April 7, 2025, 9:10 am | Read time: 7 minutes
In Germany, breast cancer is one of the most common cancers in women — around 74,500 are newly diagnosed every year. In addition, more than 6,000 women are diagnosed with early-stage breast cancer, where the tumor has not yet spread to the surrounding tissue. Men are also affected, albeit rarely. In view of these figures, it is clear that speed of treatment can save lives. A US study shows how important it is for an operation to be successful quickly in order to minimize the risk of death. And how different the latter is for affected women.
Previous research shows that every week of delay in surgery after a breast cancer diagnosis can increase the risk of death. In practice, however, the recommended surgery period of 30 to 60 days is not always adhered to — partly for medical reasons, partly for organizational reasons. It was previously unclear whether all breast cancer subtypes react equally sensitively to delayed surgery.1 This is precisely where the current study attempts to provide clarity.
Overview
Increased Mortality Risk for Certain Tumor Types
Not all breast cancers are the same. Depending on its biological nature, the disease can behave very differently. The study by the University of Oklahoma Health Sciences Centers evaluated more than 34,000 breast cancer cases and provides evidence that the risk of serious consequences increases earlier and faster than previously thought for certain tumor types. The study also attempted to identify specific risk patterns that could enable personalized scheduling of breast cancer operations — and thus go beyond the previous blanket 60-day recommendation of the Commission on Cancer.2 The Commission is an association of professional organizations that aims to improve the care of cancer patients.
Study Design and Methods
The researchers used the SEER Medicare Registry for their study. This is an extensive US database that pools clinical and insurance-related information on older female cancer patients (aged 65 and over).
The scientists analyzed the data of 34,248 women aged 66 and over who were diagnosed with localized or regional breast cancer between 2010 and 2017 — i.e., a tumor that had not yet spread throughout the body. All patients underwent surgery without prior chemotherapy, meaning that surgery was the first treatment after diagnosis.
The study investigated how the time between diagnosis and surgery — the so-called “time to surgery” (TTS) — affects the risk of dying from breast cancer. This refers to the time between the tissue sample (biopsy) and the actual surgery date. This time was measured in days for each patient. A period of 30 days was used as a benchmark, as this had been determined in previous studies to be an appropriate period for prompt surgery.3
To make it easier to compare the results, the women were divided into three groups — depending on the biological structure of the tumor. Two characteristics were decisive:
Hormone Sensitivity (Hormone Receptor Status, HR)
Some types of breast cancer grow under the influence of female hormones such as estrogen or progesterone. Tumors that have many so-called hormone receptors react to these hormones and are referred to as HR-positive (HR+). If these receptors are missing, they are referred to as HR-negative (HR-) — such tumors are usually more aggressive and more difficult to treat. Whether a tumor is hormone-dependent is shown by how many of its cells have so-called hormone receptors.4
HER2 Status
HER2 is a protein that occurs in excessive quantities in some breast cancer patients and can stimulate tumor growth. If a tumor produces a lot of HER2, it is called HER2-positive (HER2+). If it does not, it is HER2-negative (HER2-).
The combination of these two characteristics results in three important groups for analysis:
- HR+/HER2-: the most common type. These tumors respond to hormones but do not show excessive HER2 activity.
- HER2+: tumors with high HER2 levels, regardless of hormone status.
- HR-/HER2- (triple-negative): Tumors that do not respond to either hormones or HER2. These are particularly difficult to treat as they offer fewer treatment options.5
Use of Different Analysis Methods
Inverse Propensity Score Weighting
To ensure that differences such as age, previous illnesses, or income do not distort the results, the researchers used a statistical method called “inverse propensity score weighting.” This ensures that all patient groups — despite their differences — are as comparable as possible. This can be thought of as a kind of “equalization calculation” in which certain characteristics are mathematically adjusted to enable fair comparisons.
Fine Gray Model
In order to find out how the mortality risk changes with increasing waiting time until the operation, the scientists used a special calculation model: the so-called “Fine Gray model.” This model is particularly helpful because it calculates the risk of death from breast cancer but also takes into account other causes of death — which is particularly important for older patients.6
B-Spline Function
Another mathematical model was also used: the “B-spline function.” This sounds complicated, but it simply means that risks can be represented not only in weeks or months but precisely day by day. This makes it possible to show very precisely from which day onwards the risk increases — and by how much.
From Day 42, Every Day Counts!
The study shows that the longer a breast cancer patient waits for her operation after diagnosis, the higher the risk of dying from the disease. This applies to all types of breast cancer investigated — but not to the same extent.
The increase was most pronounced in women with the most common type of breast cancer — i.e., tumors that respond to hormones (HR+) and do not produce HER2 growth protein. In these patients, the risk began to increase noticeably from the 42nd day after diagnosis — and very quickly. For example, if they waited 120 days for their operation, their risk of death was almost three times higher than if they had surgery after 30 days. The long-term survival rate also worsened: after five years, eight out of 100 patients with late surgery had died, compared to only three out of 100 with early surgery.
In patients with HER2-positive breast cancer, the increase was slower but still noticeable: the longer the waiting time, the higher the risk. The difference in mortality after five years was around four percentage points.
The correlation was weakest for so-called triple-negative tumors (i.e., those that react neither to hormones nor to HER2). Here, too, there was an increase, but this could not be clearly demonstrated statistically.
What Is the Significance of the Results?
The study makes it clear that not all breast cancer patients should be treated the same when it comes to the timing of surgery. While a delay may be less dramatic for some, it can be life-threatening for others. This challenges previous beliefs, such as the idea that hormone-sensitive breast cancer is generally slow-growing and less aggressive.
The researchers suspect that certain biological processes could play a role immediately after diagnosis. For example, changes in the tissue or inflammatory reactions triggered by the biopsy have a stronger effect on some types of tumors than others.
In Addition
Not all patients receive the same follow-up treatment. Women with hormone-dependent breast cancer are less likely to receive chemotherapy than others. As a result, the tumor often remains active in the weeks leading up to surgery, which can have negative consequences.
The recommended maximum period of 60 days until surgery is sensible — but it should be less than this for certain types of tumors if possible. Earlier surgery could significantly reduce the risk of death, particularly in the case of hormone-sensitive breast cancer without HER2.
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Classification of the Study
The study is particularly significant because it is based on data from a large number of patients and looks at three different types of breast cancer separately. Unlike many previous studies, it shows the risk not just roughly by month but precisely — day by day. It, therefore, sets new standards when it comes to determining the best time for an operation.
Possible Limitations
However, there are also limitations: The data comes exclusively from the USA and only concerns women aged 66 and over who are insured via the state healthcare system Medicare. Younger patients and patients from other countries were not included, which means that the results cannot be directly applied to all those affected.
In addition, some biological details about the tumor were missing, such as certain proteins or genetic values, which could help to assess the personal risk even more accurately. The cause of death was also not always clearly determined, as it was taken from death certificates.