Breast Cancer Research Highlights

Grantee: Hanna Irie, MD, PhD
Institution: Icahn School of Medicine at Mount Sinai Hospital in New York City, New York
Area of Focus: Leukemia, Immunology, and Blood Cell Development
Term: 7/1/2018 to 6/30/2022

“We’re studying genes that fuel triple-negative breast cancer, which may help lead to the development of new drugs to combine with standard treatments. Our goal is lifelong remission.”

The Challenge: Triple negative breast cancer (TNBC) can be very aggressive and can quickly spread to other parts of the body. Unlike other types of breast cancer, TNBC has limited medical treatments. Chemotherapy is effective for many patients with TNBC, but there are others who don’t benefit from chemotherapy. Researchers need to identify new treatment strategies for TNBC, including finding new molecular targets that will allow for the development of new drugs.

The Research: With support from an American Cancer Society grant, Hanna Irie, MD, PhD, and her team discovered that high levels of the PTK6 gene in women with TNBC may predict that they won’t respond well to treatment. To learn about how PTK6 affects the spread of cancer and its resistance to chemotherapy, Irie’s research team is studying how this gene controls cell growth and how it interacts with the immune system.

The Goal and Long-Term Possibilities: By providing insights about how PTK6 promotes the spread (metastasis) of TNBC, Irie’s work may lead to the development of new targeted drugs to block the PTK6 gene, with the goal of limiting the spread of TNBC.

Grantee: Swarnali Acharyya, PhD
Institution: Columbia University’s Institute for Cancer Genetics in New York City
Area of Focus: Cell Structure and Metastasis
Term: 1/1/2017 to 12/31/2020

“We’re studying what makes breast cancer spread to vital organs because
that’s the cause of about 90% of deaths from cancer. Our research should pave the way
for the development of new treatments that may stop metastasis and possibly even
improve cure rates.”

The Challenge: About 3 out of 10 women with metastatic breast cancer (MBC) that has spread to other areas in the body (such as the bones) survive at least 5 years. There is an urgent need to understand and effectively stop metastases to prolong survival.

The Research: Immunotherapy change how the cells of the immune system work. Some of these drugs kill cancer cells by boosting the ability of a certain type of immune cell called T-cells. These drugs are very successful with some types of cancer, but they have had more limited effects against MBC.

Swarnali Acharyya, PhD, is using the funding from her American Cancer Society grant to study a different type of immune cell—B cells. Her team has identified a type of B cell (called CXCR2+) that fuels the cancer cells, allowing them to spread. 

The Goal and Long-Term Possibilities: Acharyya expects to learn more about how the immune system controls breast cancer metastasis. Her team’s results may pave the way for a new type of immunotherapy drug that targets B cells to help control the spread of breast cancer and help more patients live longer.

Grantee: Jennifer Rosenbluth, MD, PhD
Institution: Harvard Medical School in Boston, Massachusetts
Type of Research: Cancer Drug Discovery
Term: 7/1/2017 to 6/30/2019

“I have been fascinated by methods that allow us to grow breast tissue in a dish in the lab.
This allows us to grow and study cells in the breast that may be on the road to cancer. If we
can understand the earliest changes in the breast that precede cancer, we can learn to
prevent cancer from ever developing.”  

The Challenge: Women who inherit mutations of the BRCA1 gene have a high risk of developing breast cancer as well as ovarian cancer. Those cancers may develop when a woman is young, and they tend to be aggressive. Those cancers may develop at any age, but if they occur when a woman is younger, they tend to be more aggressive. The current strategies to prevent and screen for breast cancers in women at higher risk include:

• Starting yearly mammograms at a younger age than women at average risk
• Other tests or procedures, which could include taking medicines to lower the risk, adding screening tests with a breast MRI, and having more frequent check-ups (such as every 6 to 12 months) with a doctor
• Preventative (prophylactic) surgical removal of the breasts 

One theory researchers have is that these cancers might develop from abnormal precancerous cells (called precursor cells or progenitor cells) in the breasts of women with inherited BRCA1 mutations. But there hasn’t been a way to study these cells outside of a woman’s body.

The Research: With an American Cancer Society grant, Jennifer Rosenbluth, MD, PhD, and her team are using a 3-dimensional method of growing breast tissue in a lab, where it can be studied. When grown under specific conditions, the cells spontaneously form structures like the duct structures of a human breast, where most types of breast cancer form.

Rosenbluth’s team is studying the growth of abnormal precancerous cells in hopes of finding ways they can be destroyed before they become cancer cells or tumors.

The Goal and Long-term Possibilities: By understanding the earliest changes in these cells, Rosenbluth may be able to identify targets for new drugs that can possibly be used to prevent breast cancer in women with a BRCA1 mutation. They also hope their model of cancer prevention “in a dish” can be used to study other types of cancer.

Grantee: Yehui Zhu, MSN
Institution: University of Pittsburgh School of Nursing
Area of Focus: Oncology Nursing
Term: 7/1/2017 to 6/30/2019

“We’re working to explain why some postmenopausal women with breast cancer have joint or muscle pain during their treatment with aromatase inhibitors and some do not.” 

The Challenge: After treatment for breast cancer, some postmenopausal women take a type of drug called aromatase inhibitors (AI) each day for 5 or more years to help keep the cancer from coming back. These prescription drugs, which lower estrogen levels produced in fat tissue, include anastrozole (Arimidex), exemestane (Aromasin), and letrozle (Femara).

About 50% of women who take an AI develop side effects like joint pain, muscle pain, and muscle stiffness. There’s no clear understanding about why this occurs. But these symptoms affect a woman’s ability to function and her quality of life, and may lead her to stop taking the drug too soon. 

The Research: Yehui Zhu, MSN, and her team published an article based on their research that defined 5 main symptoms related to taking an AI:

1. Joint/muscle pain
2. Hot flashes
3. Low interest in sex
4. Joint/muscle stiffness
5. Lack of energy

The Goal and Long-term Possibilities: Based on Zhu’s results, she and her team advise that nurses should assess women taking an AI for these 5 symptoms. The nurse should evaluate frequency of symptoms, intensity, and distress in terms of the effect on quality of life or ability to do the tasks she wants to.

Grantee: Gloria Echeverria, PhD
Institution: University of Texas M.D. Anderson Center in Houston
Area of Focus: Tumor Biology and Genomics
Term: 7/1/2017 to 6/30/2019

"By studying biopsies from triple-negative breast cancers, I learned that glitches in how cancer cells generate energy may allow some breast cancers to resist chemotherapy. My goal is to turn the tables on these cancer cells by using a drug to target those glitches."

The Challenge: For many women, with triple-negative breast cancer (TNBC), their first treatment is chemotherapy, followed by surgery. Nearly 50% of these women have cancer cells that resist the effects of chemotherapy. Cancers that aren’t killed by chemotherapy are called chemoresistant. When a woman doesn’t respond well to chemotherapy used as a first treatment, she has a much higher risk of the breast cancer coming back and dying from it. 

The Research: With support of a grant from the American Cancer Society, Gloria Echeverria, PhD, recently published findings about chemoresistance in TNBC. She implanted untreated, human TNBC cells into mammary glands of mice.

Then she used a state-of-the-art technique called DNA barcoding to mark each cell with a unique tag, so she could track how the TNBC cells responded to the typical chemotherapies used for treatment. She also tracked how many unique types of tumor cells were able to survive chemotherapy.

The team also tested a combination treatment using usual chemotherapy followed by a treatment called IACS-10759, previously developed at MDAnderson. This work in mice suggests the combination treatment likely killed more cancer cells and its effects lasted longer than either IACS-10759 alone or chemotherapy alone.

Through their work, the researchers learned that chemoresistance seems to be temporary. The way TNBC cells “protect themselves” from chemotherapy isn’t a permanent change in their structure. They found that when chemotherapy was halted for a “drug holiday,” some of the tumors that initially survived chemotherapy were more vulnerable to chemotherapy when it was restarted. 

The Goal and Long-term Possibilities: The team’s findings suggest that combination treatments, like the ones they are testing, may help treat TNBC. Ultimately, they hope their work can support the discovery of new targeted therapies. 

Grantee: Jennifer Tsui, PhD, MPH
Institution: Rutgers, The State University of New Jersey
Area of Focus: Cancer Control and Prevention: Health Policy and Health Service
Term: 7/1/2017 to 6/30/2022

"Overall, low-income and racial/ethnic minority patients, particularly those with Medicaid coverage, have worse cancer outcomes. Evidence shows that they are more likely to be diagnosed late, less likely to get and complete treatment, and less likely to survive than higher income or non-minority patients. Our goal is to improve those outcomes."

The Challenge: Research shows that US patients who are insured by Medicaid, have low incomes, or who are part of a minority group often get low-quality cancer care and are more likely to die from certain cancers than patients with private insurance or Medicare. One reason may be a delay in starting cancer treatment because of the time it takes for patients to move from primary care to specialty cancer care. But researchers don’t often study specific factors linked with health care transitions.

The Research: With support from an American Cancer Society grant, Jennifer Tsui, PhD, MPH, is studying the underlying processes, such as referral practices, communication between primary care and specialists, and management of other chronic conditions, that may affect how a patient moves between healthcare providers or settings. She’s specifically studying Medicaid patients who were recently diagnosed with breast or colorectal cancer.

She plans to develop strategies to improve transitions from primary care to specialty care, focusing especially on patients with multiple chronic conditions and challenging social circumstances. She’ll also study whether changes brought about by the Affordable Care Act (ACA) help providers and health systems adopt best practices and improve cancer care. 

The Goal and Long-term Possibilities: Tsui’s goal is to recommend specific changes that would improve transitions in care within the Medicaid system. The team expects their findings to be shared with Medicaid officials and other stakeholders.

Grantee: Sabrina Spencer, PhD
Institution: University of Colorado in Boulder
Area of Focus: Cell Cycle and Growth Control
Grant Term: 7/1/2018 to 6/30/2022

“The cells in our body have a life cycle, and can grow and divide at different rates. After each round of the cell division cycle, every cell makes a critical “decision.” Should it grow by dividing? Or should it not divide? We’re using new technology to reveal ways to control the divide-not-divide ‘decision’ in cancer cells.”

The Challenge: Normal cells in our body grow and divide in an orderly way. They die when they are worn out or damaged, and they divide so new cells can be made to take their place. Cancer happens when there is a change in a cell or cells that causes them to grow out of control. When this happens, they keep growing and making new cells really quickly. The cancer cells crowd out normal cells.

The Research: With a grant from the American Cancer Society, Sabrina Spencer, PhD, and her team are developing a high-tech tracking and recording system to see how nutrients, chemicals that cause growth, and cell damage or stress might influence the cell to divide or not divide. Spencer’s team is tagging proteins to track them and using a microscope to make time-lapse movies of cells. This allows the researchers to study what is happening to these cells.

The Goal and Long-term Possibilities: Spencer’s research may lead to a better understanding of when and how cells “choose” to divide, which may reveal new ways to stop cancer cells from growing.