New Hope on the Horizon for Triple-Negative Breast Cancer Patients: Cleveland Clinic Launches Phase 1 Clinical Trial for TNBC Vaccine

Published Oct 26, 2021

Sydney Schaefer

How the Vaccine Works

  • New hope for triple-negative breast cancer patients is potentially on the horizon in the form of a vaccine.
  • Researchers at the Cleveland Clinic have launched a phase 1 clinical trial for their vaccine that will hopefully prevent this aggressive form of breast cancer.
  • The vaccine will work by targeting a protein called alpha-lactalbumin; some 70% of triple-negative breast cancers make the protein.

New hope for triple-negative breast cancer patients is potentially on the horizon in the form of a vaccine. How? Well, researchers at the Cleveland Clinic in Ohio have launched a phase 1 clinical trial for their vaccine that will hopefully prevent this aggressive form of breast cancer.

“The ultimate goal, ultimately, not of this trial, but future trials, would be to be able to prevent breast cancer, triple-negative breast cancer in those who are at very high risk for it,” Dr. G. Thomas Budd, an oncologist at the Cleveland Clinic and principal investigator of the study, tells NBC’s TODAY Show. “Initially this would be people with family histories and genetic mutations known to predispose them to triple-negative breast cancer.”

Watch Dr. Budd live on the Cleveland Clinic’s YouTube channel beginning at 9:30 a.m. Wednesday. He’ll address everything you need to know about the vaccine:

It’s no doubt that this vaccine trial is exciting news, but it will likely take decades before any further strides are made; it takes years for the U.S. Food and Drug Administration to approve new drugs and vaccines (with the exception of the emergency Covid vaccine approval) as many phases of clinical trials are needed. This trial is just the first phase.

“This phase 1 study is a dose-finding study with an endpoint of assessing whether there is an immune response to the vaccine,” Dr. Charles Shapiro, professor of medicine, hematology and medical oncology at the Icahn School of Medicine at Mount Sinai, tells SurvivorNet. “Phase 1 trials are necessary as they often represent first in human experience after some treatment is promising in the pre-clinical setting. By definition, a phase 1 (trial) is too small to draw any conclusions about the anti-cancer effects.”

“Every treatment we know as effective in breast cancer was once in a phase 1 trial setting,” he adds. “Hats off to the Cleveland Clinic for mounting this trial, but time will tell if this vaccine is clinically effective in triple-negative breast cancer.”

Regardless of how long it will take to know the vaccine’s effectiveness, it’s still a major advancement. “The study is a very important development in strategies of cancer prevention and suppressing tumors before they develop either as a recurrence or new breast cancer,” Dr. Nancy Chan, a breast oncologist and director of breast cancer clinical research at NYU Langone’s Perlmutter Cancer Center, tells SurvivorNet.

How the Vaccine Works

The vaccine will work by targeting a protein called alpha-lactalbumin, which is a protein that regulates the production of lactose in the milk of nearly all mammals, including humans. Women create this protein when lactating; it’s the major protein in breast milk (20% to 25% of total protein), according to a study published by the National Library of Medicine. There’s no other time when normal human cells create this protein, Dr. Budd tells TODAY.

Then why would the vaccine target a protein women make while breast feeding? Well, some 70% of triple-negative breast cancers make the protein, he says.

Since the only other time women create this protein is when breast feeding, the vaccine trial includes a small group of women — between 18 to 25 people — who aren’t lactating, won’t become pregnant for the duration of the trial and have recently completed treatment for early-stage triple-negative breast cancer. While these women have NED — no evidence of disease — they remain at high risk for cancer recurrence.

The trial participants will each receive varying doses of the vaccine in order to determine its side effects and whether it produces the desired immunologic response. Participants will receive three doses of the vaccine, two weeks apart. According to researchers, the main goal of the phase 1 trial is determine what vaccine dosage should be used in further studies — phase 2, then phase 3, based on discovered side effects and immune response.

“The vaccine activating the immune system against this ‘retired’ protein provides pre-emptive immune protection against emerging breast tumors that express alpha-lactalbumin,” Dr. Chan says. “The vaccine also contains an adjuvant that activates an innate immune response that allows the immune system to mount a response to prevent development of emerging tumors.” The study’s scientific rationale was first confirmed in mice experiments, according to Dr. Chan.

“What we hope to do is, first, (is) show that we can mount an immune response against one protein that is expressed in the majority of triple-negative breast cancer,” Budd says. “And if we can, we might be able to vaccinate patients or people who are at risk to develop breast cancer, and then prevent them from getting it in the first place — that’s the long-term goal.”

What is triple-negative breast cancer? SurvivorNet experts explain.

Understanding Triple-Negative Breast Cancer

If you’ve been diagnosed with triple-negative breast cancer, it means that your cancer isn’t being fueled by any of the three main types of receptors commonly found in breast cancer — estrogen, progesterone or HER2 protein. This type of breast cancer disproportionally affects younger women and women of color. It also accounts for a higher percentage of breast cancer deaths with a higher rate of recurrence, Dr. Chan says.

It should also be noted that a higher number of triple-negative breast cancers are due to an inherited risk of developing breast cancer and ovarian cancer due to the BRCA1 and BRCA gene mutations. The BRCA1 (BReast CAncer 1) or BRCA2 (BReast CAncer 2) genes help cells repair their DNA damage. Having a change, or mutation, in one of these genes increases a woman’s risk of getting breast cancer. These gene mutations are commonly passed down in families; if a parent carries a BRCA gene mutation, there’s a 50-50 chance you could be carrying it as well.

Because triple-negative breast cancer isn’t being fueled by any of the three main receptors types, the cancer won’t respond to certain therapies, including hormone therapy or HER2-targeted agents like trastuzumab (brand name: Herceptin).

“There are few targeted treatment options for these patients and a lot of research studies are focused on developing new agents that will help women with triple-negative breast cancer live longer and with less toxicity from treatment,” Dr. Chan tells SurvivorNet.

Typically, chemotherapy is the go-to treatment, and there are several options.

“If the disease burden is not too great, meaning that a woman doesn’t have a lot of symptoms, we can often start with oral chemotherapy,” Dr. Elizabeth Comen, a breast oncologist at Memorial Sloan Kettering Cancer Center, tells SurvivorNet. “In my practice, sometimes we start with something called Xeloda. This is a medicine that’s oral that you can take pills in the morning and pills in the evening.”

Chemo for Triple Negative Breast Cancer

“After three months of treatment, we can say, ‘How has the response been? Has the disease burden decreased?’ (This) is what we hope to see, and ideally we will continue on that treatment for as long as possible,” Dr. Comen adds. But, “at some point, a woman may become resistant to the treatment that she’s on. That very often means IV (intravenous) chemotherapy.”

Triple-negative breast cancer is an aggressive form of the disease. If the cancer is advanced, your doctor may also recommend participation in a clinical trial that involves immunotherapy or targeted therapies. It’s possible you could be a good candidate for a later phase of this vaccine clinical trial, but make sure to talk to your doctor in order to make a more well-informed decision.

Contributing: SurvivorNet staff

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