François-Clément Bidard, MD, PhD: Circulating Tumor Cells May Help Improve Outcomes in Metastatic Disease
2022 San Antonio Breast Cancer Symposium
François-Clément Bidard, MD, PhD, of the Institut Curie, discusses overall survival results from the STIC CTC trial. To guide the choice between chemotherapy and endocrine therapy for patients with metastatic, estrogen receptor–positive/HER2-negative breast cancer, researchers compared circulating tumor cell (CTC) count to physician’s choice of treatment. The data suggest that the CTC count resulted in better long-term outcomes (Abstract GS3-09).
Disclaimer: This video transcript has not been proofread or edited and may contain errors.
The purpose of the STIC CTC study was to interrogate the clinical utility of circulating tumor cell count as a biomarker to drive the treatment decision between endocrine therapy and chemotherapy in ER-positive HER2-negative metastatic breast cancer patients. What we did is we collected, on one hand, the clinicians best estimate whether a patient should be treated with endocrine therapy or chemotherapy, and on the other hand, we also collected a circulating tumor cell count by the CELLSEARCH system.
Then, the design of our study is like the MINDACT trial, so patients with concurrent estimates. Patients for whom endocrine therapy was a best treatment option according to physician's choice and also had a low CTC count, these patients were treated with endocrine therapy. On the other side of the spectrum, patients that were to be treated with chemotherapy according to the physician and a high CTC count also received chemotherapy.
What is interesting is that we had 40% of patient with discrepant estimates between the clinician estimates and the CTC count. What the overall survival results reported earlier show is we have a benefit in terms of overall survival for the population of patients who were clinical low, which means endocrine therapy was a favorite treatment option according to the physician, and had a CTC-high count. And so these patients were treated with chemotherapy in the experimental arm. That benefit is very clinically meaningful, because the delta, the difference, between the two median overall survival was 16 months.
The main limitation of our trial is that the trial was run prior to the use of CDK4/6 inhibitor in first line. I have to be clear here, our results do not apply to CDK4/6 inhibitor naive-patients. For these patients, endocrine therapy plus CDK4/6 inhibitor must remain standard of care and the CTC count has not demonstrated any utility in that setting. However, what is very relevant is that CDK4/6 inhibitors are now moving to the adjuvant setting and we also have patients that are progressing on first-line CDK4/6 inhibitor. We know that for these patients we currently don't know exactly how to propose the best treatment between a first line of chemotherapy and/or a further line of endocrine therapy, and we believe that our results advocate in favor of the use of circulating tumor cell count as one of several biomarkers that could help improving the second-line therapy.
In the next year to come, there will be performed changes in the way we treat patients and the second-line setting. For some patients, will have, still, endocrine therapy agents, for other patients who will have chemotherapy or antibody-drug conjugates. We will have to integrate many biomarkers, which could be ESR1 mutation, which could be HER2-low status. The STIC CTC trial advocates in favor of fusing the circulating tumor cell counts. It is not the only biomarker, but it is a strong prognostic biomarker that could help deciding between different treatment options.
Marleen Kok, MD, PhD, of the Netherlands Cancer Institute, discusses the most important advances in early breast cancer treatment during the past year for patients with triple-negative, HER2-positive, and estrogen receptor–positive disease. Dr. Kok also addresses long-term treatment toxicities and quality of life.
Aditya Bardia, MD, MPH, of Massachusetts General Hospital, discusses results from the phase III EMERALD trial, the first study to demonstrate improved progression-free survival vs standard of care in estrogen receptor (ER)-positive, HER2-negative metastatic breast cancer with one to two prior lines of endocrine treatment, with or without one line of chemotherapy. This finding applied to all patients in the study, including the subgroup with ESR1 mutations (Abstract GS3-01).
Ruth O’Regan, MD, of the University of Rochester Medical Center, discusses the Breast Cancer Index (BCI), a genomic assay that can assess the risk of late distant recurrence (5–10 years after diagnosis) of hormone receptor–positive, early-stage breast cancer. Among premenopausal women with this disease who were enrolled in the SOFT trial, those with a high BCI score had an increased risk of distant recurrence. Those with a low BCI score benefited more from the addition of ovarian suppression therapy to endocrine therapy after 12 years of follow-up (Abstract GS1-06).
Ann H. Partridge, MD, MPH, of Dana-Farber Cancer Institute, discusses results from the POSITIVE trial, which showed that a temporary interruption of endocrine therapy in women with hormone-responsive breast cancer in order to attempt pregnancy, does not affect short-term disease outcomes. The study found that 74% of women had at least one pregnancy, most (70%) within 2 years. Birth defects were low (2%) and were not clearly associated with treatment exposure. Dr. Partridge explains that these data stress the need to incorporate patient-centered reproductive health care in the treatment and follow-up of young women with breast cancer (Abstract GS4-09).
Andrea De Censi, MD, PhD, of Italy’s E.O. Ospedali Galliera, discusses phase III findings showing that low-dose tamoxifen (so-called babytam) given for 3 years still significantly prevents recurrences from noninvasive breast cancer after a median of 7 years from treatment cessation. Babytam at 5 mg/d for 3 years significantly lowered recurrence from noninvasive breast cancer at 10 years without “excess” adverse events (Abstract GS4-08).