According to Yuan Yuan, M.D., the treatment of node-positive breast cancer patients after neoadjuvant chemotherapy is an important step forward as ongoing research reveals the potential role of minimally invasive systemic treatments. There may be a transition away from the use of nodal dissection.
For example, in the ongoing phase 3 A011202 trial (NCT01901094), radiotherapy to unresected axilla and regional lymph nodes was compared with axillary lymph node dissection and regional lymph node dissection in terms of recurrence-free survival for invasive breast cancer. We are evaluating whether it is non-inferior to radiation therapy. . The study enrolled patients with node-positive breast cancer who received neoadjuvant chemotherapy followed by surgery to remove one to eight lymph nodes. 1
Furthermore, Yuan added that in addition to research in the field of surgical treatment, the role of circulating tumor DNA (ctDNA) testing is also an area that requires further elucidation. He noted that the increasing use of ctDNA analysis across clinical trials may further establish the role of minimally invasive biomarker collection methods in the field of breast cancer treatment.
The ongoing Phase 3 SERENA-6 trial (NCT04964934) is an example of ctDNA-based breast cancer research. SERENA-6 is a combination of a CDK4/6 inhibitor and either camizetrant (AZD9833) or an aromatase inhibitor for patients with hormone receptor-positive, HER2-negative metastatic breast cancer in whom ESR1 mutations are detectable by ctDNA testing before disease progression. I’m researching. 2
“We have a lot to interpret, and sometimes we don’t have enough drugs to help these patients,” Yuan said in the State of the Science on Breast Cancer study. said in an interview with OncLive® after the Summit™. She chaired the meeting.
In the interview, Yuan discussed how targeted lymph node dissection may change the treatment approach for node-positive breast cancer patients, questions regarding the utility of ctDNA testing in disease monitoring, and treatment plans for positive patients. He talked about the need to strengthen research and guidance on the subject. ctDNA results.
Yuan is a Professor of Medicine, Chief of Breast Oncology, and Medical Director of the Breast Oncology Disease Research Group at Cedars-Sinai Medical Center in Los Angeles, California. She is also a clinical professor of health sciences at the University of California, Los Angeles.
OncLive: In neoadjuvant therapy, how do you determine the optimal extent of axillary surgery in patients with lymph node metastases?
Yuan: Over the past five to 10 years, the trend in treatment has been to minimize surgery and make it as safe as possible. A series of clinical trials led to our old approach of lymph node dissection down to the sentinel lymph node. Currently, standard practice for patients who are clinically node-negative is to perform a sentinel lymph node (dissection) when neoadjuvant chemotherapy has been completed and surgery is scheduled. If a patient has clinical N1 disease, meaning less than three positive lymph nodes, we look to see if we can successfully downstage the lymph nodes with systemic therapy. Therefore, surgery can be kept to a minimum. Targeted lymph node dissection or targeted lymph node removal (also known as) minimizes toxicity to the patient. That is now evolving.
However, we are awaiting data on patients who demonstrated a complete response (CR with neoadjuvant therapy). For example, if a patient (for example) initially had 3 or 4 (positive) lymph nodes on their MRI, when they had another MRI after chemotherapy or immunotherapy, the MRI would show that the lymph nodes were complete. What should I do if it shows that it is missing? do? Standard practice remains lymph node sampling and dissection. (But) can we minimize the overall intervention? We’re looking forward to large datasets (to answer that question).
What research is needed to solidify the role of ctDNA results in treatment decision-making for breast cancer patients in metastatic and neoadjuvant settings?
ctDNA is a very interesting topic. This has been around for a while, but I personally didn’t make much use of it until recently. In the neoadjuvant setting, more questions than answers remain. For example, the I-SPY group has published robust data using ctDNA in a neoadjuvant setting. A rapid decline in ctDNA (levels) predicts higher pathological CR rates and higher event-free survival. That’s interesting.
In the metastatic setting, for disease monitoring (using ctDNA). We are asked every day by patients: How do they know they don’t have cancer? Currently, patients are not satisfied with that answer. Usually we cite guidelines. There is no strong evidence to support frequent use of tumor markers such as CEA or CA 27.29, or frequent scanning, but perhaps in high-risk patients, i.e., stage II and III node-positive, high-risk patients. It may take a day. Disease – We may be able to use ctDNA as a way to monitor (disease). That remains to be seen.
What questions remain regarding the optimal treatment of patients with disease recurrence per ctDNA?
(Another) dilemma is that over time you can see ctDNA appearing and growing, but nothing shows up on the scan, so you can’t confirm the (diseased) histology by estrogen receptor/HER2 staining. That’s it. It’s a puzzling and confusing stage to treat patients who relapse after a few months (or maybe you thought they did), but now you’re confused about what to do with them. Even if we (decide) to give chemotherapy (to those patients at that point), are we changing the trajectory of their disease or are we barely moving the lead time arrow? Isn’t it? It’s difficult.
Additionally, I have received (various) second opinions (on ctDNA) from my colleagues. Sometimes[ctDNA levels]go up and down, go up and down, and show unstable numbers. The patient is extremely nervous and sits in a chair wondering when the disease will return. There are a lot of psychological factors that we don’t know how to deal with.
I hope that one day, when (a patient) first shows abnormal ctDNA (levels), there will be a clear pathway (to guide us). Should the oncologist sit back and wait another 3 months, or should they repeat the ctDNA biopsy and once the initial findings are confirmed, then begin a plan of action? Algorithm is missing. Should we give chemotherapy to patients who don’t have visible disease and just have positive ctDNA (levels), or can we do something smarter, a targeted therapy?This is a blank space and we need to fill it with knowledge and answers that we don’t currently have.
References
Comparison of axillary lymph node dissection and axillary radiation for patients with node-positive breast cancer treated with chemotherapy. ClinicalTrials.gov. Updated February 2, 2024. Accessed October 4, 2024. https://clinicaltrials.gov/study/NCT01901094 Phase III study evaluating AZD9833+ CDK4/6 inhibitor in HR+/HER2-MBC with detectable ESR1m prior to progression (SERENA-6) (SERENA-6). ClinicalTrials.gov. Updated on September 27, 2024. Accessed October 4, 2024. https://clinicaltrials.gov/study/NCT04964934
Source link
