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 wasnât 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%
- HR-/HER2-: 77.0%
What Are The Symptoms Of Her2
Some patients diagnosed with HER2-positive breast cancer may not present with any symptoms. When symptoms are present, they may include:
- A new lump in the breast, armpit area or around the collarbone
- Thickening or hardening in the breast
- A change in breast size or shape
- Changes to the nipple, such as sores or crusting, an ulcer or inverted nipple
- Clear or bloody nipple discharge
- Changes to the skin including redness, puckering, or dimpling
- Breast tenderness or pain
If the cancer has progressed to the metastatic stage, further symptoms may be present dependent on where the cancer has spread. Learn more about metastatic breast cancer here.
Treating Aggressive Breast Cancers
Women diagnosed with breast cancer undergo testing to determine the form of the disease and whats driving its growth. This information is key to developing an individualized treatment strategy. Choice of treatment also depends on how extensive the cancer is within the breast, whether it has metastasized, and whether the patient is menopausal.
When either HER2-positive or triple-negative breast cancer is diagnosed early, surgery is often performed to remove the tumor and its surrounding tissue or the entire breast . Nearby lymph nodes sometimes are removed as well.
Neoadjuvant therapy, a treatment given as a first step before the primary treatment, is standard for both HER2-positive and triple-negative breast cancers if the tumor can be surgically removed. Chemotherapy is often used as a neoadjuvant therapy before surgery to shrink the tumor. The goal is to reduce the area that needs to be removed so the surgery can be less extensive, possibly avoiding a mastectomy. For HER2-positive cancer, chemotherapy may be combined with targeted therapy, medication that acts on the specific cause of the cancer.
After neoadjuvant therapy and surgery, the treatment strategies for HER2 and triple-negative breast cancers differ.
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Can Other Drugs Interfere With Hormone Therapy
Certain drugs, including several commonly prescribed antidepressants , inhibit an enzyme called CYP2D6. This enzyme plays a critical role in the body’s use of tamoxifen because CYP2D6 metabolizes, or breaks down, tamoxifen into molecules, or metabolites, that are much more active than tamoxifen itself.
The possibility that SSRIs might, by inhibiting CYP2D6, slow the metabolism of tamoxifen and reduce its effectiveness is a concern given that as many as one-fourth of breast cancer patients experience clinical depression and may be treated with SSRIs. In addition, SSRIs are sometimes used to treat hot flashes caused by hormone therapy.
Many experts suggest that patients who are taking antidepressants along with tamoxifen should discuss treatment options with their doctors, such as switching from an SSRI that is a potent inhibitor of CYP2D6, such as paroxetine hydrochloride , to one that is a weaker inhibitor, such as sertraline or citalopram , or to an antidepressant that does not inhibit CYP2D6, such as venlafaxine . Or doctors may suggest that their postmenopausal patients take an aromatase inhibitor instead of tamoxifen.
Other medications that inhibit CYP2D6 include the following:
- Quinidine, which is used to treat abnormal heart rhythms
Should I Have Breast Reconstruction And When
This is another question that has a multi-layered answer. It involves both medical and personal considerations. Some women opt not to have reconstruction. Others believe it benefits their appearance and psychological recovery.
This is another question that has a multi-layered answer. It involves both medical and personal considerations. Some women opt not to have reconstruction. Others believe it benefits their appearance and psychological recovery.
If youre having one or both breasts removed and are considering reconstruction, the stage of your cancer may dictate the timing of the reconstructive surgery. For patients with early-stage breast cancer, Dr. Abraham says immediate reconstruction is reasonable. With a Stage III cancer, you should discuss with your oncologist and surgeon whether immediate reconstruction is advisable.
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Mutations In The Juxtamembrane Domain
The juxtamembrane domain, containing 39 amino acids , is involved in receptor dimerization and stability. Several authors have described reoccurring mutations in this domain with a functional activating effect in different cancer types . However, these studies do not specify if these mutations occur in patients with HER2-positive breast cancer. In our search of mutations in the COSMIC and cBioPortal databases, we found two mutations, R678Q and V697L, present in HER2-positive breast carcinoma. In vitro studies indicate that R678Q is an activating mutation that confers sensitivity towards treatment with trastuzumab, lapatinib, afatinib, and neratinib and has been classified as a hotspot . No functional data exist for mutation V697L, but it has been described as a mutational hotspot and data available for other cancer types suggest its oncogenic effect.
Chemo Drugs For Breast Cancer That Has Spread
- Taxanes: Paclitaxel , docetaxel , and albumin-bound paclitaxel
- Ixabepilone
- Gemcitabine
- Antibody drug conjugates
Although drug combinations are often used to treat early breast cancer, advanced breast cancer often is treated with single chemo drugs. Still, some combinations, such as paclitaxel plus gemcitabine, are commonly used to treat metastatic breast cancer.
For cancers that are HER2-positive, one or more drugs that target HER2 may be used with chemo.
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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.
When Herceptin Is Used
Herceptin can be used to treat:
- early-stage HER2 positive breast cancer, following surgery and/or radiotherapy and chemotherapy, to reduce the risk of the cancer coming back
- advanced HER2 positive breast cancer that has spread from the breast , to slow the growth of the cancer and increase survival time
- advanced HER2 positive stomach cancer that has spread out of the stomach
- advanced HER2 positive gastro-oesophageal cancer, which affects where the food pipe meets the stomach
If you have breast, oesophageal or stomach cancer, you will have tests to check if the cancer is HER2 positive before herceptin is offered.
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Cish And Silver In Situ Hybridization
The CISH approach and SISH method capture the advantages of both IHC and FISH. It detects HER2 gene-copy number by using a single HER2 probe. The CISH was approved by the FDA to evaluate feasibility for anti-HER2 agent. In addition, CISH has the lowest correlation with IHC 2 staining and highest with IHC 0, 1, and 3 results. Previous researches have shown about 9799% of concordance between CISH and FISH. Several clinical trials have defined criteria as 3+ for IHC test or FISH-positive tumors whereas others, like the Finland Herceptin trial, have relied on the CISH results. However, this method needs further investigations in future.
What Is Her2 Breast Cancer Testing
HER2 stands for human epidermal growth factor receptor 2. It is a gene that makes a protein found on the surface of all breast cells. It is involved in normal cell growth.
Genes are the basic units of heredity, passed down from your mother and father. In certain cancers, especially breast cancer, the HER2 gene mutates and makes extra copies of the gene. When this happens, the HER2 gene makes too much HER2 protein, causing cells to divide and grow too fast.
Cancers with high levels of the HER2 protein are known as HER2-positive. Cancers with low levels of the protein are known as HER2-negative. About 20 percent of breast cancers are HER2-positive. HER2 positive cancers tend to grow and spread faster than other types of breast cancer. But treatments that specifically target HER2-positive breast cancer can be very effective.
HER2 testing looks at a sample of tumor tissue to find out whether you have HER2-positive breast cancer.
Other names: human epidermal growth factor receptor 2, ERBB2 amplification, HER2 overexpression, HER2/neu tests
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Novel Antibody Drug Conjugates
Following the success and FDA approval of two Antibody Drug Conjugates , there are multiple other agents currently in clinical trials. Like DS-8201, these newer ADCs have a cleavable linker that accounts for what is called the bystander effect. Bystander effect is responsible for the death of antigen-negative cells , hence it is important in both the efficacy and safety of the drug. Here we discuss a few ADCs with published clinical trial results.
These second-generation ADCs are thought to overcome the resistance of HER2+ cells to T-DM1. One of the ADCs currently in clinical trial, SYD985 , was shown to be effective in T-DM1-resistant patient-derived tumor models . Results of the dose-escalation/dose-expansion study with this agent demonstrated clinical activity in heavily pre-treated HER2+ patients, with a partial response of 33% and a median PFS of 7.6 months . Currently, the Phase III randomized TULIP trial is evaluating the drug SYD985 against other standard of care options for previously treated HER2+ breast cancer patients.
Another ADC currently in Phase III trial is BAT8001 , which uses a novel non-cleavable linker between trastuzumab and the maytansine payload. A phase I dose-escalation study revealed the drug to be safe, and it also showed efficacy in heavily pre-treated HER2+ patients. A randomized multi-center Phase III trial is ongoing in China .
Heart Monitoring On Herceptin
Heart problems can sometimes develop while you’re taking herceptin and they can be serious.
Before treatment starts, you’ll have a test to see how well your heart is working for example, an echocardiogram or a multi-gated acquisition scan.
Your heart will also be regularly checked during treatment.
It’s important to tell your doctor if you’re being treated with herceptin and you get:
- shortness of breath during the day or night
- swollen ankles
If you develop a problem with your heart during treatment, it will usually improve if you have a short break from taking herceptin.
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Increased Risk Of Leukemia
Very rarely, certain chemo drugs, such as doxorubicin , can cause diseases of the bone marrow, such as myelodysplastic syndromes or even acute myeloid leukemia, a cancer of white blood cells. If this happens, it is usually within 10 years after treatment. For most women, the benefits of chemo in helping prevent breast cancer from coming back or in extending life are far likely to exceed the risk of this rare but serious complication.
What Is The Grade Of My Tumor
Grading is not the same as staging. Both are indicators of a cancers severity and prognosis, but they use different criteria. Staging deals with the tumor size, location and the distribution of cancer cells in your body. But grading is based on how the cancer cells appear under a microscope.
The more abnormal-looking the cells are, the more likely they are to quickly grow and spread. Grades usually run from I to III. A higher grade is a more aggressive cancer. Its possible to have a Stage I tumor thats also a Grade III cancer.
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How Big Is My Tumor
Tumor size is another factor that will determine your course of treatment. Your doctor uses the size of your tumor to stage, or further categorize your cancer .
The tumors dimensions are estimated by a physical exam, a mammogram, an ultrasound or an MRI of the breast. The precise size wont be known until a pathologist studies the tumor after surgical removal.
Side Effects Of Herceptin
Herceptin often causes side effects, although many of these will become less severe over time.
The following side effects are experienced by around 1 in 10 people:
- a reaction to the medicine, such as chills, a high temperature, swelling of the face and lips, headache, hot flushes, feeling sick, wheezing and breathlessness
- tiredness and difficulty sleeping
Cancer Research UK also has more information about the common side effects of herceptin.
Tell your doctor if you have particularly troublesome side effects, as there may be medicines available to treat them.
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How Can I Reduce My Risk Of Breast Cancer
There are several steps you can take to lower your risk of breast cancer, and many are relatively easy. Consider:
- Losing excess weight
- Eating a diet with plenty of nutrient-rich foods, particularly fruits and vegetables
- Quitting smoking and other forms of tobacco use
- Avoiding drinking alcohol in excess
Her2+ Status Cancer Stage And Survival
The importance of HER2 status for survival will depend on how far the cancer has spread. If itâs only in the breast, then it wonât make much difference. Most women in the early stage of the disease do well because a surgeon can remove the tumor.
Itâs when a breast tumor grows and spreads to lymph nodes or farther away in the body that HER2 status becomes more important for treatment and survival. Thatâs because there are now drugs that target HER2, but these work only for cancers that are HER2+. A common drug for HER2+ breast cancer is trastuzumab , but there are others. Because there are more treatments, women with more advanced HER2+ breast cancers today will on average have better survival rates than those with more advanced HER2- breast cancers.
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How Are Breast Tumors Tested For Her2
Either a test called an immunohistochemistry test or fluorescence in situ hybridization test is used to find out if cancer cells have a high level of the HER2 protein.
See Testing Biopsy and Cytology Specimens for Cancer and Understanding Your Pathology Report: Breast Cancerto get more details about these tests.
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
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Is Her2 Breast Cancer Curable
The chances of successfully treating HER2 breast cancer is high if the cancer is detected in early stages. HER2 cancers, however, are often high grade tumors in stage III at the time of diagnosis. If HER2 cancer has metastasized at the time of diagnosis, it is treatable but not curable in most individuals.
With the development of medications that specifically target HER2 proteins, HER2-positive breast cancers now have a much better outlook than in the past. HER2-positive cancers that have been in remission for five years are less likely to recur.
Trastuzumab Targets Breast Cancer In Clinical Trials
Researchers launched three clinical trials of trastuzumab in the mid-1990s for patients with HER2-positive metastatic breast cancer. By 1998, the results of the phase 3 clinical trials showed that breast cancer in patients treated with trastuzumab and chemotherapy grew at a slower rate than in patients treated with chemotherapy alone. Subsequent clinical trials also showed positive outcomes among women with early-stage HER2-positive breast cancer.
On November 16, 2006, the US Food and Drug Administration granted approval to trastuzumab used with chemotherapy as an adjuvant treatment for women with HER2-positive breast cancer. The drug has improved survival rates for women with stage 1 to 3 HER2-positive breast cancer by more than 30 percent.
HER2 protein is expressed at high levels in several other cancers besides breast cancer, and in 2010, FDA approved the use of trastuzumab in combination with the chemotherapy drug cisplatin and a type of cancer drug called a fluoropyrimidine to treat some patients with HER2-positive gastric or gastroesophageal junction cancers.
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Progress In Treating Her2
HER2-positive and triple-negative breast cancer are among the most aggressive forms of breast cancer and traditionally have had lower survival rates than other types of the disease. However, early detection with routine screening has contributed to improved survival for both in recent years. Further, treatment advancesall available at Regional Cancer Care Associates , one of the nations largest networks of cancer specialists with locations in New Jersey, Maryland, and Connecticutalso have helped improve outcomes in HER2-positive cancer. Meanwhile, intensive research and emerging therapeutic strategies are offering new hope for women with triple-negative breast cancer.
Four RCCA medical oncologists recently explained what drives the development of these breast cancers, how they are treated, and how women can play an important and potentially life-saving role in identifying the cancers in their earliest stages, when they can be treated most effectively.
Aileen Chen, MD, a board-certified medical oncologist practicing with RCCA in Freehold and Holmdel, NJ says, Its an exciting time in the fight against breast cancer. Next-generation sequencing technology is detecting genetic mutations that we can treat with targeted therapies in many forms of the disease. This has enhanced our ability to practice personalized medicine by customizing a patients treatment based on her molecular and genetic profiles.