Lajos Pusztai, MD, DPhil, a professor of medicine and co-leader of Genetics, Genomics, and Epigenetics at Yale Cancer Center, discusses the promise of circulating tumor DNA (ctDNA) assays in breast cancer. 

Currently, ctDNA assays are not approved or endorsed for use in breast cancer, says Pusztai. However, testing for ctDNA is gaining ground for monitoring response to immunotherapy in colorectal cancer. 

Notably, during the 2020 San Antonio Breast Cancer Symposium, findings from a biomarker analysis of the I-SPY 2 trial demonstrated that patients with high-risk early-stage breast cancer who did not clear their ctDNA prior to completing chemotherapy had a significantly higher risk of not achieving a pathologic complete response compared with patients who were ctDNA negative. 

As such, ctDNA appears to be a highly sensitive tool in the tumor-marker space, Pusztai explains. Although ctDNA is currently a research tool, it has been shown to have higher sensitivity compared with the established, protein-based biomarkers. It is likely that ctDNA assays will demonstrate continued clinical utility and emerge as a useful biomarker in breast cancer, concludes Pusztai. 

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Lajos Pusztai, MD, DPhil, discusses the promise of circulating tumor DNA assays in breast cancer.  



Dr. Pusztai on the Promise of ctDNA Assays in Breast Cancer 

Lajos Pusztai, MD, DPhil, professor of medicine and co-leader of Genetics, Genomics, and Epigenetics at Yale Cancer Center, discusses the role of circulating tumor DNA (ctDNA) as a biomarker of response in patients with high-risk early-stage breast cancer. 

During the 2020 San Antonio Breast Cancer Symposium, findings from a biomarker analysis of the I-SPY 2 trial showed that ctDNA results were available in 96% of patients prior to treatment and 3 weeks after treatment initiation, and 86% were available at pretreatment, 3 weeks after treatment initiation, and prior to administration of anthracyclines. Notably, detection of ctDNA varied by disease subtype; 86% of patients with triple-negative breast cancer were ctDNA positive at baseline compared with 48% of patients with estrogen receptor–positive, HER2-negative disease, says Pusztai. 

Three weeks after neoadjuvant chemotherapy with or without pembrolizumab (Keytruda), over half of patients who were ctDNA positive at baseline cleared their ctDNA and achieved a pathologic complete response (pCR), says Pusztai. Moreover, patients who did not clear their ctDNA prior to completing chemotherapy had a significantly higher risk of not achieving a pCR, concludes Pusztai.

Lajos Pusztai, MD, DPhil, discusses the role of circulating tumor DNA as a biomarker of response in patients with high-risk early-stage breast cancer.  



Dr. Pusztai on the Role of ctDNA as a Biomarker in Breast Cancer 

Lajos Pustzai, MD, DPhil, professor of Medicine (Medical Oncology), chief of Breast Medical Oncology, co-director, Yale Cancer Center Genetics, Genomics and Epigenetics Program, Yale Cancer Center, discusses how treatment for patients with HER2-positive breast cancer has evolved over time.

One of the first successful examples of treatment for this patient population is trastuzumab (Herceptin), Pusztai explains.

In the wake of this agent's development, two more promising therapies have been added to the field, which are pertuzumab (Perjeta) and ado-trastuzumab emtansine (T-DM1). These drugs have demonstrated efficacy in both the early-stage and late-stage settings, he adds.

Lajos Pustzai, MD, DPhil, professor of Medicine (Medical Oncology), chief of Breast Medical Oncology, co-director, Yale Cancer Center Genetics, Genomics and Epigenetics Program, Yale Cancer Center, discusses how treatment for patients with HER2-positive breast cancer has evolved.

Lajos Pustzai, MD, DPhil

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