Scientists Spot Clues to Predicting Breast Cancer’s Return

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WEDNESDAY, March 13, 2019 — Figuring out which breast cancer patients will live disease-free after treatment is a bit of a guessing game. But new research indicates breast cancer cells hold molecular clues that may allow doctors to predict who is at high risk of having a recurrence up to 20 years later.

It has long been known that women who are successfully treated for breast cancer can still face a substantial risk of a recurrence years later. But there’s no way to zero in on which women are at high risk, and which are unlikely to see the cancer come back.

Right now, doctors can look at certain factors to get a handle on a woman’s recurrence risk, said Christina Curtis, one of the senior researchers on the new study.

Women with breast cancer that is ER-positive, for example, have higher odds of a recurrence years after being treated. (That means the cancer’s growth is fueled by estrogen.) The same is true of cancer that has spread to multiple lymph nodes by the time it’s diagnosed.

But those details don’t tell the whole story, said Curtis, an assistant professor of medicine and genetics at Stanford University.

“Unfortunately, [current methods] are not as precise as we’d like them to be,” she said. “There’s a huge unmet need.”

So for their study, Curtis and her colleagues looked to the medical histories of more than 3,000 women diagnosed with breast cancer as far back as 1977. For almost 2,000 of those patients, the researchers were able to dig into the molecular details of their cancer — including the level of activity in certain cancer-linked genes, and the presence of particular genetic mutations.

When the investigators pulled that information together, they saw that certain subgroups of women faced a high risk of recurrence over the long term.

That included one-quarter of women whose original cancer was ER-positive but negative for the protein HER2 — a common scenario in breast cancer.

For that one-quarter, the odds of a recurrence over the next 20 years ranged between 42 percent and 55 percent, the findings showed.

Similarly, a portion of women with “triple-negative” breast cancer remained at high risk of recurrence over 20 years. Triple-negative cancer has no receptors for estrogen, HER2 or the hormone progesterone — and most recurrences happen within the first five years.

Dr. Harold Burstein is a medical oncologist at Dana-Farber Cancer Institute in Boston. He said the new findings could “open a door” toward better-tailoring patients’ treatment.

“This study points the way toward understanding, with far more detail, what patients can expect as far as their risk of recurrence,” said Burstein, who was not involved in the study.

He cautioned, however, that this is not something patients can ask their doctors about tomorrow. More research is needed before the findings can be translated into a test for use in everyday practice, Burstein said.

The hope, Curtis said, is that when patients are diagnosed with breast cancer, doctors will be able to analyze their tumor for molecular red flags — and then “stratify them upfront.”

If a woman has a cancer that’s likely to come back down the road, that might change her treatment.

Burstein pointed to an example: Hormone therapy, with drugs that block estrogen’s effects, is a standard treatment for ER-positive cancer. But, he said, there’s “controversy” over how long that treatment should last.

If doctors could better predict which patients had a high recurrence risk, those women might want to continue hormone therapy past the standard five years.

At this point, though, it’s not known whether such a treatment tactic would change the long-term outlook for those patients, said Dr. George Plitas, a breast cancer surgeon at Memorial Sloan Kettering Cancer Center in New York City.

“How would this be incorporated into clinical practice? It’s unclear right now,” Plitas said.

That said, he pointed to another contribution of the new findings. They give insight into the biology that helps determine whether a woman will have a recurrence years later. And that could help researchers develop new treatment approaches for those patients.

“This identifies potential molecular pathways for intervention,” said Plitas, who played no role in the research.

“I tell my patients that we live in amazing times,” he noted. “And this study highlights the fact that [treatment] is going to keep getting better.”

The findings were published online March 13 in Nature.

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