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Can Her2 Positive Breast Cancer Return

What’s The Risk Of Recurrence

HER2-Positive Breast CancerReduce Your Risk of Recurrence | Access Health

Everyone who has had breast cancer has some risk of recurrence, but its typically low.

In general, the more time that goes by, the lower the risk of recurrence. Cancer is most likely to recur in the first two years after treatment, and once people get to five years of living cancer-free after treatment, its considered to be a significant milestone to be celebrated. Recurrence after that five year markrare, but possibleis called late recurrence.

Theres still so much that is unknown about cancer recurrence, but researchers have found some patterns in recent years that point to clues about why it happens. These factors might be linked to a higher risk of breast cancer recurrence:

  • Having high blood sugar
  • Not eating enough fruits and vegetables
  • Having had a surgical site infection after your surgery

Certain characteristics of your original cancer also might mean a higher risk of recurrence, such as:

  • A tumor of more than five centimeters across
  • Cancer cells that are HER2-positive
  • Cancer cells that are triple negative
  • Cancer cells in four or more axillary lymph nodes at the time of surgery
  • Cancer cells in the chest muscles or breast skin

You might be at higher risk for late recurrence if you had:

  • A tumor of more than two centimeters
  • A high number of affected lymph nodes
  • A hormone receptor-positive cancer
  • A HER2-negative cancer
  • Hormone therapy for only a short time after surgery

Identifying Breast Cancer Subtypes Associated With Late Recurrence

Researchers have developed a multistate model to identify 11integrative subtypes of breast cancer with different risks of recurrence,according to the findings of a study published online in Nature.

Although it is known that women with definitively treated early-stagebreast cancer, particularly estrogen receptor -positive cancer, canexperience disease recurrence up to 20 years following initial diagnosis,long-term follow-up data of molecularly characterized cohorts of breast cancer arelacking. Nevertheless, early identification of women at high risk for breastcancer recurrence remains important.

The multistate model described in the paper accounts for differentdisease states, time scales, competing risks of mortality, and baseline characteristicsacross different molecular subgroups to predict individual risk of breastcancer recurrence. This model was fitted to a dataset from 3240 patientsdiagnosed with breast cancer between 1977 and 2005, including 1980 patientswith corresponding molecular data. The median clinical follow-up of this cohortwas 14 years. Other smaller datasets were used for external validation of themodel.

In addition, specific subgroups of triple-negative breast cancer werealso identified as being associated with either an increased risk of recurrencemany years after initial treatment, or a very low risk of distant recurrence inER-positive/HER2-negative patients who were relapse-free at 5 years.

What Women Can Do Themselves

There are some things women can do themselves to lower their risk of late recurrence.

  • Regular exercise is associated with a lower risk of death from breast cancer as well as death from all causes.
  • It’s important for everyone to have their vitamin D level tested, although the role of vitamin D is still uncertain. Vitamin D deficiency is associated with bone loss, a concern for most people who have coped with breast cancer.
  • Losing weight if you are overweight, or maintaining a healthy weight is important as well.

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What Are Risk Factors For Breast Cancer Recurrence

Anyone with a breast cancer diagnosis can have a recurrence. Your risk of cancer recurrence depends on several factors:

  • Age: Women who develop breast cancer before age 35 are more likely to get breast cancer again.
  • Cancer stage: Cancer stage at the time of diagnosis correlates with the risk of the cancer being able to recur. Several factors determine cancer stage: tumor size, cancer grade and cancer spread to lymph nodes or other parts of the body. Cancer grade indicates how unusual cancer cells look in comparison to healthy cells.
  • Cancer type: Aggressive cancers like inflammatory breast cancer and triple-negative breast cancer are harder to treat. Theyre more likely to come back and spread.

Circulating Tumor Cells At 5 Years Post


In addition, liquid biopsy for the presence of circulating tumor cells at five years post-diagnosis may also help predict late recurrence.

In a 2018 study published in the Journal of the American Medical Association , women who had cancer cells in their blood five years after diagnosis were roughly 13 times more likely to experience a recurrence as those who did not. The finding was significant only for women who had estrogen receptor-positive tumors, and none of the women who had circulating tumor cells in their blood but estrogen receptor-negative tumors experienced a recurrence.

Using liquid biopsies to predict recurrence is still in the investigational stage and not currently used when making decisions on whether or not hormonal therapy should be continued beyond five years.

That said, these findings, along with molecular subtyping offers hopes that doctors will be better able to predict who should receive extended hormonal therapy in the future.

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How Are Breast Tumors Tested For Her2

Women newly diagnosed with invasive breast cancers should be tested for HER2.

A biopsy or surgery sample of the cancer is usually tested with either immunohistochemical stains or Fluorescent in situ hybridization .

See Testing Biopsy and Cytology Specimens for Cancer and Understanding Your Pathology Report: Breast Cancerto get more details about these tests.

Side Effects And Quality Of Life

Women treated with Herceptin and chemotherapy were more likely to have a severe side effect not related to blood counts compared to women treated with Herceptin alone 29.8% vs. 11.9%.

The most common side effects of any grade were:

  • low white blood cell counts
  • loss of appetite
  • fatigue
  • nausea

Health-related quality of life scores went down faster in women treated with Herceptin plus chemotherapy, compared to women treated with Herceptin alone, 2 months after starting treatment and 1 year after starting treatment.

In light of the lower toxicity and more favorable profile, trastuzumab monotherapy can be considered an adjuvant therapy option for selected older patients, the researchers wrote.

In an editorial accompanying the article, researchers not affiliated with the study agreed with the conclusion.

on the basis of the results of the RESPECT trial, it is possible to consider that adjuvant trastuzumab monotherapy could be an option for a subset of patients, particularly those who may have a higher risk of toxicity with chemotherapy and those with a lower anatomic risk of disease recurrence , they wrote. It is important to stress, however, that the choice of therapy in older patients should never be made on the basis of age alone. Comprehensive geriatric assessment is the standard of care for evaluation before chemotherapy and should generate a care plan to be implemented during treatment to minimize the risk of complications and maintain and functionality.

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Treatment For Breast Cancer Recurrence

If your care team thinks you might have a cancer recurrence, theyll recommend diagnostic tests, like lab tests, imaging or biopsies, both to be sure the cancer has come back and to get more information to guide your treatment.

Treatment options depend on where the cancer has recurred and what treatment youve had before:

  • Local recurrence is likely to be treated surgically first with a mastectomy if you didnt have one already or a surgical removal of the tumor if you did. After surgery, chemotherapy and radiation are commonly used, as well as hormone therapy or targeted therapy if your kind of cancer will respond to one or both of them.
  • Regional recurrence is also typically treated first with surgery to remove affected lymph nodes. After the surgery, youll likely have radiation and possibly chemotherapy, hormone therapy and/or targeted therapy, too.
  • Distant recurrence is mainly treated with drug therapychemotherapy, hormone therapy, targeted therapy or a combination of these. Surgery and/or radiation might be used, too, but only in cases where the aim is relieving symptoms.


Why Breast Cancer Can Spread

Brain metastases developed from HER2 postive and triple negative breast cancer

Any type of breast cancer can spread. This happens when cancer cells get into healthy cells around the breast. If they spread, cancer cells usually go to other parts of the breast first. Lymph nodes near the breast tend to be the next place cancer cells go. From there, cancer cells can travel to other parts of the body farther from the breast.

About one in every five breast cancers are HER2-positive. This means they have extra copies of a gene that makes the HER2 protein. HER2-positive breast cancer can grow and spread faster than other breast cancers because HER2 protein speeds that growth.

Whether breast cancer spreads also depends on several other things. These include:

  • If your tumor is HER2-positive or a different type
  • The stage your cancer was when you were first diagnosed
  • The size of the tumor
  • Whether cancer was also found in nearby lymph nodes

On the positive side, treatments that aim right at the HER2 protein can work very well. These targeted medications raise the odds that you can beat the disease back.

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Risk Of Recurrence: Early And Late

Research has shown the HER2-positive early breast cancers are two to five times more likely to recur than HER2-negative tumors. Even very small HER2-positive tumors with negative lymph nodes have a much higher risk of recurrence relative to tumors that are HER2-negative. Treatment with Herceptin can cut this risk by half.

The pattern of breast cancer recurrence may also differ. Small tumors are also more likely to have a metastatic recurrence if they are HER2-positive.

Despite the fact that HER2-positive and estrogen receptor-negative tuors are more likely to recur early on than estrogen receptor-positive and HER2-negative cancers, late recurrences are much less common.

With estrogen receptor positive breast cancers, the cancer is more likely to recur after 5 years than in the first 5 years, and the risk of recurrence remains steady each year for at least 20 years following the diagnosis. In contrast, those who have HER2 positive tumors and reach their 5 year mark are much more likely to be “in the clear” and remain recurrence free.

How Is Breast Cancer Recurrence Managed Or Treated

Your treatment depends on the type of cancer recurrence, as well as past treatments. If cancer develops in a reconstructed breast, your surgeon may want to remove the breast implant or skin flap.

Treatments for local and regional breast cancer recurrence may include:

  • Mastectomy: Your surgeon removes the affected breast and sometimes lymph nodes.
  • Chemotherapy:Chemotherapy circulates in blood, killing cancer cells.
  • Hormone therapy:Tamoxifen and other hormone therapies treat cancers that thrive on estrogen .
  • Immunotherapy:Immunotherapy engages your bodys immune system to fight cancer.
  • Radiation therapy: High-energy X-ray beams damage and destroy cancer cells.
  • Targeted therapy: Treatments target specific cancer cell genes or proteins.

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Her2s Genetic Link To Breast Cancer Spurs Development Of New Treatments

Single breast cancer cell and microenviornment visualized by transparent tumor tomography.

When NCI-supported researchers discovered that the HER2 gene is important for breast cancer growth, this led to the development of the drug trastuzumab and other targeted treatments that have improved survival for women with HER2-positive breast cancer.

Vaccine Derived From Her2 Protein May Help Prevent Breast Cancer Recurrence

Vaccine study for HER2

A new breast cancer vaccine that is derived from the HER2 protein may help prevent recurrence in patients with HER2-positive disease and appears safe. Phase II study results of the vaccine were released at the 2014 Breast Cancer Symposium, September 46, in San Francisco.

The HER2 protein, also known as human epidermal growth factor receptor 2, is found on the surface of certain cancer cells, including breast cancer. In normal cells HER2 helps control cell growth. Cancer cells, however, can make too much of the protein, which can cause cells to grow more quickly and be more likely to spread to other parts of the body.

The HER2-derived vaccine, known as GP2, is designed to provoke the bodys immune system to fight cancer by recognizing tumor cells that express HER2. It is administered in addition to standard breast cancer treatment, such as Hercpetin® , with the goal of preventing recurrence.

Based on these findings, the GP2 vaccine appears promising in addition to standard therapy in women with HER2-positive breast cancer, as it might have the potential to safely and effectively prevent recurrences. The researchers also speculate that GP2 works with Herceptin in a specific way to stimulate immune response and that further research into this interaction is warranted.

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Integrative Subtypes And Late Recurrence

Researchers recently developed a model to identify 11 integrative subtypes of breast cancer with different risks and timing of recurrence, according to the findings of a 2019 study published online in Nature.

Four integrative subtypes were identified that were associated with a high risk of late recurrence . Altogether, these four subtypes accounted for roughly 26% of breast cancers that were estrogen receptor-positive and HER2 negative.

These subtypes included tumors that had an enriched copy number alterations in genes that are thought to drive the growth of cancer , including:

  • CCND1
  • RPS6KB1
  • MYC

They were also able to identify a subgroup of triple-negative tumors that were unlikely to recur after five years as well as a subgroup in which people continue to be at risk of late recurrence. A Breast Cancer Recurrence Calculator including integrative subtypes has been developed but, at the current time, this is meant for research purposes alone.

Moffitt Cancer Center Serves Her2 Positive Breast Cancer Survivors

Moffitt Cancer Centers Don & Erika Wallace Comprehensive Breast Program offers advanced monitoring, preventive treatments and supportive care services to women and men with a history of HER2 positive breast cancer, including those who were treated at other hospitals and cancer centers. We encourage you to consult with one of our oncologists specializing in breast cancer if you have any concerns about your risk of recurrence.

Medically reviewed by Dr. Hatem Soliman

Fill out a new patient registration form online or call to reserve an appointment with a Moffitt physician. We encourage women and men with or without referrals to visit us for regular cancer screening and expert breast health advice.


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Why The Study Was Done

HER2-positive breast cancers make too much of the HER2 protein. The HER2 protein sits on the surface of cancer cells and receives signals that tell the cancer to grow and spread. About one out of every four breast cancers is HER2-positive.

Because HER2-positive breast cancer is considered more aggressive than HER2-negative breast cancer, it is usually treated with a combination of Herceptin, an anti-HER2 medicine, and chemotherapy after surgery.

Still, older women have a higher risk of side effects from chemotherapy. So the researchers wanted to see if treating older women diagnosed with early-stage HER2-positive disease with Herceptin alone after surgery offered the same benefits as treating them with Herceptin plus chemotherapy.

The Myth And Stigma Of The 5

HER2 Early-Stage Breast Cancer: Peri-Operative Therapy

Many people still believe that breast cancer, even hormone-positive disease, is essentially cured after five years this can lead to misunderstandings in families. Loved ones who don’t understand late recurrence may downplay your feelings, or criticize you when you think “brain tumor” each time you get a headache.

Until information on late recurrence becomes more widely known, and even though it’s frustrating, you may need to educate loved ones about the risk, and why you should be concerned when you develop new or unexplained symptoms.

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Understanding Her2+ Status And Survival

Doctors use three markers to help define breast cancers and guide treatment. One of those is the HER2 protein. The other two are hormone receptors . When a cancer has none of these, doctors call it triple negative. Until recently, there wasnt much information about how these markers changed survival rates for breast cancer.

A recent study looked at the National Cancer Institute data to see if there were differences in survival for women based on these markers. The study shows there are. Overall, women who have HR+ and HER2- breast cancer do best. But in the later stages, those who have the HER2+ type have better survival rates than those with HER2-. Breast cancers that are triple negative have the lowest survival rates. The 4-year survival rates are as follows:

  • HR+/HER2-: 92.5%

How Common Is Breast Cancer Recurrence

Most local recurrences of breast cancer occur within five years of a lumpectomy. You can lower your risk by getting radiation therapy afterward. You have a 3% to 15% chance of breast cancer recurrence within 10 years with this combined treatment. Based on genetic testing, your provider may recommend additional treatments to further reduce your risk.

Recurrence rates for people who have mastectomies vary:

  • There is a 6% chance of cancer returning within five years if the healthcare providers didnt find cancer in axillary lymph nodes during the original surgery.
  • There is a one in four chance of cancer recurrence if axillary lymph nodes are cancerous. This risk drops to 6% if you get radiation therapy after the mastectomy.

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Researchers Develop Additional Her2

Despite these successes, many women with breast cancer dont benefit from current HER2-targeted treatments, or they become resistant to the effects of these drugs after initial treatment.

Therefore, researchers continue to test new or modified drug combinations. For example, in 2012, FDA approved pertuzumab as a treatment for women with HER2-positive metastatic breast cancer to be used in combination with trastuzumab and docetaxel , a chemotherapy drug. In 2017, pertuzumab received approval for use in combination with the same drugs as an adjuvant treatment for patients with HER2-positive early breast cancer at high risk of recurrence. Pertuzumab works by blocking HER2 from sending signals to other proteins that cause cells to grow and replicate.


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