Surgical Pioneer Flips the Script on Early Breast Cancer Treatment

OncologyLive, Vol. 20/No. 20, Volume 20, Issue 20

Armando E. Giuliano, MD, a 2018 OncLive Giants of Cancer Care® award winner in Surgical Oncology, disrupted the treatment landscape for early breast cancer when he introduced sentinel lymph node biopsy. The result led to improved quality of life and reduced the need for radical breast cancer procedures for many patients.

Armando E. Giuliano, MD

“I’ve never worked a day in my life.”

On his curriculum vitae, Armando E. Giuliano, MD, lists 10 current positions including the Linda and Jim Lippman Chair in Surgical Oncology, executive vice chair of Surgical Oncology in the Department of Surgery at Cedars-Sinai Medical Center, and codirector of the Saul and Joyce Brandman Breast Center—A Project of Women’s Guild.

He is currently serving as the immediate past president of the Society of Surgical Oncology. What’s more, he still treats patients, conducts clinical trials, and trains new surgeons. He was scheduled to leave the day after this interview to give a presentation in China.

Despite all of that, he’ll tell you he has never worked a day in his life. He’s busy, sure. But he doesn’t consider any of that work.

“I love doing this,” he said. “This is not work. There really is a great joy in caring for patients.”

Giuliano can’t remember a time he didn’t want to be a doctor, but had he not gone into medicine, he likely would have become a lawyer like his 2 brothers. “They tell me doctor jokes; I tell them lawyer jokes. There are a lot more lawyer jokes.”

That said, breast cancer surgery wasn’t part of the plan. He went to Pritzker School of Medicine at the University of Chicago to become a cardiologist but got interested in surgery after studying with George Block, MD, a professor at the school and a world-renowned expert in surgery for inflammatory bowel disease and rectal and colon cancer.

Giuliano’s career path changed again a few years later, based on the order of F. William Blaisdell, MD, then chief of surgery at San Francisco General Hospital, where Giuliano did his residency. Blaisdell is known as the father of modern trauma surgery and helped organize one of the country’s first citywide trauma systems at San Francisco General in the early ’70s.

Giuliano wanted to be a vascular surgeon like Blaisdell, but the surgical chief had other plans. To the younger man’s profound disappointment, Blaisdell told him he was going to the University of California, Los Angeles (UCLA), Jonsson Comprehensive Cancer Center to work with Donald L. Morton, MD, a pioneering investigator and oncology surgeon.

“When I tell my residents this, they can’t believe this happened,” Giuliano said. “He was the chief and he said, ‘You’re going to UCLA.’ I said, ‘Doing what?’ He said, ‘Cancer research.’”

The move was not a popular one in the Giuliano household. He had zero interest in oncology and even less interest in leaving Northern California. His wife, Cheryl, who holds a PhD from the University of Chicago, had started a job as an English professor at Stanford University, and they loved the Bay Area. She burst into tears when he told her they were going to Los Angeles.

“It was a different time,” Giuliano said. “When the chief said ‘Go,’ you went. I couldn’t say no to him.”

Whether it was because Blaisdell saw in him the makings of a cancer specialist or through sheer luck, Giuliano fell in love with oncology research and treating patients with cancer.

“They’re the most wonderful patients to care for,” he said. “They are extremely frightened. They know they have a bad problem, and if you can help them, they’re extraordinarily grateful. It’s very satisfying to help a patient with cancer.”

Teaching Compassion

Giuliano took a lot of lessons from his mentors, but what impressed him most about both Blaisdell and Block was their humanity. By any measure, the men were giants in their respective fields, but they never forgot that the patient comes first.

“He was a great technical surgeon, but what really impressed me was the quality of the care he gave his patients,” Giuliano said of Block. “Here’s this distinguished, famous professor, and he would take care of any patient and treat them with the utmost respect and care. Every patient deserved the best care.

“He influenced a lot of young men and women. He was the sort of person who really exemplified what it means to be in medicine.”

San Francisco has always attracted a broad range of people, perhaps never more so than in the 1970s. Giuliano said that Blaisdell exemplified the same level of consideration for every patient, no matter his or her station in life.

“Bill was compassionate to every person who came into the [emergency department]. Some were down on their luck or mentally ill,” he said. “Bill treated every one of them with great respect and taught his residents to do the same. But he was a demanding professor to each of his trainees.”

Giuliano tries to live those lessons.

“No matter who you are or how big you become, it’s all about taking care of 1 patient at a time,” he said. “Giving them the best quality, the most concern, the most empathy and compassion that you can.”

Giuliano also takes pains to pass on the lessons he has learned. He has trained nearly a hundred aspiring cancer surgeons in his day, including 3 former presidents of the American Society of Breast Surgery. The UCLA Department of Surgery has awarded him the Golden Scalpel Award for Teaching Excellence 5 times, including in 1991, when Giuliano also won the Outstanding Teaching Award from the David Geffen School of Medicine before he left.

“Being a teacher and mentor is a chance to help residents and fellows, help young people in their careers, and help many others. They go out, do what I taught them, and help a lot of different people with cancer. It spreads your influence in a way,” Giuliano said, insisting that he learns at least as much as he teaches. “It’s an enjoyable experience to see young surgeons initially struggle to learn a new art and see them succeed and move on and do great things. It’s your most important professional legacy.”

Faith in the Science

In the early 1990s, Giuliano got the idea for sentinel node biopsy from Morton, who had discovered a way to minimize the amount of lymph node dissection for malignant melanoma. Standard procedure for breast cancer treatment at the time called for the removal of all lymph nodes, which often caused lymphedema, with its associated pain, swelling, and stiffness in the arm or shoulder.

“That was just a tremendous problem, a real quality-of-life issue,” Giuliano said. “Many patients fear the lymphedema as much as they fear the cancer.”

Several attempts to identify a sentinel node failed, and he told Morton that it just wouldn’t work in breast cancer. “Morton said, ‘Research means search again. Keep trying,’” Giuliano said.

Daniel Kirgan, MD, then a fellow working in Giuliano’s laboratory, proposed a clinical trial, and the 2 of them sketched out the design on a cocktail napkin 1 night during an impromptu working session in a restaurant. Giuliano and investigators at the John Wayne Cancer Institute, where he was then chief of surgical oncology, published data in 1994 showing that sentinel node biopsy was an accurate, effective way of identifying cancerous lymph nodes.

“We inject a blue dye into the patient’s breast tumor and look for a node that takes up the dye, the theory being, if that tumor drains first to that lymph node, it was the first one to have the cancer,” he said. “That’s the sentinel node concept.

“The real aha moment was when we actually saw a blue node. It was really an incredible experience.”

Results from a second study showed that if the sentinel node was negative, there was no need to remove other nodes. Giuliano said that surgeons and oncologists accepted that idea quickly. But he wondered if the sentinel node were positive, would it be safe to remove just that node and leave the others, even knowing it was likely that other nodes might contain cancer?

Bernard Fisher, MD, one of the inaugural recipients of the Giants of Cancer Care® award, published results in the 1970s showing there was no difference in survival between lymph node removal, no lymph node removal, and lymph node radiation for women with early breast cancer after 25 years of follow-up. Giuliano expected his study, eventually called ACOSOG Z0011, to be well received. After all, Fisher, the legendary former chairman and principal investigator of the National Surgical Adjuvant Breast and Bowel Project, performed his experiments without the advantages of chemotherapy, tamoxifen, or additional treatment, so it seemed clear to Giuliano that there was something about the biology of breast cancer that meant the disease didn’t always spread beyond lymph nodes.

It didn’t go that way. “I have a drawer full of hate mail saying that ACOSOG Z0011 was unethical,” he said.

Results published in 2011 demonstrated conclusively that lumpectomy and tangential whole-breast irradiation (WBI) was noninferior to complete axillary lymph node dissection (ALND) for overall survival (OS) in some women with early-stage breast cancer. At a median follow-up of 6.3 years, the 5-year OS was 91.8% in patients who underwent ALND and 92.5% for patients treated with sentinel lymph node dissection (SLND) alone. Later that same year, Giuliano and his team showed that sentinel lymph node dissection was noninferior to ALND for OS, and patients experienced less pain and had more arm mobility.

The New York Times said the discoveries had flipped “standard medical practice on its head.” While rates of radical mastectomy began declining in the ’80s, in part because of Fisher’s work, the prevailing practice for decades had been radical lymphadenectomy if the breast cancer had metastasized into the lymph nodes.

“Surgeons were reluctant not to do the operation. It turns out, we don’t have to do that operation for most women with breast cancer,” Giuliano said. “That was a major change in the management of breast cancer, one that still is hard to accept.”

Some well-regarded research institutions declined to participate in ACOSOG Z0011, and the findings were controversial. The pushback was intense, but Giuliano never doubted the results.

“I really felt like the data were there,” he said, adding that roughly 97% of women in ACOSOG Z0011 received some kind of additional treatment. “When you add all the additional therapy they get, to me, it seemed clear that the surgery was excessive.”

Ten-year OS results first presented at the 2016 ASCO Annual Meeting and published in 2017 in the Journal of the American Medical Association proved him right. At a median follow-up of 9.3 years, OS with SLND alone was noninferior to complete ALND (86.3% vs 83.6%) in women with cT1-2N0 breast cancer and metastases to ≤2 sentinel lymph nodes who underwent WBI, breast-conserving surgery, and adjuvant systemic therapy. Locoregional recurrence rates were 5.3% with SLND compared with 6.2% with ALND.

The Reward for Hard Work: More Work

Armando and Cheryl Giuliano have been together nearly 60 years, first meeting in Mr Gerhardt’s seventh-grade homeroom back in Long Island, New York. The couple have a set of twins, Amanda and Christopher. Cheryl retired as an English lecturer and director of Writing Programs at UCLA.

“She’s never helped me with one of my papers, by the way,” Giuliano said with a laugh.

Giuliano foresees breast cancer surgery, like all treatment for breast cancer, becoming more personalized. In an ideal world, he said, improving efficacy of systemic therapy will make many operations unnecessary, and he’s currently researching how to avoid positive margins and reoperations.

“It’s a matter of identifying the margins intraoperatively or preoperatively,” he said. “We’re also in the laboratory looking for markers for triple-negative tumors.”

Giuliano has, by any reasonable measure, had an extremely successful career, and although he’d love to find a cure for breast cancer and work himself out of a job, retirement is a nonstarter. Really, what else is he going to do?

“There’s nothing else I can do,” he said. “I’m the only guy who played golf in college and quit when he went to medical school.”