Title:Rewriting survival

A new era in breast cancer research and care

Fifty years ago, a breast cancer diagnosis meant a similarly aggressive path for nearly everyone: highly invasive surgery to remove as much tissue as possible—sometimes including not just the breast but the lymph nodes and chest muscle—often combined with toxic chemotherapy and radiation.

Those who survived typically lived with years of physical and psychological effects, including chronic pain and limited mobility, cognitive decline, lymphedema, anxiety about recurrence, and the lasting emotional toll of the physical changes to their bodies. The effects of these issues reverberated throughout families and communities of support.

Over the last half-century, Georgetown University’s Lombardi Comprehensive Cancer Center has been at the forefront of upending the “one-size-fits-all” approach through precision medicine research—part of a broader shift toward more individualized care that has transformed this landscape. Depending on the tumor type and stage of disease, some breast cancer patients can now avoid chemotherapy or surgery entirely, while others receive treatment tailored to their tumor’s specific profile.

“As a field, we have moved from a blunt approach to a much more nuanced, individualized approach—sparing people unnecessary toxicity and financial burden while maintaining excellent outcomes,” says Louis M. Weiner, director of Georgetown Lombardi and the MedStar Georgetown Cancer Institute, and professor of oncology at the School of Medicine. “That’s what our researchers are working towards: reductions in mortality and improved quality of life for patients who are real people with families and futures, not statistics.”

The arc of progress traces back to researchers such as Marc Lippman, a Georgetown professor of oncology whose groundbreaking work on estrogen receptors in the 1970s laid the foundation for targeted hormone therapies that have since saved countless lives. As a young researcher at the National Cancer Institute, Lippman and his colleague Gail Bolan developed a model of hormone-dependent human breast cancer with little preliminary data to guide them.

The discovery that estrogen fuels breast cancer growth opened the door to targeted therapies that now cure the majority of women diagnosed with the disease. Unlike chemotherapy, which indiscriminately kills all fast-growing cells—cancer cells along with hair follicles and nail cells, for example— targeted therapies are designed to disrupt the specific cellular machinery that drives the cancer itself.

“A remarkable aspect of this discovery is that it was met with a tsunami of opposition by people who couldn’t reproduce the study,” recalls Lippman. “When, eventually, our conclusions were shown to be entirely correct it provided a powerful impetus to our work.”

Lippman served as director of Georgetown Lombardi from 1988 to 2001, building one of the premier breast cancer programs in the country before leading major cancer centers at the University of Michigan and the University of Miami. He returned to Georgetown Lombardi in 2018, where he continues pursuing research on preventing cancer recurrence and reducing treatment toxicity.

“I’ve focused on this my entire career,” he says. “What makes me most proud is seeing the brilliant researchers who I had the privilege of mentoring go on to become leaders, at Georgetown and elsewhere.”

In the years of research that followed Lippman’s published findings, drugs like tamoxifen and others were developed and are now routinely used to block estrogen or the production of estrogen to treat breast cancer.

That early work in hormone receptors set the stage for today’s precision medicine approaches at Georgetown Lombardi, where researchers are working to refine treatments to spare patients unnecessary intervention while improving outcomes.

Leading through innovation

Breast cancer is still the most commonly diagnosed cancer among American women, accounting for nearly one in three new cancer diagnoses each year. Yet decades of advances in screening, treatment, and early detection have led to a boom in the survivor population. Today, the largest number of cancer survivors in the United States are breast cancer survivors, according to the American Cancer Society.

As the survivor population grows and ages, so does an urgent question: how do we fundamentally transform what it means to live with and beyond this disease?

“Our goal is to maximize both quantity and quality of life—giving patients with early-stage disease the best chance at cure without overtreating them, while helping those with advanced disease live well for as long as possible,” says Claudine Isaacs, associate director for clinical research and medical director of Georgetown Lombardi’s Fisher Center for Hereditary Cancer and Clinical Genomics Research.

Pursuing that goal requires a research enterprise with the scale and expertise to address breast cancer from every angle. As one of just 57 National Cancer Institute–designated Comprehensive Cancer Centers in the United States—a distinction Georgetown Lombardi first earned in 1974—the institution is required to meet rigorous standards across research, patient care, and community engagement.

Since its founding in 1970, Georgetown Lombardi’s impact has been sustained through breakthrough discoveries across multiple fronts.

One major area of progress has been developing more targeted treatments. Breast oncologist Sandra Swain, associate dean for research development at Georgetown University Medical Center, led the groundbreaking CLEOPATRA (CLinical Evaluation Of Pertuzumab And TRAstuzumab) trial that revolutionized treatment for HER2-positive metastatic breast cancer—one of the disease’s most aggressive forms.

By adding a third drug, pertuzumab, to the standard two-drug regimen, the research led to significantly improved survival outcomes and established a new standard of care used worldwide today. For patients with HER2-positive disease, this precision approach means powerful, life-extending treatment. For everyone else, it means avoiding toxic therapies that wouldn’t improve their chance of survival.

Other researchers have focused on minimizing treatment’s lasting physical toll. David Song, professor of plastic surgery, and chief medical officer and vice president of medical affairs for MedStar Georgetown University Hospital, pioneered lymphatic surgery techniques to reduce the risk of one of breast cancer treatment’s most debilitating long-term complications, lymphedema, which is painful swelling caused by the build up of lymphatic fluid. His team has also developed nerve-preserving approaches that maintain sensation after mastectomy, including nipple re-sensitization surgery.

Still others are working to improve outcomes at the population level. Marc Schwartz, associate director for population science at Georgetown Lombardi and co-director of the Fisher Center along with Isaacs, has helped pioneer approaches that have transformed genetic testing in mainstream cancer care.

His team led one of the first studies offering genetic testing to women at the time of breast cancer diagnosis to help guide treatment decisions—a practice now standard nationwide. Schwartz also conducted the largest telephone-based genetic counseling study ever, proving that phone counseling worked just as well as in-person sessions at a fraction of the cost. This breakthrough expanded access for people in rural areas and underserved communities, making vital genetic information available to far more patients and their physicians

“What makes us a comprehensive cancer center is excellence across multiple fronts—from the lab to the clinic to the community,” says Weiner. “Each breakthrough builds on decades of work, and together, they represent a fundamental transformation in how we treat this disease.”

Science takes a village

Georgetown Lombardi has built a research ecosystem that brings together clinicians, basic scientists, genetic counselors, population health experts, and patients—not just within its own walls, but through partnerships with institutions nationwide and globally. For Isaacs, this expansive collaborative approach is essential.

“Science takes a village—a large village,” Isaacs says. “It’s important to recognize where to lead and where we need to collaborate, because you don’t get answers from doing research in isolation.”

One example of a fruitful cross-disciplinary approach is work on chemotherapy-related cognitive changes, commonly known as “chemo brain.”

Jeanne Mandelblatt, director of the Georgetown Lombardi Institute for Cancer and Aging Research and professor of oncology and medicine at the School of Medicine, first discovered that women carrying a genetic variant associated with Alzheimer’s known as APOE4 were more likely to experience cognitive impairment following chemotherapy. She then partnered with William Rebeck, a professor of neuroscience, to explore this finding further in his lab.

“Through this collaboration, we’ve been able to replicate and extend findings to understand what parts of the brain are affected that we might target with treatments,” Mandelblatt says. “This is exciting because cognitive impairment is so common. We’re hopeful we will understand who experiences this really troublesome side effect and why.”

The work caught the attention of Lippman, whose expertise offered a new lens. When Lippman heard Mandelblatt present this finding, he had a realization: since the chemotherapy drugs in question don’t cross the blood-brain barrier, they must trigger inflammatory molecules elsewhere in the body that ultimately affect the brain.

He identified a key inflammation driver called RAGE (Receptor for Advanced Glycosylation End-products) as a potential culprit. Working with Barry Hudson, an associate professor of oncology, the team established that by inhibiting the expression of the RAGE protein, they could prevent cognitive decline in mice receiving chemotherapy. The work has now advanced to clinical trials led by Candace Mainor, a medical oncologist at MedStar Georgetown University Hospital.

Georgetown Lombardi’s commitment to collaboration extends to large multi-institutional clinical trials like I-SPY, where the center plays an active role alongside peer institutions internationally.

The trial’s innovative adaptive design allows multiple therapies to be evaluated simultaneously, using pre-surgical treatment as a “test drive” for personalized therapy. Over 15 years, the global trial has enrolled more than 2,500 patients and tested 25 new treatments. Clinicians use serial MRI scans to track tumor response in real time, tailoring treatment accordingly.

The trial’s ultimate goal, Isaacs explains, is “to provide each individual patient with the most personalized therapy that can be offered.” Several treatments first tested in the trial have subsequently earned FDA approval, including pembrolizumab for triple-negative breast cancer.

For Weiner, this commitment to collaborative science is central to Georgetown Lombardi’s identity and impact.

“Patients expect collaboration—not competition. Our common enemy is cancer,” he says. “We live that principle by pursuing high-impact partnerships that transform outcomes for women with breast cancer.”

Training tomorrow’s leaders

Sustaining this culture requires investing in the next generation of researchers. For Rebecca B. Riggins, professor of oncology and associate director of education and training at Georgetown Lombardi, developing future breast cancer researchers is about cultivating a mindset.

“We have to start early in the pipeline with modeling for students and trainees that breast cancer research is interdisciplinary,” she explains. “You don’t always know where the next big thing is going to come from, which is why we need to keep a holistic approach and think of research as a long- term investment.”

Georgetown’s Tumor Biology Ph.D. program, part of the Biomedical Graduate Education program, exemplifies this commitment by training scientists in the interdisciplinary approaches essential to advancing cancer research. More broadly, demonstrating the power of Georgetown Lombardi’s training ecosystem, Georgetown trainees have gone on to lead major breast cancer programs at premier institutions around the country, including Johns Hopkins’ Sidney Kimmel Comprehensive Cancer Center, Sandra and Edward Meyer Cancer Center at Weill Cornell Medicine, Harvard’s Dana-Farber Cancer Institute, and MD Anderson Cancer Center at the University of Texas, to name a few.

The commitment to training reaches even younger scholars. Working with KID Museum in Bethesda, Maryland, Riggins and Kenneth Tercyak, professor of oncology and co-lead of Georgetown Lombardi’s Cancer Prevention and Control Program, created the Young Scholars Program—an annual initiative offering middle and elementary school students hands-on experiences in STEM and cancer research.

“I think we really owe it to our community to engage everyone,” Riggins says. “Early exposure to exciting and meaningful science experiences needs to start as early in the learning process as possible.”

Closing the gap

For all the extraordinary progress in breast cancer treatment, Georgetown Lombardi’s researchers are clear-eyed about the gap between scientific achievement and equitable outcomes.

Black women face a 40% higher mortality rate from breast cancer than white women, despite having similar or lower incidence rates. This disparity persists across every molecular subtype and every stage of disease, underscoring inequities in access to care and other systemic variables that affect outcomes.

Even as treatment improves, disparities in screening access and health care navigation mean many women don’t benefit from these advances until the disease has progressed, according to Distinguished Professor Lucile Adams-Campbell, associate director for minority health and health disparities research and senior associate dean for community outreach and engagement.

The Ralph Lauren Center for Cancer Prevention at Georgetown Lombardi addresses this directly. Located in Ward 8 of the District, the center provides comprehensive navigation for early detection, through screening, diagnosis, treatment, and prevention. Patient navigators connect individuals to specialized care at MedStar Health and clinical trials at Georgetown Lombardi.

“The Ralph Lauren Center has enabled us to be more inclusive, which is central to our mission,” says Adams-Campbell, the center’s founding director. “There are now people from all over Washington, DC, including more people of color, coming to Georgetown for care.”

Adams-Campbell notes that not all minorities are underserved, and not everyone who is underserved is a racial minority. Recognizing this complexity, her team discovered that patients were significantly more likely to enroll in clinical trials upon receiving support for issues such as housing insecurity, food access, and financial hardship through Georgetown’s medical-legal partnership, the Cancer Legal Assistance and Well-being (Cancer LAW) project through Georgetown’s Health Justice Alliance program.

“When we address patients’ financial and social challenges, they are better able to make decisions that are good for their health,” she says.

Unanswered questions

Even as Georgetown researchers work to ensure existing advances reach everyone, significant scientific challenges remain. For example, resistance to endocrine therapies—drugs that target hormone receptors—plagues even the most successful treatments.

“In many cases, resistance—whether it’s after five years, 10 years, or maybe even longer—becomes a problem,” Riggins explains. “Why does this occur? And, importantly, is that ‘why’ something we can uniquely target?”

Some subtypes present their own stubborn mysteries. Lobular breast cancer, the second-most common subtype, has only recently gained focused attention. This tumor type is prone to late recurrence—even 20 years after initial diagnosis—long after many people think their risk is gone. Georgetown researchers, including Riggins, are working to understand the unique biology of lobular tumors and develop better imaging strategies for detection.

These are just two of many unanswered questions researchers are pursuing. Yet progress achieved over the past few decades in breast cancer demonstrates what’s possible. Between 1975 and 2019, breast cancer mortality decreased by 58%—dropping from about 48 to 27 deaths per 100,000 women. That translates to millions of lives saved, all because of research.

Finding answers to today’s research questions could save millions more lives and continue to positively impact survivors’ quality of life.

“Behind every breakthrough, every new therapy, there are real people,” Weiner says. “That’s what drives everything we do—ensuring those people get more time, and better time, with the people they love.”

Lauren Wolkoff is a communications consultant based in Washington, DC. She received her MA in Latin American Studies from Georgetown’s School of Foreign Service.