Molecular Test May Help Identify Ultralow-Risk Breast Cancer Patients

A molecular test may be able to accurately identify which patients will have a very low risk of death from breast cancer even 20 years after diagnosis and tumor removal, according to researchers at the University of California San Francisco (UCSF). They have been working with colleagues in Sweden and report in JAMA Oncology that “ultralow-” risk breast cancer patients could be treated less aggressively.

“Having a test that accurately identifies a population of women, who have very little risk to begin with, should be welcomed by patients and clinicians alike. These tools will enable doctors to better personalize therapy to safely minimize treatment,” said lead author Laura Esserman, MD, MBA, professor and director of the UCSF Carol Franc Buck Breast Care Center. 

Dr. Esserman said clinicians can now test small node-negative breast cancers, and if they are in the ultralow-risk category, women can be told that they are highly unlikely to die of their cancers and do not need aggressive treatment, including radiation after lumpectomy.

Until now, tools that could reliably identify ultralow-risk tumors at the time of diagnosis have not been available because physicians lacked the assurance that late recurrence could truly be avoided.  In the current study, researchers sought to determine whether a 70-gene test could accurately and reliably identify tumors with indolent behavior and assess the risk of cancer recurrence up to 20 years after diagnosis.

The California investigators collaborated with the Stockholm Breast Cancer Study Group to evaluate patients who have been tracked for decades and were part of a randomized clinical trial of tamoxifen vs. no systemic therapy. The STO-3 low-risk trial included 1,780 lymph node–negative patients with tumors ≤ 3 cm in diameter. The women were randomized to 2 years of adjuvant tamoxifen (40 mg daily) vs. no adjuvant treatment.

Tumor profiles were conducted on 652 women, of whom 311 had received tamoxifen. The majority of the women (79%) had received mastectomies and lymph node removal. The multigene test classified 42% of the patients as high risk and 58% as low risk. The investigators found that low-risk patients had a 95% survival rate at 5 years, but many later died from their disease. The test classified 15% of the cases as ultralow risk, suggesting that such tumors are an inherent part of the spectrum of breast cancers.

The 70-gene test could aid clinicians and patients in determining the optimal treatment course, and to inform choice of systemic therapy as well as local therapy, according to the researchers. They found that in an unscreened population, 15% of women will have ultralow-risk tumors. With widespread screening, approximately 25% of postmenopausal women could have ultralow-risk breast cancer that would rarely be associated with recurrence or death, according to the authors.