Early research leads to positive outlook for patients with aggressive triple-negative breast cancer

For The Baltimore Sun
Early data from a Hopkins clinical trial brings new hope to women with a hard-to-treat form of breast cancer.

Brenda Berchtold drives six hours to Baltimore every three weeks from Erie, Pa., to keep her standing as medical marvel.

First diagnosed with hard-to-cure "triple-negative" breast cancer in 1986 that returned and spread, Berchtold has been in remission since trying an experimental immune therapy at the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins.

"It really was like winning the lottery," said Berchtold, a 51-year-old former dental hygienist and mother of two. "It's an amazing drug."

The drug, called Atezolizumab, is a form of immunotherapy, a new treatment option for patients with some types of lung cancer, bladder cancer and melanoma. Based on early data from a clinical trial, the treatment, which helps the immune system fight cancer, looks promising for women with metastatic, triple-negative breast cancer.

In the first 24 weeks of the study, which included 54 patients, six patients had no progression of cancer, and the drug continued to work for longer than six months while they were taking it, according to Hopkins doctors. Two of the patients' tumors shrank partially. And two patients' tumors disappeared completely.

One of those two was Berchtold. "I saw 70 percent shrinkage in my tumor after the first dose," she said.

"This isn't typical for women with the aggressive triple-negative form of breast cancer," said Dr. Leisha Emens, an associate professor of oncology at the Johns Hopkins University School of Medicine and one of the lead researchers of the study. Emens is known for her work creating a therapeutic breast cancer vaccine, the subject of a 2008 series in The Baltimore Sun.

Triple-negative breast cancers, which represent about 15 percent to 20 percent of breast cancer cases, tend to grow and spread more quickly than most other types of breast cancer. Patients with triple-negative breast cancer are typically offered surgery and radiation, but drug treatments have traditionally been limited to chemotherapy. Triple-negative breast cancer cells lack the three targets of most breast cancer therapies — estrogen receptor, progesterone receptor and HER2 protein.

The immunotherapy drugs, on the other hand, can help "wake up" the immune system to attack cancer cells, says Dr. Len Lichtenfeld, deputy chief medical officer for the American Cancer Society.

More research and larger clinical trials are needed, Lichtenfeld says. "But these treatments have many of us excited about the potential to really make a difference."

Immunotherapy drugs could be a "game changer" in the treatment of hard-to-beat cancers, including melanoma and triple-negative breast cancer, he says.

Atezolizumab targets a protein that's more common in triple-negative breast cancers than in other breast cancer subtypes. The drug works by blocking a way for tumor cells to hide from the immune systems cells capable of attacking them.

"I've been impressed," said Emens, who first reported the findings in 2014 and updated them this spring at American Association for Cancer Research's annual meeting in Philadelphia. "The neat thing is the durability of the response."

Many patients who did well in the trial have continued to see results. That suggests, Emens said, that the immune system may develop a "memory" during this treatment, similar to what occurs when patients receive vaccinations.

The researchers are now looking at ways to identify cancer patients who are more likely to respond to this therapy, Emens says.

Dr. Roisin Connolly, another Kimmel Cancer Center breast cancer oncologist, is planning a clinical trial later this year that will include triple-negative breast cancer patients and use a combination of immunotherapy and epigenetic drugs, which can turn genes off and on.

"The whole area of immunotherapy has exploded because of promising early results," said Connolly, who is also an assistant professor at Hopkins' School of Medicine. "Our hope is to build on these early results and improve outcomes even further for patients with breast cancer, especially those with triple-negative breast cancer."

Atezolizumab recently made medical news in a study that showed it shrank tumors in some patients with bladder cancer.

The drug is being developed and manufactured by Genentech, part of Swiss drug maker Roche Group, which also funded the breast cancer study. The company expects it to take a few years before they can seek FDA approval for Atezolizumab for triple-negative breast cancer, pending the results of an study that is currently enrolling, according to Holli Kolkey, Genentech associate director for corporate relations.

Emens has received research funding from other pharmaceutical companies, but the arrangements are being managed in accordance with the Hopkins' conflict-of-interest policies, the university said in a statement.

Other scientists were involved in the Atezolizumab research, including doctors from the Comprehensive Cancer Centers of Nevada and the Dana-Farber Cancer Institute in Boston.

The drug could give new hope to many triple-negative breast cancer patients, like Berchtold, who have fallen victim to its high recurrence rate.

After Berchtold's cancer was first diagnosed in 1986 after a lump was found under her upper right arm, she underwent radiation and chemotherapy. When the cancer came back in 1993, she underwent chemotherapy again. But in 2007, it returned on the other side and spread.

She was diagnosed at stage 4 and referred to Emens. A vaccine Emens developed didn't help Berchtold, but the Atezolizumab study did.

Leslie Edmond, a 44-year-old human resources director from Silver Spring, started taking the drug in 2013, after a tumor showed up on her collarbone five years after she'd been treated for triple-negative breast cancer with chemotherapy, radiation and a bilateral mastectomy (the removal of both breasts). The drug shrank the tumor on her collarbone by more than 70 percent, and another small tumor in her neck disappeared.

"This is how women like me are living with cancer today," said Edmond, who continues to take Atezolizumab.

In addition to the promising results, the drug has been well-tolerated by most patients, Emens says. Edmond said she experienced no side effects and continues to work and remain active.

Two patient deaths during the study are being investigated but aren't believed to have been related to the drug's side effects, according to Hopkins.

Berchtold hasn't had nausea, hair loss or any of the other common side effects of most cancer treatments. She's developed thyroid problems, but that may be unrelated to the immunotherapy since thyroid disease runs in her family, Berchtold said.

Berchtold stopped taking the drug for a year, but after labwork showed that she was at risk for the cancer to return, she was able to rejoin the study and hopes to continue receiving the infusions every three weeks.

"It's a lot," she said of the frequent six-hour trips to Hopkins. "But Dr. Emens has been wonderful."

She has scans every six weeks to monitor the results.

"It's a scary thing, I'm not going to lie," said Berchtold. "But I never stopped hoping. I knew I had to keep trying."

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How it works

Unlike other breast cancer therapies, Atezolizumab targets a protein, called PD-L1, that's more common in triple-negative breast cancers than in other breast cancer subtypes. If PD-L1 binds with another protein on immune system cells, it delivers a signal that shuts off their ability to attack cancer cells. Atezolizumab works by binding with the PD-L1 protein, disrupting the signal and allowing the immune system cells to work.

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