Immune System Discovery May Stop Breast Cancer

The study of a protein, critical in causing asthma, allergies and other diseases, has led scientists at Benaroya Research Institute at Virginia Mason (BRI) to discover a new strategy for stopping breast cancer.

BRI researchers Emma Kuan, PhD, and Steven Ziegler, PhD, have pinpointed how the protein, called thymic stromal lymphopoietin (TSLP), helps breast cancer tumors survive and grow. Even more significant, the researchers showed that blocking TSLP can significantly inhibit the growth of breast tumors and halt metastasis to the lung. This discovery opens the door to new strategies that could stop breast cancer tumors from growing and spreading. It may also be applied to other tumors that involve TSLP.

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Steven Ziegler, PhD                                          Emma Kuan, PhD

“Breast cancer becomes especially dangerous once it spreads to other parts of the body,” Dr. Kuan says. “Our work suggests that blocking TSLP could prevent this from happening and potentially save the lives of women worldwide.”

The research was published recently in Nature Immunology. TSLP was discovered 15 years ago by the Ziegler Laboratory, as well as other labs, to initiate the inflammatory cascade that leads to the development of asthma, allergies and other diseases.

How TSLP Helps Tumors

Researchers had previously found elevated TSLP levels in several different tumor types, but its role in tumor biology was unclear. Drs. Kuan and Ziegler solved this mystery by using preclinical models to investigate what happens to breast cancer tumors when TSLP is taken away.

Their research revealed that the tumors didn’t grow nearly as large – or metastasize nearly as much – when they didn’t have access to TSLP. In fact, the breast cancer cells died without access to TSLP, resulting in markedly smaller tumors and a lack of lung metastases, compared to tumors where TSLP was present.

“The tumors can get started without TSLP, but they need it in order to stay alive and metastasize through the body,” Dr. Ziegler says.

Hijacking Immune Cells

Once the researchers determined that TSLP was critical, they set out to uncover how it worked – and became the first to discover that tumors turn immune cells into accomplices that express TSLP. Importantly, the researchers found that the same cells that make TSLP in the models also make TSLP in human breast cancer patients, and human breast tumor cells respond to TSLP in the same way.

Stopping Tumor Growth

When Drs. Kuan and Ziegler used an antibody to block TSLP, it stopped tumors in their tracks – even when they had already started growing. Within six weeks, the tumors had shrunk significantly, more of their cells were dying and they had stopped spreading to the lungs. This suggests that anti-TSLP therapy could work in human patients with existing tumors.

“Blocking TSLP could potentially contain not just breast cancer, but many other tumors that have elevated TSLP – including pancreatic cancer, cervical cancer and multiple myeloma,” says Dr. Kuan.

A drug that blocks TSLP has already been developed and initial trials have shown that it’s safe in patients with asthma, so scientists are hopeful clinical trials could be launched for cancer patients in the relatively near future.

“We’re currently working on a better way to block only the TSLP that helps tumors,” Dr. Kuan says. “And we are really hopeful that this could become a viable strategy for containing tumors long-term, without interfering with TSLP in other healthy cells.”

New Cancer Biorepository

For their research, Drs. Ziegler and Kuan used samples from BRI’s new biorepository, the Virginia Mason and Benaroya Research Institute Tumor Repository (VM BRITE). The biorepository houses the medical history and blood and tumor samples of research participants with a variety of cancers.

“As BRI studies the immune system and tries to understand why it veers off course, we learn how it relates to other diseases such as cancer,” says BRI President Jane Buckner. “We want to pursue these discoveries to improve the lives of people with autoimmune diseases, cancer and hopefully many other diseases.”


A version of this story originally appeared in the Benaroya Research Institute Autoimmune Life Blog

 

Knitters Show Their Support for Worried Mammography Patients

… because a little piece of yourself goes into everything you knit …

~ McCall’s Knitting Slogan, 1955

During Breast Cancer Awareness Month, it is easy to put on a pink ribbon to show your support. At Virginia Mason Federal Way, the team not only puts on their pink ribbons – they take out their knitting needles and get crafty to show support to patients who are called back after a screening mammogram.

A mammogram is a low-dose X-ray exam of the breasts to look for changes that are not normal. The results are examined by a radiologist, who looks for changes in breast tissue that cannot be felt during a breast exam. It’s the most effective way to find breast cancer early. Like with any screening test, going in for a mammogram can cause some worry about what the radiologist may or may not find. Receiving a callback for more testing (such as a diagnostic mammogram, ultrasound or biopsy) can heighten this anxiety with the thought of possibly having breast cancer.

The Federal Way mammography team understands getting a callback can be a trying time for patients and three years ago started doing something special during Breast Cancer Awareness Month to show they truly cared. Judy Gross, radiology lead, coordinated the creation of handcrafted pink washcloths knitted by team members to give out to concerned callback patients.

“The team understands this is a difficult time for these patients,” said Vicki Wiitala, Federal Way Radiology’s clinic manager. “We want to do something special for them to show we care.”

2013 Knitters

This year’s team of knitters included Virginia Mason Federal Way mammographers Dolores Range, Kathy Druzianich, Judy Gross, Jeanette Mishler and JoAnne Molinari (all pictured), plus Naomi France, RN; Teresa Fox, RN; and many family and friends.

And while knitting a pink washcloth seems like a simple gesture, it takes a village of volunteers to knit the amount needed for the month of October. The Federal Way clinic usually sees 15 to 20 patients per week who are required to come back for a diagnostic mammogram or additional views. The team needed to knit more than 100 pieces to give out during October. And all the knitting is done on the team’s own time – at home and during breaks. Besides the joy of knitting, why do they put in all this effort? Several of the team members have a family history of breast cancer, so they recognize the importance of raising awareness about having a screening mammogram.

“The goal of a mammogram is to find cancer when it is small,” explains Peter Eby, MD, who is the section head for breast imaging at Virginia Mason. “We recommend screening mammograms once a year starting at age 40. The odds of getting breast cancer at that young age are low, but finding it early gives women the best chance of beating it.”

Although the pink washcloths help raise awareness, it’s really more about comforting patients. “We felt giving out the washcloths brightened a patient’s day when they are going through a stressful and scary time,” explained Vicki.

It is not uncommon to be called for a second look after a screening mammogram, and it is important to remember most women do not get breast cancer if they are called back in.

“In fact, 7 out of 8 women don’t get breast cancer,” said Dr. Eby. “And 75 percent of callbacks turn out to be false alarms, but we still need to perform a complete and high quality evaluation. In most cases, we can tell patients there is nothing to worry about before they leave the department.”

In the end, a callback can be stressful, but knowing that most findings on a screening mammogram are not cancer can help ease the worry. And if not, there is always the pink washcloth to let you know you’re in the caring hands of a great team.

To find more information about mammograms and other imaging tests for early detection and diagnosis of breast diseases, visit the Virginia Mason Breast Clinic.

New Treatment Options Available for Women with Early-Stage Breast Cancer

Patient Amy Asbury Benefits from Groundbreaking Clinical Trial

Learning you have breast cancer on a Friday afternoon makes for a frightening and uncertain weekend. What helped Amy Asbury cope with the news was knowing the treatment wheels were already in motion.

“What really impressed me about Virginia Mason was they were already assembling a team to meet with me,” remembers Amy.

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Amy Asbury and her dog, Brody, enjoy a walk.

The following Monday, Amy had an MRI to confirm her diagnosis: ductal carcinoma in situ (DCIS), the presence of abnormal cells inside the breast’s milk ducts. She didn’t wonder about treatment options for long, meeting all the members of her cancer care team just two days later. In successive appointments in the Floyd & Delores Jones Cancer Institute at Virginia Mason, Amy met her oncologist, radiation oncologist and breast cancer surgeon, all with the personal, ongoing support from her dedicated breast cancer nurse coordinator.

“They went through the entire range of options with me,” says Amy. “Originally, I thought I’d hear them out, then look for a second opinion. But I walked out of there thinking I absolutely want these people to be my doctors.”

Because a routine mammogram had caught Amy’s cancer early, she was a candidate for lumpectomy and radiation therapy. What she didn’t know was that a new approach to both treatments would have postsurgical benefits she couldn’t have imagined.

Amy was joking when she asked Virginia Mason breast surgeon Janie Grumley, MD, if her lumpectomy could double as a breast reduction. Dr. Grumley had a surprising answer: her training in a method known as oncoplastic breast surgery — incorporating plastic surgery techniques in cancer removal — meant Amy’s lumpectomy could actually leave her breasts looking better than before her diagnosis. “Of course the goal is to get the cancer out, but it’s an unexpected plus when the surgeon can operate with a nice cosmetic result, too,” says Amy.

As Dr. Grumley performed Amy’s lumpectomy and reshaped her right breast, Virginia Mason plastic surgeon Alexandra Schmidek, MD, simultaneously reduced Amy’s left breast to make both sides symmetrical. Having cancer surgery and reconstruction all at once was a major benefit in itself, but that wasn’t the only treatment that was accomplished in just one operation.

Instead of the typical lumpectomy follow-up involving weeks of daily radiation treatments, Amy received a one-time treatment with intraoperative radiation therapy (IORT), requiring only minutes to administer during her surgery. Virginia Mason is the first medical center in Washington state to offer IORT to women with early-stage breast cancer as part of a clinical trial. Michelle Yao, MD, Virginia Mason radiation oncologist, operates a portable therapy unit that delivers cancer-killing radiation by catheter directly to the site of the tumor, avoiding the unnecessary exposure of surrounding tissues. The application of radiation inside the breast is so precise and effective, one dose is equivalent to weeks of external beam radiation therapy.

For Amy, the option of skipping multiple radiation treatments more than made up for the regular follow-up visits she’ll have as part of the IORT clinical trial. Pictures are taken of her surgery site at these visits, and any side effects are recorded. But Amy hasn’t had a single thing to report.

Recovery was very doable, no side effects, and I only missed about a week of work,” says Amy. “IORT made perfect sense for me and my early stage cancer. And I feel like I’m contributing to the science of better ways to treat this disease.”

***

This story was originally published in the Virginia Mason 2012 Annual Report.

Breast Cancer: Genetic Testing Helps Reduce Anxiety for Some

iStock_000020255467XSmallA few months ago in The New York Times, actress Angelina Jolie shared her story about testing positive for a faulty gene that increases the risk of breast cancer. She said she went public with her decision to have a preventive double mastectomy, “because there are so many women who do not know they might be living under the shadow of cancer.”

The “shadow” she refers to is an inherited genetic mutation that affects specific genes, identified as BRCA1 and BRCA2. In Angelina’s case, her mother had breast cancer and died of ovarian cancer: a significant clue that Angelina might carry the mutation. Since the children of a mother or father with a BRCA mutation have a 50 percent chance of inheriting it, the actress chose to be tested.

For many women, the media coverage likely raised more questions than answers: Should I find out if I have the BRCA gene mutation? What does increased risk really mean? What can I do if I have the mutation?

Fortunately, Virginia Mason helps women answer these questions through the expertise of hereditary cancer risk consultant Cathy Goetsch, ARNP. Providing cancer genetics services for more than 17 years, Cathy is uniquely qualified to assess women’s personal risk of cancer and determine if genetic testing is appropriate for them.Cathy, who sees patients referred from all over the region for her specialized services, looks at a number of factors that not only clarify if a patient should pursue genetic testing, but also help ensure testing is covered by a patient’s insurance plan, if they have one. Criteria vary based on individual history, but can include:

  • A known BRCA mutation in the family
  • Two or more same-side family members with breast cancer, or a member with breast cancer before age 45
  • First degree relative with ovarian cancer
  • Male family member with breast cancer

“Ideally we want to first test a family member who has breast or ovarian cancer to confirm their cancer is actually caused by a BRCA mutation,” says Cathy. “Then we know that if the patient without cancer tests negative for the mutation, they have no higher risk than the general population. But if they are the first tested and are negative for a specific BRCA mutation, despite cancer in the family, that doesn’t eliminate the possibility they are at higher risk for another reason.”

It’s the gray areas – such as whether a BRCA mutation or some other inherited risk may be affecting a family – that make Cathy’s role so important. Then there’s evaluating the risk itself. Studies show women with a BRCA mutation face a 40 to 87 percent lifetime risk for breast cancer, and an 11 to 54 percent risk of ovarian cancer. But Cathy will tell patients it’s not as simple as that.

“More recent studies, using broader patient populations, are showing the lifetime risk may not be as high as once thought,” Cathy says. “And what those statistics don’t tell you is that better technology for breast cancer detection means the majority of these cancers, if they happen, are caught early at a very treatable stage.”

An important distinction Cathy makes for her patients is she is there to help them manage their cancer risk, not take it away. Part of that distinction is educating women who are considered high risk about their treatment options. There is close surveillance, which consists of a prescribed schedule of exams and advanced imaging to monitor for the disease. Chemoprevention, which involves a drug regimen that fights cancer by manipulating hormones, is proven to reduce cancer risk in certain patients. Finally, preventive mastectomy, the surgery undergone for Angelina Jolie, is shown to reduce the risk of breast cancer by about 90 percent (even with the surgery, a woman’s risk is never completely gone).

While mastectomy can be an appropriate choice for a BRCA-positive woman, it may not eliminate her need for further treatment, particularly if early cancer already exists. Drug therapy, chemotherapy and radiation can still be needed following surgery, or in the future.

For some women, 90 percent reduction is a number that works and is worth the effort, while others are encouraged to learn that having a BRCA mutation does not mean a 100 percent chance of getting breast cancer, so they don’t rush into surgery.

“Many people feel reassured by genetic counseling and subsequent testing because they are empowered by the knowledge,” says Cathy. “They are having it done for their kids or other loved ones, and they learn there are things they can do to manage their risk – the choice is up to them.”

To learn more about hereditary cancer risk, call Cathy at (206) 223-6193 or visit the Hereditary Cancer Risk Assessment Web page.

What is breast self-awareness?

I don’t spend much time thinking about my “bosom buddies” except when I’m shopping for a bra or bathing suit (tasks I avoid at all costs). However, during October, when the world is awash in pink, it’s hard not to think about breast cancer. Statistics say approximately 1 in 8 women in the United States will get breast cancer at some point in their lifetime.

“Finding a cancer early gives you more options for treating it, and may increase your long term survival,” says Carly Searles, ARNP, from the Virginia Mason Breast Clinic. “We recommend a screening mammogram for women age 40 and older, a yearly clinical breast exam and breast self-awareness.”

So, how does one become more breast self-aware? Historically, a breast self-exam (BSE) was recommended for women once a month – usually after their period. But, some women found it awkward or stressed over doing the correct steps. Currently, it is OK for women to choose not to do the step-by-step BSE. But, this doesn’t mean ignoring one’s breasts until a new bra or bathing suit is needed.

“You don’t need to worry if you’re uncomfortable checking your breasts in a systematic way, like with a breast self-exam,” says Searles. “But you should notice how your breasts normally look and feel, so if any changes do occur, you can let your health care provider know right away.”

 The way breasts look and feel can be affected by getting a period, having children, losing or gaining weight, and taking certain medications. Breasts also tend to change with age. However, some warning signs to keep in mind are:

  •  New lump in the breast or underarm (armpit).
  •  Thickening or swelling of part of the breast.
  •  Irritation or dimpling of breast skin.
  •  Redness or flaky skin in the nipple area or on the breast.
  •  Pulling in of the nipple or pain in the nipple area.
  •  Nipple discharge other than breast milk, including blood.
  •  Any change in the size or the shape of the breast.
  • Pain that seems to concentrate in one area of the breast.

These signs don’t necessarily equal breast cancer. I once found a painful lump in my armpit that turned out to be a cyst, which is a noncancerous fluid-filled lump. And while I felt a little silly for automatically thinking I had cancer, the important thing is that I called my health care provider. By being aware and knowing it’s important to call your doctor, you don’t have to wait and wonder if you find a breast change that causes concern.

Intraoperative Radiation Therapy (IORT)

Here’s something we think you will be hearing a lot more about very soon. Virginia Mason is the first medical center in Washington state to offer intraoperative radiation therapy (IORT) to treat women with early stage breast cancer. Watch this 4-minute video to learn more.