triple positive breast cancer headerIn 1974, First Lady Betty Ford went public with her breast cancer diagnosis and subsequent mastectomy, launching breast cancer into the national consciousness. Watergate was still fresh in everyone’s minds, and Mrs. Ford said that part of the reason she spoke so openly about breast cancer at a time when the subject was taboo is that she wanted no cover-ups in the Ford Administration.

Ford’s decision to share her experience resulted in what researchers called the “Betty Ford Blip.” Her story raised awareness of the disease, leading millions of women to go for screening. As a result, diagnoses of breast cancer in the United States rose sharply, and with awareness and early detection, thousands of women were able to treat breast cancer at an earlier, more manageable stage. Nearly 20 years later, in 1992, the pink ribbon became the national symbol for Breast Cancer Awareness Month. Now, twenty-six years later, without fail, the month of October is awash in pink ribbons and calls for awareness and early detection. But even as Angelina Jolie added a new burst of steam to the campaign of awareness that Betty Ford started, a group of breast cancer patients was being left behind.

Once breast cancer metastasizes into other areas of the body, it becomes much more dangerous. And while the National Cancer Institute spends more than $500 million dollars per year on breast cancer research, only two to five percent of this funding goes to study how the disease spreads. First there was Betty Ford. Then there were pink ribbons. Then there was Angelina Jolie. Now a new generation of breast cancer patients is pushing to increase awareness for a group of breast cancer patients that has been largely overlooked this whole time, namely those with metastatic disease.

FROM STAGE II TO STAGE IV

Christine Howard was diagnosed with Stage II breast cancer in 2012 when she was 41 years old. Breast cancers at this stage are considered curable. Christine underwent surgery, radiation and chemotherapy which included Herceptin (trastuzumab) for a year. Howard says she knew the cancer had spread to a lymph node, and she thought about

the possibility of recurrence despite completing the intense treatment program, but she put it out of her mind as much as possible and moved on with her life. Then in January of 2016, Howard was having some back pain and recurrent pneumonia, and during the course of treatment, she learned the cancer had come back.

“When I learned the cancer had returned, my physician at the time told me to get my affairs in order,” says Howard. “I didn’t feel comfortable with the care I was receiving, so I switched to UCHealth University of Colorado Hospital (UCH) and found Dr. Kabos. I felt so much better immediately.”

Peter Kabos, MD, deputy director of the University of Colorado Cancer Center’s Breast Cancer Research Program, found that Howard’s cancer had spread to her bones. He immediately changed the plan for her care, giving Christine a targeted treatment against a protein called human epidermal growth factor or HER2, and another against estrogen receptors (ER), which were driving her cancer. In addition, Bennie Lindeque, MD, PhD, a professor of Orthopedics at CU School of Medicine, performed surgery on Howard’s legs which had been weakened by the cancer. Then came another blow.

They found the cancer in Howard’s brain as well.

“I was starting to have a hard time on occasion,” says Howard. “When I was driving, I would feel fuzzy but that could have been chemo-brain. My boyfriend took me in for brain MRI and new scans showed spots on my brain.”

Howard had three sessions of stereotactic radiation surgery, which is precisely targeted form of radiation commonly used to treat brain metastases from breast cancer. Shortly thereafter, she enrolled in a clinical trial to keep her cancer from spreading any further. After a detailed discussion about standard of care therapy and the available clinical trials, Christine decided to enroll in an innovative study using a combination of three drugs that she could take orally at home.

Christine Howard

Christine Howard with her boyfriend

“TRIPLE POSITIVE” BREAST CANCER

There are three well-established predictive markers of breast cancer. They are estrogen receptors (ER), progesterone receptors (PR), and the growth factor receptor HER2, these receptors may be blocked with targeted drugs to stop cancer growth. Breast cancers lacking these three markers
are referred to as “triple-negative” but clinicians and scientists are quickly learning more about cancers that have all three receptors, which are often called “triple-positive.” There are treatments against each target individually, but when multiple drivers are present, as in “triple- positive” breast cancer, blocking one often results in cancer nimbly switching to driving its growth with the other two.

When you first meet Christine Howard, you would never know she has advanced cancer. Christine’s hair has grown back following chemotherapy, and because of the surgery to strengthen her legs, she gets around well. Not only does she have metastatic breast cancer, but her cancer is the “triple-positive” form of the disease. Serendipitously, in 2017 when Howard learned that her cancer had returned, a clinical trial to treat triple-positive breast cancer had just opened at CU Cancer Center.

The study combines tucatinib, which inhibits HER2, with letrozole targeting ER and PR hormone receptors, and the drug palbociclib, which targets CDK proteins that help cancer cells rush through the process of replication. The three had not been tried together until Elena Shagisultanova, MD, PhD, a breast cancer specialist at UCH, hypothesized there could be a way to target all three drivers at the same time with better results than targeting combinations of any two. The clinical trial is open nationwide through the Academic Breast Cancer Consortium, giving access to this exciting novel combination across the United States.

“When metastatic cancer spreads to the brain, it can be especially challenging,” says Kabos. “Many medications aren’t effective in the brain, but exciting early clinical trial data for tucatinib shows that it may be one of the drugs that can penetrate the blood-brain barrier to combat brain metastases. It was the ideal choice for Christine at the time.”

The tucatinib, palbociclib and letrozole clinical trial has allowed Christine more time with her loved ones and friends. It has also given her time to pursue her new passion: Howard is passionate about raising awareness about metastatic breast cancer. She wants to tell people that the sea of pink we see each October is not always helping scientists find new, more effective treatments for women with more advanced breast cancers.

“We need more research,” says Howard “What works for me may not work for someone else. And I am hoping that if the combination I’m on stops working, maybe a year from now research could lead to something else available.”

First through Facebook communities and now through the organization Living Beyond Breast Cancer, Howard has also become a patient advocate for other women living with metastatic disease.

When Betty Ford shared her breast cancer story, she brought the disease out of the shadows. Angelina Jolie gave awareness another boost when she had surgery to reduce her risk of getting cancer. Christine Howard is hopeful that she, in some small way, can remind us that women with advanced breast cancer require and deserve the same kind of attention as first ladies and movie stars.

*The tucatinib, palbocilib and letrozole trial is coordinated by the Academic Breast Cancer Consortium and currently open for enrollment at the University of Colorado Cancer Center; University of Texas Health and Science Center in San Antonio, TX; Stony Brook University, NY; University of Arizona, Tucson, AZ; and University of New Mexico, Albuquerque, NM and will also be accruing patients at Northwestern University, Chicago, IL.

The trial is funded by the Pfizer ASPIRE Award in Breast Cancer Research. Cascadian Therapeutics and Pfizer are providing the study drugs tucatinib and palbociclib. For more information about trial eligibility and participation, contact brad.mackay@ucdenver.edu or emily.berens@ucdenver.edu.