Delay of more than 42 days for breast cancer surgery raises death risk for certain subtypes, study finds

Patients with certain subtypes of breast cancer may face a higher risk of death from the cancer if they wait more than 42 days after diagnosis to have surgery, according to newly published research from the University of Oklahoma.

The research team was surprised that the subtypes of breast cancer most affected by delayed surgery were those with the best prognosis: hormone receptor-positive breast cancers, meaning the cancer uses estrogen or progesterone to grow, and HER2-negative cancers, which do not have high levels of the HER2 protein that is associated with more aggressive cancer growth.

These subtypes, whose initial treatment is surgery, tend to grow more slowly. But when surgery was delayed in the study, patients’ risk of death from the cancer increased exponentially.

The risk began to increase at 42 days without surgery, and by 60 days, the patient’s risk of death was 21% times higher. By 90 days, the risk was 79% times higher, and by 120 days, the risk was 183% higher.

In contrast, hormone receptor-negative and “triple negative” subtypes, which are aggressive and invasive, changed very little during treatment delays.

“This is an important finding because 42 days can go by very quickly, but it’s also concerning because recent studies show that both the frequency and length of delay are increasing,” said lead author Takemi Tanaka, Ph.D., a professor of pathology in the OU College of Medicine. The study is published in the journal Breast Cancer Research.

Many factors can cause surgery delays, Tanaka said. The diagnosis and preoperative process can take several days, and patients may have work or family obligations that further delay the surgery date. Some may want a second opinion, and other women of childbearing age may want to pursue egg preservation (if they will undergo chemotherapy after surgery), so they can have a baby in the future. All are important considerations, she said.

“In 2022, the Commission on Cancer recommended that most women with breast cancer undergo surgery within 60 days. That was a major victory, but some women may need to have surgery sooner than 60 days,” Tanaka said. “And while we want people to understand the risk of delaying treatment, we also want them to have time to pursue egg preservation or get a second opinion.”

Researchers have several hypotheses as to why treatment delay increases the risk of death in these particular subtypes of breast cancer. One is that, because they are slower-growing, they have more room for change, unlike cancers that are already invasive. Another hypothesis focuses on the biopsy, which appears to cause an inflammatory response that may fuel tumor growth. In a publication last year, Tanaka showed that nonsteroidal anti-inflammatory drugs (NSAIDs) can suppress inflammation in a mouse model of breast cancer after biopsy.

Research in this area has been ongoing. In 2020, Canadian researchers analyzed 34 studies on 17 types of cancer and found that treatment delay was a critical contributing factor to risk of death in several types of solid tumors, notably a 6% to 8% increased risk for each four-week delay in treatment.

However, Tanaka’s research is believed to be the first to study whether all breast cancer patients have an equal risk of death, or if the risk differs among subtypes. Importantly, she also measured whether patients died specifically from their breast cancer. Other studies have looked at overall survival, which includes causes of death other than cancer.

Tanaka’s new study also both confirms and builds on her previous study showing 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. There was a 47% likelihood of tumor upstaging for patients who underwent surgery beyond 90 days.

In addition, her previous study used data from the National Cancer Database, a hospital-based database that collects cancer data from across the nation. For the current study, she used data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database, which is more representative of the population, she said.

Further study is warranted, Tanaka said, and she will soon launch a clinical trial on the OU Health Sciences campus in Oklahoma City to seek more answers about how treatment delay contributes to an increased risk of death.

Patients with certain subtypes of breast cancer may face a higher risk of death from the cancer if they wait more than 42 days after diagnosis to have surgery, according to newly published research from the University of Oklahoma.

The research team was surprised that the subtypes of breast cancer most affected by delayed surgery were those with the best prognosis: hormone receptor-positive breast cancers, meaning the cancer uses estrogen or progesterone to grow, and HER2-negative cancers, which do not have high levels of the HER2 protein that is associated with more aggressive cancer growth.

These subtypes, whose initial treatment is surgery, tend to grow more slowly. But when surgery was delayed in the study, patients’ risk of death from the cancer increased exponentially.

The risk began to increase at 42 days without surgery, and by 60 days, the patient’s risk of death was 21% times higher. By 90 days, the risk was 79% times higher, and by 120 days, the risk was 183% higher.

In contrast, hormone receptor-negative and “triple negative” subtypes, which are aggressive and invasive, changed very little during treatment delays.

“This is an important finding because 42 days can go by very quickly, but it’s also concerning because recent studies show that both the frequency and length of delay are increasing,” said lead author Takemi Tanaka, Ph.D., a professor of pathology in the OU College of Medicine. The study is published in the journal Breast Cancer Research.

Many factors can cause surgery delays, Tanaka said. The diagnosis and preoperative process can take several days, and patients may have work or family obligations that further delay the surgery date. Some may want a second opinion, and other women of childbearing age may want to pursue egg preservation (if they will undergo chemotherapy after surgery), so they can have a baby in the future. All are important considerations, she said.

“In 2022, the Commission on Cancer recommended that most women with breast cancer undergo surgery within 60 days. That was a major victory, but some women may need to have surgery sooner than 60 days,” Tanaka said. “And while we want people to understand the risk of delaying treatment, we also want them to have time to pursue egg preservation or get a second opinion.”

Researchers have several hypotheses as to why treatment delay increases the risk of death in these particular subtypes of breast cancer. One is that, because they are slower-growing, they have more room for change, unlike cancers that are already invasive. Another hypothesis focuses on the biopsy, which appears to cause an inflammatory response that may fuel tumor growth. In a publication last year, Tanaka showed that nonsteroidal anti-inflammatory drugs (NSAIDs) can suppress inflammation in a mouse model of breast cancer after biopsy.

Research in this area has been ongoing. In 2020, Canadian researchers analyzed 34 studies on 17 types of cancer and found that treatment delay was a critical contributing factor to risk of death in several types of solid tumors, notably a 6% to 8% increased risk for each four-week delay in treatment.

However, Tanaka’s research is believed to be the first to study whether all breast cancer patients have an equal risk of death, or if the risk differs among subtypes. Importantly, she also measured whether patients died specifically from their breast cancer. Other studies have looked at overall survival, which includes causes of death other than cancer.

Tanaka’s new study also both confirms and builds on her previous study showing 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. There was a 47% likelihood of tumor upstaging for patients who underwent surgery beyond 90 days.

In addition, her previous study used data from the National Cancer Database, a hospital-based database that collects cancer data from across the nation. For the current study, she used data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER)-Medicare-linked database, which is more representative of the population, she said.

Further study is warranted, Tanaka said, and she will soon launch a clinical trial on the OU Health Sciences campus in Oklahoma City to seek more answers about how treatment delay contributes to an increased risk of death.