Johns Hopkins Kimmel Cancer Center

Novel Drug Combo Offers Hope for Advanced HER2-Negative Breast Cancer

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woman lymph armpit examination. Node-Positive Breast Cancer

Researchers at the Johns Hopkins Kimmel Cancer Center have unveiled a promising new treatment approach for advanced HER2-negative breast cancer, using a three-drug combination that significantly improved responses in patients suffering from the disease.

The study, published in Nature Cancer, involved a combination of a histone deacetylase (HDAC) inhibitor, which halts tumor cell division by inducing chemical changes, along with two types of immunotherapy known as checkpoint inhibitors—working by unleashing the immune system’s power to target and destroy cancer cells.

Led by Evanthia Roussos Torres, PhD, the study enrolled 24 women with HER2-negative metastatic breast cancer, including both hormone receptor-positive and triple-negative cases. The results were striking, with an overall response rate (ORR) of 25 percent across all participants and an even more impressive ORR of 40 percent among those with triple-negative breast cancer.

Breast cancer is the most common cancer among American women, with approximately 300,000 new diagnoses each year in the United States. The majority of these cases are hormone receptor-positive and HER2-negative, underscoring the significance of developing effective treatments for this patient population.

Triple-negative breast cancer, accounting for 10–15 percent of cases, poses particular challenges due to its aggressive nature and limited treatment options.

Importantly, the study demonstrated the safety and tolerability of the combination therapy, with no patients needing to discontinue treatment due to adverse effects. The average progression-free survival (PFS) at six months was 50 percent, indicating that half of the participants experienced no disease progression during this period.

“Our results support the hypothesis that pre-treatment with the HDAC inhibitor entinostat, combined with dual immune checkpoint inhibitors, is a safe and promising strategy for metastatic breast cancer,” Torres said, emphasizing the significance of the findings.

She also underscored the need for further evaluation in larger phase II studies to assess the treatment’s efficacy more comprehensively.

“To our knowledge, this is the first published study that investigates treatment with an HDAC inhibitor in combination with dual immune checkpoint inhibitor therapy in patients with advanced breast cancer,” said Elizabeth Jaffee, PhD, a co-author of the study.

The researchers noted that while immune checkpoint inhibitors have revolutionized the treatment landscape for many solid tumors, their effectiveness in breast cancer has been limited. This novel combination therapy presents a potential solution to this challenge.

“Our study highlights the need for a deeper investigation of the breast cancer tumor microenvironment with a focus on changes in myeloid (immune) cell populations to determine their role in sensitization of the tumor microenvironment to treatment with immune checkpoint inhibitors,” Torres concluded in a press statement.

Bad Luck Causes Most Cancer, New Study Finds

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Cancer cells in a culture from human connective tissue.

Humans want to believe we control our own destinies. If we exercise for 30 minutes every day, eat healthy, avoid cigarettes, alcohol, and drugs, meditate, and participate in the health trend du jour, it seems logical that we will live longer, be happier, and avoid diseases like cancer. Unfortunately, it seems fate is more chaotic than that. A new study published in Science suggests that most cancers are unavoidable. They’re caused more often by bad luck than anything else.

Mutation, which drives cancer, is actually totally normal. In fact, its the engine of evolution–if not for mutation, our genes wouldn’t make the random changes that once in a while end up giving us a new, important skill–like making enzymes that break down lactose, or resistance to disease. But often, those mutations get out of control. Cells divide and divide until they overpower the useful cells in our body and kill us. That’s what cancer is.

According to Bert Vogelstein and Cristian Tomasetti at the Johns Hopkins Kimmel Cancer Center, many of these cancers are unavoidable. They’re just part of nature.

“We all agree that 40 percent of cancers are preventable,” Vogelstein said at a press conference. “The question is, what about the other cancers that aren’t known to be preventable?”

Vogelstein explained that each time a cell’s DNA is copied, mistakes are made. Most of these mistakes are harmless, and as noted above, some of them can even be beneficial. “But occasionally they occur in a cancer driver gene. That’s bad luck,” Vogelstein says. Several of these bad-luck mistakes can add up to a cancerous cell.

Their study sets out to determine how often these mistakes are preventable–whether by not smoking or maintaining a healthy weight–how often they are genetic, and how often they occur by chance. The answer may surprise people who have spent decades believing they can control the development of cancer in their bodies. According to the paper, 66% of cancerous mutations are random, 29% are preventable, and only 5% are genetic.

The numbers vary depending on the type of cancer. Lung cancer is indeed usually caused by cigarette smoke, while childhood cancer is often random. The authors hope that these statistics will help some parents feel less responsible for their children’s disease.

An earlier paper by the authors on the same topic stirred up controversy in the scientific community. Some feel that publicizing this viewpoint will make people less likely to follow advice about cancer prevention. This new study is likely to be even more controversial.

Of course, cancer science is incredibly complicated. Mutations are not the only thing that matter in driving cancer. Factors like hormones can also play a role in determining who the disease hits hardest. “We’re not saying the only thing that determines the seriousness of the cancer, or its aggressiveness, or its likelihood to cause the patient’s death, are these mutations,” Vogelstein told NPR. “We’re simply saying that they are necessary to get the cancer.”

Source: Science via NPR