Optimizing Therapies for HR+ Early-Stage Breast Cancer
What role does risk stratification play in determining therapy for HR+ early-stage breast cancer?
Hope S. Rugo, MD, FASCO
This is a critical area. It is a key aspect of determining appropriate treatment and extent of treatment, and we are still learning more about how to appropriately stratify based on clinicopathologic and genomic characteristics. Gene expression tests are used widely to understand prognosis and benefit from chemotherapy, but there are ongoing issues in HR+ disease including disease heterogeneity and how to optimally treat very young women with HR+ disease.
We use clinicopathologic data in combination with gene expression tests to stratify risk, but this approach doesn't always provide us with the necessary information for determining the optimal adjuvant or neoadjuvant treatment. The adjuvant CDK4/6 inhibitor trials will be helpful, as they will allow for longer follow-up of patients with high- and intermediate-risk disease.
Additionally, newer predictors, such as gene expression signatures that may estimate the benefit from immunotherapy, are also being evaluated.
What factors influence your choice between endocrine therapy and chemotherapy for HR+ early-stage breast cancer?
Multiple factors have an influence on the choice of therapy, including the extent of disease and tumor biology. We have also learned that the intensity or extent of estrogen positivity plays a role in endocrine sensitivity. In terms of tumor biology, understanding tumor proliferation and chemotherapy sensitivity is critical.
We are currently using gene expression tests, but it is clear that these are insufficient, even within the context of age and tumor burden. Additional markers that help to identify up-front or emerging resistance to endocrine therapy are critical. Data from the CDK4/6 inhibitor adjuvant trials has further complicated this question — as now the issue is where optimal outcome can be achieved in less chemotherapy-responsive, higher-risk disease with the addition of abemaciclib or ribociclib.
Considering recent research, is extended endocrine therapy actually beneficial?
I believe it is, but careful consideration needs to be given to the decision to extend therapy. Disease burden is of course our first consideration, but sensitivity to endocrine therapy, development of resistance, and response to chemotherapy in appropriate cases need to be taken into consideration. Interestingly, several analyses have suggested that patients with low proliferative and genomic risk, but a higher disease burden, might be most likely to benefit from extended duration endocrine therapy due to the long natural history of this disease. We are now exploring the use of switching the type of endocrine therapy in the high-risk adjuvant setting and the use of circulating tumor DNA (ctDNA) to optimize therapy.
What role do CDK4/6 inhibitors play in the adjuvant setting for HR+ early-stage disease?
Both abemaciclib and ribociclib have reduced the risk of recurrence and the risk of distant recurrence in patients with intermediate or high-risk early-stage breast cancer. The duration of therapy varies, and eligibility criteria overlap; however, the recent NATALEE trial included a diverse population, including an intermediate-risk group (stage II, node-negative with additional risk factors) to evaluate the role of the CDK4/6 inhibitors among such populations. The striking aspect of this trial was the carry-over effect, shown most clearly in the monarchE study with 5-year follow-up. Even 3 years after completing treatment with abemaciclib, the data showed an increasing impact on disease-free survival and distant disease-free survival. Although there has been no overall survival impact yet, fewer patients with abemaciclib in monarchE are living with metastatic disease.
What are the most critical research gaps or upcoming trials that could reshape how we manage HR+ early-stage breast cancer in the upcoming years?
A few main things to address are improving risk stratification, how to use ctDNA to improve outcome, and understanding if use of oral selective estrogen receptor degrader (SERDs) in sequence improve outcome and their optimal therapy duration.
So far, studies using ctDNA to assess risk and guide therapy changes have been challenging due to the low number of positive ctDNA results. Moreover, ctDNA detection has sometimes coincided with metastatic disease already visible on scans in case of several aggressive cancers. We still don't know the optimal treatment approach when molecular evidence of disease is found, which is making studies focus on adding targeted therapy or changing endocrine therapy.
Several trials are evaluating oral SERDs in the early stage setting for the treatment of high-risk disease. While these trials will also collect ctDNA, patient eligibility is not based on these tests.
One very important area that requires additional research is understanding early-stage breast cancer in young women, where tumors seem to behave poorly — particularly in women under the age of 40 — even when patients are treated with optimal therapy. Understanding optimal therapy is a key research focus, and further investigation of biological drivers in both ductal and lobular cancers is warranted.
The OFFSET trial aims to determine the value of adjuvant chemotherapy vs ovarian function suppression in conjunction with standard endocrine therapy and CDK4/6 inhibitors as indicated. However, this study is challenging to enroll in.
Hope S. Rugo, MD, FASCO, has disclosed the following relevant financial relationships:
Serve(d) as a director, officer, partner, employee, advisor, consultant, or trustee for: Chugai; Puma; Sanofi; Napo; Mylan
Received research grant from: AstraZeneca; Daiichi Sankyo, Inc.; F. Hoffmann-La Roche AG/Genentech, Inc.; Gilead Sciences, Inc.; Lilly; Merck & Co., Inc.; Novartis Pharmaceuticals Corporation; Pfizer; Stemline Therapeutics; OBI Pharma; Ambrx
Hashtags
Try Our AI Features
Explore what Daily8 AI can do for you:
Comments
No comments yet...
Related Articles
Forbes
31 minutes ago
- Forbes
Resilient Leadership: How Women And Workplaces Adapt Under Pressure
Leadership has never been easy, but the terrain leaders stand on today feels shakier than ever. Economic anxiety, rising workplace stress, and declining trust in institutions are reshaping how leaders in business, healthcare, and beyond navigate their about meeting quarterly goals, managing teams, and making decisions in a climate where employees are worried about making rent. Customers are skeptical of institutions, and hostility toward authority figures can flare at any moment. Recent data released by Modern Health captures just how stark the reality is. Nearly 8 in 10 employees say they routinely sacrifice their mental health to keep up with work demands. More than half have considered quitting to protect their well-being, and among young workers, one in seven is already actively job-hunting because of mental health concerns. 'We're seeing a perfect storm,' explained Alison Borland, Modern Health's Chief People and Strategy Officer. 'The rising cost of living, economic uncertainty, and job market instability are fueling unprecedented levels of financial anxiety. Millennials and Gen Z are facing a combination of high student debt, high housing prices, and elevated mortgage rates, contributing to financial strain not experienced by prior generations.' That strain doesn't stay outside the office door. It enters the workplace with employees and becomes embedded in workplace culture. The Cycle of Stress Borland notes that financial stress creates a vicious cycle. Workers under strain experience sleep disruption, mood changes, and burnout, which in turn reduce productivity and deepen financial insecurity. 'Employers can't control the economy,' Borland said, 'but they can break this cycle by acknowledging financial stress as a driver of burnout, offering early preventative support, integrating financial wellness into mental health strategies, and fostering a culture where employees can use that support without guilt or fear of being seen as less productive.' This is no small shift. It requires organizations to move beyond offering benefits on paper and instead create a workplace where those benefits are usable without stigma. A recent survey by the American Society for Reproductive Medicine highlights similar themes: culture matters as much as policy when it comes to whether support systems succeed. Employees need both structural support and cultural permission to take advantage of it. Retention at Risk The link between retention and well-being has never been clearer. 'Our data proves there is a retention crisis in the making,' Borland stated. 'With nearly 70% of young workers staying in toxic jobs or avoiding needed career moves because of economic fears. If employers want to keep top talent, they have to stop forcing people to choose between financial stability and mental health.' That means retention strategies cannot be limited to reactive fixes like exit interviews or burnout leave. Instead, Borland emphasizes a proactive model: preventative mental health support, a culture where it's safe to unplug, and recognition of financial stress as a core factor in well-being. Approximately 96% of employees say preventative mental health support would improve their work lives, and those who receive it report stronger loyalty and lower burnout. In other words, protecting employee mental health isn't just compassionate leadership; it's a retention strategy. The Erosion of Trust Even as organizations wrestle with economic anxiety, they're also contending with another powerful force: declining trust in public institutions and leadership. Dr. Amy Bucher, Chief Behavioral Officer of Lirio, has seen firsthand how skepticism affects engagement. Through her work with Precision Nudging interventions, she's observed dramatic shifts in how people respond to health messaging. 'Back in 2021, many people expressed distrust of COVID-19 vaccination recommendations from the CDC,' Dr. Bucher shared. 'The replies we received were often emotionally charged, resistant, and sometimes even hostile. It was clear that institutional trust was a major barrier to engagement.' Although that hostility briefly eased as messaging expanded beyond COVID, she says polarization is once again on the rise. That erosion of trust carries heavy consequences. People who distrust institutions are less likely to get preventive care, which increases both health and financial costs down the line. The lesson for leaders? Rebuilding trust requires empathy, transparency, and a willingness to engage in two-way communication. 'Leaders must communicate in ways that resonate with non-experts and offer enough dialogue to instill confidence,' Bucher said. 'One of the most powerful things leaders can do is create space for empathy, both inside the organization and in how we engage with the public.' The Promise of Behavioral Science and AI One hopeful note is the role behavioral science and AI can play in bridging the gap between organizations and the people they serve. According to Bucher, 'AI helps us scale empathy. It can recognize patterns, predict what someone is likely to respond to, and then match that with the right behavioral science approach. That's incredibly powerful when you're trying to reach millions of people in a way that still feels personal.' But, she warns, the key is maintaining autonomy. People need to feel that they have a choice in their decisions. When nudges acknowledge autonomy, engagement improves, and trust grows. Leaders in every sector can take note that respect for autonomy is both a moral stance and a practical one. Women-Owned Businesses in the Spotlight While individuals wrestle with personal anxiety, business leaders are also making tough calls in a volatile economy. New research from Umpqua Bank sheds light on how women-owned businesses are navigating these challenges. The survey of 334 leaders revealed a cautious optimism: 36% rated the U.S. economy as excellent or good, and 62% believe conditions will hold steady or improve in the next year. Still, uncertainty looms large. More than half of women-owned businesses plan to prioritize cost-cutting over growth in the coming months, with inflation, recession fears, and tariffs topping their worry list. Yet many are also finding ways to invest. An estimated 30% expect to expand their real estate footprint, and nearly 40% are likely to borrow for business growth. Kathryn Albright, Executive Vice President and Head of Global Payments and Deposits for Umpqua Bank, sees resilience in these leaders. 'Many women-owned business leaders are responding to economic pressures with a focus on creativity and strategic reinvestment rather than cost-cutting alone. They're examining operations through a fresh lens, looking for opportunities to automate select back-office functions and redeploy staff to higher-value activities.' She adds that adaptability and innovation are common threads: 'Women business leaders are staying nimble, remaining open to pivot operations or adopting AI to work smarter and more efficiently. Rather than retreating, they approach challenges with a solutions-oriented attitude.' Balancing Profitability and People Perhaps the most difficult balance for leaders today is maintaining profitability while safeguarding employee well-being. Albright notes that many businesses are tracking employee engagement scores alongside customer feedback, recognizing that the two are interconnected. By automating repetitive tasks, companies can both cut costs and allow employees to focus on meaningful work, boosting efficiency without sacrificing morale. That mindset reflects a broader truth: in this climate, resilience is not built by pushing harder but by thinking smarter. Leaders who adapt, listen, and innovate are more likely to retain talent, maintain trust, and withstand economic pressure. Leadership in an Era of Pressure Economic anxiety and distrust are not fleeting issues. They are reshaping the very nature of leadership. The old model of command-and-control management is ill-suited to a workforce burdened by financial strain and skeptical of authority. Instead, the leaders best positioned for success are those willing to adapt by addressing mental health proactively, fostering cultures of transparency and empathy, and building resilience in both their balance sheets and their people. 'Business leaders recognize that highly engaged employees drive stronger business outcomes,' Albright said. 'At the same time, they're identifying ways to streamline operations, automating repetitive tasks to reduce costs while also freeing up employees to focus on more meaningful, solutions-oriented work. This not only improves efficiency and profitability but also fosters a more motivated, resilient team that's better equipped to deliver exceptional customer experiences.' For Borland, the lesson is simple: when companies protect well-being, performance follows. Under pressure, leaders are discovering that the path forward is not about eliminating uncertainty but about navigating it with empathy, creativity, and courage.
Yahoo
44 minutes ago
- Yahoo
Cardiologists Are Begging You To Eat More of This High-Protein Food if You're Over 60
Cardiologists Are Begging You To Eat More of This High-Protein Food if You're Over 60 originally appeared on Parade. More than 5% of American adults have heart disease, making it an incredibly common medical condition. Unfortunately, heart disease is also the leading cause of death for men and women, causing one in three deaths. Because the risk of developing it increases with age, cardiologists say it's crucial to pay attention to your risk factors as you get older. While there are some risks for developing heart disease that you can't control (like your genetics), lifestyle factors (like your diet) are largely within your control. Heart-healthy diets tend to focus on fruits and vegetables, but choosing the right protein is also a crucial element of eating to support heart health, according to Dr. Cheng-Han Chen, MD, interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA.🩺SIGN UP for tips to stay healthy & fit with the top moves, clean eats, health trends & more delivered right to your inbox twice a week💊 Not all protein is created equal when it comes to heart health, though. 'Protein's effects on heart health depend on the source of the protein,' points out , director of the Hypertension Center at Northwell's Staten Island University Hospital. With that in mind, there's one high-protein food cardiologists recommend reaching for regularly to support your heart health—especially if you're over The High-Protein Food Cardiologists Want You To Eat if You're Over 60 If you're over 60, cardiologists recommend adding salmon to your plate more often. 'Salmon is a high-quality protein and an excellent choice for heart health,' Dr. Chen says. 'It's one of the best natural sources of omega-3 fatty acids.' Dr. Behuria agrees, explaining, 'Salmon is a good source of high-quality protein, which is relatively high in omega-3 fatty acids."Omega-3 fatty acids may help increase HDL ('good') cholesterol in the body and lower LDL ('bad') cholesterol, Dr. Chen points out. High levels of LDL cholesterol is linked to a buildup of plaque in the arteries, which increases the risk of heart attack and stroke. The omega-3 fatty acids in salmon may also help reduce inflammation in the body, according to Dr. Behuria. While some short-term inflammation in the body can be helpful for tissue repair and healing, chronic inflammation is linked to a host of serious health conditions, including type 2 diabetes and cancer. Related: l Omega-3 fatty acids support healthy blood vessel function too, Dr. Chen says. Not only do healthy blood vessels allow the cardiovascular system to shuttle oxygen and nutrients around the body, but good vascular health is also linked to a lowered risk of heart attack, stroke and peripheral artery disease, he explains. Worth noting: A 3.5-ounce serving of sockeye salmon has 22.3 grams of protein, per the United States Department of Agriculture (USDA). Why Protein Is Important for Heart Health as You Age Many people don't associate protein with heart health, but cardiologists say there's a definite connection here. 'Protein supports heart health by helping preserve muscle mass,' Dr. Chen says. 'Since the heart itself is a muscle, maintaining overall muscle strength can benefit its function.'Protein also supports healthy blood vessels and helps with tissue repair, he points out. And it can also help you maintain a healthy weight, Dr. Chen says, adding, 'all of which contribute to cardiovascular health as you age.'Related: How to Incorporate More Fish Into Your Diet The Dietary Guidelines for Americans recommends eating seafood twice a week, but only 19% of Americans actually hit those recommendations. Dr. Chen suggests aiming to have two servings of omega-3-rich fish per week. If you don't want to eat salmon that often, he recommends rotating in fish like mackerel and cod too. 'Prepare them in a heart-healthy way, like baking or grilling, rather than frying,' Dr. Behuria recommends. Up Next: Sources: Heart Disease Prevalence, Centers for Disease Control and Prevention Heart Disease Facts, Centers for Disease Control and Prevention Heart Health and Aging, National Institute on Aging LDL: The 'Bad' Cholesterol, Medline Plus Chavda VP, et al. Inflammation: The Cause of All Diseases. Cells. 2024. DOI: 10.3390/cells13221906. Dr. Supreeti Behuria, MD, director of the Hypertension Center at Northwell's Staten Island University Hospital Dr. Cheng-Han Chen, interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA Food Central, United States Department of Agriculture Dietary Guidelines for Americans Errickson LB, et al. Seafood Consumption Trends among U.S. Consumers: Influences of the COVID-19 Pandemic. Foods. 2024. DOI: 10.3390/foods13172682. Cardiologists Are Begging You To Eat More of This High-Protein Food if You're Over 60 first appeared on Parade on Aug 16, 2025 This story was originally reported by Parade on Aug 16, 2025, where it first appeared.
Yahoo
an hour ago
- Yahoo
This Diet Helps Lower Dementia Risk, And We May Finally Know Why
The Mediterranean diet and others like it have been extensively linked to reducing the risk of disease, cognitive decline, and premature death. Now a new study provides more evidence that this choice of foods can protect against dementia – as well as giving us some clues as to why. A team from Rush University Medical Center in Chicago wanted to look specifically at the MIND (Mediterranean-DASH Intervention for Neurodegenerative Delay) diet, which combines elements of the Mediterranean diet with the DASH (Dietary Approaches to Stop Hypertension) diet. That's a lot of acronyms, but it essentially means lots of vegetables, whole grains, fish, and poultry, and not so much dairy, red meat, and fried food. Related: The researchers investigated links between this balance of food items and hippocampal sclerosis – a condition linked to dementia and Alzheimer's, where neurons die off in the brain's hippocampus. Analyzing the postmortem brains of 809 people for whom diet information had been logged for several years before their death, the study found that those who stuck closest to the MIND diet were less likely to show signs of hippocampal sclerosis. "These findings suggest that consuming a healthy diet, such as the MIND diet, may decrease the likelihood of hippocampal sclerosis and may support hippocampal health," write the researchers in their published paper. The diet's impact on dementia risk has been well established by prior research. This latest study offers fresh insight into a significant part of the reason why that link is there: the foods in the MIND diet appear to protect the hippocampus in particular. Crucial to remembering, learning, and navigating, damage to the hippocampus is closely tied to dementia. While not everyone with hippocampal sclerosis has dementia, or vice versa, there's a significant overlap between the two conditions. The research accounted for a variety of demographic and genetic factors, but isn't enough to prove direct cause and effect. What it does show, together with earlier studies, is a strong probability that dementia risk is to some extent affected by what we eat. "To our knowledge these are the first findings in human studies to report that the association of diet and dementia is partially mediated by hippocampal sclerosis," nutrition epidemiologist Puja Agarwal told Hannah Millington at Newsweek. It's not clear how hippocampal sclerosis gets started, but scientists are continuing to discover more about it, and its connections to dementia. It's not the first time it's been shown that the health of this part of the brain could be affected by diet. Future studies may endeavor to understand why this link exists. It's possible that the anti-inflammatory and antioxidant effects of the foods in the MIND diet are helping to guard the brain's neurons from damage in some way. "To further understand the mechanisms linking diet and nutrients with the overall brain health, investigating diet's relationship with other biomarkers of neuroinflammation and oxidative stress in the brain will be critical," write the researchers. The research has been published in JAMA Network Open. Related News A Signal of Future Alzheimer's Could Hide in The Way You Speak Something Inside Your Gut Could Be Like a Natural Ozempic New Vaccine For Two Deadly Cancers Shows Promise in Clinical Trial Solve the daily Crossword
