Study Demonstrates Importance of Prompt Surgery for Patients With Breast Cancer

According to a new study by researchers and clinicians at OU Health Stephenson Cancer Center, the time between a person’s diagnosis with breast cancer and surgery to remove the tumor is much more important than previously understood. The study, published in the Annals of Surgical Oncology, provides evidence of importance to physicians and patients alike: Waiting more than two months to have breast cancer surgery may lead to a larger tumor size and spread of the cancer to the lymph nodes.

To conduct the study, the research team analyzed seven years of patient outcomes from the National Cancer Database. They intentionally chose an early-stage breast cancer, called T1N0M0, which is known for its small tumor size and good prognosis. Although many factors influence when surgery is scheduled, the team was searching for the answer to a specific question: What is the safe amount of time to wait before having the tumor removed?

“The field of medicine does not really have specific guidelines about how long is a safe window of time,” said Stephenson Cancer Center researcher Takemi Tanaka, Ph.D., an associate professor in the Department of Pathology. “We wanted to know the time frame of when the disease progressed.”

The answer was, in part, surprising. Researchers discovered that patients with a hormone receptor-positive breast cancer who didn’t receive surgery until 61 to 90 days after diagnosis were 18% more likely to have their tumor size upstaged (changed to a more serious stage) compared to patients who received surgery within the first 30 days after diagnosis. For patients with hormone receptor-positive cancers who waited beyond 90 days for surgery (a small fraction of patients), there was a 47% likelihood of tumor size upstaging compared to patients who underwent surgery within 30 days. The time frame for lymph node status, which indicates localized spread of the cancer, was also significant. After 91 days, patients with hormone receptor-positive breast cancer were 35% more likely to progress from no cancer in the lymph nodes to having cancerous nodes removed during surgery.

The surprising element was the hormone receptor positivity status. Generally, patients with hormone receptor-positive breast cancer (meaning the cancer uses estrogen or progesterone to grow) have better outcomes than those with hormone receptor-negative breast cancers, because their growth rate is known to be much slower. “It takes many years to develop breast tumors,” Tanaka said. “For a slow-progressing tumor like hormone receptor-positive disease, the speed of disease progression in a range of 60-90 days after diagnosis was much faster than we thought, and a concept of a safe time window is becoming more crucial during the COVID-19 pandemic.”

“Two-thirds of breast cancers are estrogen-positive; that’s the most common form of breast cancer,” said William Dooley, M.D., surgical oncologist at Stephenson Cancer Center and a professor in the Department of Surgery. “It is that subgroup of breast cancer where we’ve been able to avoid chemotherapy in the majority of cases by giving anti-estrogen therapy over the past 15 to 20 years. That’s why those patients were thought to have a better prognosis. As this study demonstrates, that may not quite be true – we still need to remove the tumor fairly promptly. Unfortunately, over the past two decades, the time between diagnosis and surgery has actually increased each year.”

For patients with hormone receptor-negative breast cancers, the research team also observed a time-dependent disease progression trend, although it was not statistically significant. “When we find breast cancer, we need to act with deliberation moving forward, and make sure there aren’t barriers to having care done,” Dooley said. “The most important thing for patients with hormone receptor-positive breast cancer is that the cancer be removed completely. Other parts of the treatment may be less time-dependent, but removing the tumor needs to be first and foremost in everyone’s mind.”

The research team is continuing the study to determine the long-term effect of surgical delays on survival, as well as potential causes of delay, including barriers to care among marginalized populations. They are also investigating biologic explanations for disease progression before surgery. The study is an interdisciplinary project that involves students, post-doctoral fellows and professionals from several disciplines, including Tanaka’s basic science/epidemiology research expertise and Dooley’s clinical focus. Three students have driven the project, including OU College of Medicine students Natalie Hills and Rachel Davis, and Macall Leslie, a data analyst in Tanaka’s lab who is graduating soon with a master of public health degree from Johns Hopkins University.

By analyzing patient outcomes in the National Cancer Database, the researchers had access to about 70% of the U.S. population with a cancer diagnosis. Because the database contains information only from facilities accredited by the Commission on Cancer, the 30% of diagnoses that are uncaptured likely represent patients who are treated at under-resourced facilities and potentially experience greater delays. In addition, American Indians are not well-represented in the database.

“We are greatly concerned about those medically underserved populations this study did not catch,” Leslie said. “It is important that healthcare professions highlight medically underserved populations who are likely to have greater trouble accessing care in a timely manner.”