and spread, so our assumption going into the study was that reproductive factors would not be associated with a woman’s risk of this cancer subtype,” Phipps said. “We were surprised by these findings because researchers have known for quite some time that women who have children, especially those who have them at an early age and have multiple full-term pregnancies, have a lower risk of breast cancer overall.”

While never giving birth appears to be protective against triple-negative breast cancer, the researchers found that women who remain childless have about a 40 percent higher risk of estrogen-receptor-positive breast cancer – the most common form of the disease, which can be treated with estrogen-blocking drugs – as compared to those who have one or more offspring. This higher risk of estrogen-receptor-positive breast cancer among women who have not had children is well established, and it is thought to be related to the fact that such women do not undergo pregnancy-related changes in the breast that confer a lifelong protective effect.

“The mechanisms by which full-term pregnancy contributes to an increased risk of triple-negative breast cancer and a decreased risk of other forms of the disease are not clear,” Phipps said. “We do know that the hormones of pregnancy induce certain changes in the cellular structure of the breast. Overall, those changes seem to make the breast less susceptible to cancer. It is possible, however, that the increased risk of triple-negative breast cancer we found in women who had given birth may be due to some abnormal response of their breast tissue to the hormones of pregnancy. Another possibility is that pregnancy somehow makes the breast more susceptible to certain carcinogens even while reducing breast cancer risk overall,” she said.

For the study, which was based on data from the Women’s Health Initiative, Phipps and colleagues analyzed the detailed reproductive histories of some 150,000 postmenopausal women, more than 300 of whom went on to develop triple-negative breast cancer. “This particular study is significant because it is one of the largest studies ever conducted on the impact of reproductive history on triple-negative breast cancer,” Phipps said.

Triple-negative breast cancer, which refers to any breast cancer that does not express the genes for estrogen receptor (ER), progesterone receptor (PR) or Her2/neu, accounts for only 10 percent to 20 percent of all breast cancers, and only in the past decade have researchers become aware that this cancer subtype exists. “This research reinforces the notion that breast cancer is not just one disease,” Phipps said.

“The mechanisms that lead to triple-negative breast cancer are likely different from those that lead to other forms of the disease. We still have a lot to learn about what causes this more aggressive form of breast cancer, but we hope that research like this will help us develop better tools to identify those women at greatest risk.”

It is known that this cancer subtype is more predominant in African American women and it tends to be diagnosed at an earlier age. Researchers also know there is a strong link between genetic mutations in the so-called “breast cancer gene,” BRCA1, and triple-negative breast cancer.

“More research is needed to better understand the causes of the most aggressive and lethal forms of breast cancer. While this study adds to our knowledge base, it should not change women’s approaches to breast cancer screening,” Phipps said.

The National Heart, Lung and Blood Institute of the National Institutes of Health funded the study, which also involved researchers from Albert Einstein College of Medicine, Georgetown University, Harbor-UCLA Medical Center, Stanford University, State University of New York at Stony Brook, the University of Buffalo, the University of Pittsburgh and Wake Forest University.

What, Me Worry? And Worry, and Worry

I know a woman who has lived more than 30 years after a diagnosis of estrogen-negative beast cancer. When I asked her recently if she still worried about it returning, she said, “Not really.” I love that the fear eventually goes away, but I hope it is far sooner than 30 years , as by then I will be 90 and, at the rate I am going, I will no doubt have already forgotten just about everything.

Now, though, the concern remains. It’s not a constant worry, not something I jump to immediately. I do not live a paranoid existence, waiting for the next health shoe to drop. But occasionally, when I have a minor issue, two and two adds up to cancer in my crazy mind.

I have a history of stomach ulcers, which I usually can control with diet. It has been almost eight years since they bothered me. Lately, though, I have ignored my usual healthy eating and have been having too much Diet Coke, fried foods, and coffee.

So my stomach has been hurting. I self-medicate—antacids, aloe vera juice, lots of water. And, of course, no Diet Coke, fried foods, and coffee. And I am fine.

But it was a long winter and I ended up with a nasty cold that did not go away, so I resorted to the comfort of Alka Seltzer Plus, which clears up my head marvelously. It also contains aspirin, which is a sin against ulcers.

So this past week, I was awakened at night with the stomach pain. Pain that kept me up. I’d had a martini and knew my stomach could not handle it.

But I worried that I had stomach cancer. Before I had breast cancer, I never jumped to that conclusion. I knew it was my ulcers acting up and I dealt with it. If I needed stronger medicine, I got it.

This time I decided to go to the doctor for peace of mind. He, however, also did not like the idea of stomach pain waking me up, so he ordered an endoscopy. “I do not think I am going to find anything, but I would feel better if we checked you out,” he said.

He also raised the specter of stomach cancer, something he has not mentioned in the nearly 20 years I have been going to him. But there was the big red flag was on my chart: breast cancer. Breast cancer once means the possibility some other cancer eventually. Of course, I always had the risk of cancer in my future, but it did not seem all that real. I was happily oblivious to that possibility.

And I am now told by doctor after doctor that my risk is elevated. I am at code orange, always open to a full-body search, that happy oblivion gone.

And so, despite my reluctance to have unnecessary tests, despite fairly conclusive evidence that this was all related to stomach ulcers, I had the endoscopy.

I am fine. My stomach was simply irritated. The doctor took a biopsy and, even though results are not back, he says he is confident it is not cancer. The stomach looks and acts like it has in the past. I also am confident it is nothing more than irritation.

He gave me stronger medicine and I now stay away from problem foods and aspirin,. And I no longer am worried about stomach cancer.

Mostly. And for now. I am almost five years past diagnosis and I may celebrate my anniversary by instituting a no-worry rule.

I do worry, though, that I can pull that off.

Dose-dense chemo best for hormone-negative

Dose-dense chemotherapy is most effective for hormone-negative breast cancer, according to a review of clinical trials published in the Journal of the National Cancer Institute. The trials used doxorubicin (Adriamycin) and cyclophosphamide (Cytoxan) followed by paclitaxel. Dose-dense treatments for TNBC resulted in better overall and disease-free survival.

Anthracyclines Better for TNBC

Adriamycin and Cytoxan, two common chemo drugs called anthracyclines, used in conjunction with a taxane are an effective treatment for TNBC, but not for other types of breast cancer. In a commentary on treatment protocols in the journal Oncology, Ruth O'Regan, M.D., the the Emory University School of Medicine, notes that the combination works best in adjuvant treatment—that is, chemo after surgery.

Antioxidant may help fight TNBC

According to a news release from the Kimmel Cancer Center at Thomas Jefferson University, researchers there have shown the effectiveness of antioxidant in fighting tumor growth. The research is in the February 15 issue of Cancer Biology and Therapy. The study looked at the protein Caveolin-1 (Cav-1), which can inhibit cancer, cardiovascular disease, and muscular dystrophy and can be of special significance to triple-negative cancers In previous studies, Cav-1 was effective in killing breast cancer cells when used with Taxol.

The news release:

PHILADELPHIA—Researchers from Jefferson's Kimmel Cancer Center have genetic evidence suggesting the antioxidant drugs currently used to treat lung disease, malaria and even the common cold can also help prevent and treat cancers because they fight against mitochondrial oxidative stress—a culprit in driving tumor growth.

For the first time, the researchers show that loss of the tumor suppressor protein Caveolin-1 (Cav-1) induces mitochondrial oxidative stress in the stromal micro-environment, a process that fuels cancer cells in most common types of breast cancer.

"Now we have genetic proof that mitochondrial oxidative stress is important for driving tumor growth," said lead researcher Michael P. Lisanti, M.D., Ph.D., professor of cancer biology at Jefferson Medical College of Thomas Jefferson University and member of the Kimmel Cancer Center at Jefferson. "This means we need to make anti-cancer drugs that specially target this type of oxidative stress. And there are already antioxidant drugs out there on the market as dietary supplements, like N-acetyl cysteine."

These findings were published in the online February 15 issue of Cancer Biology & Therapy.

Lisanti's lab previously discovered Cav-1 as a biomarker that functions as a tumor suppressor and is the single strongest predictor of breast cancer patient outcome. For example, if a woman has triple negative breast cancer and is Cav-1 positive in the stroma, her survival is greater than 75 percent at 12 years, versus less than 10 percent at 5 years if she doesn't have the Cav-1 protein, according to Dr. Lisanti.

The researchers also established Cav-1's role in oxidative stress and tumor growth; however, where that stress originates and its mechanism(s) were unclear.

To determine this, Jefferson researchers applied a genetically tractable model for human cancer associated fibroblasts in this study using a targeted sh-RNA knock-down approach. Without the Cav-1 protein, researchers found that oxidative stress in cancer associated fibroblasts leads to mitochondrial dysfunction in stromal fibroblasts. In this context, oxidative stress and the resulting autophagy (producton of recycled nutrients) in the tumor-microenvironment function as metabolic energy or "food" to "fuel" tumor growth.

The researchers report that the loss of Cav-1 increases mitochondrial oxidative stress in the tumor stroma, increasing both tumor mass and tumor volume by four-fold, without any increase in tumor angiogenesis.

"Antioxidants have been associated with cancer reducing effects—beta carotene, for example—but the mechanisms, the genetic evidence, has been lacking," Dr. Lisanti said. "This study provides the necessary genetic evidence that reducing oxidative stress in the body will decrease tumor growth."

Currently, anti-cancer drugs targeting oxidative stress are not used because is it commonly thought they will reduce the effectiveness of certain chemotherapies, which increase oxidative stress.

"We are not taking advantage of the available drugs that reduce oxidative stress and autophagy, including metformin, chloroquine and N-acetyl cysteine," Dr. Lisanti said. "Now that we have genetic proof that oxidative stress and resulting autophagy are important for driving tumor growth, we should re-consider using antioxidants and autophagy inhibitors as anti-cancer agents."

The diabetic drug metformin and chloroquine, which is used for the prevention and treatment of malaria, prevent a loss of Cav-1 in cancer associated fibroblasts (which is due to oxidative stress), functionally cutting off the fuel supply to cancer cells.

This research also has important implications for understanding the pathogenesis of triple negative and tamoxifen-resistance in ER-positive breast caner patients, as well as other epithelial cancers, such as prostate cancers.

"Undoubtedly, this new genetically tractable system for cancer associated fibroblasts will help identify other key genetic 'factors' that can block tumor growth," Dr. Lisanti said.

An overview of Basal-Like and TNBC

Medcscape has just published a good review article on the interrelationship between basal-like and triple-negative breast cancers, with a good definition of each one, and the implications for treatment and prognosis. When I was diagnosed in 2006, TNBC was just hitting the radar screen, and few people talked about it or any other form of hormone-negative breast cancer. It is nice to see the progress, nice to see that TNBC has become and important research focus. If only the writers would focus less on the negatives up front and explain that, in fact, most women do survive this disease.

Did Cancer Make You Want to Sing About George Clooney?

I love this story!

During chemotherapy for triple-negative breast cancer in 2008 and 2009, singer-songwriter Laura Roppe wrote 13 songs that became her album "I'm Still Here." One song, "George Clooney," says "I bet he smells real good." I bet he does, Laura.

The lyrics to another song, "Float Away:"

She says, this life’s too heavy

I’ve reached the breaking point

If I check out now

I can leave it all behind

And float

Float away

But she hears the voice

Of her little girl

Only thing that matters

In this whole world

Gotta find a way

Not to fade away

The San Diego Reader ran an interview with Laura. You can buy her album for $12 and $3 shipping.

Good for you, Laura, for turning to your art during this journey.

A Hint on How and Why TNBC Spreads?

Princeton University researchers have discovered the mechanism by which triple-negative breast cancer might spread. This discovery, they say, could lead to the development of drugs for metastatic TNBC. Check out the story in the New Jersey Star Ledger.