Article Topic: Breast Cancer

For Your Health – Not Just Pink: Key cancer screenings for men and women

For Your Health Graphic








As we begin our annual move toward fall and more normal routines of work, school and family, it can be a great time to make sure that all of us are up to date with our recommended cancer screening tests. 

There’s probably no better reminder of this than the upcoming Breast Cancer Awareness Month in October.  The pink ribbons we see on websites, cereal boxes and t-shirts symbolize the importance of breast cancer and of cancer screenings. One out of 4 cancers diagnosed in women is breast cancer, so take the step now to get breast cancer screenings scheduled.

Dr. Graham A. Colditz

And while October focuses on mammograms for breast cancer, this translates just as well to other key tests for colon, lung, cervical and prostate cancers.    

Screening tests not only help find cancers earlier when they’re more treatable but some can also help prevent certain cancers from developing in the first place. Below are general recommendations for five cancers – four apply to women, three to men.   

People with a family history of cancer may need to begin screening at earlier ages than most. So, it’s important for younger adults in particular to talk to their providers about their risk of cancer and when it’s best for them to start getting screened.

Breast Cancer (Begin age 40) 

While there are still some small differences in the breast cancer screening recommendations from individual organizations, most are now unifying behind women starting mammograms at age 40, and getting them regularly every year or every other year.    

Cervical Cancer (Begin age 25) 

Screening for cervical cancer helps to both find cancer early, and to help prevent the disease by finding and treating pre-cancers. The American Cancer Society recommends that most women begin screening at age 25 with an HPV (human papillomavirus) test every five years. Nearly all cervical cancers are caused by HPV infections.  If an HPV test by itself isn’t available, an HPV test plus Pap test every 5 years is recommended, or a Pap test by itself every 3 years.  

Colon Cancer (Begin age 45) 

Colon cancer screening is another that can help prevent cancer – as well as help find disease in earlier, more treatable stages.  Most people should start screening at age 45, and there are a number of different tests to choose from.  Colonoscopy is the most common test and usually only needs to be done every ten years.  Home stool tests, such as a fecal immunochemical test (FIT) and stool DNA test, are quicker and easier than colonoscopy but need to be done more often.   

Lung Cancer (Begin age 50, if history of smoking) 

Yearly lung cancer screening is recommend beginning at age 50 for certain people who smoke or have quit in the last 15 years.  It’s important to talk to a healthcare provider to see if you qualify for screening and then to decide if screening is right for you.  Currently, screening is only recommended in people who’ve smoked the equivalent of 1 pack a day for 20 years.   

Prostate Cancer (Begin age 50, or 40 – 45 in Black men and others at higher risk) 

Most men should talk to a healthcare provider about prostate cancer screening starting at age 50.  Black or African-American men and others at high risk because of their family history should have this talk at age 45 and maybe even younger. Compared to other types of cancer screenings, there can be a more subtle balance between the potential benefits and harms of screening for prostate cancer. So, it’s important to discuss the test with a healthcare provider and then decide if it’s right for you.   

Cancer screening saves lives.  And millions of us missed our regular screenings during the height of the coronavirus pandemic and still need to catch back up.  So, make your health a priority and take some time this fall to check with your provider to see if you’re up to date with your tests and schedule any you may need.   

It’s your health.  Take control.  

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Dr. Graham A. Colditz, associate director of prevention and control at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis, is an internationally recognized leader in cancer prevention and the creator of the free prevention tool YourDiseaseRisk.com®.

Two-pronged immunotherapy eliminates metastatic breast cancer in mice

Metastatic breast cancer has no cure and has proven stubbornly resistant to one of the most innovative and promising new cancer treatments: immunotherapy.

Now, researchers at Washington University School of Medicine in St. Louis have identified a way to treat the area surrounding breast tumors that have spread to bone so that such tumors become vulnerable to attack by the body’s immune system. When the researchers boosted the activity of certain immune cells, called T cells and macrophages, these immune cells worked together to clear metastatic breast tumors that had spread to the bones of mice, and continued to eliminate tumor cells that eventually returned.

The study is published March 8 in Cancer Discovery, a journal of the American Association for Cancer Research.

Macrophages are myeloid immune cells that attack cancer cells through the body’s innate immune response to general threats, such as tumors or viruses. Such macrophages further activate T cells by showing the T cells what they should be looking for, thereby harnessing the adaptive immune response as well. In this case, these macrophages present T cells with bits of recognizable tumor — called tumor antigens — from dead cancer cells, and the antigens direct the killing activities of T cells.

“After breast cancer has spread to other parts of the body, it becomes extraordinarily difficult to treat; current therapies can only try to slow it down,” said senior author Sheila A. Stewart, PhD, the Gerty Cori Professor of Cell Biology & Physiology. “About 70% of patients with metastatic breast cancer have tumors that have spread to their bones. Our study suggests we may be able to use two treatments — one to sensitize the myeloid tumor microenvironment to immunotherapy, and one to activate T cells — to target these bone metastases in a way that eliminates the tumor, prevents the cancer from returning and protects against bone loss in the process.”

Stewart, also a research member of Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine, and her colleagues found that blocking a molecule called p38MAPK reprograms the tumor microenvironment to become more vulnerable to attack by the immune system, including by immune cells and signaling molecules called anti-tumor cytokines. While a p38MAPK inhibitor alone reduced tumor size, it didn’t eliminate the tumor entirely. So, the researchers investigated whether adding another therapy that activates T cells and boosts their ability to find and destroy the tumor cells could be more effective at eliminating the metastatic cancer cells.

Common immunotherapies — called immune checkpoint inhibitors — are often described as “taking the brakes off” immune T cells, ushering them into battle against cancer. In this case, Stewart described the new approach as “hitting the gas” on T cells, supercharging them to be more effective against the cancer.

The researchers investigated two models of human metastatic breast cancer in mice and found that the metastatic tumors were eliminated in mice that received a p38MAPK inhibitor and an immune therapy called an OX40 agonist, which binds and activates T cells. All these mice were still alive and tumor-free at least 80 days after treatment. Among mice receiving either of the two treatments alone, only about half of them were still alive 60 days after treatment.

“If we targeted the microenvironment to make it more sensitive to T cells and simultaneously hit the gas on the T cells, all of the mice were cleared of the metastatic tumors,” Stewart said. “If we came back after two weeks and challenged the mice again with the same tumor cells, their immune systems could clear those cells as well. It appears that their immune systems developed long-term memory and knew to attack those returning cancer cells. The mice look like they’re basically vaccinated against the cancer.”

Three different OX40 agonists are being investigated in phase 2 clinical trials for cancer, including breast cancer. And p38MAPK inhibitors have been investigated in a number of inflammatory disorders, including rheumatoid arthritis and chronic obstructive pulmonary disease.

“We are hopeful that our study will interest companies that make these drugs, so that we can work toward developing a clinical trial that could investigate this strategy in patients with metastatic breast cancer,” Stewart said.

How Siteman approaches triple-negative breast cancer treatment

According to the American Cancer Society (ACS), triple-negative breast cancer (TNBC) accounts for 10-15 percent of all breast cancers. It develops more quickly, is more likely to spread and is harder to treat than other breast cancers. Because it’s such an aggressive cancer, TNBC has a poorer prognosis than other invasive breast cancers.

What is triple-negative breast cancer?

Triple-negative breast cancer is a type of breast cancer whose cells have tested negative for estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor 2 (HER2). Unlike other invasive breast cancers, TNBC does not respond to hormone therapy or therapies that target HER2.

Diagnosed with triple-negative breast cancer? You’re not alone.

If you have recently received a TNBC diagnosis, you likely feel a great deal of fear. Common fears that TNBC patients have include:

  • Lack of targeted drug treatments
  • Treatment not working
  • Cancer recurrence
  • Dying

While a TNBC diagnosis can be scary, remember that it is not a death sentence. There are effective treatments for this cancer and many women go on to beat TNBC and live full lives, cancer-free. The earlier the cancer is caught, the easier it is to treat. This is why mammograms and early detection are so important.

Survival rates for triple-negative breast cancer

Survival rates for TNBC depend on how far the disease has progressed. According to the ACS, 5-year survival rates are as follows:

  • Localized (contained to the breast): 91 percent
  • Regional (spread outside the breast to nearby structures or lymph nodes): 65 percent
  • Distant (spread to distant parts of the body such as lungs, liver or bones): 12 percent
  • All stages combined: 77 percent

It’s important to keep in mind that survival rate statistics for TNBC are an estimate. Your experience as a TNBC patient is unique, and statistics reflect outcomes of previous patients and past treatments. Speak with your doctor about your specific situation and what your prognosis looks like.

The Siteman approach

With expert physicians, skilled support staff and the latest technology, we give our TNBC patients the comprehensive care they need to fight their cancer. In addition to clinical care, our researchers are making strides in developing ways to use the body’s immune system to fight breast cancer, including vaccines.

TNBC treatment options at Siteman

As a TNBC patient, making treatment decisions can be stressful. At Siteman, our exceptional providers offer a variety of triple-negative breast cancer treatment options:

  • Surgery: oftentimes, patients first need to have either the lump removed (lumpectomy) or the entire breast removed (mastectomy). Then, they will receive chemotherapy to target any remaining cancer cells.
  • Chemotherapy: because hormone therapy and HER2 drugs aren’t effective treatment options for women with TNBC, chemotherapy is the main systemic treatment option. Patients may receive chemo prior to surgery (neoadjuvant chemo), either by itself or with pembrolizumab to shrink a large tumor. Patients may also receive chemo after surgery (adjuvant chemo) to reduce the chances of recurrence.
  • Targeted drugs: for women with TNBC who have a BRCA mutation and whose cancer no longer responds to more common breast cancer chemo drugs, their treatment teams may turn to other chemo drugs (such as carboplatin) or targeted drugs (called PARP inhibitors).
  • Radiation therapy: radiation usually comes after lumpectomies or mastectomies. High-energy radiation targets the breast to kill any remaining cancer cells. The process takes about 20 minutes. Most women receive radiation four to five days a week for about six weeks.

Populations at increased risk for TNBC

There are certain risk factors that put a woman at greater risk for TNBC. You may be at increased risk if:

There are many factors that contribute to these racial disparities that are still unknown. However, Black and Hispanic patients are more likely to have unsatisfying communication with their doctors, experience discrimination in health-care settings and have a harder time getting to and from their appointments.

Clinical trials for TNBC

Clinical trials are often used for triple-negative breast cancer treatment. Prior to taking part in a clinical trial, patients will first undergo standard treatments. However, if those treatments haven’t been successful, patients may choose to take part in a clinical trial in the hopes of a better outcome. If you are a TNBC patient interested in participating in a specific clinical trial, please speak with your physician about the trial.

The choice to participate in a clinical trial is highly personal, and one you should make after speaking with your provider about potential benefits and risks. While most health insurance plans cover clinical trials, make sure to first verify your coverage with your insurance carrier.

Our breast cancer specialists

The breast cancer specialist team at Siteman comprises outstanding Washington University medical oncologists, radiation oncologists, surgeons, radiologists, geneticists and psychologists. The diverse expertise of our specialists is what allows them to create individualized treatment plans for all triple-negative breast cancer patients.

Success among Siteman triple-negative breast cancer patients

In 2016, when Celina Campbell found a quarter-sized lump in her breast, she assumed it was just a swollen area due to a minor injury. However, breast cancer runs in Celina’s family and her cousin had just received a TNBC diagnosis. Because of this, she began to suspect the lump could be cancer. After following up with a breast surgeon, it was indeed confirmed that Celina, too, had TNBC.

While triple-negative breast cancer treatment was very emotionally and physically draining, Celina remained determined to overcome her diagnosis. And, after eight sessions of chemotherapy, no more lump could be found. Now, six years later, Celina lives a full life and her cancer is considered fully cured.

Throughout her cancer journey, Celina received the most exceptional care and support from Siteman’s breast cancer specialist team. Former Washington University medical oncologist William Popovic, MD, laid out a thorough and personalized treatment plan for Celina, putting her at ease with his warm demeanor and genuine concern. All of the staff dedicated themselves fully to Celina’s journey, always working to help her understand her cancer and her treatment. The expertise, commitment and compassion of Washington University breast cancer specialists at Siteman allowed Celina to take charge of her life and to become an incredible inspiration to other TNBC patients.

Patient support

In addition to providing unmatched clinical care, Siteman provides compassionate support to help each and every patient cope with the emotional and physical tolls of cancer treatment.

  • Nurses: specially trained to help breast cancer patients cope with symptoms, treatment and side effects.
  • Nurse navigators: clinically trained to provide guidance and answer questions at any point.
  • Registered dietitians: provide guidance about nutrition and meals or snacks that will be good for you as you move through treatment.
  • Psychologists: provide free mental health care for you and your family members.
  • Palliative care specialists: provide support to help you manage pain and other side effects of your treatments.

You’ve been diagnosed with triple-negative breast cancer. Now what?

If you’ve received a TNBC diagnosis, you may be experiencing a range of emotions including fear, anger and sadness. Siteman providers are here to support you every step of the way throughout your cancer journey. With our exceptional physicians, psychology services and survivorship care, we are committed to caring for your body, mind and wellness, even after treatment ends.

If you are experiencing symptoms that may point to breast cancer, or if you have received a TNBC diagnosis and would like a second opinion from a breast cancer specialist at Siteman, please call 800-600-3606.

How Siteman approaches metastatic breast cancer treatment

Finding out you have metastatic breast cancer (also known as advanced or stage IV breast cancer) can be very scary. While there is no cure, treatment can slow the cancer, extend the patient’s life and improve quality of life.

What is metastatic breast cancer?

Metastatic breast cancer refers to cancer that originated in the breast and has spread to another part of the body. First, cancer cells break away from the original tumor in the breast. Then, they travel through the bloodstream or lymphatic system to other parts of the body. When breast cancer spreads, it most commonly does so to the liver, brain, bones, lymph nodes or lungs.

Which breast cancers are most likely to metastasize?

All breast cancers have the potential to metastasize. However, human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancers are more aggressive. For this reason, these types of breast cancer are more likely to spread than others.

Afraid of your metastatic breast cancer diagnosis? You’re not alone.

If you or a loved one has recently been diagnosed with metastatic breast cancer, you may be feeling a great deal of fear. Common fears of stage IV breast cancer patients include:

  • Fear of cancer progression
  • Making treatment decisions
  • Worry about loved ones
  • Uncertainty about the future
  • Financial pressures
  • Dying

Your fears and concerns are surely valid. Still, it is important to remember that many metastatic breast cancer patients continue to live full and meaningful lives. Siteman breast cancer specialists are here to provide you with only the most exceptional care to give you the best possible chances for a positive outcome.

Risk factors for metastatic breast cancer

Although all breast cancers have the potential to spread, there are certain factors that increase the chances of that happening. These include:

  • Previous breast cancer diagnosis
  • Type of cancer (HER2-positive or triple-negative)

Metastatic breast cancer survival rates

Breast cancer is the second leading cause of cancer death in women, with metastatic breast cancer causing the vast majority of those deaths. According to the American Cancer Society (ACS), the five-year survival rate for women with metastatic breast cancer is 28 percent. For men with metastatic breast cancer, that rate is 22 percent.

While these statistics may seem daunting, keep in mind that metastatic breast cancer is treatable at any stage. What’s more, treatments are continuously improving and have proven to help metastatic breast cancer patients live longer and more fulfilling lives.

Bone metastasis and pain management

Breast cancer can spread to any area of the body. However, breast cancer most often metastasizes in the bones. Bone metastases affect more than half of women who develop stage IV breast cancer. The most common sites of bone metastasis are the ribs, spine, pelvis and long bones in the arms and legs.

Patients with bone metastases are at risk of bone fractures, spinal cord compression and bone pain. This pain tends to be constant. It may get worse with physical activity and usually doesn’t go way with rest. As a result, sleeping can be difficult.

The good news is that there are drugs that can reduce these symptoms by strengthening and protecting your bones. There are many benefits to these drugs for those suffering from bone metastasis. These include:

  • Reduced pain due to bone metastasis
  • Lower risk of bone fractures
  • Reduced need for surgery to repair bone fractures
  • Reduced need for radiation to treat bone pain
  • Blocked progression of bone metastasis

The Siteman approach to metastatic breast cancer

With expert physicians, skilled support staff and the latest technology, we ensure that our metastatic breast cancer patients receive the comprehensive care they need. In addition to clinical care, our researchers are making strides in developing ways to use the body’s immune system to fight breast cancer, including vaccines.

Siteman conducts more clinical trials than any other cancer center in the region. Several new drugs have emerged from our clinical studies that have had a promising impact on metastatic breast cancer. Meanwhile, more and more innovative breast cancer drugs continue to be developed.

Metastatic breast cancer treatment options

Washington University breast cancer specialists at Siteman offer the following treatment options for all types of metastatic breast cancer.

  • Chemotherapy: to destroy as many cancer cells as possible
  • Radiation therapy: to relieve or control pain in a specific area
  • Hormone therapy: to shrink or slow the growth of hormone receptor-positive metastatic breast cancer
  • Targeted therapy: to target specific characteristics of cancer cells, such as proteins that foster cancer cell growth
  • Surgery: to prevent broken bones or cell blockages in the liver

The type of treatment you receive will depend on the type of breast cancer that you have.

Hormone therapy for metastatic breast cancer

Hormone therapy differs based on the hormone receptor (HR) status and the human epidermal growth factor receptor 2 (HER2) status of your cancer. For example:

HR-positive – If you have estrogen receptor-positive (ER+) or progesterone receptor-positive (PR+) breast cancer, hormone therapy will likely be the first treatment you’ll receive. Hormone therapy drugs lower estrogen levels or block estrogen receptors. Hormone receptor-positive cancers tend to grow more slowly than hormone receptor-negative cancers.

HR-negative – This type of breast cancer doesn’t have any hormone receptors. For this reason, the cancer won’t be affected by treatments intended to block hormones in the body. Instead of hormone therapy, chemotherapy is the main treatment for hormone receptor-negative breast cancers.

HER2-positive – This type of breast cancer involves an overabundance of HER2, a protein that promotes the growth of cancer cells. Treatment for HER2-positive breast cancers involves a combination of chemotherapy and drugs that target the HER2 proteins. These drugs block the HER2 receptors from receiving growth signals in order to slow or stop the growth of the cancer. HER2-positive cancers tend to be more aggressive than HER2-negative cancers.

HER2-negative – This type of breast cancer involves cancer cells that have a small amount or none of the HER2 protein. HER2-negative cancer cells may grow more slowly and are less likely to come back or spread than HER2-positive cancer cells. If your cancer is HER2-negative and hormone receptor-positive, hormone therapy will likely be the first treatment you’ll receive.

Siteman advances in metastatic breast cancer treatment

Washington University experts at Siteman continue to pave the way for innovative breast cancer treatments through cutting-edge research. Some of our groundbreaking studies include:

Low-dose estrogen study – Research conducted at Washington University in 2009 revealed that raising estrogen levels may benefit women whose metastatic breast cancer no longer responds to standard anti-estrogen treatment. In 30% of study participants, their tumors either shrank or stopped growing.

Nanoparticles chemotherapy study – In 2018, our researchers discovered that when chemotherapy agents are exposed to radiation emitted by visible light, the drugs produce reactive particles that are toxic to cells. In contrast to traditional light therapy, this technique can target and attack cancer cells deep inside the body.

Breast cancer vaccine study – Washington University surgeon William Gillanders, MD, has led the development of personalized breast cancer vaccines. In this study, the research team took a small tissue sample from a patient’s tumor. Then, they used it to develop a personalized vaccine based on the tumor’s unique genetic information.

Our metastatic breast cancer specialists

The breast cancer specialist team at Siteman comprises outstanding Washington University medical oncologists, radiation oncologists, surgeons, radiologists, geneticists, psychologists and others. The diverse expertise of our specialists allows them to create individualized treatment plans for all metastatic breast cancer patients.

Success among Siteman metastatic breast cancer patients

Debbie Davis was only 34 when she was diagnosed with stage I breast cancer in 1993. She had no family history of cancer. While Debbie was terrified of her diagnosis and the uncertainty that came with it, she quickly transformed that fear into determination. She made the decision not to let her breast cancer stop her from living a fulfilling life. She maintained this mindset even after being diagnosed with metastatic breast cancer seven years later.

Throughout her decades-long cancer journey, Debbie has continuously received the most exceptional care and support from physicians at Siteman. Her treatment has included chemotherapy, radiation therapy and clinical trials. The expertise, dedication and compassion of Washington University breast cancer specialists at Siteman have allowed Debbie to take charge of her life and to be an incredible inspiration to other breast cancer patients.

Debbie’s cancer journey is just one of Siteman’s many breast cancer success stories.

Patient support

In addition to providing unmatched clinical care, Siteman provides compassionate support to help patients cope with the emotional and physical tolls of cancer treatment.

  • Nurses: specially trained to help patients cope with symptoms, treatment and side effects
  • Nurse navigators: clinically trained to provide guidance and answer questions at any point
  • Registered dietitians: provide guidance about nutrition and meals or snacks that will be good for you as you go through treatment
  • Psychologists: provide free mental health care for you and your family members
  • Palliative care specialists: provide support to help you manage pain and other side effects of your treatment

You’ve been diagnosed with metastatic breast cancer. Now what?

If you’ve been diagnosed with metastatic breast cancer, you may be experiencing a wave of emotions including fear, anger and sadness. Siteman providers are here to support you every step of the way throughout your cancer journey. With our exceptional physicians, psychology services and survivorship care, we are committed to caring for your body, mind and wellness, even after treatment ends.

If you are experiencing symptoms that may indicate your breast cancer has spread, or if you have received a stage IV breast cancer diagnosis and would like a second opinion from a breast cancer specialist at Siteman, please call 800-600-3606.

For Your Health: Simple steps to lower breast cancer risk

For Your Health Graphic 2020








For a disease as scary as breast cancer, one positive and very important message that deserves to be heard more often during Breast Cancer Awareness Month is that it’s a disease that can be prevented.

Research shows that about half of all breast cancer cases could be avoided with healthy steps most women can take. That translates to around 130,000 fewer cases each year in the U.S.

And it’s almost never too early, or too late, to take steps that can lower risk. The teen and young adult years are ideal, since it’s an important period in growth and development that can have a pronounced impact on cancer risk later in life. Still, healthy habits picked up in midlife and beyond can have significant benefit, too.

Get started with these behaviors, which are also great for the overall health of the entire family.

Colditz

Add movement to your days and keep it fun –dance, garden, play or walk.

One of the many benefits of regular physical activity is a lower risk of breast cancer. If you’re new to activity – or haven’t done it regularly in a while – take the pressure off and just choose something fun that gets you moving more than you normally would. After a while, you can do more if you want, building up to around 30 minutes of moderate activity a day. For families: Be active together. Walk to the grocery store, play ball in the park or tend a plot in a community garden.

Skip the alcohol.

We now know there’s really no risk-free amount of drinking when it comes to cancer, especially breast cancer. The best choice for your health and otherwise is simply not to drink. Choose healthy, alcohol-free drinks instead, bringing your own to gatherings if you need to. For families: Talk with your children about the risks of alcohol and binge drinking, and don’t center family meals and parties around alcohol.



Eat more plants.

Healthy, plant-based eating has many benefits, including lowering one’s risk of breast cancer. Being plant-based doesn’t mean you need to drop meat altogether. But it does mean adding more whole grains, beans, fruits and vegetables to your meals and snacks – and cutting back on meat, especially red and processed meat. For families: Ease into plant-based eating by looking up vegetarian recipes as a family and going meatless one day a week.

Keep weight steady.

We hear so much about weight these days that it’s easy to become numb to its importance to our health. But overweight and weight gain in adulthood increases the risk of at least 13 different cancers. Keeping your weight steady – just not gaining weight – is a great goal that can have big health benefits, even if you’re overweight. For families: Keep high-calorie, low-quality snacks out of the house. Replace things like sugary soda, chips and cookies with fruits and vegetables, air-popped popcorn and fizzy water.

Stay smoke-free or get smoke-free.

We can now add breast cancer to the list of many diseases caused by smoking. So, if you smoke, quitting is the most important thing you can do to improve your health. Visit smokefree.gov or call 1-800-QUIT-NOW (1-800-784-8669) for help. For families: Talk with your kids from an early age about the dangers of smoking – and vaping. And be a good smoke-free role model.

Behaviors like these can’t erase a woman’s chances of getting breast cancer. A lot of different factors come together to cause the disease, many of which are out of a woman’s control. But healthy choices can help lower risk, and that applies to pretty much all women – younger, older, those with a family history of cancer and those without.

And that is a really positive, empowering message.

It’s your health. Take control.

For more ways to lower your risk of breast and other cancers, visit 8ightways.org.

Dr. Graham A. Colditz, associate director of prevention and control at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine in St. Louis, is an internationally recognized leader in cancer prevention. As an epidemiologist and public health expert, he has a long-standing interest in the preventable causes of chronic disease. Colditz has a medical degree from The University of Queensland and a master’s and doctoral degrees in public health from Harvard University’s T.H. Chan School of Public Health.

$5 million supports innovative breast cancer trial at Siteman

A $5 million grant from the Department of Defense will support research at Washington University School of Medicine in St. Louis aimed at improving breast cancer therapies. The study, which includes a clinical trial at Siteman Cancer Center at Barnes-Jewish Hospital and the School of Medicine, will focus on HER2-positive breast cancer. Such tumors are dotted with an overabundance of so-called HER2 receptors.

About 20 percent of women with breast cancer have HER2-positive tumors. Drugs that block HER2, such as Herceptin, have improved survival rates dramatically for these patients.

But these drugs’ use has been limited to patients who have too many copies of HER2. Recent studies led by Washington University researchers, however, have shown that other breast cancer patients with different HER2 defects may benefit from HER2 inhibitors. In these patients, mutations in HER2 can fuel cancer growth. Standard testing for HER2 positive breast cancer won’t identify patients with HER2 mutations.

“We’re figuring out how to treat breast cancer based on the mutations present in the specific patient’s tumor,” said co-principal investigator Ron Bose, MD, PhD, an associate professor of medicine and Siteman research member. “We’ve developed a diagnostic test for mutations in HER2 that cause overactive signaling, and we have a good drug for patients with these mutations in their tumors. These new diagnostic and therapeutic tools may let us identify more women with HER2-driven cancers and treat them with HER2 inhibitors.”

Based on data from 2017, Bose and his colleagues estimate that about 4,000 women have metastatic breast cancer with HER2 mutations and could potentially benefit from this strategy. Drug combinations targeting tumor proteins are generally less toxic than standard chemotherapy, which is not very effective in controlling metastatic cancer and is the only current treatment option for these patients.

The clinical trial at Siteman will investigate a HER2 blocker called neratinib. Trial participants will be patients with metastatic breast tumors that have HER2 mutations and are estrogen-receptor positive, meaning these tumors also are fueled by estrogen. Because these tumors are fed by two fuel sources, participants will receive neratinib to block HER2 and fulvestrant to attack the estrogen receptor.

“In a past clinical trial, we tested neratinib alone, and we saw that about 30 percent of patients had a positive therapeutic benefit from the drug,” said co-principle investigator Cynthia X. Ma, MD, PhD, an associate professor of medicine and Siteman research member. “Now, we want to see whether adding fulvestrant will improve that outcome and help more patients.”

To more fully understand how patients respond to the drugs, the researchers will implant the patients’ tumors into mice that then will receive the same treatment regimens. Additional drugs also will be tested in these mouse models to see if other treatment combinations suggest promising directions for future clinical trials.

The mouse models will provide insight into why some tumors become resistant to neratinib therapy. The scientists will perform genome sequencing and protein analysis on these tumors, seeking clues to how some of them develop the ability to evade drugs that had been lethal to them initially.

Collaborating sites for the clinical trial include Dana-Farber Cancer Institute at Harvard Medical School and Baylor College of Medicine.

This work is supported by the U.S. Department of Defense, grant numbers 12473122 and 12473075.

Washington People: Mary Politi

Medical students aren’t the only learners in Mary Politi’s class on how health information is conveyed and received. Sometimes other faculty members attend also, to improve how they consider treatment options and discuss them with patients.

Politi, whether in person or through evidence-based decision tools she develops with others at Washington University School of Medicine in St. Louis, works with patients to empower them and help optimize their care.

“If we can better match the care patients want and need to the care they get, we can improve their patient experience and overall health” said Politi, an associate professor of surgery and a health psychologist in the school’s Division of Public Health Sciences.

A New Jersey native, Politi earned a bachelor’s degree in psychology from Barnard College at Columbia University in 2001 and a doctoral degree in clinical psychology, with a health psychology concentration, from George Washington University in 2006. She completed her clinical internship and postdoctoral fellowship in behavioral medicine at Brown University before joining the Washington University faculty.

Timothy J. Eberlein, MD, the Bixby Professor of Surgery and head of the Department of Surgery at the School of Medicine, said Politi is “a superb researcher” and an important mentor and role model to junior faculty members and trainees in the department and at Siteman Cancer Center, where she is a researcher.

“She has spent enormous amounts of time helping others while maintaining her own incredible productivity,” said Eberlein, who also is director of Siteman. “She is an incredible human being. Not only is she a fabulous researcher, she is without a doubt one of the nicest people at WashU.”

In addition to researching and teaching about health-care communications and shared decision-making, Politi also has helped develop digital tools to help:

  • People choose health insurance plans that best meet their health and financial needs.
  • Breast cancer patients choose whether or when reconstruction is right for them after a mastectomy.
  • Patients with Hepatitis C and advanced kidney disease decide which treatment option is best.
  • Support rural cancer patients’ participation in clinical trials.

“Together, we look at ways to support decisions to positively affect their health,” Politi said. “If you really start asking people questions about what it is they value and what their daily life is like, you learn a lot about how their health fits into that picture.”

Read the full profile on the School of Medicine site.

Light-triggered nanoparticles show promise against metastatic cancer

A new anti-cancer strategy wields light as a precision weapon. Unlike traditional light therapy — which is limited to the skin and areas accessible with an endoscope — this technique can target and attack cancer cells that have spread deep inside the body, according to researchers at Washington University School of Medicine in St. Louis. 

Light emitted as part of traditional cancer-imaging techniques, to locate metastatic tumors, also can trigger light-sensitive drugs, according to the new study. In addition, the research shows that when such drugs are packaged into nanoparticles that target lit-up cancer cells, the light-sensitive drug produces toxic free radicals that kill the tumor cells. The researchers showed that the technique worked effectively in mice with multiple myeloma, a cancer of white blood cells, and aggressive metastatic breast cancer.

The study is published online in Nature Communications.

“Cancer that has spread remains the major reason patients die,” said senior author Samuel Achilefu, PhD, the Michel M. Ter-Pogossian Professor of Radiology at the School of Medicine. “Our study shows that this phototherapeutic technology is particularly suited to attacking small tumors that spread to different parts of the body, including deep in the bone marrow.” 

The technology harnesses a chemotherapy drug called titanocene. As a chemotherapy agent alone, titanocene has not worked well in clinical trials, even at relatively high doses. But when exposed to the radiation emitted by visible light, titanocene produces reactive particles that are toxic to cells, even at low doses. 

Achilefu and his colleagues packaged low doses of titanocene inside nanoparticles they targeted to proteins known to sit on the surface of cancer cells. They found that when the nanoparticles make contact with cancer cells, their membranes fuse together, releasing the titanocene into the cells. 

The investigators then deliver a common cancer imaging agent called fluorodeoxyglucose (FDG), a type of sugar. Energy-hungry cancer cells take up the FDG at high rates, causing tumors to glow in a positron emission tomography (PET) scan. This glow also triggers the titanocene, releasing free radicals and killing the cells.

Since the titanocene and the light-emitting FDG are targeted to the same place at the same time only in tumors, the technique is believed to be less toxic than standard radiation and chemotherapy. Research also shows that the body rids itself of titanocene through the liver, while FDG is cleared through the kidneys. That the two components are disposed of separately minimizes damage to other organs. When separated, the two components are not toxic, according to the investigators. 

Mice with multiple myeloma were treated using this strategy once a week for four weeks. In the weeks following, the treated mice had significantly smaller tumors and survived longer than the control mice. Fifty percent of treated mice survived at least 90 days. Of the control mice, 50 percent survived 62 days. The mice with breast cancer also showed an anti-tumor effect when treated using this strategy, though less pronounced than in those with multiple myeloma, likely due to the extreme aggressiveness of the breast cancer cell line, according to the researchers. The investigators also found that certain types of multiple myeloma surprisingly were resistant to this technique. They determined that the resistant multiple myeloma cells lacked the surface proteins used to target the titanocene-loaded nanoparticles.

“This is an opportunity to learn because it’s similar to what is seen in patients — some of the cells become dormant but don’t die after treatment,” said Achilefu, who also is a research member at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. “When we looked closer at the cells that were resistant to our phototherapy, we saw that the surface protein we are targeting was not there. So next, we want to find out if we can pinpoint another surface protein to target and kill these resistant cells along with the myeloma cells that did respond to the original therapy, which could lead to complete remission.”

Achilefu envisions doctors being able to one day use this type of technology to prevent cancer from recurring. 

“We are interested in exploring whether this is something a patient in remission could take once a year for prevention,” Achilefu said. “The toxicity appears to be low, so we imagine an outpatient procedure that could involve zapping any cancerous cells, making cancer a chronic condition that could be controlled long-term.”

Chemo-loaded nanoparticles target breast cancer that has spread to bone

Breast cancer that spreads often infiltrates bone, causing fractures and intense pain. In such cases, chemotherapy is ineffective because the environment of the bone protects the tumor, even as the drug has toxic side effects elsewhere in the body.

Now, scientists at Washington University School of Medicine in St. Louis have developed a nanoparticle that can deliver chemotherapy directly to tumor cells that have spread to bone. In mice implanted with human breast cancer and exposed to circulating cancer cells likely to take up residence in bone, the researchers showed the treatment kills tumor cells and reduces bone destruction while sparing healthy cells from side effects.

The study is available online in the journal Cancer Research.

“For women with breast cancer that has spread, 70 percent of those patients develop metastasis to the bone,” said senior author Katherine N. Weilbaecher, MD, a professor of medicine. “Bone metastases destroy the bone, causing fractures and pain. If the tumors reach the spine, it can cause paralysis. There is no cure once breast cancer reaches the bone, so there is a tremendous need to develop new therapies for these patients.”

In the study, the researchers showed that breast cancer cells that spread to bone carry molecules on their surface that are a bit like Velcro, helping tumor cells stick to the bone. These adhesion molecules also sit on the surface of cells responsible for bone remodeling, called osteoclasts.

“In healthy bones, osteoclasts chew away old, worn out bone, and osteoblasts come in and build new bone,” said Weilbaecher, who treats patients at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine. “But in cancer that spreads to bone, tumors take over osteoclasts and essentially dig holes in the bone to make more room for the tumor to grow.”

Weilbaecher said she and her colleagues were surprised to find that the same adhesive molecule on the surface of osteoclasts also is present in high levels on the surface of the breast tumors that spread to bone. The research showed that the molecule — called integrin αvβ3 — was absent from the surfaces of the original breast tumor and from tumors that spread to other organs, including the liver and the lung. The researchers confirmed that this pattern also was true in biopsies of human breast tumors that had spread to different organs.

A collaboration with co-senior author Gregory M. Lanza, MD, PhD, a professor of medicine and of biomedical engineering, then led to the design of a nanoparticle that combines the bone-adhesion molecules with a form of the cancer drug docetaxel, which is used to treat breast cancer as well as other tumors. The adhesive molecules allow the nanoparticle to penetrate the otherwise protective environment of the bone matrix in a way that, in essence, mimics the spreading of the tumor cells themselves. The result is a delivery method that keeps the chemotherapy drug contained in the nanoparticle until the adhesion molecules make contact with the tumor cell, fusing the nanoparticle with the cell surface and releasing the drug directly into the cancer cell.

“When we gave these nanoparticles to mice that had metastases, the treatment dramatically reduced the bone tumors,” Weilbaecher said. “There was less bone destruction, fewer fractures, less tumor. The straight chemo didn’t work very well, even at much higher doses, and it caused problems with liver function and other toxic side effects, which is our experience with patients. But if we can deliver the chemo directly into the tumor cells with these nanoparticles that are using the same adhesive molecules that the cancer cell uses, then we are killing the tumor and sparing healthy cells.”

New imaging technique aims to ensure surgeons completely remove cancer

Of the quarter-million women diagnosed with breast cancer every year in the United States, about 180,000 undergo surgery to remove the cancerous tissue while preserving as much healthy breast tissue as possible.

However, there’s no accurate method to tell during surgery whether all of the cancerous tissue has been successfully removed. The gold-standard analysis takes a day or more, much too long for a surgeon to wait before wrapping up an operation. As a result, about a quarter of women who undergo lumpectomies receive word later that they will need a second surgery because a portion of the tumor was left behind.

Now, researchers at Washington University School of Medicine in St. Louis and California Institute of Technology report that they have developed a technology to scan a tumor sample and produce images detailed and accurate enough to be used to check whether a tumor has been completely removed.

Called photoacoustic imaging, the new technology takes less time than standard analysis techniques. But more work is needed before it is fast enough to be used during an operation.

The research is published May 17 in Science Advances.

“This is a proof of concept that we can use photoacoustic imaging on breast tissue and get images that look similar to traditional staining methods without any sort of tissue processing,” said Deborah Novack, MD, PhD, an associate professor of medicine, and of pathology and immunology, and a co-senior author on the study.

The researchers are working on improvements that they expect will bring the time needed to scan a specimen down to 10 minutes, fast enough to be used during an operation. The current gold-standard method of analysis, which is based on preserving the tissue and then staining it to make the cells easier to see, hasn’t gotten any faster since it was first developed in the mid-20th century.

For solid tumors in most parts of the body, doctors use a technique known as a frozen section to do a quick check of the excised lump during the surgery. They look for a thin rim of normal cells around the tumor. Malignant cells at the margins suggest the surgeon missed some of the tumor, increasing the chances that the disease will recur.

But frozen sections don’t work well on fatty specimens like those from the breast, so the surgeon must finish a breast lumpectomy without knowing for sure how successful it was.

“Right now, we don’t have a good method to assess margins during breast cancer surgeries,” said Rebecca Aft, MD, PhD, a professor of surgery and a co-senior author on the study.  Aft, a breast cancer surgeon, treats patients at Siteman Cancer Center at Barnes-Jewish Hospital and Washington University School of Medicine.

Currently, after surgery a specimen is sent to a pathologist, who slices it, stains it and inspects the margins for malignant cells under a microscope. Results are sent back to the surgeon within a few days.

To speed up the process, the researchers took advantage of a phenomenon known as the photoacoustic effect. When a beam of light of the right wavelength hits a molecule, some of the energy is absorbed and then released as sound in the ultrasound range. These sound waves can be detected and used to create an image.

“All molecules absorb light at some wavelength,” said co-senior author Lihong Wang, PhD, who conducted the work when he was a professor of biomedical engineering at Washington University’s School of Engineering & Applied Science. He is now at Caltech. “This is what makes photoacoustic imaging so powerful. Essentially, you can see any molecule, provided you have the ability to produce light of any wavelength. None of the other imaging technologies can do that. Ultrasound will not do that. X-rays will not do that. Light is the only tool that allows us to provide biochemical information.”

The researchers tested their technique by scanning slices of tumors removed from three breast cancer patients. For comparison, they also stained each specimen according to standard procedures.

The photoacoustic image matched the stained samples in all key features. The architecture of the tissue and subcellular detail such as the size of nuclei were clearly visible.

“It’s the pattern of cells – their growth pattern, their size, their relationship to one another – that tells us if this is normal tissue or something malignant,” Novack said. “Overall, the photoacoustic images had a lot of the same features that we see with standard staining, which means we can use the same criteria to interpret the photoacoustic imaging. We don’t have to come up with new criteria.”

Having established that photoacoustic techniques can produce usable images, the researchers are working on reducing the scanning time.

“We expect to be able to speed up the process,” Wang said. “For this study, we had only a single channel for emitting light. If you have multiple channels, you can scan in parallel and that reduces the imaging time. Another way to speed it up is to fire the laser faster. Each laser pulse gives you one data point. Faster pulsing means faster data collection.”

Aft, Novack and Wang are applying for a grant to build a photoacoustic imaging machine with multiple channels and fast lasers.

“One day we think we’ll be able to take a specimen straight from the patient, plop it into the machine in the operating room and know in minutes whether we’ve gotten all the tumor out or not,” Aft said. “That’s the goal.”

Wong TTW, Zhang R, Hai P, Zhang C, Pleitez MA, Aft RL, Novack DV, Wang LV. Fast label-free multilayered histology-like imaging of human breast cancer by photoacoustic microscopy. Science Advances. May 17, 2017

This work was supported by the National Institutes of Health, grant number DP1 EB016986 and R01 CA186567, and by Washington University’s Siteman Cancer Center’s 2014 Research Development Award.