What to Know About Breast Cancer Recurrence

Learn how likely breast cancer recurrence is and about BCRF-supported research to treat and prevent it

Breast cancer, especially when caught in its early stages, is highly treatable. Most people diagnosed with breast cancer will not experience a recurrence, the term for when cancer returns after initial treatment. Even so, recurrence does happen, but thanks to research advances, in many cases it can be managed. Unfortunately, however, recurrent or de novo stage 4 breast cancer is still responsible for virtually all breast cancer deaths, and an estimated 42,000 women will die from the disease this year.

Read on to learn about breast cancer recurrence, risk, breast cancer recurrence rates by subtype, and how BCRF investigators are working to prevent and treat breast cancer recurrence.

What is breast cancer recurrence?

Breast cancer recurrence is when breast cancer comes back after treatment and after a period where no signs of cancer were detected. If breast cancer recurs, it usually means that some cancer cells survived the initial treatment. This can occur even after surgery, radiation, chemotherapy, and other therapies. If some cancer cells remain in the body, over time they can start growing again and spread, leading to breast cancer recurrence.

The risk and timing of recurrence depend on multiple factors, including the cancer type and molecular subtype, stage at diagnosis, tumor biology, and type of treatment received, explained more below.

When can breast cancer recur?

Breast cancer recurrence can happen months to years after finishing treatment. Early relapse is considered recurrence of the disease within months to a few years after initial treatment.

Some triple-negative breast cancers (TNBCs) have a greater risk of early relapse. In contrast, hormone receptor (HR)-positive breast cancers have a higher risk of late recurrence (three to ten years after initial treatment) or even very late recurrence (10 or more years later).

What are the different types of breast cancer recurrence?

Breast cancer recurrence can occur in the same location as the original cancer or in different areas of the body. Local recurrence is when the cancer returns in the same breast or in a scar or chest wall after a mastectomy. The risk of local recurrence depends on several factors, including the type and stage of the original tumor, whether all cancer was removed with surgery (margin status), and whether treatment included radiation therapy.

Regional recurrence means the cancer has come back in nearby lymph nodes, such as those in the underarm, neck, or chest after initial treatment. This type of breast cancer recurrence indicates that the disease has spread beyond the original tumor site but has not yet reached distant organs. Regional recurrence is more likely in patients with positive lymph nodes at diagnosis, larger tumors, or incomplete surgical margins.

Distant recurrence is metastatic or stage 4 breast cancer, meaning the cancer has spread to distant sites in the body, like bones, liver, lungs, or brain. Distant breast cancer recurrence is often the result of cancer cells that had already migrated from the breast before or during treatment but remained dormant for some time before beginning to grow and spread.

What are breast cancer recurrence rates?

Breast cancer recurrence rates are a measure of breast cancer returning after initial treatment and vary based on factors such as stage, subtype, lymph node involvement, treatment type, and tumor biology. Breast cancer recurrence rates reflect a large population and not necessarily an individual person’s recurrence risk.

For early-stage breast cancer, the rate of local recurrence (in the same breast or chest wall) within the first five years after standard treatment is five to 10 percent. The rate of distant (metastatic) recurrence ranges from 10 to 30 percent for early-stage disease, depending on the subtype.

TNBC accounts for 10 to 15 percent of all breast cancer diagnoses but has the highest percentage of breast cancer recurrence among all breast cancer subtypes. TNBC and another aggressive but rare form of the disease called inflammatory breast cancer (IBC) have the highest recurrence rates within the first three to five years following treatment, but the rate drops after five years. Recurrence rates are high for these types not only because of their aggressive biology but because they are more challenging to treat initially: TNBC lacks several therapeutic targets while IBC often presents at later stages.

The rate of recurrence of HR-positive breast cancer has a different trajectory than other breast cancer subtypes. Recurrence is generally lower for this subtype, but the risk of recurrence can persist for many years and even decades after initial treatment. Approximately 200,000 women are currently living with metastatic breast cancer and most cases (about 70 percent) are HR-positive.

Breast cancer recurrence rates by stage

Breast cancer recurrence rates vary significantly by stage at diagnosis. The stage of a breast cancer is determined by characteristics including tumor size, hormone receptor status, and HER2 status. Early-stage cancers are defined as stages 0-3 while advanced-stage cancers are metastatic/stage 4.

The breast cancer recurrence rates by stage are as follows:

• The risk of recurrence is relatively low for stage 1 breast cancer: typically less than 10 percent over 10 years with treatment.
• For stage 2 breast cancers, where the disease may have spread to nearby lymph nodes, the risk of recurrence increases to about 10 to 20 percent, depending on tumor biology and treatment type.
• Stage 3 breast cancer has more extensive lymph node involvement or larger tumors, so recurrence rates are higher and range from 30 to 50 percent or more.
• Metastatic/stage 4 breast cancer cannot technically recur because it is not currently curable but it can be managed and may respond to a number of treatment options for several years.

Treatments for breast cancer recurrence

Current breast cancer treatments—including endocrine therapies, HER2-targeted drugs, and chemotherapies—have significantly reduced recurrence rates, especially when tailored to tumor subtypes. If breast cancer does recur, treatment depends on the biology of the tumor and whether recurrence is local, regional, or distant (metastatic).

When possible, local recurrence is treated with surgery followed by radiation therapy (if not previously given). Additionally, local recurrence can be treated with systemic therapies such as endocrine or other targeted therapies and chemotherapy based on the receptors present on the tumor.

Regional recurrence involving nearby lymph nodes may require lymph node removal, radiation, and systemic treatment to reduce the risk of further spread.

Distant recurrence can be managed as a chronic condition. Treatment typically involves endocrine therapy, chemotherapy, HER2-targeted drugs, or immunotherapy, depending on the breast cancer subtype. Advances in personalized medicine are enabling treatments to be more precisely matched to the characteristics of the recurrent breast cancer.

About recurrence scores for breast cancer

A recurrence score for breast cancer is a numerical estimate that helps predict the likelihood of breast cancer recurrence following initial treatment of HR-positive/ HER2-negative breast cancer. Recurrence scores are derived from genomic tests that analyze the activity of specific genes in the tumor DNA.

• Oncotype DX® is one of the most widely used genomic tests and evaluates the expression of 21 genes to generate a Recurrence Score (RS), which ranges from 0 to 100. A lower RS suggests a lower risk of recurrence and limited benefit from chemotherapy, while a higher RS indicates greater recurrence risk and a likely benefit from more aggressive treatment.
• MammaPrint®, developed by BCRF investigator Dr. Laura van ‘t Veer, analyzes 70 genes within a tumor to assess recurrence risk. The 70-gene signature provides a binary risk result: low or high.
• Prosigna® PAM50 test uses a 50-gene signature and offers a risk score along with subtype classification, helping determine prognosis and the breast cancer’s response to treatment.
• EndoPredict® uses a 12-gene signature to predict the risk of early and late breast cancer recurrence in patients with HR-positive/HER2-negative breast cancer. It helps guide treatment decisions by assessing the likelihood of recurrence within 10 years.

Clinicians consider various factors when determining which genomic test is right for the patient, including patient-specific ones like breast cancer stage and subtype, age, other medical conditions, and family history. They also consider the goal: Some tests can predict recurrence risk or response to treatments while others can help tailor treatment. Taking all these factors together, these tests are valuable tools to help to personalize care and avoid overtreatment when recurrence risk is low. For instance, they are useful for guiding treatment decisions such as the need for chemotherapy in addition to endocrine therapy or for making decisions about whether endocrine therapy can be stopped after a certain amount of time in low-risk patients.

Ways to help reduce your risk of recurrence

There are several strategies patients and their doctors can implement that, in combination, can reduce their risk of breast cancer recurrence.

• Regular surveillance screening—via mammograms and other imaging techniques—is essential for detecting recurrence as early as possible, when it may be most treatable.
• Follow-up plans should be tailored to individual patient risk factors such as the hormone receptor status, initial breast tumor size, and lymph node involvement. For patients with HR-positive breast cancer or other high-risk factors, it may be necessary to follow them for 10 or more years after diagnosis.
• For many patients, continuing adjuvant therapy can significantly lower the risk of breast cancer recurrence. For example, endocrine therapy for HR-positive breast cancer can decrease the risk of recurrence, even as far out as 10 or more years after diagnosis. Other treatments like HER2-targeted therapies and chemotherapies are often used to eliminate any residual cancer cells that may remain and cause a future recurrence.
• Finally, maintaining a healthy lifestyle can help reduce your breast cancer recurrence risk. Getting regular exercise, eating a balanced diet rich in fruits and vegetables, limiting alcohol, and maintaining a healthy weight have all been associated with improved breast cancer outcomes.

Research on breast cancer recurrence

BCRF investigators are focused on improving prediction and detection tools, developing more effective treatments for recurrent breast cancer, and identifying the underlying biology that drives breast cancer recurrence to prevent it in the first place.

Patients diagnosed with HR-positive breast cancer face a risk of recurrence that extends for many years. Several BCRF investigators are working to better predict this risk by improving genomic tests for estrogen receptor (ER)-positive breast cancer specifically. Others are studying blood-based biomarkers (liquid biopsy), tumor and patient-related factors, and lifestyle factors to identify predictors of recurrence and develop interventions that lower risk and improve outcomes. BCRF researchers are also using liquid biopsy to detect recurrent breast cancer as early as possible, allowing for more personalized surveillance screening.

A number of BCRF investigators are addressing breast cancer recurrence by unraveling the underlying biology. They seek to identify molecular drivers of recurrence and unique targets on dormant tumor cells, which may lead to strategies to stop the cancer from progressing. Research includes:

• Ongoing efforts to identify factors that contribute to late recurrence, including those that are unique to certain types of breast cancer and can cause unusual metastatic spread and very late recurrence (15 to 20 years after initial diagnosis).
• Examining breast cancer stem cells (BCSCs), which can lay dormant but then reactivate many years after initial treatment. Uncovering what triggers this activation can provide clues to target and eliminate them.
• Exploring what makes the environment in distant metastatic sites hospitable to BCSCs. This information can be leveraged to develop ways to disrupt the environment and limit BCSCs’ survival.
• Developing vaccines against BCSCs to prevent the seeds of breast cancer recurrence from forming.

Thanks to research, more and more patients with breast cancer are living longer and fuller lives after initial diagnosis and treatment. In fact, BCRF investigators are engaged in research with survivors to improve their quality of life and lower recurrence risk. Strategies include developing individualized diet and exercise plans following breast cancer diagnosis and finding ways to help patients stick to their therapy plan and keep up with follow-up visits. Researchers are also studying ways to improve communication between patients and healthcare providers so that patients can stay informed about their risk of breast cancer recurrence and make decisions about their continued care.