UW-Madison study trying to unlock secrets of breast cancer's 'exceptional survivors'

DE PERE - Tammy Mocarski remembers her surgeon leaning over her as she woke up in recovery after having what appeared to be a harmless, pea-sized tumor removed from the crease below her left breast.

"He wanted to be the one to tell me," she said.

He didn't like the tumor's margins, so he took 15 lymph nodes. Four of the 15 had cancer cells. It was stage 2A breast cancer. And it turned out to be HER2-positive, which tends to be more aggressive and spread more quickly than other cancers.

"My first thought was I'm not going to see my kids grow up," Mocarski recalled, sitting cross-legged on a recliner in her living room and choking back tears as she thought of her four sons, who were between the ages of 2 and 7 at the time. She was only 36.

Sixteen years and six recurrences later — including a metastatic diagnosis in 2006 — Mocarski is surviving long odds. Statistics suggest less than 10% of women diagnosed with metastatic breast cancer will live 10 years or more. But her sons are all in college — the oldest one in medical school — and she is still very much alive.

Is it genetics? Her immune system? Her cancer treatment plan? Lifestyle? Environment?

In the hope of finding an answer, and perhaps helping other women live longer, Mocarski is part of a University of Wisconsin-Madison study of "exceptional survivors" of metastatic breast cancer. These women continue to live while others die despite the same or better prognosis. The study is led by Mark Burkard, an associate professor and breast cancer oncologist at the University of Wisconsin Carbone Cancer Center at UW-Madison.

"If the reason some people are living longer is within our control — treatment, lifestyle or immune response — we could potentially help others be exceptional survivors, too," Burkard said. "There may be things not in our control to modify: specific genetics of these tumors. But then we could predict who would survive longer and we may plan her treatment differently."

Burkard initially enrolled 15 women from Wisconsin in the study, scraping together enough funding from the Carbone Cancer Center to do genetic analysis of their tumors or tissue samples from biopsies.

He has since received $300,000 from the Avon Breast Cancer Crusade and is now scouring the country for 38 more so-called exceptional survivors to study. Ideally, Burkard would add even more to the study if additional research funding could be secured.

DNA analysis is possible because medical facilities are required by law to store tumor and tissue samples for at least 10 years. But genomic analysis of tumor and tissue samples costs $2,000 to $2,600 per sample.

Burkard also will take blood or saliva samples to look at study participants' immune systems, and have them fill out questionnaires about their lifestyle and living environment. 

A colleague at the University of Alabama-Birmingham is mining a national database for long-term survivors. An immunology colleague at UW-Madison will look at the immune cells that infiltrate the tumors to examine patients' immune responses to cancer.

"We have a series of anecdotes that some have an exceptional response to treatment," Burkard said. "The more genetically different the tumor is from you, the better the chance the immune system will detect it."

Just last May, the FDA approved the first new drug aimed at the genetic characteristics of a tumor, rather than where it started. Breast cancer might look like a lung cancer or melanoma, for example. So a drug potentially could be repurposed — specifically to the genetics of the tumor —  and work as well for breast cancer as it does, say, lung cancer.

"We're starting to say: Rather than define it by the name of where it started, define it by the gene," Burkard said. "We're not completely away from it because some cancers are more likely to have that gene than others."

'I have hunches'

Burkard said studying the most unusual cases, such as exceptional breast cancer survivors, offers the opportunity to learn the most because these cancers are the most extreme in how they behave.

"I have hunches," he said. "My first hunch is there's a set of genes in the cancer that causes them to be slower growing. My fellow scientists heartily disagree and say it's the immune system or environment of the cancer or the treatment. Alcohol, exercise and obesity have been linked with some factors that might be relevant." 

Twenty years ago, a mother and daughter who both were in the final months of metastatic breast cancer banked their DNA, as did a younger daughter who assumed she would end up with the disease, too. They hoped a researcher someday could analyze their DNA and learn from it.

"I am glad I'm alive to see that day," said Linda Cook, the daughter from Plover, who didn't have breast cancer at that time but had her blood drawn for DNA testing at the UW-Madison Carbone Cancer Center in anticipation of a diagnosis.

Cook's mother, Myra Hansen of Stevens Point, and sister, Diane Fuller of Traverse City, Mich., both died within a year or so of banking their DNA. They will be part of the study, along with Cook, thanks to their scientific foresight.

Myra Hansen's breast cancer was diagnosed at age 60 — 19 years before she died in 1998. While she was never diagnosed with metastatic cancer, Cook suspects that cancer was in her mother's bones the final year or two because she had back pain. Cook's sister, diagnosed with metastatic breast cancer at age 46, died in 1999 after surviving 12 years — several years longer than most women.

Cook, 64, was diagnosed with breast cancer almost 10 years ago, and metastatic breast cancer about eight years ago. Her chances of surviving beyond five years were roughly 26%. The cancer spread to her spine, ribs and right hip. She currently is in her fifth round of radiation treatment.

"Nothing's going to change for me and my treatment and my lifetime, but how exciting this is if we can help someone else live longer," Cook said of the study. "Perhaps by studying my family's genetic code, we can find that link and metastatic breast cancer would no longer be incurable." 

All ages

The study is enrolling women of all ages. Shirley Lake, 85, of Madison was diagnosed with stage 2 breast cancer in 1998. It metastasized 3 ½ years ago.

"You're never home free," she said.

Mocarski suspects her treatment and oncologist Michael Volk, have had a lot to do with her survival.

The development of Herceptin — a drug that has improved survival rates for women with stages 1 to 3 HER2-positive breast cancer by more than 30% — had just received FDA approval when Mocarski started taking it.

The last two medications she took — each for about four years — had just been approved by the FDA for HER2-positive breast cancer, Mocarski said.

She's currently not taking any cancer medication. But her blood has been tested every four weeks for 16 years because she knows cancer could still in her body.

"There's no indication of metabolic activity right now," she said. "But my first surgeon told me don't ever let them tell you you're in remission. Microscopic cells can be asleep for five, 10, 15 years."

Her longtime oncologist, Volk, plans to retire next year, and she never expected to outlive his career, she said. She met Burkard when the cancer spread to one of her lungs, and saw him again earlier this year, when he asked her to participate in the study.

"I was surprised, flattered and uncomfortable because it was, 'We want to study you because you probably shouldn't be here, but you are,' " said Mocarski.

The walls of her family room feature pictures of her and husband Jay's sons as little boys shortly after her diagnosis, and their high school graduation portraits — pictures she is grateful to see every day, as the boys launch their adult lives in college and beyond.

She still sets short-term goals. She doesn't want to be greedy.

There's no history of breast cancer in Mocarski's family. All four of her boys were born before she turned 35, and she breastfed them. She never smoked.

She tries not to think too much about defying the odds. 

"I get a lot of survivor's guilt," she said. "In 16 years, I've met a lot of people, including a couple of friends, who have passed away from the disease, and their prognosis was better than mine. I feel grateful every day."