A Journey Across the Atlantic Leads to a Path in Surgical Oncology

When Eleftherios “Terry” Mamounas, MD, MPH, came to the United States to continue his medical career, his plan called for a 5-year stay. Mamounas yearned to practice medicine and expand his surgical career outside of the place he grew up, leading him to Pittsburgh, Pennsylvania. Thirty-five years later, it’s safe to say that his original plan has changed.

Born and raised in Greece, Mamounas attended the University of Athens School of Medicine. Afterward, he left to pursue a surgical residency in America. His dream led him to Pittsburgh, Pennsylvania, where he completed his residency at McKeesport Hospital, later of which become part of the University of Pittsburgh Medical Center Hillman Cancer Center.

“Years later, I’m still here [in the United States],” he said. “Plans changed. [I was] offered a career opportunity that was very hard to pass by.”

Mamounas serves as the medical director of the Comprehensive Breast Program at the University of Florida Health Orlando Health Cancer Institute, a professor of surgery at University of Central Florida College of Medicine, and clinical professor of clinical sciences at Florida State University College of Medicine. Additionally, he is the chair of the NRG Oncology Breast Committee and a prior chair of the Breast Committee at the National Surgical Adjuvant Breast and Bowel Project.

At the start of his residency, surgery alone wasn’t enough to quench his thirst for knowledge and to conduct research, so he also pursued a master of public health degree in epidemiology at the University of Pittsburgh, which led him to cancer epidemiology.

“I was really always intrigued by cancer and why it is such a difficult disease to cure,” Mamounas explained.

Further understanding the epidemiology of cancer was another cog in the machine that led Mamounas down the path toward becoming a Giant of Cancer Care. Notably, Mamounas reflects that anxieties stemmed from the cultural differences in treating and diagnosing cancer in Greece and in America.

“Cancer was a disease that was very tough to beat and it was a very difficult disease [to treat]. When I [was growing up] in Greece, patients weren’t even told they had cancer, often because it was a taboo,” Mamounas said. “Although we would tell the family, we would not tell the patient because [cancer] was seen as a curse word.”

Searching For a Cure

Breast cancer is a unique field, according to Mamounas, because it was the first malignancy that began fully exploring the possibility of randomized clinical trials. For example, he recalled that, Bernard Fisher, MD, of the University of Pittsburgh—a 2013 Giant of Cancer Care inductee in breast cancer—had brought forth research on the theory of breast cancer dissemination and biology, leading to developments in the identification, treatment, and prevention of breast cancer. This left the door open for other researchers, including Mamounas, to leave their mark on the field.

“After I finished my first month [at the University of Pittsburgh], Fisher said, ‘If you really want to pursue a career in breast cancer research, look me up after you finish your residency,’ which I did,” said Mamounas. “I then went back and did 2 years of oncology research fellowship with the National Surgical Adjuvant Breast and Bowel Project [NSABP].”

Mamounas said Fisher’s advice drove him to be the best cancer researcher and doctor he could be and that studying under such an influential figure in cancer care had a lasting impact on his work.

He recalled Fisher telling him he didn’t want to work with people who were interested in breast cancer research; rather, Fisher was looking for people who were passionate about the field.

“That really resonates today. You have to be passionate about what you do, and if you are, then you will succeed,” Mamounas noted.

After completing a surgical oncology fellowship at Roswell Park Cancer Institute in 1992, Mamounas returned to the University of Pittsburgh and the NSABP, where he became involved in designing clinical trials involving the taxanes a new class of drugs for breast cancer at the time. In 1997, he was appointed chair of the Breast Committee of the NSABP, a position that he held until 2014 when he became chair of the Breast Committee of NRG Oncology. During his tenure as the committee chair, he has been involved in the design and conduct of several large-scale randomized clinical trials evaluating adjuvant and neoadjuvant chemotherapy, adjuvant endocrine therapy, targeted therapies—such as trastuzumab (Herceptin), pertuzumab (Perjeta), and lapatinib (Tykerb) for HER2-positive breast cancer, and locoregional therapies, such as sentinel lymph node biopsy and partial breast irradiation. One area of his work related to the evaluation of the role of genomic classifiers as well as response to neoadjuvant chemotherapy for prediction of risk of locoregional recurrence in early-stage breast cancer. Some of the findings of this work have now led to the conduct of prospective clinical trials that could help optimize patient selection for adjuvant radiotherapy, he explained.

More recently, as part of the NSABP, Mamounas was involved in the phase 3 KATHERINE trial (NCT01772472), launched in January 2013, in which investigators compared ado-trastuzumab emtansine (Kadcyla; T-DM1) to trastuzumab as an adjuvant treatment for patients with HER2-positive breast cancer with residual tumor present in the breast or axillary lymph nodes following preoperative therapy.

Primary results from the pivotal trial published in the New England Journal of Medicine showed that T-DM1 reduced the risk of recurrence of invasive breast cancer or death by 50% compared with trastuzumab.¹

“The main results of KATHERINE [led to change] almost overnight in the treatment of breast cancer for patients who have residual disease after neoadjuvant chemotherapy,” he said. “Although these are all group achievements, that was one of the most important moments in my career, to even have played a small part in [this] trial.”

Following the phase 3 trial, Mamounas was lead author on a subgroup analysis of KATHERINE, which aimed to assess the clinical benefit of T-DM1 across patient subgroups.² “The subgroup analysis showed that the benefit extended to all patients; it affirmed that you can treat patients [across all] subgroups in that category. From that standpoint, it was practice affirming.”

Mamounas also led the phase 3 NRG Oncology/ NSABP B-42 study (NCT00382070), in which postmenopausal patients with stage I to IIIA hormone receptor (HR)–positive breast cancer who were disease-free after 5 years of treatment with an aromatase inhibitor or tamoxifen followed by an aromatase inhibitor received 5 years of letrozole or placebo.³ Findings from this study showed that in postmenopausal women with breast cancer, extended letrozole treatment improved disease-free survival following 5 years of aromatase inhibitor–based therapy.

“This was one of the trials that led to the establishment of extended adjuvant therapy with an aromatase inhibitor. It impacted how we treat patients because we now have data to support treating with these extended adjuvant endocrine therapies for a significant benefit,” Mamounas said.

Beyond the initial findings from the trial, Mamounas and colleagues continued to perform translational analyses, aiming to determine which patient subgroups derived the most benefit from letrozole.

Although these trials are just one portion of his accomplished career, Mamounas said they have the potential to further refine the selection of patients for extended endocrine therapy.

Leading by Example

Because Fisher’s mentorship had such an influence on Mamounas, he has worked to impart that same wisdom to his own mentees.

“I often repeat my mentor’s admonition to be passionate about what you’re doing and if you find something that you’re passionate about, you will be successful,” he explained. “I often talk to residents and fellows who are ready to pursue their career and I tell them that cancer is a disease that is a challenge, and we need to be passionate and forceful about trying to find the solutions.”

One big piece of advice that Mamounas offers up-andcoming oncologists and researchers is that developing advances in cancer treatment is not a straight line. Research will inevitably involve years of ups and downs before tangible progress can be made in clinical practice. He stresses the importance of understanding the nature of clinical work vs research work.

However, he said, entering the field of academic research later in a career can be difficult. He implores his residents to get involved with research projects and search for ways to join institutions with a heavy emphasis on research.

“You can always see more patients and do more clinical work. That will never leave you. However, the research is something that is important to dedicate yourself to early and [often],” he said. “This is not something you do over the weekend; this is something that, if you’re seriously interested in making a difference, you have to pursue.”

Although his drive to continue academic research remains strong, Mamounas said retirement has crossed his mind.

He has toyed with the idea of painting more, and traveling. “Painting is my passion. It almost became a career choice, but that changed [early on].”

Mamounas’ favorite things to paint include still life, such as flowers, rocks, and water landscapes. In his travels around the world, he shares that as he sees these beautiful landscapes, he is seeing the still life painted pictures in his mind.

Above all, he lists his biggest successes are his children, Joe, Paul, Matina, and his wife, Lisa.

Between cancer research, clinical practice, and his family, “this has been essentially what it’s all about in life.”

Mamounas emphasized that the revolving door of research never stops. When one clinical trial is completed, along with the answers that we obtain, several new questions arise that lead to other trials that could take a decade of work to see them through. As long as he has the opportunity to take part in it, it is hard for Mamounas to envision himself dedicating the majority of his time to anything else yet.

“I’d like to keep my mind sharp and to try to help patients with breast cancer,” he said. “When you treat a disease that is so common, even small increments in survival could save millions of lives worldwide.”

References

1. von Minckwitz G, Huang CS, Mano MS, et al. Trastuzumab emtansine for residual invasive HER2-Positive breast cancer. N Engl J Med. 2019;380(7):617-628. doi:10.1056/NEJMoa1814017
2. Mamounas EP, Untch M, Mano MS, et al. Adjuvant T-DM1 versus trastuzumab in patients with residual invasive disease after neoadjuvant therapy for HER2-positive breast cancer: subgroup analyses from KATHERINE. Ann Oncol. 2021;32(8):1005-1014. doi:10.1016/j.annonc.2021.04.011
3. Mamounas EP, Bandos H, Lembersky BC, et al. Use of letrozole after aromatase inhibitor-based therapy in postmenopausal breast cancer (NRG Oncology/ NSABP B-42): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2019;20(1):88-99. doi:10.1016/S1470-2045(18)30621-1