Remembering Iconic ‘Breakfast at Tiffany’s’ Star Audrey Hepburn The Major Advances & New Mystery Since Appendix Cancer Took The Actress’s Life

The loving actress is not only remembered for her famed work, but also for being incredibly caring about those close to her, focusing less on the cancer she had, according to a 2017 PEOPLE cover story.

Her longtime partner Robert Wolders said, “The doctors gave her three months to live. She acknowledged being afraid of the pain but not being afraid of dying.”

Wolders even explained how Hepburn was “desperate” to spend her last Christmas back home in Switzerland, and thanks to her close friends, she was able to do so.

“She would probably have succumbed during the flight from L.A., so we went by private jet made possible by [designer and close friend] Hubert de Givenchy and her friend Bunny Mellon, and the pilots descended carefully to reduce the pressure slowly. She was basically on life support,” Wolders said.

He continued, “Because she had had a very busy period for UNICEF prior to her illness, in fact, I said to her once, ‘Would it have been better if we hadn’t exhausted ourselves to this extent traveling as much for UNICEF as we did.’

“And she was slightly perturbed and she said, ‘Robbie, think of all we would’ve missed.’ So I know that in her last day she regretted that she could not carry on the work because she was very passionate about it.”

Hepburn, a 5-foot-7 mom of two, was so giving before her January 20, 1993, death, that she even requested to give her partner, son, and friend Givenchy gifts.

Wolders recounted, “On the last Christmas, she asked a friend to buy three special winter coats: for Givenchy, [her son] Sean and me. She said, ‘Please think of me when you wear them.’ Later on, when we went to bed, she said, ‘It was the most beautiful Christmas I ever had.'”

The late UNICEF Goodwill Ambassador is also remembered by her friend, a pianist, composer and conductor, Michael Tilson Thomas, for her grace before she passed away.

Tilson said, “She had this ability to make everyone who met her feel that she was really seeing them, and recognizing what was special about them.

“Even if it was just in the course of the few moments that it takes to sign an autograph and a program. There was a state of grace about her. Somebody who is seeing the best in a situation, seeing the best in people.”

Understanding Audrey’s Battle With Appendix Cancer

Audrey Hepburn was diagnosed with cancer of the appendix in 1992, and underwent surgery to treat her disease at Cedars-Sinai Medical Center in Los Angeles. She passed on January 20, 1993, near her home in Lausanne, Switzerland, at the age of 63.

Hepburn battled a rare appendiceal cancer called pseudomyxoma peritonei (PMP). PMP is in the same family of cancers as colon cancer.

This type of cancer begins as a small polyp in the appendix, and can then spread to other areas of the body. A risk factor for many cancers, including colon cancers, is smoking; Hepburn was a life-long smoker.

Pseudomyxoma Peritonei is a rare disease characterized by the presence of mucin (a type of protein) in the abdominal (peritoneal) cavity. The most common cause of PMP is appendix cancer but several types of tumors (including non-cancerous tumors) can cause PMP as well.

The Appendix Cancer Pseudomyxoma Peritonei Research Foundation states that patients diagnosed with appendix cancer have reported experiencing symptoms including:

• Appendicitis
• Increased abdominal girth
• Bloating
• Pain/discomfort in the abdominal regioncan be a dull ache or sharp pains similar to appendicitis
• Hernia symptomsoften initially diagnosed as a hernia, especially in men
• In women, symptoms of an ovarian cyst or tumoroften initially misdiagnosed as ovarian cancer
• Ascites (fluid) buildup in the abdominal cavity

Types of Appendix Cancer

There are various types of appendix cancer, according to the Appendix Cancer Pseudomyxoma Peritonei Research Foundation:

• Low grade mucinous neoplasms of the appendix (formerly known as mucinous cystadenomas) are non-cancerous tumors of the appendix.
• Adenocarcinomas are cancerous tumors created by gland-forming cells that line the inside of the appendix. They may spread to other parts of the body, other organs in the abdomen or to the local lymph nodes.
• Signet-ring cell adenocarcinomas (so called because of the physical appearance of the cells under the microscope) are a subset of adenocarcinomas of the appendix. Signet ring cell cancers are generally considered more aggressive than other adenocarcinomas because they are faster growing, more likely to spread to local lymph nodes and harder to completely remove at the time of surgery.
• Adenocarcinoid cancers (also known as Goblet Cell Carcinoids or Goblet Cell Adenocarcinoma) are a hybrid tumor of both adenocarcinoma and a neuroendocrine (or carcinoid cancer). The expected behavior of adenocarcinoid tumors tends to follow that of the adenocarcinoma portion of the tumor.
• Neuroendocrine (Carcinoid) tumors arise from a subset of cells lining the appendix known as neuroendocrine cells. They are generally considered to be slow growing and have a very different behavior than adenocarcinomas of the appendix.

Major Advancements in Appendix Cancer

Luckily, since Hepburn’s passing, there have been some major advancements in the fight against appendix cancer.

Back in 2004, a woman named Pam Philips went to see surgical oncologist Dr. Armando Sardi at Mercy Medical Center in Maryland after she was misdiagnosed for years while enduring abdominal pain and discomfort, only to be told by Sardi that her body was battling a type of appendiceal cancer, according to WBAL-TV.

Speaking to the news outlet about her case, Philips said, “We need to get the word out to primary doctors so they can diagnose early, so you won’t go years with this growing in your abdomen.” But in 2015, a surgery with a high success rate become available for patients battling the disease.

Dr. Sardi said the cancer is very curable these days with the help of hyperthermic intraperitoneal chemotherapy (HIPEC) surgery, something which kills cancer cells in the abdomen and reduces recurrence chances.

He explained, “The treatment is called HIPEC. Really what it consists of is going in and removing all the tumor first. That’s the most important thing to do. It takes between 8 and 12 hours. Then you give 90 minutes of heated chemotherapy.”

WATCH: What Is Hyperthermic Intraperitoneal Chemotherapy

Hyperthermic intraperitoneal chemotherapy (HIPEC) is a surgery in which a patient's abdominal cavity is filled with chemotherapy drugs that have been carefully heated to a temperature slightly higher than the body's average temperature.

While the drug is injected into the cavity, the patient is placed in a special cooling blanket to ensure the body does not overheat.

This is also accomplished with some manual work from the surgeon and others in the room, who will rock the patient back and forth for hours to ensure the drug reaches every part of the cavity.

If this is done correctly, the drug can kill the cancer cells that remain after surgery, therefore reducing any chance of recurrence.

There are several reasons why individuals prefer HIPEC treatments, such as:

• single treatment during a single visit
• decreased risk of toxic effects because the drug is confined to the abdomen
• surgeon can administer a more intense dose of chemotherapy

This procedure works best in individuals with soft tissue sarcomas, appendix cancer, desmoplastic small round cell tumors (DSRCT), and other cancers in the abdominal cavity.

However, despite this type of surgery being available to anyone dealing with appendix cancer, investigators have recently been having a tough time what’s behind the growth of people being diagnosed with the disease over the past 20 years.

Although the disease remains very rare, findings from a 2020 study revealed that the number of people having of malignant appendiceal tumors increased by 232% in the U.S. between 2000 to 2016, ONC Live reported this year.

Andreana N. Holowatyj, PhD, MSCI, an assistant professor of medicine and cancer biology at Vanderbilt University Medical Center and Vanderbilt-Ingram Cancer Center (VICC), told ONCLive that these cancer been found to be affecting more younger adults.

Holowatyj said, “My team conducted a few studies, particularly one that wanted to look at the burden of appendix cancers in young adults.

“And what we strikingly found there was that, in contrast to the fact that about 1 in every 5 colorectal cancer patients is diagnosed before the age of 50, we found that 1 in every 3 [30.8%] appendix cancer patients are diagnosed before age 50.4.

“Noting this really disproportionate burden in younger patients really spurred a lot of the subsequent work that my lab has done and continues to do.”

She also noted that the disease is more prevalent in patients of color, adding, “Appendix cancer, much like many other cancers, has a lot of different characteristics on a cellular level, or what the cells look like under the microscope.

“So, there's a lot of pathological differences that lead to different histologies. Again, with the rarity of this malignancy, it’s really hard to study. Specifically, what is the genetic predisposition in this one group of patients with, let’s say, appendiceal adenocarcinoma versus goblet cell carcinoma? That’s the trajectory we’re hoping to move forward in with our clinical study that’s now open at Vanderbilt and across the country, for patients with appendix cancer, but it's too soon to say.”

Holowatyj, along with her colleagues, also shared data they found on the “prevalence and spectrum of inherited cancer susceptibility gene sequence variations in patients with appendiceal cancer and the utility of germline genetic testing for this population.”

They discovered that about 1 in 10 patients had an inherited gene sequence variation which was linked with cancer susceptibility.

Pseudomyxoma Peritonei & How to Find Help After a Rare Cancer Diagnosis

Tens of thousands of people, like Hepbrun, are diagnosed with rare types of cancer every year. And people facing an uncommon diagnosis may find it difficult to find someone who specializes in their illness. Here's what our SurvivorNet experts say about ways that patients can find helpful resources and get the help they need.

SurvivorNet's Clinical Trial Finder is a great way to connect with privately and publicly funded clinical trials conducted around the world. It can be a particularly useful resource for cancer patients with rare conditions as a tool for finding doctors who are experts on their diseases. Often, the most specialized doctors in a specific field end up leading clinical trials that push our understanding of diseases forward.

Clinical Trials Can be Life-Saving for Some

Contributing: SurvivorNet Staff

Learn more about SurvivorNet's rigorous medical review process.

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