Stress increases cancer spread in mice

From a News Release from the UCLA Jonsson Comprehensive Cancer Center

Chronic stress acts as a sort of fertilizer that feeds breast cancer progression, significantly accelerating the spread of the disease in animal models, researchers at UCLA's Jonsson Comprehensive Cancer Center have found.

Researchers discovered that stress is biologically reprogramming the immune cells that are trying to fight the cancer, transforming them from soldiers protecting the body against disease into aiders and abettors. The study found a 30-fold increase in cancer spread throughout the bodies of stressed mice, compared with those that were not stressed.

It has long been thought that stress fuels cancer growth in humans. This study provides a model that not only demonstrates that stress can speed up cancer progression but also details the pathway used to change the biology of immune cells that inadvertently promote the spread of cancer to distant organs, where it is much harder to treat.

The study is published in the Sept. 15 issue of the peer-reviewed journal Cancer Research.

"What we showed for the first time is that chronic stress causes cancer cells to escape from the primary tumor and colonize distant organs," said the study's first author, Erica Sloan, a Jonsson Cancer Center scientist and a researcher with the UCLA Cousins Center for Psychoneuroimmunology. "We not only showed that this happens, but we showed how stress talks to the tumor and helps it to spread."

In addition to documenting the effects of stress on cancer metastasis, the researchers were also able to halt those effects by treating stressed animals with drugs that block the nervous system's reprogramming of the metastasis-promoting immune cells, called macrophages.

Beta blockers, used in this study to shut down the stress pathways in the mice, are currently being examined in several large breast cancer databases for their role in the potential prevention of recurrence and cancer spread, said Dr. Patricia Ganz, director of cancer prevention and control research at the Jonsson Cancer Center. If preliminary findings indicate benefit, early-phase clinical trials are being considered at the Jonsson Cancer Center testing beta blockers as a means of preventing breast cancer recurrence.

Other healthy lifestyle behaviors, such as exercise and stress-reduction techniques, may also influence the biological pathways described in the study.

"We're going to be focusing on younger women, because they may have a multitude of things weighing on them when they're diagnosed with breast cancer. Younger women have more significant life demands and typically are under more stress," Ganz said.

Ganz said her proposed research will focus on "host factors," or things affecting the patient that may be aiding cancer progression and which could help explain why a group of patients with the same type and stage of disease have varying rates of recurrence and cancer spread.

"This study provides evidence for a biological relationship between stress and cancer progression and identifies targets for intervention in the host environment," Ganz said. "Because of this study, we may be able to say to a patient in the future that if you follow this exercise regimen, meditative practice or take this pill every day, it will help prevent recurrence of your cancer. We can now test these potential interventions in the animal model and move those that are effective into the clinic."

In Sloan's study, mice with breast cancer were divided into two groups. One group of mice was confined in a small area for a short period of time every day for two weeks while the other group was not. The breast cancer cells were genetically engineered to include the luciferase gene, which is the molecule that makes a firefly glow. The growth and spread of the cancer in the mice was monitored using sensitive cameras that can pick up the luciferase signal. This allowed Sloan and her team to observe both the development of primary tumors and the spread of cancer throughout the body, said senior study author Steven Cole, an associate professor of hematology–oncology and a Jonsson Cancer Center researcher.

What was interesting, Cole said, was that the primary tumors did not seem to be affected by stress and grew similarly in both groups of mice. However, the stressed animals showed significantly more metastases throughout the body than did the control group. The cancer, in effect, acted differently in the stressed mice.

"This study is not saying that stress causes cancer, but it does show that stress can help support cancer once it has developed," Cole said. "Stress helps the cancer climb over the fence and get out into the big, wide world of the rest of the body."

Cole said Sloan detailed the biology of the stress-induced changes in the cancer cells along every step of the pathway, providing a roadmap by which stress promotes cancer metastasis. Additionally, Sloan proved that using beta blockers in stressed mice prevented the same cancer progression seen in the stressed mice that did not receive medication.

When cancer occurs, the immune system sends out macrophages to try to repair the tissue damage caused by the uncontrolled growth of cancer cells. The macrophages, in an attempt to help, turn on inflammation genes that are part of the normal immune response to injury. However, the cancer cells feed on the growth factors involved in a normal immune response. Blood vessels that are grown to aid healing instead feed the cancer the oxygen and nutrients it needs to grow and spread, and the extracellular matrix, which provides structural support for normal cells, is attacked during the immune response, helping the cancer cells escape from the primary tumor and spread to distant parts of the body.

"Many of the genes that promote cancer metastasis get turned on during the immune response by macrophages," Cole said. "This study shows that stress signaling from the sympathetic nervous system enhances the recruitment of macrophages into the primary tumor and increases their expression of immune-response genes that inadvertently facilitate the escape of cancer cells into other parts of the body."

Sloan showed that the beta blockers prevented the macrophages from hearing the signals sent by the sympathetic nervous system and stopped them from infiltrating the tumor and encouraging cancer spread.

The study was funded by the National Institutes of Health, the U.S. Department of Defense and the Jonsson Cancer Center.

UCLA's Jonsson Comprehensive Cancer Center has more than 240 researchers and clinicians engaged in disease research, prevention, detection, control, treatment and education. One of the nation's largest comprehensive cancer centers, the Jonsson Center is dedicated to promoting research and translating basic science into leading-edge clinical studies. In July 2010, the center was named among the top 10 cancer centers nationwide by U.S. News & World Report, a ranking it has held for 10 of the last 11 years.

ACE inhibitors increase, beta-blockers reduce cancer risk

According to a study published in Breast Cancer Research and Treatment, ACE angiotensin-converting enzyme inhibitors may increase the risk of cancer recurrence, but beta-blockers may reduce it. Used together, they can cumulatively reduce risk. Ace inhibitors are used for everything from reducing blood pressure, treating heart failure, preventing strokes, and moderating kidney damage. Beta-blockers treat abnormal heart rhythms, angina, high blood pressure, and migraine.

This is lab research on mice, so the effects on humans still need to be studied. If beta-blockers are effective in humans, this could lead to an effective treatment for TNBC, according to Patricia Ganz, MD, study researcher and director of cancer prevention and control research at UCLA’s Jonsson Comprehensive Cancer Center. She was interviewed for an article on the research in HemOnc Today.

And the study shows that we should evaluate all our medicines, as our drugs affects our entire bodies.

The research was based on data from the Life After Cancer Epidemiology (LACE) study of 1,779 patients diagnosed with early-stage breast cancer.

Read more about TNBC in my book, Surviving Triple-Negative Breast Cancer.Please consider a donation to Positives About Negative to keep this site going.  

This work is entirely supported by readers.  Just click on the Donate button in the right of the page.  Thank you!

Source: Ganz, Patricia, Habel, Laurel, Weltzien, Erin, Caan, Bette Cole, Steven, 'Examining the influence of beta blockers and ACE inhibitors on the risk for breast cancer recurrence: results from the LACE cohort', Breast Cancer Research and Treatment , pp. 1-8 (2011).

Journey Into Spring: Easter

As Christians around the world celebrate Easter, let us offer our hearts and prayers to all those who strive to make the world a more loving, kind, and just place, no matter their religion or beliefs.

Below are some of the prayers we offered in my church on Good Friday. I cannot top them, so I share them below.

Prayers for Authorities

Let us pray for those in authority throughout the world....

For all the peoples of the earth, their leaders, and all who hold office....

For Barack our President, for our Congress and Supreme Court, our local governments and courts, and all civil servants....

For peacemakers, diplomats, and those who strive for peace and the general welfare; for the armed services and all in harms way because of war....

For doctors and nurses, hospitals and hospices; for police and firefighters; for all who protect the weak and serve the common good....

For farmers and corporations, for workers and trade union leaders, reformers and visionaries....

For artists and performers; for poets and writers; for journalists and filmmakers....

That they may receive every godly gift of discernment, compassion, integrity and courage, to build healthy communities and make a lasting peace on earth, let us pray to the Lord.

Prayers for Those who Suffer

Let us pray for all who are suffering and in need....

For the poor and oppressed, the exploited and despairing, the sick and the suffering....

For victims of envy, discrimination and revenge....

For all who live in fear, anguish, rage, and violence....

For all who hunger for food, for work, a home, and a holy purpose in their lives....

For all who face death, the loss of love, the crushing of dreams, the crippling of body or mind, let us pray to the Lord.

For all who long for family, friendship, children, a sense of belonging and being known....

For all in danger and captivity, all who long for peace and freedom and safety....

That we may follow Christ in sharing all human suffering as our own....

Loving God, comfort all who suffer, and teach us to cherish Christ’s image in all people: those who are like us and those who are strange to us. Strengthen our hearts in your service, and fulfill in our works of compassion your Love made flesh, Jesus Christ our Lord. Amen.

Prayers for People of Faith

Let us pray for those whose faith is not our own....

For Jews, Muslims, Hindus, Buddhists, Native Americans, Shintoists, Sikhs, and every people of faith....

For their rabbis, mullahs, priests, lamas, shamans and holy teachers....

For those whose faith is known to God alone....

For all who condemn, persecute or martyr others in the name of religion....

For all who suffer and die for their conscience’s sake....

That as Christ came as a stranger to befriend us, we may learn to welcome those unknown and alien to us, let us pray to the Lord

Journey Into Spring: Survivors In the Himalayas

A group of cancer survivors from Iowa is on their way to Mount Everest base camp this week, part of a three-week trek that will cover 65 miles and end up at 18,200 feet. The group of 14 ranges in age from 27 to 64 and is led by Richard Deming, MD, medical director of Mercy Cancer Center in Des Moines.

Brian Triplett from Davenport is with the group to blog about the adventure, with some remarkable photos from Dr. Deming.

Way to kick cancer's ascent, folks!

Read more from The Des Moines Register.

Journey Into Spring: Tiptoeing Through the Tulips

My friend, Deb Wiley, posted this amazing photo on her blog, Planting Queen. Deb says the photo reminds her of "what gardening is all about: Joy." I recommend a visit to her blog for more excellent photography and perspective.

Journey Into Spring: Aren't We All a Bit Like Venus Now?

The Poem, "Truth in Advertising," by Andrea Cohen seems fitting for those of us who have been through breast surgery. It's all about how Venus de Milo would be some average chick if she had both arms. Garrison Keillor read the poem today on Writer's Almanac.

Overview of TNBC Teleconference April 12, 2011

Below are my notes of the teleconference today, "Triple-Negative Breast Cancer: Medical Review," with Lisa Carey, M.D. sponsored by Living Beyond Breast Cancer and the Triple-Negative Breast Cancer Foundation. Ultimately, a transcript and podcast will be available that will offer more comprehensive information. For now, though, this is what I jotted down.

• How research has progressed:

In 2005—TNBC had not even been named yet.

By 2010—several hundred publications in that year alone.

• Prognosis of TNBC is not entirely different from other types, but it is more likely to relapse because it does not respond to typical treatment, such as tamoxifen or an aromatase inhibitor.

• Most cases of TNBC are cured by standard therapy, but there still is room for improvement.

• About a third of breast cancer deaths come from TNBC.

• 70 percent of TNBC tumors are basal like—

• Claudin low breast cancer, a new subtype, is also likely to be TNBC.

• It is increasingly clear that TNBC is not one disease, but many.

• The question of who gets breast cancer has gotten complicated lately. If you ask that question broadly, the answer is genetic mutations such as BRCA1 and BRCA2. But only about 5-10 percent of all breast cancers are related to the genetic mutations. The rest are sporatic breast cancers—we do not know what causes them. Reproductive risk factors are “soft factors”—don’t have a big influence. We have to change the question to “What causes specific types of breast cancer?”

• The Carolina Breast Cancer Study (there have been three versions; it’s a large study) looked specifically at groups who weren’t normally studied—African-Americans and young women. Carolina study was set up to oversample these groups. Researchers found that basal-like was overrepresented in young women and African-American. Nearly 1/3 of cases in young African-American women.

• It also looks like some of the risk factors may differ between types. Reproductive risk factors may be different for TNBC cancers—we don’t know how to act on that yet. Makes us less global in our recommendations.

• TNBC carries a comparatively worse risk factor. But risk seems to happen in the first three years and, after about 6,7,8 years, the risk of relapse lower for those with TNBC.

• If cancer comes back, HR+ more likely to come back in bones, TNBC more likely to involve lungs and the brain. Much research is being done now on brain relapses.

• Inherited breast cancer—BRCA1 and BRCA2—women with these have 50-80 percent risk of breast cancer over their lives. Recommend mastectomy and removal of ovaries for these women. If women with BRCA1 mutations gets cancer, 80 percent of time it is TNBC. This is called BRCA-associated breast cancer. Why is there such close associations? If a woman without mutation gets TNBC, what does this tell us? We don’t know yet.

• Chemotherapy is the mainstay across all subtypes. Has a bad rap that is deserved. Can have complications and side effects that we can increasingly manage. But it has less than a 1 percent risk of serious complications. Advances in chemotherapy have clearly made a difference in treatment with TNBC—dense-dose chemo, addition of taxanes. Have made some significant advances in treatment. Chemo quite effective and will be in use for many years, and we will continue to work to reduce side effects.

• It is not true that TNBC not sensitive to drugs. It is sensitive to chemo. Studies on neo-adjuvant chemo (before surgery) showed quite clearly that the response to drugs is greater in TNBC than in other cancers.

•Anti-angiogenic treatments are treatments that target the blood vessels. Cancers have a system for creating their own blood supplies. Avastin is an antibody-based therapy that targets the blood supply. One thing that is frustrating for us: When we use drugs like Avastin, they seem to be effective, but there is not a selection strategy as to who should get them and who should not. Studies of women treated with chemo and Avastin found equal benefit between TNBC and other types of cancers. One argument is that this is a targeted drug for TNBC. European trial looked at chemotherapy alone and chemo with Avastin in neoadjuvant setting. Not a strong impact, but TNBC had slightly more of an impact. Lends support to the position that this is a valuable place to research.

• EGFR as a target—EGFR inhibitors. Studies on chemo alone as well as chemo plus treatment for TNBC showed a relatively low response rate—not enough to give to all patients with TNBC.

• Greatest interest recently in a new class of drugs called PARP inhibitors. Connected to BRCA1—one of its roles is repairing cell’s damage to DNA. Without BRCA, cell does not have the system for repairing itself. Has to go to emergency back-up systems. If BRCA working, cancer cells are more likely to be killed. PARP inhibitors work with cells that are less likely to repair themselves.

• No PARP inhibitors approved yet. Interesting study in BRCA-associated cancers. Women given just a PARP inhibitor—without chemo---and the tumor shrunk. Drugs in early development, may be a positive way forward for those with inherited mutations.

• What about women without inherited mutations? (Sporatic cancers.) A study on women with metastatic TNBC who were given iniparib, a PARP inhibitor, which was added to the therapy; it controlled cancers longer; women lived longer. Not replicated in a larger study, however. Disappointing result.

• Lots and lots of these approaches are being pursued. We are likely to sort this out. Many good people spending a lot of time on this.

•Ten different angiogenetic drugs being studied. PARP inhibitors also being studied.

• It is possible we are not going to have a home-run drug for TNBC. It may well be that the way forward is personalized medicine. We are trying to determine what the Achilles heel of that cancer is, and target that. TNBC will be the first type of breast cancer to try that personalized approach.

• Clinical trials are essential—consider enrolling.

Q&A

Relapse to the brain. Reseachers pay attention to brain metastases because the brain acts differently—it responds to surgery. Most common type to move to brain is Her2-positive. Second is TNBC. With Her2, can move only to brain. TNBC tends to come back in the brain as well as other places at the same time; it may have to be treated differently than Her2-positive cancer. Brain metastases research is a very active field. In the past, there had been a tendency to lump brain metastases together—breast, melanoma, lung. Now, break into different types of cancer and different types of breast cancer. The blood-brain barrier needs to be considered. Research now specifically on PARP inhibitors for TNBC that has metastasized to the brain. There have been advances in standard therapy, such as surgery, for brain metastases.

BRCA testing. Is it worth it? Most, but not all of the time. Testing might be called for in a person with a personal history of more than one cancer, any history of ovarian cancer, or any first-degree relatives with breast cancer. Suggest talking to genetic counselor.

What can do to reduce risk, especially without risk factors. Most of the time, we do not know why one woman gets breast cancer and another one doesn’t. There’s the risk of getting the cancer—research is ongoing on how to peg individual risk. Separate from that is how to reduce the risk of an already-formed cancer from coming back. Know how to prevent from recurring—surgery, chemo, radiation. Beyond that, everything is an investigation. There is reason to think a healthy lifestlye helps across the board. Simply do not know how it affects the risk of relapse.

Are treatments different for women with BRCA mutations and those without? No, at this point both would be treated the same.

CMF: One of our earliest drug regimens that has been effective but is being replaced by more modern regimens. Still being used for women who cannot tolerate newer ones. One study showed that CMF actually better than AC chemo. Not a significant benefit, but would not avoid CMF.

Follow-up Testing: What is the best method in following after treatment? ASCO Guidelines—physical and careful history every three to six months for the first three years; every six to 12 months in years four and five. Breast imaging, usually mammography, but sometimes MRI every year. In most cases, no bone scans or CAT scans, or blood work.

Metaplastic breast cancer as is relates to TNBC. Metaplastic are relatively unusual. (As few as 1 percent of all cases.) It is a specific subtype. Most breast cancers are either ductal or lobular. Others are pathologically different. Metaplastic has a funny appearance. Unusual. Almost always TNBC. Don’t know if there is a specific treatment difference. Acts like other breast cancers. May have more of the claudin low subtype.

If you have cancer in one breast, should you have the other breast removed? Prophylactic mastectomy in general is limited to those with an inherited risk. If have risk factors and are having mastectomy, it makes some sense to remove both breasts at the same time. For women who have sporatic TNBC, the decision between lumpectomy and mastectomy is a personal one. The decision there is not different for women with TNBC as opposed to others.

Reminder: TNBC Teleconference Tomorrow

You can still register for the "Triple-Negative Breast Cancer: Medical Update" teleconference tomorrow, April 11, at noon Eastern time, with Lisa A. Carey, MD. Register through the sponsors, the TNBC Foundation and Living Beyond Breast Cancer.

You CAN Survive Triple-Negative

Triple-negative breast cancer has caught the attention of major researchers throughout the world, which is a great thing—it means that we are learning more and more about how to prevent and treat this illness. The downside of the research popularity is that the media and medical journals have developed depressing and frightening catch phrases for it, such as deadly, particularly aggressive or, my favorite, a lethal triad. People who write these words do not realize that they can terrify the women who read them, hitting like a heavy thud on our hearts. Researchers are trying to define the disease. Patients are trying to beat it.

The aggressive nature of hormone-negative is a comparative measure. That is, these cancers are, in general, more aggressive than hormone-positive cancers—although, in some cases, only slightly more aggressive. And some hormone-negative cancers can actually be less aggressive than some hormone-positive cancers. Scientists work in generalizations, defining how the disease affects women as a group. Individual cases vary and, researchers increasingly say, are as unique as our DNA.

How researchers classify triple-negative, for example, can vary. My own case—negative for estrogen and her2, but weakly positive for progesterone—puts me in a fairly narrow subset. Yet I had two oncologists tell me that they classify weakly positive as a negative, meaning I would be triple-negative. Researchers disagree, usually considering any level of positive as being positive. It is possible, though, that my weakly positive progesterone put me in a less agressive subset that is so small it is seldom researched.

So let’s look at some of the data and what they mean. And rather than simply accepting the gloomy picture that is often presented, let’s approach this in the enterprising spirit of yeah, but….

It is true that hormone-negative breast cancers can be more aggressive than hormone-positive. But the majority of women who get the disease survive.

It is true that most cases of recurrence come within the first three years. But that means that those who hit five years are looking at an excellent prognosis. A better long-term prognosis, in fact, than those with hormone-positive.

It is true that triple-negative is more likely to have spread to the lymph nodes. But many women with TNBC have no positive nodes—and, if they do, they still beat the disease and survive.

I have learned to turn statistics around to improve my perspective. For example, when research says that 30 percent of the women with triple negative died in a particular study, I turn this around and realize that 70 percent of the women survived. And I plan to be one of those women. And if, in another study, a triple-negative woman faces a two-fold increased risk of death compared with hormone-positive, I look at the fact that the difference might be between a 10 percent risk of and a 20 percent risk. And, while those decreased odds are startling and sobering, they still can mean an 80 percent chance of not dying. Even starting with a poorer prognosis, the odds can still be with you.

 

NOTE: This is an excerpt from 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.

Linda Hallam: 1951-2011

My friend and colleague Linda Hallam died March 29, 2011. She had been diagnosed with triple-negative breast cancer in July 2010. She is mourned by her husband, sons, siblings, friends, colleagues, and the triple-negative community. Another huge loss. I wrote about her in an earlier post, but words do fail me on this one.

My prayers to Linda's family.

Her obituary, in The New York Times, gives a little sense of this accomplished woman.

Pilot study to look at stress in young women with TNBC

A two-year study at Southern Methodist University will analyze the psychological and social challenges faced by young minorities with triple-negative breast cancer. Researchers will survey up to 60 women recently diagnosed with TNBC or those who test positive for a mutation of the human gene that suppresses tumors, BRCA1.

Below are portions of a news release from SMU. (I have edited out phrases such as an "aggressive form" and, my favorite so far, "this unconventional subtype.")

The study is probing patients' stress, anxiety and concerns about the psychological and social hurdles they face, said Georita M. Frierson , principal investigator. SMU is collaborating on the Triple Negative study with the University of Texas Southwestern Simmons Cancer Center, a National Cancer Institute-designated cancer center.

"We don't know anything about this population psychologically," said Frierson, an expert in behavioral health psychology and an assistant professor in the SMU Department of Psychology. "But based on this study, for any of their concerns we could tailor a psychological intervention to help other women like the women in my pilot. These women will be our pioneers in the psychological area to help their sisters that may have Triple Negative in the future."

For younger, minority women: Different cancer, different challenges


Triple Negative patients face far different challenges than women with traditional hormonal-type breast cancer, whose psychological and social challenges have been widely examined in the published psychological cancer literature, Frierson said. Traditional hormonal-type patients are typically over age 50, in a later career phase, raising their families, and probably have peers who may be struggling with a chronic illness.

In contrast, a Triple Negative patient is young, maybe mid-career, may not have started a family, and her peers are largely healthy and active. Because Triple Negative is a very aggressive cancer, Triple Negative patients can have lower survival rates and higher recurrence rates, and the medical treatment is different from hormonal-type cancer, Frierson said. For example, while chemotherapy can be an effective treatment for the Triple Negative patient, it can lead to short-term menopause, which may or may not be reversible, she said.

Breast cancer is the second leading cause of cancer death among women after lung cancer. In 2010, there were more than 192,300 new breast cancer cases in the United States, with more than 40,000 deaths.

The subtype is called Triple Negative because it tests negative for all three of the hormone receptors that fuel many types of breast cancer: estrogen, progesterone and human epidermal receptor 2. Some traditional breast cancer hormonal treatment therapy drugs, such as Tamoxifen, aren't effective against Triple Negative Breast Cancer.

Results will establish protocol to develop interventions


Health care providers, social workers and others can use the study data to develop programs to reduce and manage stressors in the lives of Triple Negative patients, Frierson said.

"We want to fill a gap that needs to be addressed," she said. "The information from this pilot can help us develop programs and support groups to ease the burden on Triple Negative survivors. When we talk about breast cancer, many people think about the woman in her 50s. But these are young cancer survivors. Really understanding those differences is important."

Health providers who have agreed to refer patients with medical approval by their physicians include: U.T. Southwestern and Parkland Hospital in Dallas; and Moncrief Cancer Institute in Fort Worth. As a partner in the study, The Cooper Institute in Dallas will provide participants with fitness testing. The survey is also online, so a woman outside the Dallas-Fort Worth area can answer a one-time questionnaire and participate in the study.

The survey, which takes 45 minutes to an hour to answer, asks questions about physical activity, diet, nutrition, compliance with doctor appointments, stress levels, body image, quality of life, relationships, friendships, fertility, depression, anxiety, sleep and fatigue.

The research is funded with a two-year, $50,000 grant from The Discovery Foundation, Dallas.

Smoking and Alcohol Use Not Associated with TNBC in Postmenopausal Women

Postmenopausal women who smoke and use alcohol do not face an increased risk of TNBC, according to research using data from the Women's Health Initiative. The study enrolled 148,030 women, 300 of whom had TNBC and 2,479 of whom had estrogen-positive disease. Smoking and alcohol use were both associated with ER+ breast cancer, but not with TNBC. The research was published in Cancer Causes Control in March 2011. Drinking actually slightly reduced the risk of TNBC.

Still, smoking is associated with lung cancer, so it is never a good thing. As for drinking, everything in moderation.

Vitamin D Reduces Risk for ER+, But May Increase ER- Risk

Orlando, Fla. -- In mice models of breast cancer, researchers at the Georgetown Lombardi Comprehensive Cancer Center, a part of Georgetown University Medical Center, found that vitamin D significantly reduced development of estrogen receptor-positive (ER+) breast cancer both in lean and obese mice, but had no beneficial effect in estrogen receptor-negative (ER-) cancer. In fact, obese mice destined to develop ER- breast cancer were clearly worse off than lean ER- mice if they were given vitamin D in their diet.

The researchers, who will present their study at the American Association for Cancer Research (AACR) 102nd Annual Meeting 2011, also found that vitamin D reversed insulin resistance in obese mice, no matter which breast cancer subtype they later developed. In lean mice, however, there was no evidence that vitamin D increased insulin sensitivity.

"Use of vitamin D supplementation is clearly tricky. In the many studies that have been done studying the effect of vitamin D in different cancer types, there is no straight link between use and benefit," says the study's lead investigator, Leena Hilakivi-Clarke, Ph.D., a professor in the Department of Oncology.

For example, in the colon, vitamin D seems to reduce the risk of cancer development, but it may not have any effect on later stage colon cancer. There is also concern that vitamin D may increase the risk of prostate, esophagus and pancreatic cancer. In work she has conducted in endometrial cancer, Hilakivi-Clarke found that although vitamin D was not beneficial in lean mice, in obese animals it reverses both early and advanced stages of the cancer.

"This is not a vitamin that should be taken lightly," she cautions. "People need sufficient amounts because it has beneficial effects for overall health that have nothing to do with preventing cancer. But for those who want to boost their use of vitamin D, it is important that they have their individual levels tested by a physician, and that they discuss their desire to use supplements."

IMPACTS OF VITAMIN D INTAKE IN MICE MODELS (findings in Hilakivi-Clarke lab)

	Lean mice	Obese mice
ER+ breast cancer	Risk reduced	Risk reduced
ER- breast cancer	Dose dependent benefit	No benefit
Insulin resistance	No benefit	Reversed
Endometrial cancer	No benefit	Risk reduced

IN HUMANS

In their ER- breast cancer study, the researchers fed lean mice two doses of vitamin D - 15 or 20 K international units [IU] VD3 - from puberty onset onwards for 24 weeks. They found that the lower dose (15 K IU) of VD3 significantly reduced mammary tumor incidence as well as time for tumors to develop in lean mice, when compared to mice that were fed control diet. A higher dose (25K IU) was used in mice fed the obesity-inducing diet because vitamin D becomes trapped in fatty tissue and thus is reduced in the blood stream, Hilakivi-Clarke says. Obese mice destined to develop ER- cancer that were given vitamin D developed the highest incidence of breast cancer.

In their ER+ breast cancer, only the higher vitamin D dose (20K IU) was used. This dose significantly reduced breast tumor incidence in lean mice, compared to control or obese animals. Additionally, obese mice fed vitamin D developed fewer tumors than obese mice not supplemented with it, says Hilakivi-Clarke.

In both mouse models of breast cancer, obese mice developed insulin resistance, and vitamin D supplementation reversed it. However, vitamin D in lean mice tended to reduce insulin sensitivity in both mouse models, she says.

The researchers are currently studying possible mechanisms by which vitamin D may reverse obesity induced increase in breast cancer and insulin resistance, and preliminary results suggest vitamin D reverses the action of genes which promote inflammation, cell proliferation and survival, and this might involve epigenetic modifications.

Contact: Karen Mallet
km463@georgetown.edu
215-514-9751
Georgetown University Medical Center

Journey into Spring: Treasured Resources

I am rich with people. They are my renewable, sustainable resources, although I define those terms to mean they renew and sustain me.

This weekend, my husband and I went away for a Weekend with Peeps in Minneapolis and northern Iowa. We did a few museums, wandered around the Upper Mississippi, nosed around the mill district by St. Anthony Falls along the old mills on the Minneapolis riverfront, drove by Lake Harriet, with its gracious homes and trails packed with families, ate at an old firehouse, and ended up in church in Cedar Falls, Iowa.

Most important, though, were the people with whom we shared these experiences—Shawn and Berit, two of my former students who graduated the same year and who make their livings as writers; Mary Kay and Will, design stars who moved to Minneapolis from New York several years ago and who share their expertise with me as I prepare another edition of the magazine textbook I co-authored; Elizabeth, another former student, who is now an Episcopal priest.

We shared talks about everything from magazine design to parenting to religion and politics to Native American art. The kinds of talks you can start in the middle because build on a deep foundation.

I am blessed with interesting people in my life, people I appreciate and respect, people who appreciate and respect me. People with whom hours disappear in thoughtful discussions, laughter, and shared memories.

So we returned home tonight fairly pooped, but thoroughly renewed, beautifully sustained.

Rich with people.

Journey into Spring: Friendships

Friendships are central to a strong life. Our friends can be our backbone when we are weak, our brains when we are confused, our hearts when we are stricken with grief. They are a treasure, and they are hard to find.

In Dear Heart Come Home, A Path of Midlife Spirituality, Joyce Rupp writes about our middle years as being times of change and growth, much like adolescence, when we begin to question ourselves, where we are going with our lives, and wonder how to be the best us we can be. About her own life, she says:

I’ve searched for a link in my relationship with others and wondered who I wanted to spend the rest of my life with in friendship….

In midlife, she says, we can ask questions we might not have thought of before, we are intentional about our lives in a way that was not possible when we were building our careers and families. And we can wonder if the friends who surround us are the ones we need.

Several years ago, I realized I had two friendships that were toxic. These women, on final assessment, neither wanted to know who I was beneath the surface s nor appreciated what little they did know about the self that mattered to me. I made a conscious decision to break off these relationships. It was actually sadly easy. I simply stopped calling them and they did not call me. And that was that. I guess the ease with which those ties were broken demonstrate that they were extremely weak and reinforced my decision to move on.

I had other excellent friendships that were important to me, so I enjoyed and maintained those. And I had colleagues to supplement these relationships.

Lately, though, I have realized there are women I want to know better and I have made a conscious effort to build new friendships. One, with a woman at church who is wise and funny and good. Another, with a woman I have known for more than 30 years but who I am finally getting to know better, a fellow cancer survivor and writer. Another is a woman who belongs to my dinner group and who loves the outdoors like I do, who I have also known for decades but only peripherally.

I love that I am learning about these women’s lives, and I am sharing myself with them. The me that I am at this moment is thriving with these new anchors in my life. And it has been surprisingly easy. I email, they answer right away, we do lunch, we talk, we laugh, we commiserate, we eat.

These new friends nourish my spirit. Maybe we’ll never be best friends. Or maybe we will be, but I don't spend my time worrying about where we are going. One thing I know now is that the present is a time to celebrate. So, I quietly throw some mental confetti in honor of these new friends. And pop a bottle of virtual champagne in a toast to women everywhere who help one another walk down our roads of change.

And I look forward to growing in friendship.

Journey into Spring: Bumps on the Road

This is more difficult than I had thought—or than I had hoped. As I write this, a colleague with triple-negative breast cancer is on life support in a Florida hospital after a massive stroke that might have been triggered by the spread of her cancer.

When another colleague who has battled cancer heard the news, she wrote to me, “This is such an insidious disease.”

Insidious is right. Menacing, sinister, dangerous. Interestingly, one synonym for insidious is subtle. And one of cancer’s many challenges is that it is hardly a straightforward disease, with a definite path and a clear outcome. Chances are great that you will survive and get on with your life, as most women do, changed by the experience, often for the better. There is always the chance, though, that it will return, that it will kill.

How can you tell where your path leads? Even with the markers we get from doctors—no signs of cancer—the fear of recurrence is there, and it is real, because recurrence is real. It gets less common after three years for TNBC and increasingly less common after that. But it is real. It never goes away.

And, even though we think we know our bodies, it is easy to lose trust in that knowledge when cancer struck the first time and we tried to talk ourselves into the fact that it was nothing. So is today’s headache really a sinus problem? Is that bone pain actually because of too much exercise? Is that bruise because of lifelong clumsiness that causes me to run into most things in my path?

In the last conversation I had with Linda, she said she was doing well, the treatment was working and she was going on with her life. She had been diagnosed a year and a half ago. She was on my list of people with whom I needed to reconnect. I did, in fact, “friend” her on Facebook just last week, so she knew I was thinking of her. But I never got around to sending the “How are you?” email.

She read my blog and I could often see she was on the site. I wish there were a way to quickly say "hi!" to my individual readers; I suspect that is coming.

Linda was working on her doctorate, which she expected to finish this spring or summer. She had a great academic future ahead of her, as a woman with significant professional experience. One question I wanted to ask was whether she had a job lined up, as she probably did. I was eager to follow her new career, as it was one I shared, and I had encouraged her to get the Ph.D.

But now I have to settle for hearsay—they think the stroke was cancer-related. They don’t know.

They do not expect her to live.

So I mourn the future she should have had, but celebrate the rich past she left behind. And, once again, I am left looking for answers, wondering exactly what happened here.

Insidious.

Dangerous.

Menacing.

Subtle.

Journey into Spring: Are We There Yet?

Technically it has been spring for days now. In Iowa, we have had snow, tornadoes, and 70-degree weather all in one week. Yes, I guess that sounds like spring.

So, are we already there? Is our journey over, now that the calendar says spring is on schedule? Or is this journey one of those without a clear ending?

When I was going through treatment, I used visualization exercises to help me relax, shutting my eyes and imagining a place of calm and happiness. The image that often came to mind was of the path to our summer cabin. Not the cozy cabin itself, nor the stunning mountain outside the window, or the meadow full of wildflowers.

Just the path.

Really? Was my subconscious working in metaphors? Telling me that, for that moment, the path was what I had, that there was something wonderful up ahead, but for now the focus was on this little journey?

It's a sweet path, lined with trees and, for a few days a year, wild roses. But the scenery elsewhere is spectacular, while the path is, by comparison, ordinary.

I guess if I had imagined the grandeur of the mountain I would have thought I was going to die. Or maybe my subconscious tapped into something--the feeling that, up ahead, there were great things. I just needed to keep going and I would get there.

So, snow today. Who knows what tomorrow. Soon, though, spring.

And, in seven weeks, my five-year anniversary.

Cruciferous vegetables can help fight TNBC

Lab research has once again shown the health benefits of broccoli, kale, cabbage, and other cruciferous vegetables, specifically demonstrating their effects on fighting triple-negative breast cancer. Indole-3-carbinole, which is found in high quantities in these vegetables, has long been considered a potential cancer fighter. Now, research in Italy published in Breast Cancer Research, demonstrates that it shows promise as an injectable anti-cancer agent for TNBC tumors as well as for those that are hormone-responsive. You can download a PDF of the research here.

Researchers worked in the lab on tumor cells. Clinical trials on humans would be the next step. In the meanwhile, it might be good to keep these veggies in your fridge:

Bok Choy

Broccoli

Brussels Sprouts

Cabbage

Cauliflower

Kale

Radish

Wasabi

Donate just $25 to this site and receive a copy of my book, Surviving Triple-Negative Breast Cancer. 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.  Your support is all that keeps this whole thing going.

Journey into Spring: Pondering Our Legacies

When our parents died, my siblings and I had so much to say about them that we packed their gravestone with imagery—mountains, books, flowers, verses.

They were born and raised in Colorado, which explains the mountains, which they loved. Both were readers, therefore the books. They grew and enjoyed beautiful flowers, hence the posies. And, each day when my dad went to work at the steel mill, my mom kissed him and said, “God be with you ‘til we meet again.” That, of course, was on the stone.

I am impressed with the stone carver for packing this all into a nicely designed marker.

But the fact was that we could not encapsulate Mom and Dad’s lives into one simple image. There was too much of them, too much to say.

What do you think your kids would say on your stone? What would you want them to say? Thinking of your life this way makes you focus on the real meaning of what you have done, of what you will leave behind when you die. And, yes, you will eventually die. Cancer makes us think more about our eventual death, but people without cancer die too. We might just be a little more aware of that possibility.

So, what would your stone say?

I have no idea what my kids might say about me. I remember when Josh was in the second grade and I was going to teach a class about The Lion, the Witch, and the Wardrobe at his school. One of his classmates asked what I was like, and he said, “She’s funny.” That always makes me smile—that my sweet little seven-year-old liked that I was funny. I would like to think I am more than that at this point, but I am not entirely sure what it might be. I had not expected him to say I was funny then, so I don’t know what to expect now.

What would I want to say about myself, though? Perhaps that I made a difference, that I was a force for good. That is a goal, one that I can keep my eye on, aspire to, hope for, live by.

It’s a challenging exercise, forcing you to assess where you have been and where you would like to be, who you are and who you would want to be.

Journey into Spring: Celebrating Good Eggs

Sociologists say that brothers and sisters grow up in a different families, even if we are only a year apart in age. Family dynamics, they say, can be varied enough to change the environment significantly. A parent might have been working last year who is not working this year. Or a sibling’s illness could have stressed the family’s resources and patience. And the year before your big sister became prom queen is far different from the one during which she wore a rhinestone tiara.

Research is mixed on the effects of birth order. Some studies say the oldest in the family is the smartest, with intelligence dropping from there. Scientists speculate that the effects are broader than this, that the oldest children are healthier because they get the strongest sperm and eggs.

As the youngest of five, I take exception to the intelligence issue. But I do sometimes wonder if birth order was the reason I got cancer when none of my older siblings did.

Other research speculates that babies born in the winter are sicker than their spring and summer counterparts, the thinking being that winter babes are more likely to get germs in utero that bug them their entire lives.

I was born at the last of December.

So, I got the old, buggy eggs.

But never mind. I really love my siblings. What’s more, I like them. So, I am glad none of them got cancer and I hope that trend continues. I am not going to dwell on the issue of whether or not birth order was a reason I got sick and they didn’t. I will not acknowledge that they are smarter than me, though.

I am glad they are in my life and I always have been. They are all smart and seriously funny. I have told my oldest sister that she should be a comedian—she could just tell an audience a story about buying rice at WalMart and have them laughing so hard they cry. My brothers tell stories about growing up that make me realize that they, indeed, grew up in a different family. Sometimes I am surprised they grew up at all, what with diving from cliffs into the river, starting their car in the winter with ether and being knocked out in the process, and speeding through intersections because their car could not stop. They make the stories like a comedy routine, one riffing off the other. My middle sister is more sweet than funny, the caretaker of the family, the one we can count on for prayers and unconditional love.

The photo above is of me and my two brothers. I am nearly 5-foot 10-inches, so you can get an idea of what big guys they are, in stature and in personal strength. You need a video to hear their quips, though.

So, on this gorgeous spring day, with highs in the 70s, I remember that summer day three years ago when I shared a mountain hike with some of my favorite people, my brothers. True blessings in my life, true treasures.

Even if they did get all the good eggs.