What originally drew you to oncology (or specifically, breast and colorectal cancers), and how has your perspective evolved over the course of your career?

My interest in oncology developed during my internal medicine internship and residency at Baylor College of Medicine in Houston. Coming out of medical school, the one specialty I was certain I would not pursue was medical oncology. Prior to beginning the internship, Baylor asked us to rank our areas of interest to help guide subspecialty service assignments. I ranked oncology last—so, of course, I was assigned to that service.

During the month-long inpatient rotation, it became evident that available therapies for most solid cancers were woefully inadequate. However, I was drawn to the important role of multicenter, randomized phase III clinical trials—largely funded by the National Cancer Institute at that time—in providing a participatory mechanism for improving treatment outcomes for solid tumors, particularly early breast cancer.

I decided to request the oncology service during my residency years, which included outpatient exposure, especially in the care of patients with breast cancer. My early career plan was to become a community oncologist in my hometown of Houston, so after completing six months as chief resident in medicine at the Houston VA Hospital, I remained at Baylor for my medical oncology fellowship.

During my fellowship, my outpatient experience and my interest in breast cancer continued to grow. I was particularly drawn to the landmark phase III trials conducted by the National Surgical Adjuvant Breast and Bowel Project (NSABP), headquartered at the University of Pittsburgh under the leadership of Dr. Bernard Fisher. During the final months of my fellowship, the annual meeting of the American Society of Clinical Oncology was held in Houston, which allowed me to attend. I was immediately struck by the collaborative culture of the NCI-sponsored cooperative groups, which enabled community oncologists to bring important clinical trials developed by the groups to their patients.

I realized I needed to practice in an environment where clinical trials were integrated into routine patient care. I was fortunate that a breast oncologist was retiring from a large multispecialty clinic in central Texas—the Scott and White Clinic, a founding member of the Southwest Oncology Group,  so the clinic was recruiting a breast medical oncologist to take over her practice. Once there, I was given the opportunity to become a member of the NSABP.

Over my career, I became increasingly interested in the design, conduct, and analysis of NSABP trials, guided by recognition of the limitations of existing standard therapies observed in my clinical practice and the potential for new therapies developed in advanced breast cancer to improve outcomes in early-stage disease.

What scientific questions or areas of inquiry are currently at the forefront of your work?

I have been fortunate to actively participate in the development and clinical evaluation of increasingly effective systemic therapies administered before and after surgery—neoadjuvant and adjuvant therapy—across the major subtypes of “early breast cancer”.  Early breast cancer refers to newly diagnosed disease confined to the breast and sometimes regional lymph nodes by standard staging. We administer drug therapy because many patients harbor occult, undetectable micrometastatic disease that may later grow and result in recurrence.

We currently face several challenges in continuing to improve outcomes in early breast cancer. The first is a “problem of plenty”: we have an increasing number of effective therapies that can be used in combination or sequentially, but their use is associated with increasing toxicity and cost while providing smaller absolute reductions in risk for recurrence.

We routinely administer our most active systemic therapies in aggressive breast cancer subtypes prior to surgery, allowing us to determine whether detectable cancer has been eliminated. If no cancer remains, patients have a low risk of recurrence, and don’t require further therapy. However, if residual cancer is present, they are at increased risk and benefit from escalated therapy that reduces that risk.

The second challenge is our inability to determine whether post-surgical therapy is effective for an individual patient. Clearance of detectable circulating tumor DNA (ctDNA) during treatment has shown promise in identifying patients who may do well with less therapy versus those who require more intensive treatment. The key to success will be technical development alongside clinical validation of highly sensitive and specific ctDNA assays. Demonstrating clinical utility of ctDNA-based assays remains a major area of interest.

How do you see the role of clinical trials evolving, especially in breast oncology?

Clinical trials will remain foundational for evaluating the efficacy and toxicity of new cancer therapies and for generating the comparative data needed to guide adoption into routine care.

Phase I studies must be conducted first to evaluate investigational therapies as single agents, followed by rational combination studies to understand efficacy, optimal scheduling, interactions, and toxicity. Phase II studies assess activity in specific tumor types and subtypes and provide the critical data needed to justify definitive phase III trials.

How do you translate long-term survival data from clinical trials (like KATHERINE) into how you guide patients in real-world clinical decision-making?

Positive results from adequately powered, well-designed phase III trials that address clear unmet clinical needs—such as the KATHERINE trial—can have an immediate impact on real-world patient care.

For more than a decade prior to KATHERINE, it was well established that patients with HER2-positive early breast cancer who received neoadjuvant therapy and had no residual disease at surgery had a low risk of recurrence. However, those with residual invasive cancer faced a substantial recurrence risk with an unmet need for escalated therapies with different mechanisms of action.

Trastuzumab emtansine (T-DM1), the first antibody–drug conjugate approved for metastatic breast cancer, had demonstrated remarkable activity when standard therapies failed. Company-sponsored trials in early breast cancer explored whether T-DM1 could replace standard therapies, which were effective and well tolerated for many early-stage patients. These studies showed T-DM1 was no more effective than standard therapies.

In contrast, the hypothesis of KATHERINE was that standard therapy should be given first to identify patients whose cancers were eradicated, reserving T-DM1 for those with residual disease. The trial reduced recurrence risk in the subset of patients with residual disease by approximately 50% and mortality risk by one-third in these high-risk patients, establishing a new global standard of care.

Without sharing any unpublished or embargoed data, could you speak to the key questions the DESTINYBreast-05 Phase III trial is aiming to answer and what its potential implications might be for the future of HER2-positive breast cancer treatment?

DESTINY-Breast05 was a follow-up to KATHERINE and addressed the unmet need among subsets of patients who remained at high risk despite receiving T-DM1. Patients presenting with bulky tumors, extensive nodal involvement, or residual nodal disease after neoadjuvant therapy still faced a 25–35% recurrence risk.

Trastuzumab deruxtecan (T-DXd), a newer antibody–drug conjugate, demonstrated remarkable activity in metastatic HER2-positive breast cancer no longer controlled with T-DM1. This provided a strong rationale to compare T-DXd with T-DM1 in high-risk early-stage patients. DESTINY-Breast05 recently demonstrated a 53% reduction in recurrence risk with T-DXd and was recently published in the New England Journal of Medicine, suggesting it will replace T-DM1 for these patients.

What are your goals/vision for the Division? 

With the recent recruitment of Dr. John Byrd as Director of the Hillman Cancer Center, an NCI-designated Comprehensive Cancer Center, our primary goal is to recruit outstanding translational clinical investigators across the Division’s sections, along with well-funded physician-scientists.

What key strengths do you see in Pitt’s oncology program?

The Cancer Center Support Grant provides critical infrastructure to support basic, translational, clinical, and population science research within multidisciplinary programs. It promotes collaboration among scientists, clinicians, nurses, biostatisticians, bioinformaticians, and others focused on addressing the enormous health and economic burden of cancer.

Members of the Division also benefit greatly from being part of the Department of Medicine, which supports career development, education, and collaboration across its many outstanding sections.

Are there interdisciplinary collaborations you’re especially excited to build or expand?

Immunology and immuno-oncology are major strengths at Pitt and Hillman. Recent recruitment of new division chiefs in Pulmonary, Gastroenterology, Renal Medicine, and other areas present new collaborative opportunities. The Aging Institute also offers tremendous potential in geriatric oncology.

How does the translational research done here at Pitt affect patient care?

Translational research is critical for understanding mechanisms of therapeutic activity, resistance, and off-target effects. It allows hypotheses from basic science to be tested clinically – “bench to bedside” – while also taking unexpected clinical observations back to the laboratory.

Is there a particular patient story or research milestone that has stayed with you throughout your career?

The presentation of the initial KATHERINE results at the 2018 San Antonio Breast Cancer Symposium, followed by publication in The New England Journal of Medicine as senior author, stands out as a major milestone.

What advice would you give to emerging clinicians and scientists considering a career in oncology?

Medical oncology and malignant hematology have increasingly become therapeutic disciplines. Collaboration among basic, translational, and clinical investigators—and the willingness of patients to participate in clinical trials—has driven the remarkable progress in oncology during my career.

While challenges remain, the privilege of supporting individuals facing life-threatening illnesses and contributing to continued advancement in cancer care is extraordinary.

Recent New England Journal of Medicine publications