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Nothing happens overnight in breast cancer research — a fact acutely felt by the more than 268,000 women diagnosed with the disease each year in the United States.

Advances usually come in baby steps. Fran Visco, president of the advocacy organization National Breast Cancer Coalition, says it’s important to talk about progress in the right context, because it may not have immediate clinical benefits for women. “Real advancements should extend life or show overall survival increases, and very few do that,” she says.

What’s more, in a crowded media environment, it can be hard to identify which advancements have actually been impactful. The good news is that those small steps year after year have added up to improved survival rates for women with early-stage cancers, and recent research and trends have the potential to benefit many more women.

As Breast Cancer Awareness Month draws to a close, we asked experts in the field which findings have been the most significant in the past year. Here are three developments not to miss.

After years with very little proof of immunotherapy’s promise in treating breast cancer, a new study has everyone excited about its potential.

Very basically, immunotherapy works when a tumor activates the immune system to knock out cancerous cells. The concept has been around for decades, and the two scientists who pioneered this way to treat cancer won the 2018 Nobel Prize in medicine. It is a treatment that has become part of the standard of care in combating cancers that are more prone to stimulating the immune system — melanoma and some forms of lymphoma, for example — but until very recently had not shown much efficacy in treating breast cancers.

Last October, however, researchers reported that, when women with hard-to-treat metastatic triple-negative breast cancer were given a combination of chemotherapy and immunotherapy, it added on a median of seven months in survival. (Metastatic refers to cancer that has spread beyond the breast to other organs.) Although the thousands of patients it impacts is relatively small when you consider how many women are diagnosed with breast cancer each year, researchers say its potential is very important.

“It’s not exciting because it’s such a huge breakthrough for that small population of patients, but because it opens the door to the possibility that there may be other uses for immunotherapy in more patients with breast cancer,” says Eric Winer, director of the breast oncology center at Dana-Farber Cancer Institute.

Debasish Tripathy, chair of the medical oncology department at MD Anderson Cancer Center, agrees, and says current research is focusing on ways to bring the treatment to more patients. “As we learn more about what turns on the immune system against cancer, and also what allows certain cancers to escape, we can develop strategies to make the tumors more recognizable to the immune system” and expand the number of patients who can be treated, he says.

In a nutshell, immunotherapy is a type of treatment that uses a drug or substance to kick the immune system into the right gear so the body will fight cancer.

There is currently a lot of conversation in the medical and advocacy communities about overtreatment of breast cancer. Thanks to excellent screening tools, women are being diagnosed earlier and earlier — more than 60,000 are diagnosed each year with in situ disease, which is cancer that has not yet spread beyond the milk duct. Unfortunately, the understanding of which cases will progress and become deadly has not improved, and many women are unnecessarily undergoing toxic treatment and life-altering surgeries simply because it’s the safe bet.

According to Winer, as researchers investigate new drug therapies, it’s just as important to explore how to safely, cautiously back off of overtreatment in some cases. “De-escalation essentially means rightsizing therapy for a particular patient and a particular tumor,” he says.

Last year, the scope of just how many women may be undergoing unnecessary treatment was elucidated by a clinical trial supported by the National Cancer Institute. Beginning in 2006, researchers from six countries enrolled more than 10,000 women with the most common type of breast cancer. Using a molecular assessment test that looks at 21 breast cancer-related genes, researchers determined which post-operative treatment was most appropriate for each patient.

For 70 percent of those women, the study found that patients can skip chemotherapy. Winer says this is “a big deal, because it’s a large population of patients and chemo is by no means free of side effects.”

Winer says de-escalating would definitely not be appropriate for some women and some cancers, however, and it’s important to recognize that there are large sub-groups of breast cancer that need different treatment approaches. He says the question is whether it’s necessary to give all the therapy that has been typical in the past: “It’s both about pulling back where we can and escalating or changing and pushing harder where we need to.”

In a nutshell, de-escalating therapy is making a concerted effort to understand and treat each patient and each tumor without giving more chemotherapy and performing more surgery than is necessary or beneficial.

As our understanding of breast cancer biology grows, research can focus more on specific tumor types. In the past several years, one area of promise is looking into how to block the effects of proteins called cyclin-dependent kinase 4/6 enzymes, which cause cell division and cancer growth.

In the last year, in part based on a trial that showed survival benefit in women with metastatic disease, the Food and Drug Administration approved the drug ribociclib for use in combination with either tamoxifen or an aromatase inhibitor for specific, advanced cancer in some women.

While Tripathy, who led the trial, says that increased understanding of biology is paying off with a lot of targeted drugs, the challenges of drug resistance and side effects remain. “Human cells — and cancer cells in particular — are very plastic and can adapt in many ways,” Tripathy explains. “We’d like to raise the bar and understand why patients develop resistance, and use cocktails of drugs that don’t just target the pathway, but also the mechanisms that may emerge.”

In a nutshell, CDK4/6 are proteins that cause cancer to grow, and researchers are trying to develop CDK4/6 inhibitors that tell those proteins to stop propagating.

Given that drug resistance is a key issue for the more than 40,000 U.S. women who still die from breast cancer each year, it should, as Tripathy notes, be a primary focus of research. However, no one can say for sure which new discoveries will finally lead to a reduction in those numbers and put an end to breast cancer. Maybe it will come down to a deeper understanding of genetics, or developing a revolutionary immunotherapy. Or, maybe researchers will find a way to prevent breast cancer altogether, such as a vaccine developed in a promising but over-hyped area of research that the National Breast Cancer Coalition has committed to investigating.

Whatever “it” is, research won’t likely uncover it this year. “The rate of progress in terms of discovery and new drugs has accelerated, and that’s a good sign,” Tripathy says. “But there are still a lot of challenges.”

Editor’s Note: An earlier version of this article contained a misspelling of Debasish Tripathy’s name. This version has been updated.

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