A highly sensitive blood test has been developed that can spot when breast cancers become resistant to standard hormone treatment, and it has been demonstrated that this test could guide further treatment.

A large number of breast cancers express the estrogen receptor, making them susceptible to hormonal treatments, but unfortunately these tumors can develop mutations in the estrogen receptor gene (ESR1) and become resistant to hormonal therapies that were previously effective.

A team of scientists led by those at The Institute of Cancer Research (London, UK) analyzed 171 consecutive patients with advanced breast cancer and all patients had recently relapsed or progressed after previous therapy. For patients who had biopsy of recurrent cancer, this biopsy was used to define the receptor status, and for the remaining patients, the pathology of the primary cancer was used. For patients who had biopsies from multiple metachronous metastatic sites, the most recent biopsy was used to define the receptor status.

DNA isolated from tissue or plasma was quantified on a QX200 Droplet Digital Polymerase Chain Reaction System (ddPCR, Bio-Rad; Hercules, CA, USA) using ribonuclease (RNase) P as the reference gene. Sequencing libraries were prepared and templated with the Ion OneTouch2 system and sequenced on a PI chip using the Ion PI OT2 200 Kit (Thermo Fisher; Waltham, MA, USA). This method proved able to detect DNA errors as sensitively as tumor biopsies, with 97% matching between two methods, and could in future remove the need for such an invasive procedure.

The stage at which the cancer was treated had a huge influence over how cancers became resistant to aromatase inhibitors, which are used as standard after surgery in postmenopausal women with ER-positive breast cancer. Mutations in ESR1 only occurred in 6% of patients first treated with aromatase inhibitors when their cancers had not spread, but in 36% of patients when the disease had already spread round the body by the time the drugs were administered. The study suggests more advanced cancers evolve drug resistance much more readily, reinforcing the importance of early diagnosis and early treatment for cancer.

Nicholas C. Turner, MD, PhD, a Consultant Medical Oncologist and team leader, said, “Looking for cancer DNA in the blood allows us to analyze the genetic changes in cancer cells without the need for invasive biopsies. Our study demonstrates how these so-called liquid biopsies can be used to track the progress of treatment in the most common type of breast cancer. The test could give doctors an early warning of treatment failure and, as clinical trials of drugs that target ESR1 mutations are developed, help select the most appropriate treatment for women with advanced cancer.” The study was published on November 11, 2015, in the journal Science Translational Medicine.

Related Links:
The Institute of Cancer Research 
Bio-Rad 
Thermo Fisher