Tailoring Treatment

SHERRY PERCIFUL was in the throes of planning her daughter’s wedding in fall 2015 when she noticed that her right breast felt sore. Life was hectic, and she couldn’t find a lump, so she held off seeing a doctor until after the Christmas holidays.

By then, the nagging sore had turned into something more: Her breast was inflamed and hot to the touch. “As soon as I saw the doctor and he looked at it, his face sort of scrunched up,” recalls Perciful, who lives in Louisville, Kentucky. “He said, ‘I don’t like the way this looks.’ At that time, I knew it had to be breast cancer. I didn’t know what kind, but I knew it was really bad.”

Perciful was diagnosed with triple negative inflammatory breast cancer, a very aggressive subtype of cancer. Her treatment was grueling. In 12 months, she suffered through 16 rounds of chemotherapy, three surgeries and 33 days of radiation.

After all that, Perciful thought she was done, but her oncologist had other plans.

Triple negative breast cancer is more likely than most other kinds of breast cancer to recur and spread. Once it does, it often does not respond to treatment. Perciful’s doctor encouraged her to travel to Indianapolis to participate in a clinical research trial aimed at preventing the cancer from returning.

The trial, led by IU oncologist Bryan Schneider, MD, relies on the burgeoning field of genomics—an area in which Indiana University School of Medicine is building a research program capable of transforming care.

The genome is the voluminous instruction manual for the human body, and a copy is tucked away in every cell. Cancer and many other diseases occur when there’s a typo—or several typos—in that document. The field of genomics seeks to identify the mistakes so the most appropriate drugs can be used to target the problem. But that’s easier said than done. Imagine scanning all 206,252 words of the classic novel Moby Dick and quickly pinpointing any errors.

Genomic advances are being applied to myriad areas of medicine, from cardiovascular disease to pediatrics to neurodegenerative disease. But perhaps no discipline has made as much progress as cancer.

The latest advances in DNA sequencing now allow researchers to analyze a patient’s tumor faster and cheaper than ever before—making it possible that genomics will soon become part of standard treatment. Anantha Shekhar, MD, PhD, executive associate dean for research affairs at IU School of Medicine, envisions a day in the not-too-distant future when every cancer patient has his or her tumor sequenced so physicians can review its genomic and molecular profile.

But there are still vast amounts of research needed to understand the results and apply them in a meaningful way.

“Within breast cancer alone, there may be as many as 400 genetic mutations that could potentially be implicated in the cancer,” Shekhar says. “At best we only have targeted drugs in development for about 40 of them. The challenge is understanding the hundreds of other mutations, sorting through them, and understanding which ones are important and which ones are something we can ignore.”

“Even if we narrow it down to 50 mutations that determine the course of the cancer, then we still have to come up with a course of treatment for those mutations,” Shekhar adds. “Each of those could require new drugs, and once treated, the tumors can acquire additional mutations. So this is going to take time, energy and resources. Therefore, another approach we are simultaneously exploring is to develop immune cell-based therapies that can target cancer cells directly.”

IU School of Medicine and Indiana University Melvin and Bren Simon Cancer Center have been given a substantial head start thanks to the generosity of the Vera Bradley Foundation for Breast Cancer.

The Vera Bradley Foundation has committed a total of $35 million to breast cancer research at IU, most recently funding the establishment of the Monogrammed Medicine program at IU Simon Cancer Center. The goal of Monogrammed Medicine is to learn how to tailor treatment for each unique woman.

Now, the school is building on the advances made in breast cancer by launching an ambitious precision genomics program that will ultimately improve care for all types of cancer. School executives are recruiting a director for the program and expect to add at least four other faculty experts to head the initiative. The team will collaborate closely with leadership of the new Brown Center for Immunotherapy and researchers dedicated to drug development.

“The Vera Bradley Foundation has laid the foundation for building an entire precision health program,” says Jay L. Hess, MD, PhD, MHSA, dean of IU School of Medicine. “It’s the idea of tailoring therapy for individual patients based on their genetic profiles, but also the way they’ll react to drugs and what their personal preferences are. The Vera Bradley Foundation has challenged us to create that for breast cancer, and it is informing us in other women’s cancers and cancers that affect all people—including men and children.”

Most importantly, the research is providing hope to patients like Sherry Perciful, a grandmother of five who, along with her husband, is co-pastor at her church.

Perciful enrolled in an IU clinical trial for women with triple negative breast cancer. Led by Schneider, who is both a practicing physician and scientist, the trial assigns participants an extra round of highly customized therapy based on a DNA analysis of their tumor. “We use the best technology on the planet to see if we can uncover a vulnerability or Achilles’ Heel in the cancer that traditional chemotherapies can’t capitalize on,” says Schneider, the Vera Bradley Investigator.

The study will analyze whether these women are more likely to be cured than women who don’t receive targeted treatment.

“I feel safer,” Perciful says. “I feel more confident that I will be able to have more time with my family, more time to spend with my husband, just more time to live life. It’s just sweet. Life is sweet.”

To support breast cancer research at Indiana University Melvin and Bren Simon Cancer Center, contact Lizzie Conkle Knol at econkle@iu.edu or 317.278.2120.