On Jan. 16, 2013, Holly Boehle looked at the expression on the face of her radiologist and knew something was wrong. Boehle had felt a lump just before the holidays and had decided to schedule a mammogram, even though she wasn’t due to start standard screening for another eight years.

The mammogram was followed up with an ultrasound, and then a biopsy. Finally, she was given the formal diagnosis: invasive ductal carcinoma, the most common type of breast cancer.

“At that moment, really everything changes,” Boehle said. “Here I am at just 42 years old with no family history, seemingly healthy, not feeling ill at all, but your world changes in just a moment when you get that news that you have breast cancer.”

The next week she traveled to Mayo Clinic’s oncology office in Rochester, Minn., where she met with clinical breast surgeon Dr. Judy Boughey who suggested Boehle consider participating in a new, ongoing study. She quickly agreed and became one of 140 women to take part in the Breast Cancer Genome-Guided Therapy Study, affectionately called “BEAUTY.”

By the end of the month, the first phase of the study was underway. Tumor tissue was taken from Boehle, and promptly brought into a lab where the sample was injected into mice with compromised immune systems. She calls them her “little Holly mice.” With her tumor tissue growing inside of them, the avatar mice are given different chemotherapy drugs in order to test the efficacy of treatment before they try it out on human Boehle.

Inside Mayo Clinic's Biobank there are thousands of cancer tissue samples processed, cataloged, and stored inside freezers. Photo courtesy of the National Press Foundation

BEAUTY’s Beginnings

Each patient in BEAUTY was given a biopsy, imaging, and chemotherapy treatment, followed by a second round of biopsy and imaging before they headed into the operating room. This gave researchers information on each patient’s blood and genetic makeup, and the sequencing information for their tumor before, during, and after chemotherapy treatment. The mouse avatars, known as patient xenografts, took up the patient’s individualized tumor 40 percent of the time, ultimately serving as a preview into the patient’s treatment outcome.

A class of chemo drug called taxanes are the standard of treatment for breast cancer, but doctors currently don’t have a genetic marker to indicate who will respond to taxane therapy and who won’t. That’s why anthracyclines and cyclophosphamide, a separate chemotherapy drug regimen, are typically given in conjunction as the first step in treatment followed by taxane therapy. However, Boughey’s team reversed the sequence for BEAUTY patients whose mice reacted well to the taxane treatment first. It turned out that those patients who responded best to the flipped treatment sequence also shared the same gene in their genetic makeup.

Based on how her little Hollies reacted to treatment, Boehle was one of those patients who were treated with a reverse chemotherapy schedule than what the typical patient with invasive ductal carcinoma is treated with. Within six months of her diagnosis, Boehle’s tumor shrank considerably as a reaction to the chemotherapy.

Being part of the trial has long-term implications for Boehle, too. If the cancer were to recur, she says, “we would already know...what works for me and what doesn’t. It really opens up a whole new world for me and other breast cancer patients in terms of individualized medicine and knowing that I don’t need to be the person who they experiment on and say, ‘Let’s try this medication or chemotherapy and see if it works and we hope that it does.’”

Four years ago, when Boughey and her team began setting up the BEAUTY study, they wanted to be able to design a treatment plan with a relatively accessible patient population. Because breast cancer is so common among women, the research team chose to start work on individualized medicine with those patients with plans to eventually work their way to other solid tumor cancers such as prostate.

By sequencing the genome for both the tumor and the patient’s inheritable DNA, researchers are able to pull the curtain back and see what’s driving the tumor to grow, why it’s different from another tumor, and how the tumor might react to drug treatments. Harnessing the genetic sequence of a tumor in conjunction with a person’s DNA will allow doctors to expand personalized cancer treatments beyond breast cancer.

Standard of Care Tumor Sequencing

Sequencing a tumor for its complete genetic information can take as little as a few days, and as long as several weeks, depending upon the stage of cancer. Once they have the results, researchers then compare them to a patient’s individual germline cells, which contain hereditary mutations that occur during conception. Patients born with germline mutations can pass on to future generations. Somatic mutations can be caused by a number of different environmental factors and can occur spontaneously. As researchers unravel which gene mutations are responsible for causing each corresponding disease, it sets the foundation for creating individualized treatments through trial-and-error.

BEAUTY Study Oncology researcher Dr. Judy Boughey explains the steps it took to rid Holly of her breast cancer tissue. Photo courtesy of National Press Foundation

“From there potential drugs can be identified that act on genes and/or pathways,” Boughey and her colleague Dr. Matthew Goetz, a clinical oncologist at the Mayo Clinic, told Medical Daily in an email. “One novel aspect of the BEAUTY clinical trial is our ability to link drug response in the patients with both germline and somatic genomic information and validate using the patient derived xenografts [mouse avatars].”

Mayo Clinic’s research team is currently writing the protocol for BEAUTY 2 based on the types of tumors they identified, and the drug resistance and successes discovered in BEAUTY 1. Because they were able to prove mouse avatars, when administered the same drug that patients were treated with, mirror the drug response seen in patients, pharmaceutical companies will be involved with this next stage by designing medications based on study participants’ response to treatment.

BEAUTY, Boughey says, will “drive forward breast cancer treatments for the future.”