Precision health helps identify which breast cancer patients are at risk for recurrence

By Krista Conger

Some breast cancers return decades later. Now, researchers at Stanford, joined by collaborators at several other institutions, have subcategorized tumors to predict recurrence, guide treatment decisions and improve drug development.

Molecular data obtained from breast cancer cells can be used to predict which patients are at a high risk for recurrence even decades after their diagnosis, according to a new study jointly conducted by researchers at the Stanford University School of Medicine and the Cancer Research UK Cambridge Institute, as well as several other institutions.

In particular, some patients whose tumors express the estrogen receptor but not another receptor called HER2 are at a persistent risk of relapse over time. Until now, there has been no way to identify those women among their peers.

The study also identifies a subgroup of women with what are known as triple-negative breast tumors whose cancers are unlikely to return after five years. The researchers also learned where and when in the body certain breast cancers are likely to metastasize.

The findings provide researchers and clinicians with a powerful new tool with which to predict a patient’s prognosis and potentially direct clinical decision-making.

“For the first time, we’ve been able to study the rates and routes of breast cancer metastases at unprecedented resolution,” said Christina Curtis, PhD, assistant professor of medicine and of genetics at Stanford and co-director of the Molecular Tumor Board at the Stanford Cancer Institute.

“A clinical challenge in breast cancer management has been distinguishing which tumors pose greatest risk of late recurrence,” said Harold Burstein, MD, PhD, associate professor of medicine at Harvard Medical School, who was not involved in the research. “This important scientific paper identifies molecular features that determine the timing of cancer recurrence. In the future, this type of genomic classification should help us separate patients who remain at jeopardy — and might warrant additional or ongoing treatment — and those who do not.”

Traditionally, physicians have relied primarily on clinical variables — such as the size and grade of the tumor at diagnosis, the degree of lymph node involvement and the age of the patient — when making treatment decisions and prognoses. More recently, genomic tests to determine which, if any, molecules are expressed by the cancer cells have been used to subcategorize breast cancers and guide treatment decisions.

The researchers were also able to identify a subgroup of women with triple-negative breast cancers — considered to be an aggressive and more difficult form of the disease to treat — who are unlikely to see their cancers recur after five years.

“This is a retrospective, observational cohort,” Curtis said. “Since then, treatment paradigms have changed for some patient subgroups. Most notably, trastuzumab — which specifically targets the HER2 receptor, has dramatically improved outcomes for patients with HER2-positive breast cancer since it was approved for use in early stage breast cancer in 2006 — was not an option for many of the women in this study. It will be important to take what we’ve learned here and determine whether we can similarly improve the outcomes of these patient subgroups at high risk of recurrence with new therapies that target their specific genomic drivers.”

Curtis and her colleagues are currently planning clinical trials to do just that. They also developed a web-based research tool that may ultimately help clinicians more accurately predict an individual’s risk of relapse and guide treatment decisions.

“We’ve shown that the molecular nature of a woman’s breast cancer determines how their disease could progress, not just for the first five years, but also later, even if it comes back.” Rueda said. “We hope that our research tool can be turned into a test doctors can easily use to guide treatment recommendations.”

The work is an example of Stanford Medicine’s focus on precision health, the goal of which is to anticipate and prevent disease in the healthy and precisely diagnose and treat disease in the ill.

Curtis is a member of the Stanford Cancer Institute and Stanford Bio-X.

The research was supported by Cancer Research UK, the Experimental Cancer Medicine Center, the National Institute for Health Research in the United Kingdom, the Breast Cancer Research Foundation, the American Association for Cancer Research and an NIH Director’s Pioneer Award (grant DP1CA238296). Stanford’s departments of Medicine and of Genetics also supported the work.

To read the full column by Krista Conger, science writer for the Stanford Medicine News Center click here.

To read the original study published March 13, 2019, in the Journal Nature, click here.

Credit: Stanford Medicine News Center