A new clinical study indicates that molecular test can pinpoint which patients will have a very low risk of death from breast cancer and that these "ultralow" risk patients could be treated less aggressively, leading to fewer toxic effects.
The medical community has focused on identifying cancer early so that it can be cured or more easily treated. While this can benefit some patients, screening also can detect cancers that are extremely low risk and not life-threatening, which could lead to patients being overtreated. The issue is compounded because breast cancer can recur many years after diagnosis.
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.
Detailed in a paper published this week in the Journal of the American Medical Association Oncology, or JAMA Oncology, the new study sought to determine whether a 70-gene test could accurately and reliably identify tumors with indolent, or slow-growing, behavior to assess the risk of cancer recurrence up to 20 years after diagnosis. The same test had shown last year that nearly half of early-stage breast cancer patients, who met traditional criteria for high risk, could safely skip chemotherapy based on the biological makeup of their tumors.
The test, called MammaPrint, was devised by University of California, San Francisco, cancer researcher Laura van't Veer, a co-author on the new study and co-leader of the breast oncology program at the UCSF Helen Diller Family Comprehensive Cancer Center (HDFCCC).
In the new analysis, the UCSF researchers collaborated with the Stockholm breast cancer study group (STO) in Sweden, to evaluate patients who have been tracked for decades and were part of a randomized clinical trial of tamoxifen vs no systemic therapy, and to find cancers with no- or almost no-risk for metastatic progression.
The STO-3 low-risk trial included 1,780 lymph-node-negative patients with tumors less than or equal to 3 centimeters in diameter, randomized to two years of adjuvant tamoxifen (40 mg daily) versus no adjuvant treatment. Adjuvant therapy is a treatment provided after the initial surgery or treatment, with the intent to suppress recurrent tumor formation.
All the women had tumors detected in the era prior to the use of screening mammography, and had their tumors surgically removed. The researchers used the removed tissues to profile a total of 652 women, of whom 311 had received tamoxifen, and 339 had not received adjuvant systemic therapy.
The multigene test classified 42 percent of the patients as high-risk, and 58 percent as low-risk. The researchers found that low-risk patients had a 95 percent survival rate at 5 years, but many later died from their disease. The test classified 15 percent (98) of the cases as ultralow risk, showing that such tumors are an inherent part of the spectrum of breast cancers, even in the era before screening.
However, according to the authors of the study, not all low-risk tumors were ultralow risk. In fact, only a quarter met the molecular definition. The women with ultralow risk tumors had an excellent prognosis, whether or not they used tamoxifen for two years.
"There are breast cancers that pose little or no systemic risk," lead author Laura J. Esserman, a breast cancer specialist and surgeon with University of California Health System, or UC Health, was quoted as saying in a news release from UCSF. "Women who have a tumor that is classified as ultralow risk by 70-gene signature can be reassured that their long-term outcome is expected to be excellent, with or without endocrine therapy."
"This is an important step forward for personalizing care for women with breast cancer," noted Esserman.