Breast Cancer Recurrence

Breast cancer recurrence: Could cancer stage and receptor status help predict risk?

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  • Breast cancer is currently the most commonly diagnosed cancer in the world.
  • About 30% of people who have their breast cancer treated and tumors removed experience disease recurrence.
  • Researchers from the University of Wisconsin have found breast cancer stage and hormone receptor status may help predict a person’s risk for their cancer to recur.

Breast cancer is currently the most commonly diagnosed cancerTrusted Source in the world. At the end of 2020, 7.8 million womenTrusted Source globally had been diagnosed with breast cancer in the past five years.

Current projections state that by 2040, there will be more than 3 million new breast cancer cases each year.

While there are various treatment optionsTrusted Source for breast cancer — some of which can remove cancer entirely from the body — there is always the chance the cancer might come back.

About 30% of people with breast cancer experience disease recurrence. And scientists are still not sure why breast cancer may return in some patients and not others.

Now, researchers from the University of Wisconsin have found that a person’s breast cancer stage and hormone receptorTrusted Source status may help doctors predict if and when their cancer might return after treatment.

The study was recently published in CancerTrusted Source, a peer-reviewed journal of the American Cancer Society.

What are the 5 stages of breast cancer?

Breast cancer is a type of cancer that begins in the breast. It occurs when cells in the breast begin to uncontrollably divide and grow, ultimately forming a tumor. This can happen due to damage or a genetic mutation in a person’s DNA.

There are five known stages of breast cancer:

  • Stage 0: Cancer is only in the breast ducts and has not spread to tissues nearby.
  • Stage 1: The tumor measures up to 2 centimeters across and it has either not affected the lymph nodes or there is a small number of cancer cells in the lymph nodes.
  • Stage 2: Tumor measures 2 centimeters and has spread to the lymph nodes, or measures 2-5 centimeters and has not spread to the lymph nodes.
  • Stage 3: Tumor measures up to 5 centimeters and has spread to several lymph nodes, or tumor is larger than 5 centimeters and has spread to a couple of lymph nodes.
  • Stage 4: Breast cancer has spread to other organs of the body, such as the brain or lungs.

What are the 3 receptors for breast cancer?

If a person has been diagnosed with breast cancer, a doctor will use imaging testsTrusted Source and a biopsy to determine the type of breast cancer they have. As there are a few different types of breast cancer, this will help the doctor determine the right course of treatment.

The doctor will also test to see if a person’s breast cancer contains proteins that are receptors for the hormones estrogen or progesterone:

Additionally, breast cancer can also have a receptor for human epidermal growth factor receptor 2 (HER2). HER2 is a protein-creating gene in the breast that if changed, can cause cells to become problematic, causing cancer.

Importance of follow-up care in breast cancer

According to Dr. Heather Neuman, associate professor in the Division of Surgical Oncology at the University of Wisconsin School of Medicine and Public Health and lead author of this study, her research team had been very interested in looking at the follow-up care for breast cancer survivors.

“Breast cancer care has evolved to the point that we are really able to personalize treatment decisions based on information such as anatomic stage and receptor status,” she explained to Medical News Today.

“However, our follow-up care recommendations have remained one-size-fits-all. Inevitably this means some patients receive more and some patients less follow-up than they really need,” she said.

“Monitoring for recurrence is one significant reason why oncology teams follow their survivors. We felt that this study was an important first step in defining what risk really looks like for survivors with different cancer types so that we could rationally plan follow-up care.”
— Dr. Heather Neuman

The cancer that has most recurrence risk

For this study, the research team analyzed data from over 8,000 people with breast cancer in stages 1–3, with different hormonal receptors.

The scientists reported the time to first cancer recurrence varied depending on which receptor — ER, PR, or HER2 — a person had.

“We have known for a long-time that different types of cancer are differently aggressive. Over time, our treatment paradigms have evolved to personalize how we treat each cancer to address this, which has led to improved outcomes for many cancer patients,” Dr. Neuman explained.

“These treatments have changed not only the magnitude of the recurrence risk but also the timing of when patients are at risk. Our study really highlights these differences,” she added.

Dr. Neuman and her team found people with ER−/PR−/HER2− breast cancer — also known as triple-negative breast cancer — had the highest risk of recurrence and it occurred the earliest. People with this type of tumor diagnosed at stage 3 had a five-year probability of recurrence of 45.5%.

Conversely, people with ER+/PR+/HER2+ breast cancer — known as triple-positive breast cancer — had the lowest recurrence risk. People with this tumor type diagnosed at stage 3 had a five-year probability of recurrence of 15.3%.

Different follow-ups needed for different types

Dr. Neuman stated she and her team were not surprised by the findings for women with triple-negative breast cancer.

“There were two findings in our study that were noteworthy. The first is the relatively low recurrence risk we saw for cancers treated in the modern era. The recurrence risk is modest for many cancer types, especially those ER+/PR+/HER2+ cancers,” she said.

However, Dr. Neuman pointed out that what was noteworthy was the patterns of recurrence they found for ER-/PR- breast cancer— regardless of HER2 status — and how it follows what doctors currently communicate to patients.

“Our traditional thinking, based on older studies, has been that most recurrences happen within five years, but after that the risk is low. That five-year time frame is something patients really hold on to. We definitely saw that pattern for triple-negative and ER-/PR-/Her2+ tumors, where the risk peaks around year three but drops close to zero by year 5.”
— Dr. Heather Neuman

“In contrast, the patterns for ER+/PR+ cancers are flatter — less of a peak — and doesn’t drop as significantly by year 5. This has real ramifications for what follow-up should look like for different cancer types,” she added.

Predicting the risk

Dr. Parvin Peddi, a board-certified medical oncologist and director of Breast Medical Oncology for the Margie Petersen Breast Center at Providence Saint John’s Health Center and Associate Professor of Medical Oncology at Saint John’s Cancer Institute in Santa Monica, California, told Medical News Today this study affirms the influence of stage and receptor status on risk of recurrence.

“As expected, patients with triple-negative breast cancer and higher stage breast cancers had (a) higher rate of recurrence compared to estrogen receptor-positive and lower stage breast cancers,” she said.

“Longer follow-up will be needed to ascertain the true risk of recurrence in patients with hormone receptor-positive breast cancers as we know they can recur many years down the line. Five years is not adequate follow-up for these patients.”
— Dr. Parvin Peddi

And Dr. Jack Jacoub, a board-certified medical oncologist and medical director of MemorialCare Cancer Institute at Orange Coast Medical Center in Fountain Valley, California, said this study confirms how doctors are changing how they determine a person’s breast cancer recurrence risk.

“When we look at (the) risk of recurrence, we look at several factors. One is the stage — that has been historically the single biggest risk for recurrence and the one that all doctors have been taught about for decades,” he explained to Medical News Today.

“Now that’s changed dramatically because it’s less about the stage and more about the disease biology,” Dr. Jacoub continued.

“Along those same lines, we look at the type of cancer it is. Breast cancer is made up of multiple different types — that’s probably more important than even stage in many scenarios,” he told MNT.

“And then we take it an additional step further along the same lines of the biology of the tumor and we look at the molecular subtyping of the tumor — which genes are turned on and off — (which) often is the most reliable way to predict the risk of recurrence. So we look at all three of those factors and so this adds to that data set,” he concluded.

New Metabolic Biomarkers May Improve the Ability to Predict Breast Cancer Recurrence

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A team of researchers, including Susan E. Waltz, PhD, of the University of Cincinnati College of Medicine, found that the RON and DEK proteins may regulate certain metabolic pathways that have previously been linked to cancer progression. Published in PLOS One, the investigators’ findings also identified a signature based on these pathways that may aid in the ability to predict recurrence of breast cancer.

“We showed that both RON and DEK are very important in breast cancer and that both…are independently associated with poor overall survival in breast cancer patients,” commented Dr. Waltz in an institutional press release. The team believes the metabolic pathways regulated by these proteins may provide new therapeutic targets.

The researchers used a nuclear magnetic resonance–based metabolomics approach to study different metabolic pathways and attempted to stratify patient outcomes using genes from those modulated by RON/DEK/b-catenin. Genes that significantly stratified relapse-free survival and distant metastasis–free survival were used to create a signature, which the researchers validated using data sets from The Cancer Genome Atlas and the Gene Expression Omnibus. A separate, combined signature was also created, which incorporated RON/DEK/b-catenin expression along with the metabolic genes. Both were tested in their capacity to predict chemotherapy response in patients with node-positive breast cancer.

The study implicated b-catenin in the regulation of glycolysis, glycosylation, the TCA cycle, NAD-positive production, and creatine dynamics. Genes in these pathways that were epistatic to RON-DEK-b-catenin primarily defined the metabolism signature. When the investigators classified recurrence-free survival, the metabolism signature achieved a larger hazard ratio (HR) (HR = 1.77) than the RON/DEK/b-catenin signature (HR = 1.48), suggesting a greater extent of stratification. However, the combined signature scored highest (HR = 1.81). This was also true regarding distant metastasis–free survival, with the combined signature (HR = 2.07) followed by the RON/DEK/b-catenin signature (HR = 1.82) and the metabolism signature (HR = 1.77). The combined signature, similarly, showed the best predictive ability for treatment response.