Targeted Therapeutic Strategies For Adjuvant Setting
Treatment of HER2-positive EBC with trastuzumab
About 2025% of patients with invasive breast cancer are HER2-positive and it is considered as an independent risk factor for recurrence and metastasis. Large number of data shows that trastuzumab combined with chemotherapy can reduce nearly 50% RR of recurrence and metastasis. In the adjuvant scenario, trastuzumab is the criteria for the treatment of HER2-positive patients with breast cancer., Despite the lack of a widely acknowledged protocol for HER2 status evaluation, these adjuvant clinical trials have explored the use of trastuzumab and yielded remarkable clinical results. Besides, central laboratory testing for HER2 status confirmation is essential before enrollment in some trials.
Trastuzumab monotherapy has been recommended in several practice guidelines for high-risk patients of cardiac serious AEs, in combination with anthracyclines., Whether the strategy of routine trastuzumab monotherapy± endocrine therapy could reduce recurrence risk is debatable. Prior phase III trials have coherently demonstrated that trastuzumab is fundamental in adjuvant settings., Trastuzumab could be used in combination with anthracycline-based chemotherapy , following a taxane-based regimen or be combined with carboplatin and docetaxel .,
Duration of anti-HER2-targeted therapy
Other strategies for the HER2-positive EBC treatment
Life Expectancy And Outlook
In the United States, its estimated that more than 42,000 women will die from breast cancer in 2020.
However, its important to know that aspects like life expectancy and your outlook can vary greatly based off many individual factors.
In the past, a diagnosis with HER2-positive breast cancer was associated with a poor outlook. Advances in drug therapies in recent years have improved the treatment options for HER2-positive breast cancer as well as the outlook for people with the disease.
According to the American Cancer Society, HER2-positive breast cancers are much more likely to respond to drugs that target the HER2 protein, despite the fact that they can grow and spread quickly.
This type of treatment is called targeted therapy. Well discuss it in more detail in a bit.
When considering your outlook, your doctor must analyze many other factors as well. Among them are:
Hormone treatments may be an option for cancer thats also HR positive.
There Are Known Risk Factors For Her2
Again, while exact cause is difficult to pinpoint, researchers have identified some risk factors for HER2-positive disease, according to Moffit Cancer Center. For example, being a higher weight, not living an active lifestyle, having a child for the first time after age 30, and using tobacco products can up your risk. This cancer is also more likely to occur in younger women, adds Brian Czerniecki, M.D., chair of the department of breast oncology at Moffit Cancer Center in Tampa, FL. According to one 2020 study, 22.63% of younger women had HER2-positive breast cancer compared with 13.41% of older women.
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What Is The Survival Rate Of Her2
Survival rates with HER2-positive cancer depends on the stage at the time of diagnosis and response to treatment. The development of targeted therapy has greatly improved survival rates for HER2-positive breast cancer. In advanced stages, HER2-positive cancers respond better to treatment than HER2-negative cancers.
According to recent National Cancer Institute data, the four-year survival rate for combined stages of cancer, based on HR and HER2 status are:
- HR-positive/HER2-negative: 92.5%
What Percentage Of Breast Cancers Are Her2
Approximately 20% of breast cancers are HER2-positive. HER2-positive breast cancers more commonly occur in women younger than 40. It is not clear what causes HER2 gene mutations, however, studies show HER2 breast cancers are not inherited. HER2-positive breast tumors are more likely to be larger and ER-negative.
A lump in the breast is almost always cancer.See Answer
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Will I Need Radiation
Most oncologists generally recommend radiation treatment for all breast cancer patients who undergo only removal of the tumor .
For women who undergo whole-breast removal, radiation may be recommended for those who are considered high-risk, especially those with tumors larger than 5 centimeters and with more than four cancerous lymph nodes.
Her2 Negative Breast Cancer Treatment Guidelines
Her2 negative breast cancer treatment guidelinesHER2-Positive vs. HER2-Negative Whats the Difference?ASCO issues evidenced-based information for management of patients with HER2-negative or HER2 status unknown advanced breast cancerHER2-positive breast cancer is one form of breast the FDA approved Herceptin as a single agent for the adjuvant treatment of HER2-positive node-negativeAdjuvant systemic therapy for HER2-positive trastuzumab for node-negative, HER2-positive breast cancer. systemic therapy for HER2-positive breast
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Promising New Research On Aggressive Breast Cancer
In HER2-positive breast cancer, a gene called HER2 is expressed that promotes an aggressive form of the disease.
Researchers Jean-François Côté and Marie-Anne Goyette explain how a new therapeutic target works to fight a very aggressive form of breast cancer.
Better treatments of HER2-positive breast cancer are closer at hand, thanks to new research by a team led by Université de Montréal professor Jean-François Côté at the cytoskeleton organization and cell-migration research unit of the UdeM-affiliated Institut de recherches cliniques de Montréal .
In HER2-positive breast cancer, a gene called HER2 is expressed that promotes an aggressive form of the disease. Affecting 20 per cent of women suffering from breast cancer in Canada, the HER2-positive subtype is associated with a poor prognosis.
We asked Côté and Goyette to tell us more.
What Is My Her2 Status
HER2 is another type of growth signal receptor which may be present on your breast cancer cells. About 25% of breast cancers are HER2-positive. HER2-positive cancers are a mix of good and bad news.
The bad news is the tumors tend to grow more aggressively than those without the HER2 receptor. The good news is that like ER/PR-positive cancers, medicines can switch the HER2 growth receptor off.
New drugs such as trastuzumab, pertuzumab, T-DM1 and lapatinib are extremely effective at this and have dramatically improved the prognosis for HER2-positive patients, Dr. Abraham says. Treatment outcomes are now as good as those with HER2-negative tumors.
But HER2-positive tumors bigger than half a centimeter or that have spread into the lymph nodes may require treatment with chemotherapy and one of the medicines specifically targeting the HER2 receptor, such as trastuzumab.
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Is The Cancer In My Lymph Nodes
Whether your breast cancer has spread to your lymph nodes the filtering mechanisms in your armpits and elsewhere in the body that are part of the immune system is one of the most important predictors of the severity of your disease.
Involvement of the lymph nodes changes the treatment plan, says Dr. Abraham. When breast cancer cells have spread to the lymph nodes, we tend to discuss more aggressive treatment options, such as chemotherapy.
Her2 Is A Protein That Accelerates Cell Growth
First, what do those letters mean? HER2 stands for human epidermal growth factor receptor 2, which is a gene that makes HER2 proteins, according to the National Institutes of Health. HER2 proteins are normally found on the surface of healthy breast cells to promote breast cell growth and repair, but when HER2 mutates, things go wrong. An excess of HER2 proteins causes cells to grow fast. When cancer cells have more HER2, this causes cancer cells to grow more rapidly, explains Swati Kulkarni, M.D., a breast surgeon at Northwestern Memorial Hospital in Chicago.
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What Are The Stages Of Her2 Breast Cancer
All breast cancers are staged by the size of the tumor and extent of spread. Breast cancers are also graded from one to three, based on how abnormal the cancer cells look and how fast they grow. Grade one is low grade cancer and three is high grade which grows and spreads rapidly.
The four stages of breast cancer are:
- Stage I: The tumor is relatively small and localized to the original site with possible spread to the sentinel lymph node, which is the first node the cancer is likely to spread to.
- Stage II: The tumor has grown and spread to a few nearby lymph nodes.
- Stage III: The tumor has grown into many lymph nodes and other breast tissue.
- Stage IV: The cancer has spread to distant parts of the body.
Another classification system is the TMN breast cancer classification, based on Tumor size , lymph Node status and distant Metastasis . It has many detailed classifications for breast cancers.
What Type Of Breast Cancer Do I Have
Breast cancers arent all the same. Doctors classify them in a number of different ways. The most basic place to start is where the cancer cells originate. Their origin is a key factor in whether or not your cancer may spread and helps dictate the kind of treatment youll get.
Most breast cancers 70% to 80% start in the milk ducts. Theyre known as infiltrating or invasive ductal carcinomas, meaning that theyve broken through the milk ducts wall and have proliferated into the breasts fatty tissue. Once there, its possible for the cancer cells to further spread to other parts of the body.
Another 10% of breast cancers start in the milk-producing glands, or lobules, and are called invasive lobular carcinomas. Theyre also capable of spreading.
Other rarer breast cancers may involve the nipple, the breasts connective tissue or the linings of blood vessels or lymph vessels.
Some breast cancers are non-invasive. They havent spread. Theyre contained within the milk ducts and are called ductal carcinoma in situ . Generally, the prognosis for patients with DCIS is very good, Dr. Abraham says.
Inform Her2 Dual Ish Test
This test is also conducted for identifying the presence of excessive copies of the HER2 gene in the breast cancer cells. The test report of the Inform HER2 Dual ISH test can help to determine the HER2 gene amplification or no HER2 gene amplification .
All the above-mentioned tests are conducted for the purpose of identifying the HER2 gene amplification or HER2 protein over-expression which is indicated by HER2-positive in the pathology report. The finding of this assists in determining HER2-positive Breast cancer. The aggressive nature of the HER2-positive breast cancers have a faster growth tendency and also spread faster and tend to relapse, which are not similar in HER2-negative breast cancers.
Different research results showed that the test report is not always correct to determine the status of HER2 protein due to the variation of the laboratory markers to classify positive and negative HER2 status. The pathologist who study the test report also follows different criteria to fix on whether the results are positive or negative. Most of the time confusion is created when the test report showed borderline and that cannot provide strong HER2-positive or HER2-negative. This lacuna needs to keep in mind during treating a patient with breast cancer, as Inaccurate HER2 test results may cause ineffective treatment prognosis. Therefore, repetition of test or alternative test must be performed to get an accurate result.
It’s A Hopeful Time For Her2
If you or a loved one are diagnosed with this cancer, remember this: There are more effective treatments available than ever. The big take-home point about HER2-positive tumors is that while this is very aggressive tumor, these very targeted treatments are incredibly effective, Dr. Kulkarni says. So while prognosis used to be poor, with the introduction of targeted treatments and more to come, people see much better outcomes, she says. Its very exciting times for HER2-positive breast cancer research, Dr. Czerniecki says.
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What Is The Treatment For Her2
Treatment for breast cancers is individualized depending on the type, grade, stage, HR and HER2 status, and any gene mutations. Treatment also depends on the age, overall health and whether the woman is menopausal or not. Treatment may be more complicated if the woman is pregnant. Patients also have the option of enrolling for clinical trials for new treatments.
A Path To Aggressive Breast Cancer
Researchers at Baylor College of Medicine have followed the progression of breast cancer in an animal model and discovered a path that transforms a slow-growing type of cancer known as estrogen receptor +/HER2+ into a fast-growing ER-/HER2+ type that aggressively spreads or metastasizes to other organs.
The study, which appears in the Proceedings of the National Academy of Sciences, has implications for breast cancer therapy as it suggests the need to differentiate cancer subtypes according to the path the cells follow. Different paths might be linked to different cancer behavior, which should be taken into consideration to plan treatment appropriately.
“In general, ER-/HER2+ breast cancer is more aggressive than ER+/HER2+ breast cancer, but the ER- type also is heterogenous in its behavior,” said co-corresponding author Dr. Jianming Xu, Baylor’s Gordon Cain Endowed Professor in Cell Biology in the Department of Molecular and Cellular Biology. “In some patients, the ER-/HER2+ cancer responds to therapy and never returns, but in others, the cancer comes back, grows rapidly, aggressively metastasizes to other organs and does not respond to treatment, which causes death. However, what determines the aggressiveness of individual ER-/HER2+ breast cancer is poorly understood.”
Following the path of cancer
Looking into what mediates different behavior in ER-/HER2+ breast cancer
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Hormone Receptor Status And Prognosis
Hormone receptor status is related to the risk of breast cancer recurrence.
Hormone receptor-positive tumors have a slightly lower risk of breast cancer recurrence than hormone receptor-negative tumors in the first 5 years after diagnosis .
After 5 years, this difference begins to decrease and over time, goes away .
For a summary of research studies on hormone receptor status and survival, visit the Breast Cancer Research Studies section.
Determining Your Her2 Status
A breast biopsy is used to determine HER2 status. The biopsy can be sent for laboratory testing with an immunohistochemistry test. The fluorescence in situ hybridization test looks for the HER2 gene in breast cancer cells.
The results of an immunohistochemistry test show different levels of HER2 positivity. For example, a tumor may be reported as 0, 1+, 2+, or 3+. Tumors with a higher number may be referred to as having an overexpression of HER2.
According to the American Cancer Society, immunohistochemistry test results should be considered as follows:
The impact of being HER2-positive on breast cancer survival is, of course, a top concern. Unfortunately, statistics can be misleading without considering other aspects of your diagnosis, including cancer stage at diagnosis and whether the tumor is also estrogen and/or progesterone receptor-positive.
With this in mind, you may also be tested for progesterone and estrogen receptors. Triple-negative breast cancers are negative for HER2, estrogen, and progesterone, while triple-positive breast cancers are positive for all three.
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What Makes This Discovery Promising
J-F.C.: With the latest scientific advances in cancer, immunotherapy and personalized medicine have generated a lot of hope. However, for HER2-positive patients, the results to date have been inconclusive, and thats why its important to better understand the immune environment surrounding this type of tumour. Indeed, its fundamental that the mechanisms and factors involved be identified to help better target treatments and those most likely to respond to them.
This is exactly what we did. We have not only shed light on a central mechanism of the functioning of some of the most aggressive tumours, but in doing so we have also unveiled a way to create an environment conducive to more effective treatment. The therapeutic potential of this study is highly significant for future clinical management of these cancers.
Relative Survival Rates For Breast Cancer
The National Cancer Institute gives 5-year relative survival rates for breast cancer based on how far the disease had spread before a doctor found it.
- Localized : 99%
- Regional : 86%
- Distant : 28%
- Unknown stage: 55%
- All stages: 90%
While these numbers can give you a general idea, they are an average for women with any type of breast cancer. They arent specific to the HER2+ type. They also come from data that researchers collected from 2010 to 2016, so they dont reflect more recent treatment advances.
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If I Have Chemotherapy Will I Need To Take Other Medications Like Trastuzumab
If your breast cancer is HER2-positive, its recommended that you take trastuzumab for one year, Dr. Abraham says. This ensures that the HER2 growth receptor on any remaining cancer cells stays shut off. Trastuzumab is not chemotherapy. The hair you lost during chemotherapy will regrow and your energy level will improve while youre taking trastuzumab.
Hormone Receptor Status And Hormone Therapy
Hormone receptor-positive breast cancers can be treated with hormone therapy drugs. These include tamoxifen and the aromatase inhibitors, anastrozole , letrozole and exemestane . Ovarian suppression, with surgery or drug therapies, is also a hormone therapy.
Hormone receptor-negative breast cancers are not treated with hormone therapies because they dont have hormone receptors.
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Blocking Her2 Slows Or Stops Some Types Of Breast Cancer
NCI-funded researcher Dennis Slamon, M.D., was among the many scientists searching for genes that can lead to cancer. In 1987, he and his colleagues discovered that the growth factor receptor gene HER2, which produces HER2 proteins, might be a good candidate.
At the same time, a team of NCI researchers led by Stuart Aaronson, M.D., were among the first to show that the HER2 protein could cause normal cells to grow uncontrollably like aggressive cancer cells.
Dr. Slamons team found that the HER2 protein is present at high levels in about 30 percent of breast cancers. They also discovered that high levels of HER2 are linked to a greater likelihood of metastasis and relapse and an overall decrease in patient survival. The group concluded that HER2 might play a role in the development and growth of breast cancer.
NCI-funded researcher Dennis J. Slamon, M.D., discovered the genetic link between HER2 and breast cancer.
This led researchers to a groundbreaking hypothesis: If HER2 could be blocked, the growth of HER2-positive breast cancer might be slowed.
One way to block the action of a protein is to use laboratory-made monoclonal antibodies that attach to a specific protein and disrupt its function. With NCI support, Dr. Slamon and colleagues from the University of Texas Health Sciences Center had a breakthrough. They showed that an antibody specific to HER2 could slow the growth of metastatic breast cancer cells and other types of cancer in a laboratory dish.