Molecular makeup

Researchers aim to determine likelihood of breast cancer recurrence

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CAMBRIDGE, U.K.—Breast cancer, the most common cancer in the United Kingdom, accounts for 15 percent of all new cancer cases. About 55,000 new cases of invasive breast cancer—roughly 150 per day—are diagnosed in the U.K. each year. Although approximately two-thirds (65 percent) of women diagnosed with breast cancer in England and Wales survive for 20 years or more, the disease still causes about 11,400 deaths annually.
A nonprofit organization thinks it may have an answer to that problem. The METABRIC (Molecular Taxonomy of Breast Cancer International Consortium) study stratified breast tumors into 11 different integrative clusters based on distinct genomic drivers.
According to a Cancer Research UK-funded study published in Nature in March, the genetic and molecular makeup of individual breast tumors provides clues as to how a woman’s disease might progress, including the likelihood of its coming back after treatment and in what time frame. In what they describe as the first study of its kind, scientists at the Cancer Research UK Cambridge Institute at the University of Cambridge collaborated with Prof. Christina Curtis at Stanford University to examine the patterns of genetic changes in tumors from nearly 2,000 women with breast cancer.
Following disease progress for more than 20 years, including whether their cancer returned, the researchers used the information to create a statistical tool to predict whether and when a woman’s breast cancer could come back. The team is working on a routine test designed to give doctors that information. The researchers hope to help doctors to tailor treatments and follow up to individuals, improving their chances of survival.
As Prof. Carlos Caldas, lead researcher at the Cancer Research UK Cambridge Institute, explained, “Treatments for breast cancer have improved dramatically in recent years, but unfortunately for some women, their breast cancer returns and spreads, becoming incurable. For some, this can be many years later, but it’s been impossible to accurately predict who is at risk of recurrence and who is all clear. In this study, we’ve delved deeper into breast cancer molecular subtypes so we can more accurately identify who might be at risk of relapsing and uncover new ways of treating them.”
Previous results from this group of researchers showed that breast cancer is not just one disease. Instead, it could be classified into one of 11 molecular subgroups. Recent research showed how these molecular subtypes have distinct clinical trajectories that cannot be predicted by looking at commonly used characteristics, such as size, stage, estrogen receptor (ER) or HER2 status, alone.
Clinical trajectories vary considerably, even between tumors that seem similar. Among women with triple-negative breast cancer, there was a distinct subgroup whose outlook is initially poor, but for whom the disease is unlikely to come back in those who survived five years.
The researchers also identified subgroups of women with estrogen receptor-positive (ER+) tumors, who were at a higher risk of their cancer coming back as much as 20 years after they were first diagnosed. As many as 12,300 women in the UK may belong to one of these late relapse subgroups and might benefit from longer courses of treatments such as tamoxifen, or more frequent check-ups.
The research also showed how molecular subgroups could behave very differently if a patient’s cancer comes back. Recurring cancers commonly spread to different parts of the body and some are more aggressive than others, affecting how much time women survive for following a relapse.
In addition to developing an affordable test for future use in hospitals, the research team is investigating personalized treatment options for different subtypes of breast cancer. The next step for the researchers will be to recruit patients into different clinical trials depending on the molecular makeup of their tumor.
Dr. Oscar Rueda, first author of the paper and senior research associate at the Cancer Research UK Cambridge Institute, summarized, “We’ve shown that the molecular nature of a woman’s breast cancer determines how her disease could progress, not just for the first five years, but also later, even if it comes back. We hope that our research tool can be turned into a test that doctors can easily use to guide treatment recommendations.”

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