Blood Test Helps Tailor Treatments for Advanced Breast Cancer

Liquid biopsies rely on blood samples drawn from cancer patients to analyze trace amounts of free-floating tumor DNA in the blood and this minimally invasive test offers several advantages over conventional tumor biopsies. Liquid biopsies may actually provide a more accurate picture of cancer in the body, as genetic sequencing of free-floating tumor DNA may better capture the diversity of genetic alterations found in cancer cells in different parts of the body, including the primary tumor and metastases.

Scientists at Memorial Sloan Kettering Cancer Center (MSK; New York, NY, USA) analyzed blood samples from 587 patients entering the phase III BELLE-2 trial, which is testing the safety and effectiveness of adding buparlisib to the standard hormone drug fulvestrant to treat women with estrogen receptor (ER)-positive breast cancer who have grown resistant to aromatase inhibitors. The team found that detecting a mutated Phosphatidylinositol-4,5-Bisphosphate 3-Kinase, Catalytic Subunit Alpha (PIK3CA) gene in a blood sample can predict how well some advanced breast cancer patients may respond to the experimental drug buparlisib. A mutated PIK3CA gene can activate the Phosphatidylinositol 3-kinase (PI3K) disease pathway, which promotes resistance to hormone therapies. Buparlisib blocks the PI3K pathway, and thus may increase a woman's sensitivity to hormone therapy.

The entire study population benefited from the combination therapy, but the presence of a PIK3CA mutation in 200 out of 587 (34%) of the patients' liquid biopsies had a striking effect. Those that received buparlisib plus fulvestrant had seven months of progression-free survival (PFS), which is the length of time after the treatment during which the patient lived with the cancer and it did not get worse, compared with only 3.2 months for those receiving fulvestrant plus a placebo. Among a total of 387 patients who did not have the PIK3CA mutation, there was no difference in PFS, suggesting that adding buparlisib did not provide any advantage. Being able to identify patients who will not benefit from the new drug combination is also important, as the side effects proved to be significant, with 25% of patients having serious adverse events such as high blood sugar and potential early signs of liver damage.

José Baselga, MD, PhD, physician-in-chief and lead study author, said, “Testing for mutations in the blood can help identify the population of patients who may benefit most from certain drugs or combinations. The liquid biopsy analyses in these studies gave us incredibly important information. Going forward, liquid biopsy will become standard practice for testing new drugs and monitoring response to current therapies. These effects are quite dramatic in patients with the PIK3CA mutation as an increase from three months to seven months is huge. For the first time, we show that inhibiting the PI3K pathway may be a viable option for patients with hormone therapy-resistant breast cancer.” The study was presented on December 11, 2015, at the San Antonio Breast Cancer Symposium, held in San Antonio (TX, USA).

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Memorial Sloan Kettering Cancer Center