Success Fuels Perez's Dreams of Helping Patients With Breast Cancer

Oncology Live®, February 2015, Volume 16, Issue 2

In Partnership With:

Partner | Cancer Centers | <b>Mayo Clinic</b>

Coping with challenges is part of the human condition, but self-awareness can have far-reaching results. Just ask Edith A. Perez, MD, about her experience attending medical school.

Edith Perez, MD

Coping with challenges is part of the human condition, but self-awareness can have far-reaching results. Just ask Edith A. Perez, MD, about her experience attending medical school.

“I always thought I would do something… it wasn’t something that I could totally articulate, but I knew I was going to do something different,” Perez recalled.

The desire to do something different started in elementary school in Puerto Rico. She talked about a classmate who boasted to the class of someday enabling people to live forever. When her turn came, not wanting to be outdone, Perez proclaimed that this would require finding a way to expand the world (which she would do).

Her intellectual appetite, it turned out, has made a marked difference for patients with breast cancer everywhere. Every day, she sets her mind on finding better treatments for the disease and to conducting research that will help others in the oncology community move forward with science aimed at improving people’s lives.

Much, although not all, of her work has concentrated on the study of compounds designed to fight HER2-positive breast cancer, leading to a 2005 discovery that changed the way the disease is treated. A study that Perez led and helped design showed that the use of trastuzumab (Herceptin), a monoclonal antibody that selectively binds to the protein alteration of HER2, in concert with chemotherapy—rather than chemotherapy alone—resulted in a 52% decrease in the recurrence of HER2-positive breast cancer in patients who had undergone surgery for the condition, and improved their survival by 33%.

“It was a real breakthrough for patient management, and I knew it would apply to thousands of patients in the United States and throughout the world,” said Perez. “We presented those data at the largest meeting ever of the American Society of Clinical Oncology, with about 16,000 people in attendance,” Perez recalled.

More importantly, she realized that “not too many physicians have the opportunity to affect that many lives to this degree, no matter how dedicated they are or how incredibly good their ideas. To see the eyes of the patients, and their gratitude for the results of the work that we have done, is very humbling, and it has been quite powerful.”

Using tumor and blood samples collected during the study, Perez and her colleagues have continued to consider the potential applications of trastuzumab. “I routinely explore things that I hope will be more efficacious and will lower toxicity,” Perez said, “because that’s huge for people’s lives.”

Many Roles at Mayo Clinic

Perez accomplishes that through a variety of roles at Mayo Clinic in Jacksonville, Florida, including her role as director of the Breast Cancer Translational Genomics Program. For more than two years, she has served as deputy director at large of the Mayo Clinic Cancer Center based in Rochester, Minnesota, and also is director of the institution’s Breast Specialty Council. The council brings together researchers from all Mayo Clinic sites to review research opportunities related to breast cancer prevention, treatment, and survivorship.

She is a Serene M. and Frances C. Durling Professor of Medicine at the Mayo Medical School; the first Mayo Clinic physician to serve on the Board of Scientific Advisors of the National Cancer Institute; and in 2007, was given her institution’s top honor for investigators when she was named a Mayo Clinic Distinguished Investigator.

Finally, Perez helped launch a fund-raising marathon that led to the January 2009 creation (and continued funding) of Mayo’s Breast Cancer Translational Genomics Program, which aims to unravel, categorize, and catalog relevant molecular alterations present in breast cancer. The goals of the work include gaining a better understanding of what drives the disease’s growth, learning what may predict sensitivity or resistance to different treatments, and identifying targets that can be used to develop new treatments, according to Perez. The event—called 26.2 with Donna, the National Marathon to Finish Breast Cancer—also includes a 5K, a half-marathon, and a relay. It attracts more than 10,000 participants, ranging from patients to elite runners, and helps raise funds not only for genomic research but also for underserved women diagnosed with breast cancer.

Research Part of Her Hectic Race

Her myriad roles make for a whirlwind schedule of workdays that stretch to 10 hours or more. In addition to her clinical trial and translational laboratory work, Perez’s schedule includes organizing, attending, and speaking at meetings all over the globe; participating in conference calls; conducting grant reviews on behalf of the National Institutes of Health (NIH); advising scientists and companies throughout the world on studies, research, and patient care; writing manuscripts; mentoring younger scientists; and making videos for posting on You- Tube to explain her current research. Perez also heads Mayo Clinic teams in conducting basic research projects funded by the NIH, including one focused on tissue biomarkers for responsiveness to adjuvant trastuzumab, and another aimed at understanding the role of the immune system in response to anti-HER2 therapies—trastuzumab, pertuzumab (Perjeta), and lapatinib (Tykerb)—in adjuvant, neoadjuvant, and metastatic settings. In large part, the projects involve analyzing the proteins and genes in tissue and blood specimens and correlating them with patient outcomes.

Perez does not consider her heavy workload a burden on her private life. “My work doesn’t feel like a lot of sacrifice. It’s what I can do best,” Perez said. “Although I would like more hours to play tennis, run on the beach, read, be with good friends, and volunteer my time, it’s not a sacrifice at all.”

Perez also manages to find time to see patients, including a few who periodically return for follow-up care, and new patients who are seeking second opinions about diagnoses. Seeing patients routinely would be difficult, Perez said, because of her travel schedule. Those she has treated, though, remain fixed in her memory.

“Some of their stories are really amazing,” Perez said. “I just respect what they have to go through, because most of them thought they were healthy until, one day, this happened to them.”

Perez was moved recently when she received an e-mail from the husband of a deceased patient. “She died before Herceptin was available, and I thought, ‘If she had lived a few more months, we would have had this novel treatment,’” Perez recalled. “This kind of experience has served as my inspiration all these years. Whenever I see a patient, I wonder, ‘Is this the patient I’m going to help next?’”

Inspired by a Loved One’s Death

A similar thought inspired Perez to study medicine. She was a 16-year-old freshman in college when her grandmother died suddenly. “I thought, ‘If I had been a doctor, I could have helped her,’” Perez recalled.

Growing up on the east coast of Puerto Rico, close to the beach and the rainforest, Perez exhibited all the skills she would later need to pursue a medical degree.

“I really enjoyed science very early in my life, although I was going to be a mathematician, not a physician,” she said. “I was really good at math, which I got from my father. Even when I was in college, I took a calculus class, and in the whole semester, I missed one question in one test. I could see the solutions easily.” By the time Perez was an intern, she was considering a specialty in breast cancer.

“It was interesting because it was evolving and complex, it had to do with people, and I realized that someone who liked to read could do well,” she said. “I thought I could be doing this for a while, and I was right.”

The daughter of a father who owned a grocery store and a mother who was a teacher turned librarian, Perez started school early, advanced an extra year during high school, graduated in two years, and, at 16, enrolled as a premedicine student at the University of Puerto Rico, Rio Piedras campus, where she earned a bachelor’s of science degree in biology three years later.

Perez stayed at the university to earn her medical degree, then completed her residency in internal medicine at Loma Linda University Medical Center in California. Having decided to pursue oncology, Perez began a fellowship in hematology and oncology at the Martinez Veterans’ Administration Medical Center, affiliated with the University of California— Davis School of Medicine. There she did work related to lung cancer and began to explore breast cancer. Then, one evening in 1995, a telephone call accelerated her path to the top of that field.

“I got a call asking if I’d be interested in transferring to the Mayo Clinic,” she said. “I was extremely happy, and I accepted the opportunity. I was very fortunate because it’s a great institution.”

New Compounds in Focus

Before moving to Mayo’s facility in Jacksonville, Perez spent six months working at the institution’s Rochester, Minnesota, location, where she devoted mornings to laboratory research and afternoons to patients. In Mayo’s laboratory, her focus was combinatorial chemistry, Perez recalled, “treating cancer cells with different medicines or new compounds and seeing how you can best kill tumor cells—is it best to combine medicines or use [just] one? These are ideas I carry today when I do lab bench work that can be translated into clinical trials.”

Since moving to Jacksonville, Perez has bolstered Mayo’s breast cancer program by attracting continuous grant funding from Evelyn Lauder’s Breast Cancer Research Foundation, becoming a founder of the genomics center, and helping to make numerous discoveries about the mechanisms of the disease.

For instance, “Many people thought that the more copies a patient had of the HER2 gene, the better their response would be to Herceptin,” Perez said. “But we found that, up to a threshold, more copies of the gene didn’t make for a better outcome.”

Perez is proud of the progress she has made during her time at Mayo Clinic, and she is eager to build on it. “I love what I do, and I want to do more,” she said. “These days, I’m much more productive than I ever was, and I’m having more fun than ever. It’s all very interesting to closely work with outstanding collaborators here at Mayo Clinic and other institutions around the world.”

One accomplishment Perez hopes she has achieved is having her research results translated into the community so they can improve the lives of patients worldwide. “It’s about more than being in the laboratory,” explained Perez. “It is more than being in front of my computer answering e-mail. Ultimately, the impact I have will make a difference for people all over the world.” And so the elementary school dream voiced years ago continues today.

Jennifer A. Crozier, MD Hematology and Oncology Fellow Mayo Clinic Jacksonville, FL

Perez Hailed as “Tireless Leader” in Fight for a Cure

“There are few people who will impact millions of lives across the world. Edith Perez, MD, is one of those special few. Perez is an international leader in the world of oncology, especially breast cancer. Her immense work ethic and dedication to innovation has led to novel research and advances in how we care for patients with cancer every day.

“In 2005, as the principal investigator of the North Central Cancer Treatment Group N9831 Intergroup trial, her groundbreaking work in the treatment of HER2-positive breast cancer showed a considerable decrease in recurrence and increase in the survival for patients treated with trastuzumab in addition to adjuvant chemotherapy. This research changed the standard of care for patients with HER2-positive breast cancer and inspired the development of many basic science studies and clinical trials.

“In addition to her stellar research prowess, Perez is an exceptional patient advocate. Perez cofounded 26.2 with Donna, The National Marathon to Finish Breast Cancer, which produces world-class events with all proceeds going to breast cancer research, care of patients, and awareness.

“Perez is a tireless leader in the fight to cure breast cancer and an exceptional role model. Despite her demanding schedule, she always makes time for education and mentorship of fellows and junior faculty. Her dedication to patients, creative vision for the future, and desire for excellence will lead to continued advancements in oncology.”

Adam M. Brufsky, MD, Comprehensive Breast Cancer Center University of Pittsburgh Pittsburgh, PA

Edith Perez, MD, has an amazing breadth of knowledge and has been involved in multiple areas of cancer care. She’s been involved, in both the design and conduct, in some of the most pivotal cancer trials, especially in breast cancer and the research conducted for trastuzumab.

“What truly sets her apart is her encyclopedic knowledge, and it’s that scope of expertise that she brings as a researcher. If you look at the major advances in the systemic treatment of breast cancer over the last 10 or 20 years, Perez has been involved in just about every one of those advances.”

Edith A. Perez, MD: A Research sampler

  1. Perez EA, Romond EH, Suman VJ, et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831 [published online October 20, 2014]. J Clin Oncol. 2014;32(33):3744-3752.
  2. de Azambuja E, Holmes AP, Piccart-Gebhart M, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): survival outcomes of a randomised, open-label, multicentre, phase 3 trial and their association with pathological complete response [published online August 14, 2014]. Lancet Oncol. 2014;15(10):1137-1146.
  3. Curigliano G, Perez EA. Immunoscoring breast cancer: TILs remember what they target [published online July 20, 2014]. Ann Oncol. 2014;25(8):1455-1456.
  4. Pagani O, Regan MM, Walley BA, et al. Adjuvant exemestane with ovarian suppression in premenopausal breast cancer [published online June 1, 2014]. N Engl J Med. 2014;371(2):107-118.
  5. Perez EA, Cortés J, Gonzalez-Angulo AM, Bartlett JM. HER2 testing: current status and future directions [published online September 11, 2013]. Cancer Treat Rev. 2014;40(2):276-784.
  6. Moreno-Aspitia A, Hillman DW, Dyar SH, et al. Soluble human epidermal growth factor receptor 2 (HER2) levels in patients with HER2-positive breast cancer receiving chemotherapy with or without trastuzumab: results from North Central Cancer Treatment Group adjuvant trial N9831 [published online June 6, 2013]. Cancer. 2013;119(15):2675-2682.
  7. Perez EA, Dueck AC, McCullough AE, et al. Impact of PTEN protein expression on benefit from adjuvant trastuzumab in early-stage human epidermal growth factor receptor 2-positive breast cancer in the North Central Cancer Treatment Group N9831 trial N9831 [published online May 6, 2013]. J Clin Oncol. 2013;31(17):2115-2122.
  8. Hurvitz SA, Dirix L, Kocsis J, et al. Phase II randomized study of trastuzumab emtansine versus trastuzumab plus docetaxel in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer N9831 [published online February 4, 2013]. J Clin Oncol. 2013;31(9):1157-1163.
  9. Perez EA, Suman VJ, Davidson NE, et al. Sequential versus concurrent trastuzumab in adjuvant chemotherapy for breast cancer N9831 [published online October 31, 2011]. J Clin Oncol. 2011;29(34):4491-4497.
  10. Perez EA, Hillman DW, Dentchev T, et al. North Central Cancer Treatment Group (NCCTG) N0432: phase II trial of docetaxel with capecitabine and bevacizumab as first-line chemotherapy for patients with metastatic breast cancer N9831 [published online November 9, 2009]. Ann Oncol. 2010;21(2):269-274.
  11. Perez EA, Suman VJ, Fitch TR, et al. A phase II trial of docetaxel and carboplatin as first-line chemotherapy for metastatic breast cancer: NCCTG study N9932 N9831 [published online August 23, 2005]. Oncology. 2005;69(2):117-121.
  12. Romond EH, Perez EA, Bryant J, et al. Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med. 2005;353(16):1673-1684.