Rethinking Endocrine Therapy in ER-Positive Breast Cancer
By: Soumya Shashikumar, MBiotech
Interviewee: Steven Quay, MD, PhD, Founder and CEO, Atossa Therapeutics
Rethinking Endocrine Therapy in ER-Positive Breast Cancer
By: Soumya Shashikumar, MBiotech
Interviewee: Steven Quay, MD, PhD, Founder and CEO, Atossa Therapeutics
Over the past several decades, advances in screening, surgery, radiation and systemic therapies have transformed breast cancer from a frequently fatal diagnosis into, for many patients, a chronic and increasingly survivable condition.
In an interview with Xtalks, Dr. Steven Quay, founder and CEO of Atossa Therapeutics, a Seattle-based biopharmaceutical company focused on breast cancer prevention and treatment, discussed how advances in endocrine therapy, prevention and trial design are reshaping care.
A physician-scientist, Dr. Quay has authored more than 400 publications across oncology, medical imaging, infectious diseases and drug delivery.
Dr. Quay spoke about how these scientific, clinical and technological shifts are influencing the development of endocrine therapies for breast cancer.
Dr. Quay noted that in estrogen receptor (ER)-positive breast cancer, which accounts for roughly 80% of cases, five-year survival now approaches 90% to 95%. As outcomes have improved, he explained, the central challenges in care and drug development are increasingly defined by long-term tolerability, treatment adherence and opportunities for earlier intervention.
In the interview, he spoke about Atossa Therapeutics’ focus on quality of life in ER+ disease, its emphasis on prevention and early-stage risk reduction, the role of adaptive platform trials such as RECAST and how tools such as generative AI may help shorten the path from discovery to clinical application.
Improving Tolerability in Long-Term Endocrine Therapy
“There’s two approaches that we have to the treatment of breast cancer that differentiate Atossa Therapeutics,” began Dr. Quay.
He first pointed to the changing context of ER-positive breast cancer, where long-term survival is now common and attention increasingly turns to how patients experience years of endocrine therapy. While current treatments are effective at suppressing estrogen signaling and reducing recurrence risk, they are also associated with side effects that can significantly affect daily life, including joint pain and vasomotor symptoms such as hot flashes and night sweats.
Dr. Quay emphasized that these effects are not merely inconvenient but can influence whether patients remain on therapy. A meaningful proportion of women discontinue treatment because of toxicity, which can in turn increase the risk of recurrence. This, he explained, places tolerability alongside efficacy as a central consideration in endocrine drug development.
In discussing their next-generation selective estrogen receptor modulator (SERM), he highlighted the importance of blinded, placebo-controlled trials in understanding side-effect profiles.
“So point one is we want to treat the cancers as aggressively in terms of the cancer killing, but in a gentler way, so quality of life has improved.”
This emphasis on preserving anticancer intent while reducing the burden of long-term therapy formed the first of the two main differentiators Dr. Quay outlined.
“There’s 39 million mammograms a year in the United States… in about 10 million of those 39 million women, there is a condition called high density, which can lead to future cancers.”
— Steven Quay, MD, PhD, Founder and CEO, Atossa Therapeutics
“There’s 39 million mammograms a year in the United States… in about 10 million of those 39 million women, there is a condition called high density, which can lead to future cancers.”
— Steven Quay, MD, PhD, Founder and CEO, Atossa Therapeutics
Prevention, Breast Density and Unmet Needs
Dr. Quay described prevention as the second main way Atossa seeks to differentiate itself, contrasting it with what he sees as a broader tendency in oncology to focus far more on treating established disease than on reducing the likelihood that cancer develops in the first place. He noted that, at a national level, only a small fraction of research resources are directed toward prevention, while the vast majority are allocated to treatment.
“The second focus is that Atossa…we really want to focus on preventing breast cancer as opposed to treating it.”
Within this prevention framework, he pointed to breast density as a key biological and clinical factor.
“There’s 39 million mammograms a year in the United States… in about 10 million of those 39 million women, there is a condition called high density, which can lead to future cancers," said Dr. Quay.
Dense breast tissue is associated with an increased risk of future breast cancer and can also reduce the sensitivity of mammography. He referenced a study conducted in Sweden in which their next-gen SERM was evaluated for its ability to reduce mammographic density, noting that changes in density are known to correlate with subsequent cancer risk and that, in that setting, the side-effect profile was similar to placebo.
He then linked this to population-level screening, observing that while mammography uptake in the US is relatively high, a substantial number of women are found to have dense breasts and may benefit from additional imaging, such as ultrasound or MRI, to improve early detection. From his perspective, access to such follow-up imaging represents an important remaining gap in prevention and risk reduction.
Dr. Quay also noted that prevention and early intervention strategies do not address all forms of breast cancer. He described triple-negative breast cancer in particular as more aggressive and lacking established molecular targets, leaving chemotherapy as the mainstay of treatment. While work in this area remains at a research stage, he characterized it as a clear unmet need, where identifying underlying drivers could enable more targeted approaches in the future.
Designing Studies That Reflect Real-World Biology
When discussing how Atossa Therapeutics designs its clinical trials, Dr. Quay emphasized the importance of enrolling patient populations that reflect the biological and demographic diversity seen in routine practice. For ER-positive disease, he described an “all-comers” approach, encompassing both women and men, as well as patients across racial and ethnic backgrounds. Although male breast cancer is uncommon, he noted that it shares the same hormone-driven biology and is therefore included in adult breast cancer trials.
He also highlighted endocrine status as a critical design variable. In postmenopausal women, low levels of estrogen produced through peripheral conversion continue to drive tumor growth and can often be suppressed with receptor blockade alone.
In premenopausal women, however, ovarian feedback mechanisms can increase estrogen production when the receptor is blocked, creating a different therapeutic context and, in some cases, necessitating additional interventions such as ovarian function suppression.
Genetic background was another consideration he raised. While most ethnic groups do not show major biological differences in breast cancer, founder mutations affecting DNA repair in certain populations, such as individuals of Ashkenazi Jewish descent, substantially alter risk and inform both screening and trial stratification.
Adaptive Platform Trials and Collaborative Models
When discussing the RECAST platform trial, Dr. Quay first outlined the rationale for adopting adaptive study designs within this program. RECAST is a multi-arm, Phase II, randomized, neoadjuvant platform trial designed to help identify which patients with hormone receptor-positive ductal carcinoma in situ (DCIS) may be appropriate candidates for active surveillance and to evaluate whether novel endocrine therapies could safely expand the group of patients who might avoid surgery.
To support these goals, he explained, the trial is built on Bayesian statistical methods that allow investigators to analyze incoming data continuously and adapt the study as it evolves, rather than waiting until the end of a fixed protocol to draw conclusions. This approach, he said, enables smaller, more targeted trials that generate insights in real time.
DCIS carries a substantial risk of progressing to invasive cancer over time, and Dr. Quay described the trial as exploring whether pharmacologic treatment combined with close imaging follow-up could offer an alternative to immediate operative intervention. As lesions are monitored longitudinally, the question becomes whether some patients might be safely observed rather than proceeding directly to additional surgery.
Dr. Quay also explained that RECAST functions as a multi-sponsor platform, in which several investigational agents are evaluated in parallel using blinded, rotating arms. Each company has access to its own data while remaining blinded to the performance of other therapies, allowing efficient, parallel testing within a shared trial infrastructure.
He added that the platform model enables operational efficiencies through standardized protocols and processes. This is shortening timelines for steps such as site activation and regulatory review compared with traditional stand-alone trials.
Finally, Dr. Quay placed RECAST within a broader ecosystem of collaboration among academia, industry and government.
Academic centers provide clinical leadership and patient access, industry contributes therapeutic candidates and regulatory expertise and organizations such as the NIH support the foundational research needed to understand disease biology and identify new targets.
In his view, this three-part partnership underpins both the RECAST model and the broader advancement of oncology trial design.
“So point one is we want to treat the cancers as aggressively in terms of the cancer killing, but in a gentler way, so quality of life has improved.”
— Steven Quay, MD, PhD, Founder and CEO, Atossa Therapeutics
“So point one is we want to treat the cancers as aggressively in terms of the cancer killing, but in a gentler way, so quality of life has improved.”
— Steven Quay, MD, PhD, Founder and CEO, Atossa Therapeutics
Global Trials, Standards of Care and the Cost of Development
When asked about conducting global clinical trials, Dr. Quay first pointed to the practical need for international enrollment to complete studies within a reasonable timeframe.
For many indications, he said, access to sufficient patient numbers requires running trials across multiple countries, even as standards of care vary between regions, with the US typically operating at a high clinical benchmark.
He noted that this variability can complicate trial expectations. However, it can also allow patients in other countries to access therapies and clinical practices that may not yet be widely available locally. In his view, global development not only supports timely study completion but also helps lay the groundwork for broader access once a therapy is approved.
Dr. Quay described the process of bringing a new drug to market as increasingly expensive and resource-intensive, with costs rising well beyond earlier historical norms.
“A new drug crossed the $1 billion cost level probably 15 years ago, and it’s now approaching multiple billions of dollars of cost before you sell your first pill.”
He added that, alongside complex regulatory pathways, the structure of insurance-based reimbursement can further complicate how value and cost are balanced at a system level. The result, he said, is that modern medicine is delivering unprecedented clinical benefit, but at a price that raises concerns about long-term sustainability.
From his perspective, one of the few areas where sponsors can directly influence this equation is the efficiency of drug development and approval. By pursuing more streamlined clinical programs, sponsors may help limit the costs ultimately embedded in new therapies.
Generative AI and the Future of Breast Cancer Drug Development
In reflecting on what most excites him about the future of breast cancer research, Dr. Quay pointed to the growing role of generative AI and large language models in drug development and data analysis. He described these tools as enabling analyses that are far beyond what can be done by the human brain alone, particularly when examining complex interactions across thousands of drugs and biological pathways.
He gave an example from work conducted with Insilico Medicine, where he asked which of approximately 4,000 FDA-approved drugs might best work together with endoxifen in more aggressive forms of breast cancer. According to Dr. Quay, this involved analyzing each drug across roughly 2,000 pathways, an exercise that would not have been feasible using traditional approaches. After several weeks, the system identified one compound as showing the strongest potential synergy: abemaciclib, a drug made by Lilly, which he said acts through pathways different from those targeted by endoxifen.
He noted that what stood out was not only the scale of the analysis, but the speed with which the insight moved into clinical testing. Roughly 100 days after the computational work was completed, the combination was being evaluated by Dr. Laura Esserman, the director of the Carol Franc Buck Breast Care Center at the University of California, San Francisco School of Medicine, and her team within the I-SPY clinical trial network, a process he contrasted with the much longer timelines that have historically characterized oncology drug development.
“We compressed a four or five-year process into 130 days.”
Dr. Quay said he sees this type of AI-enabled analysis as having the potential to influence many stages of drug development, from identifying promising combinations to accelerating the transition from computational insight to clinical evaluation.
In our interview, Dr. Quay reflected on how breast cancer care and drug development are evolving. The central shift is not only toward longer survival, but toward therapies that are both effective and easier for patients to live with.
ABOUT Steven Quay
Steven Quay, M.D., Ph.D., is a physician-scientist, entrepreneur, and recognized authority on the intersection of biomedical innovation, national security, and global biosecurity. He is the founder and CEO of Seattle-based Atossa Therapeutics, Inc. (Nasdaq: ATOS), a biopharmaceutical company developing novel therapeutics for the prevention and treatment of breast cancer.
In August 2025, Dr. Quay was appointed Senior Fellow at the Hudson Institute, where he leads policy research on The National Security Implications of the Convergence of General Artificial Intelligence and Biotechnology. His portfolio addresses emerging risks from AI-enabled synthetic biology, including dual-use research, AI-driven pathogen engineering, and supply chain vulnerabilities, while advancing governance frameworks to detect, deter, and defend against next-generation biological threats.
Dr. Quay earned his M.S., Ph.D., and M.D. from the University of Michigan, trained at MIT with Nobel Laureate H. Gobind Khorana, completed his residency at Harvard-Massachusetts General Hospital, and served on the faculties of Harvard Medical School and Stanford University School of Medicine. He is a Distinguished Alumnus of the University of Michigan.
Dr. Steven Quay has an expansive body of work characterized by 404 contributions to medical imaging, oncology, infectious diseases, and drug delivery, placing him in the top 1% of scientists worldwide. His research on intranasal drug delivery, published in 2007, is highly influential, cited 846 times, advancing the field of non-invasive therapeutics. He has also pioneered work in the development of the first nonionic, gadolinium-based contrast agents for MRI, with 14 US patents and foundational studies like his 1990 paper cited 641 times.
His 1981 discovery, with Harold Dvorak, et al., that tumor-shed vesicles drive coagulation, fibrin deposition, and neovascularization, describing them as a “tumor cocoon,” has been cited 393 times and has shaped cancer treatments, leading to the first drug targeting tumor neovascularization, Avastin® (bevacizumab). The International Society of Extracellular Vesicles, with over 2,000 researchers worldwide, was formed to extend the role of exosomes, as the vesicles he discovered are now called, in health and disease.
His patents, such as those for ultrasound contrast agents, autism, Parkinson’s Disease, and cystic fibrosis treatments, and innovative drug formulations, highlight his role in translating basic research into practical medical applications. With over 12,300 citations to his publications and an h-index of 59, Dr. Quay’s work documents a career dedicated to enhancing diagnostic and therapeutic methodologies in medicine. These metrics underscore his contributions to medical research, particularly in oncology and infectious diseases.
He is the author of two Amazon Best Seller books related to the COVID-19 Pandemic and has testified before the U.S. Congress on medical research and healthcare national policy issues, as well as advised the US State Department on complex medical questions related to national security.
Dr. Steven Quay’s media coverage highlights his significant contributions to public health discussions, garnering 16.6 million online views and securing 233,000 social media shares across a variety of high-profile outlets, including two Wall Street Journal Op-Eds. The collection features 224 distinct articles and interviews, showcasing his expertise on topics such as pandemic preparedness, biomedical research, and the ethics of high-risk scientific endeavors. With a reach spanning international audiences, this coverage underscores Dr. Quay's role as a trusted voice in translating complex scientific issues into actionable insights. A link to his Electronic Press Kit can be found here.
He founded six startups, invented seven FDA-approved pharmaceuticals, and has 94 US patents and 1070 world-wide patent filings for inventions in twenty-two different fields of medicine. He has been recognized as an Entrepreneur of the Year by Ernst & Young for two companies. The medicines he has invented have been used by over 80 million people worldwide. He is a member of the American Association for Cancer Research to help pursue his current passion is the prevention of the two million yearly breast cancer cases worldwide. A TEDx talk he delivered on breast cancer prevention has been viewed over 229,000 times.
Dr. Quay’s work bridges the frontiers of biotechnology and artificial intelligence to shape resilient, ethical, and secure innovation in an era of rapidly converging technologies.