Dr Yuan on the Evolution of Radiation Therapy Approaches in Breast Cancer

Yuan Yuan, MD, PhD, professor, director, Breast Medical Oncology Medicine, medical director, Breast Oncology Disease Research Group, Cedars-Sinai Medical Center, Health Sciences Clinical Professor, University of California, Los Angeles, discusses radiation therapy approaches across various of breast cancer subtypes, as presented at a recent OncLive® State of the Science Summit, which she chaired.

At the event, Julie K. Jang, MD, PhD, of Cedars-Sinai Medical Center, discussed patient-friendly radiation therapy in breast cancer. The traditional approach to radiation therapy in breast cancer, which involved 6 to 6.5 weeks of treatment for all patients, is evolving, Yuan begins. She states that oncologists now have more efficient and patient-friendly options that allow treatment to be completed in much shorter timeframes. For example, treatment can be condensed into schedules ranging from 15 to 20 fractions, equating to 3 to 4 weeks, or even as short as 5 fractions over 1 week, Yuan explains. These tailored approaches are particularly effective for patients with low-risk disease, offering greater convenience and reduced burden without compromising efficacy, she reports. This shift moves away from the "one-size-fits-all" mindset, acknowledging that treatment should be individualized based on disease risk, Yuan expands.

Furthermore, radiation oncologists are working diligently to minimize treatment-related toxicity and still deliver effective therapy, particularly for patients with early-stage breast cancer, she continues. The ability to adjust radiation schedules not only improves patient experience but also ensures that they receive the necessary care without unnecessary adverse effects, Yuan states. These advancements in radiation therapy represent a step towards improving the accessibility and manageability of treatment for all patients with the same high standards of care, she notes. The future of breast cancer radiation treatment is focused on efficiency, personalization, and reducing treatment burden for patients without compromising outcomes, Yuan concludes.

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Yuan Yuan, MD, PhD, discusses radiation therapy approaches across various of breast cancer subtypes.

Dr Yuan on the Investigation of Adjuvant CDK4/6 Inhibition in Breast Cancer

Yuan Yuan, MD, PhD, professor, director, Breast Medical Oncology Medicine, medical director, Breast Oncology Disease Research Group, Cedars-Sinai Medical Center, Health Sciences Clinical Professor, University of California, Los Angeles, discusses key research evaluating the efficacy and safety of CDK4/6 inhibitors in the adjuvant setting for patients with breast cancer, as presented at a recent 

® State of the Science Summit, which she chaired.

Niki Patel, MD, of Cedars-Sinai Cancer, discussed the utilization of CDK4/6 inhibitors in the post-surgical setting for breast cancer patients, Yuan begins. In her presentation, Dr Patel primarily focused on 2 practice-changing phase 3 randomized trials: the phase 3 monarchE (NCT03155997) and NATALEE (NCT03701334) trials. Findings from the monarchE trial, which led to the FDA approval of abemaciclib (Verzenio) in this context, has provided significant insights into this agent’s efficacy in the adjuvant setting, she explains. In contrast, the data from the NATALEE trial evaluating adjuvant ribociclib (Kisqali) have been presented for 2 consecutive years at major conferences, Yuan states.

One key distinction between the patient populations in these trials is that patients with clinically node-negative disease were not included in monarchE, Yuan highlights. Accordingly, monarchE's data cannot be applied to this patient population. However, data from NATALEE are relevant for high-risk, node-negative patients, particularly those with T2 tumors (2 cm or larger), Yuan states. She notes that the FDA approval for ribociclib in this setting is still pending, and the follow-up period for the NATALEE trial remains relatively short, she emphasizes.

Patel expressed a particular interest in the subset analysis of high-risk, node-negative T2 patients, given the clinical impact of the NATALEE trial, Yuan begins. Previously, such patients would have completed chemotherapy and subsequently started endocrine therapy. Now, they face an additional 3 years of treatment, leading to concerns about adverse effects such as hair thinning and fatigue, she states. The absolute benefit of this extended treatment regimen for individual patients remains unclear, and must be fully elucidated through continued research, Yuan concludes.

Yuan Yuan, MD, PhD, discusses key research evaluating adjuvant CDK4/6 inhibition in breast cancer.

Dr Yuan on Minimizing Lymph Node Surgical Intervention in Breast Cancer

Yuan Yuan, MD, PhD, professor, director, Breast Medical Oncology Medicine, medical director, Breast Oncology Disease Research Group, Cedars-Sinai Medical Center, Health Sciences Clinical Professor, University of California, Los Angeles, discusses the potential shift towards minimizing surgical intervention for lymph node management in breast cancer.

Yuan begins by stating that has been a trend towards increasingly minimizing surgical intervention whenever possible in breast cancer management, although ensuring safety remains a top priority. Over the past 5 to 10 years, numerous clinical trials have guided a shift from extensive lymph node dissection to the more conservative approach of sentinel lymph node biopsy (SLNB), according to Yuan. Today, the standard practice for patients with clinically lymph node–negative disease involves performing a SLNB once they complete neoadjuvant chemotherapy and are being prepared for surgery, she explains.

For patients with fewer than 3 positive lymph nodes, there is growing interest in determining whether surgery can be minimized if systemic therapy successfully downstages the nodes, Yuan continues. At an 

® State of the Science Summit™ on breast cancer, oncologists highlighted this topic by introducing the concept of targeted lymph node removal. This method focuses on reducing long-term surgical toxicity, such as lymphedema, by limiting the scope of lymph node dissection, she explains. Although this approach is still evolving, it offers the potential to significantly improve patient outcomes by reducing the long-term effects of more invasive surgeries, Yuan expands.

However, a critical gap remains in determining how to treat patients who achieve a complete response following chemotherapy or immunotherapy, she emphasizes. The key question is whether oncologists can safely minimize surgical intervention in these cases without compromising outcomes, Yuan notes. Large datasets and further clinical trials are essential to answer this question, allowing investigators to determine the most effective and least invasive course of action for patients, she concludes.

Yuan Yuan, MD, PhD, discusses the potential shift towards minimizing surgical intervention for lymph node management in breast cancer.

Yuan Yuan, MD, PhD, director, Breast Medical Oncology Medicine, medical director, Breast Oncology Disease Research Group, Cedars-Sinai Medical Center, discusses ongoing investigations at Cedars-Sinai of treatment de-escalation in patients with early-stage triple-negative breast cancer (TNBC) according to their pathological response.

Treatment de-escalation has become an increasing focus of research efforts in the breast cancer space. If successful, de-escalation could decrease long-term toxicities without affecting the risk of disease recurrence in patients who respond to a given therapy, Yuan begins.

Several investigator-initiated and large group trials are being conducted at Cedars-Sinai to address this question, including the phase 3 OptimICE-pCR trial (NCT05812807), Yuan states. This randomized comparator study was designed to investigate the de-escalation of treatment with pembrolizumab (Keytruda) in patients with early-stage TNBC who had achieved a pathological complete response (pCR) following neoadjuvant chemotherapy plus pembrolizumab. Patients will be randomly assigned to undergo either observation or continue single-agent pembrolizumab for up to one year, which is the standard of care for patients who achieved a pCR, Yuan adds. The trial provides an opportunity to see if observation after a pCR is a viable strategy for these patients, Yuan says.

For patients with TNBC who do not experience a pCR with neoadjuvant chemotherapy plus pembrolizumab, efforts are being made to bring currently approved antibody-drug conjugates into the post-neoadjuvant setting from the metastatic setting, Yuan continues. One such trial is the phase 3 ASCENT-05 trial (NCT05633654) of sacituzumab govitecan-hziy (Trodelvy) plus pembrolizumab vs investigator’s choice of treatment, Yuan introduces. Additionally, the phase 3 TROPION-Breast03 trial (NCT05629585) is investigating datopotamab deruxtecan (DS-1062a) in combination with durvalumab (Imfinzi) or administered alone vs investigator’s choice of treatment, she details. Both trials are being conducted in patients with TNBC who have residual disease.

All of these trials could address clinical needs for this population by improving the personalization of therapeutic approaches, Yuan concludes.

Yuan Yuan, MD, PhD,  discusses ongoing investigations at Cedars-Sinai of treatment de-escalation in patients with early-stage triple-negative breast cancer according to their pathological response.

Dr. Yuan on Ongoing Research in Patients With TNBC According to Pathologic Response

Yuan Yuan, MD, PhD, director, Breast Medical Oncology Medicine, medical director, Breast Oncology Disease Research Group, Cedars-Sinai Medical Center, discusses the importance of clinical trial participation and enrollment in patients with breast cancer.

There has been a shift in treatment advances for patients with breast cancer, Yuan explains. However, enrolling patients with breast cancer for clinical trials remain a challenge, Yuan begins. This challenge stems from several possibilities, such as the COVID-19 pandemic, Yuan suggests. Moreover, there have been many physician changes across the country, leading to what Yuan describes as a national crisis due to the shortage of research staff following the COVID-19 pandemic.

From a patient perspective, in 2023, modern clinical trials can be driven by precision medicine, Yuan explains. For example, investigators aimed to launch a clinical trial at Cedars-Sinai Medical Center targeting the 

 mutation in breast cancer, Yuan says. However, upon looking into a patient database, investigators found that only 15 patients expressed this specific mutation, she notes. This emphasizes that these types of clinical trials are a mutation-driven precision medicine process that not every patient will fit the criteria for. Therefore, these types of studies have more specific eligibility criteria, Yuan says, adding that this fractures the accessible population for trials.

Finally, access to clinical trials for underserved patient populations remain an unmet need, stemming from limitations due to patient insurance, for example, Yuan says. Therefore, investigators at Cedars-Sinai Medical Center aims to disseminate trial information to these underserved populations. All these factors continue to determine that investigators should continue to work to get the right patient and help them through trial enrollment, Yuan concludes.

Yuan Yuan, MD, PhD, discusses the importance of clinical trial participation and enrollment in patients with breast cancer.


Yuan Yuan, MD, PhD

Articles

Dr Yuan on the Evolution of Radiation Therapy Approaches in Breast Cancer

Dr Yuan on the Investigation of Adjuvant CDK4/6 Inhibition in Breast Cancer

Dr Yuan on Minimizing Lymph Node Surgical Intervention in Breast Cancer

Dr. Yuan on Ongoing Research in Patients With TNBC According to Pathologic Response

Dr Yuan on the Importance of Clinical Trial Enrollment in Breast Cancer