2 July 2021

Biomarker test for DCIS may help determine treatment

Clinical Precision medicine Technology

Around half of women with Ductal Carcinoma in Situ (DCIS) have a change in radiotherapy treatment following a precision medicine test that is being promoted by GenesisCare, a study suggests.

The test, DCISionRT, analyses seven biomarkers on the tumour cells to predict the 10-year risk of DCIS returning or developing into potentially life-threatening invasive breast cancer. This determines whether the patient needs surgery or surgery plus radiotherapy.

Oncology Republic interviews GenesisCare radiation oncologist Dr Yvonne Zissiadis about what this test might offer.

Q: How is this test different to what is already available?

A: DCISionRT is a precision medicine test that predicts the 10-year risk of DCIS returning or developing into potentially life-threatening invasive breast cancer and assesses the effect of adding radiation therapy post-surgery.

DCISionRT is the first molecular profiling tool in Australia which is designed specifically to measure the benefit of radiation therapy for DCIS patients, post-surgery, whereas previous tests have been developed to measure the benefit of chemotherapy for invasive cancer. 

It combines the latest innovations in molecular biology with artificial intelligence to provide a highly personalised risk assessment for each woman.

Among women whose DCIS was initially thought to have a low risk of recurrence or progression, two in five had their risk reclassified to an elevated stage when assessed using DCISionRT, revealing a potential need for radiation therapy post-surgery which they might not have otherwise received.

Furthermore, women under 50 with DCIS are generally considered to have an elevated risk of recurrence or progression and radiation therapy is commonly recommended for this age group. However, when using DCISionRT, almost one in two women under 50 were classified with a low risk of DCIS recurrence or progression, indicating that surgery alone may be appropriate.

Q: What data was presented recently at a conference?

A: A recent study presented at the Society of Surgical Oncology 2021 International Conference on Surgical Cancer Care demonstrated that almost half of women with DCIS had their radiotherapy treatment recommendation changed after the test; either adding radiotherapy (RT) to their treatment course or removing it, based on their risk of recurrence or progression to invasive breast cancer assessed using DCISionRT. This test has significantly impacted treatment decisions for these patients.

The presentation, entitled DCIS Biologic Risk Signature Predicts Risk of Recurrence and RT Benefit after BCS, studied 183 women from Australia with DCIS. After breast conserving surgery, those with a Low Recurrence Score (as predicted by DCISion RT test) had a non-significant 2% difference in outcome with and without RT, while those with Elevated Recurrence Score had a significant 27% benefit from RT. Consistent with prior validation studies, DCISionRT classified 43% of patients to elevated risk who were previously identified as “low risk” by individual clinical pathology factors (Grade 1/2, size ≤25mm). The results also demonstrated that women at DS elevated risk received more than a 70% relative benefit from RT. 

Q: Is this technology currently being used in Australia? 

A: Through GenesisCare’s partnership with PreludeDx, Australian women living with DCIS are now able to access DCISionRT through GenesisCare’s 38 radiation oncology centres across the country, across both private and public settings.

Eligible patients will be referred to participate in the AUS-PREDICT registry, a prospective registry gathering data on 1,500 patients to evaluate the effect of the DCISionRT test on treatment decisions in patients with DCIS following breast conserving therapy.

The research program will collect de-identified data on Australian patients diagnosed with DCIS and evaluate whether the DCISionRT test changed their radiotherapy treatment decision, then follow-up with these patients to track their outcomes over a 5 and 10-year period.

The data will help to inform new ways of finessing treatment for DCIS as well as providing precise information to guide patient and clinician decisions. Ultimately this will lead to the development of new products, treatment pathways and patient management processes in Australia.

Q: Which company manufacturers the test?

A: The DCISionRT test was developed by PreludeDx. PreludeDx is a leading personalised breast cancer diagnostics company dedicated to serving breast cancer patients and physicians worldwide. The biopsies are sent to California in the United States for testing in PreludeDx’s laboratory and then the tumour specimen and results are sent back to Australia.

GenesisCare is also partnering with PreludeDx to expand access in the United States and launch the test in the United Kingdom and Spain.

Q: How does the test work?

A: DCISionRT assesses a patient’s individual biology across seven biomarkers, along with other traditional risk factors (including age at diagnosis, size, palpability of the lesion and the tumour margin) to provide a personalised assessment that predicts the risk of a patient’s DCIS recurring over the next 10 years, as well as the benefit of radiation therapy to reduce that recurrence risk. The test calculates a personalised recurrence score (Recurrence Score, 0.0 – 10.0), identifying a woman’s risk as low or elevated.

Patients with a low DCISionRT score are considered at low risk of their DCIS returning or progressing to potentially life-threatening invasive breast cancer. For these patients, surgery alone may be appropriate. However, women with elevated risk scores may benefit from receiving radiation therapy post-surgery. No matter a patient’s score, the option to proceed or not with radiation therapy is ultimately a decision for the patient and their doctor.

The test relies on a comprehensive assessment of seven biomarkers on the tumour cells. It utilises a non-linear calculation which enables the test to account for highly complex interactions between these markers that drive progression and recurrence of DCIS.

Q: How does it help oncologists make clinical decisions?

A: Managing DCIS requires an individualised approach, with different patients requiring different treatment pathways based on their unique risk factors. Historically, doctors have relied on clinical pathology, such as tumour grade and size, to determine treatment plans for patients with DCIS. 

The innovative DCISionRT test looks at each patient’s tissue sample to provide predictive molecular information unique to each patient that will aid clinicians in identifying patients with elevated risk scores who could benefit from radiation therapy, and those who are likely to only require surgery. The test will help afford both clinicians and patients more confidence when making decisions on treatment for DCIS. 

Q: What are the limitations? 

A: As the test has just been launched in Australia, it is not currently on the Medicare Benefits Scheme or listed on the Therapeutic Goods Association in Australia. Instead, the patient’s tissue sample is sent offshore to California to a Prelude’s CLIA-approved lab for analysis. The test is frequently used in the USA and many insurers fund the test there.

This is one of the many reasons why we are partnering with PreludeDx to develop the AUS-PREDICT registry to evaluate the effectiveness of DCISionRT on treatment decisions in patients, post-surgery.

The real-world evidence captured in this registry will play a critical role in discussions with all tiers of government.

Dr Yvonne Zissiadis is a GenesisCare radiation oncologist and principal investigator of the AUS-PREDICT study. She is the site director at GenesisCare’s Hollywood radiation oncology centre, specialising in breast, blood and gastrointestinal cancers as well as having a special interest in the integration of exercise in cancer treatment and cardio-oncology. She is also the head of GenesisCare’s Breast Tumour Reference Group and has played a critical role in bringing DCISionRT to Australia for the first time.