Targeted Therapy For Women With Brca Gene Mutations
Olaparib and talazoparib are drugs known as PARP inhibitors. PARP proteins normally help repair damaged DNA inside cells. The BRCA genes also help repair DNA , but mutations in one of those genes can stop this from happening. PARP inhibitors work by blocking the PARP proteins. Because tumor cells with a mutated BRCA gene already have trouble repairing damaged DNA, blocking the PARP proteins often leads to the death of these cells. These drugs are pills and are taken once or twice a day.
Olaparib and talazoparib can be used to treat advanced or metastatic, HER2-negative breast cancer in women with a BRCA mutation who have already had chemotherapy. If the cancer is hormone receptor-positive, olaparib can also be used in women who have already received hormone therapy.
Only a small portion of women with breast cancer are born with a mutated BRCA gene, which is in all the cells of the body. This is different from the gene change happening after you are born which is found only in the cancer cells. If you are not known to have a BRCA mutation, your doctor will test your blood to be sure you have one before starting treatment with these drugs.
Side effects can include nausea, vomiting, diarrhea, fatigue, loss of appetite, taste changes, low red blood cell counts , low platelet counts, and low white blood cell counts. Rarely, some people treated with a PARP inhibitor have developed a blood cancer, such as myelodysplastic syndrome or acute myeloid leukemia .
Approved Her2 Positive Breast Cancer Therapies And Ongoing Clinical Trials
Currently, there are several treatment options targeting the HER2 receptor or its associated signaling pathways, ultimately leading to longer survival and improved patient outcome. Approved HER2 treatment options include monoclonal antibodies, small molecule RTK inhibitors, and the combination of these drugs with other chemotherapeutic agents. Drugs that are FDA approved and in ongoing clinical trials for HER2+ breast cancer are summarized in Table 1.
Table 1 FDA approved clinical studies of HER2 inhibitors against breast cancer
Trastuzumab, a monoclonal antibody which targets the HER2 receptor, was developed by Ullrich, Shepard, and Fendly at Genentech who developed murine antibodies against ErbB2 . One of the more promising antibodies, 4D5, showed anti-proliferative effects in breast tumor cell lines . This 4D5 antibody was humanized to be tested clinically , leading to the 1998 approval of trastuzumab and provided one of the first drugs for metastatic breast cancer . The antibody targets the extracellular domain IV of the HER2 receptor . This inhibits dimerization to other HER family members, hence blocking signaling pathways associated with HER receptor activation.
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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Genetics And Family History
Treatment for breast cancer may depend partly on having a close relative with a history of breast cancer or testing positive for a gene that increases the risk of developing breast cancer.
Patients with these factors may choose a preventive surgical option, such as a bilateral mastectomy.
Clinical trials are studies in which patients volunteer to try new drugs, combinations of drugs, and methods of treatment under the careful supervision of doctors and researchers. Clinical trials are a crucial step in discovering new breast cancer treatment methods.
Emerging treatments for breast cancer being studied in clinical trials include:
- PARP inhibitors that block protein used to repair DNA damage that occurs during cell division are being used and tested for TNBC.
- Drugs that block androgen receptors or prevent androgen production are being used and tested for TNBC.
If youre interested, ask your oncologist for information about available trials.
There is currently no cure for metastatic breast cancer, or breast cancer that has spread to distant parts of the body. However, early stages of breast cancer that remain localized are highly treatable 99 percent of people who receive treatment in the earliest stages of breast cancer live for 5 years or longer after diagnosis, according to the American Cancer Society.
The outlook for breast cancer depends, in large part, on the stage at the time of diagnosis. The earlier youre diagnosed, the better the outcome.
Targeted Therapy: Herceptin Biosimilars
Generic drugs donât exist for brand-name biologics. Biologics are made of large, complex molecules and produced — thanks to the magic of biotechnology — in a living system, such as an animal or plant cell. You canât replicate that.
But you can create a similar version. These drugs are called biosimilars. They have âno clinically meaningful differencesâ in terms of safety, purity, or potency.
Trastuzumab and hyaluronidase is another type of trastuzumab treatment that is injected underneath the skin.
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What Foods To Avoid If You Have Estrogen
Research shows that among breast cancer cases,
- only 5-10% were because of genetic defects.
- 90-95% were attributable to environmental and lifestyle factors such as diet. Out of these,
- Diet contributed to approximately 30-35%.
- Obesity contributed to 10-20%.
Any food that increases your risk of obesity or makes you prone to inflammation triggers breast cancer, be it of any type. These include:
- Sugary foods:
Combination Her2 Directed Therapy
The combination of lapatinib and trastuzumab has demonstrated synergy in preclinical models and has recently been shown to improve PFS in patients with MBC that had progressed on trastuzumab . In a phase III trial, 296 HER2-positive patients whose disease had progressed on trastuzumab-containing regimens were randomized to receive lapatinib alone or lapatinib with trastuzumab. The median PFS was 12.0 weeks in the lapatinib plus trastuzumab arm and 8.1 weeks in the lapatinib arm . The combination of trastuzumab and lapatinib was well tolerated, with fewer serious adverse events than would be expected with a chemotherapy containing regimen . In an updated analysis, the median OS was 14 months for the lapatinib plus trastuzumab arm, compared with 9.5 months for the lapatinib arm .
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How Should We Treat Her2+ Bc Patients Who Do Not Benefit From Trastuzumab Pertuzumab Trastuzumab Emtansine And Lapatinib
The inherent or acquired resistance to targeted therapy drugs, as well as the relatively serious side effects, limit the application of targeted therapy drugs. These two kinds of unfavorable factors are the driving forces to continue to develop new drugs. To overcome the development of drug resistance, some studies explored the possible treatment methods and identified some substances that had potential value. Specifically, the discovery and application of Taxol greatly improved the prognosis of patients. Interestingly, several studies investigated natural anti-cancer substances that had shown significant anti-cancer effects, which might prevent the tumorigenesis of BC. Furthermore, the new ADC and targeted delivery of drugs were found to be effective in treating HER2+ BC patients. In this review, we concentrate on some research studies for putative application in clinical treatment. And we summarize the signaling pathways of corresponding effective potential clinical drugs .
HER2 TK inhibitors
Improvements of drug resistance
Trastuzumab, as the first-generation targeted therapy drug, helped many HER2+ BC patients to improve their prognosis and quality of life in the future. As we mentioned above, the resistance to trastuzumab limited its application to a large extent. Thus, research and development of new drugs to overcome trastuzumab resistance may contribute significantly to the treatment of HER2+ BC patients.
Targeted delivery drugs
Natural anti-cancer substances
Natural Compound Attacks Her2 Positive Breast Cancer Cells
- Duke Medicine
- A common compound known to fight lymphoma and skin conditions actually has a second method of action that makes it particularly deadly against certain aggressive breast tumors, researchers report. The compound is called psoralen, a natural component found in foods such as figs and celery, and researchers have long understood that it that works by disrupting DNA replication and causing cell death when activated by an energy source such as UV light.
A common compound known to fight lymphoma and skin conditions actually has a second method of action that makes it particularly deadly against certain aggressive breast tumors, researchers at Duke Medicine report.
The compound is called psoralen, a natural component found in foods such as figs and celery, and researchers have long understood that it that works by disrupting DNA replication and causing cell death when activated by an energy source such as UV light.
Duke researchers have now identified another way the compound works to kill tumor cells, raising the potential for psoralen to be developed as an effective therapy for cancers that are particularly vulnerable to this second mode of action.
Psoralen also attacks another form of HER2 that is present in the nucleus of tumor cells. This form of the protein is resistant to cancer therapies such as lapatinib and trastuzumab that are otherwise effective in targeting HER2-positive cancers.
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Foods To Limit Or Avoid:
Theres evidence that avoiding fatty foods, like fried foods and packaged snack foods, is one way to help manage weight and overall health and as a result, maybe even breast cancer.
High body fat increases the mortality risk in breast cancer survivors, explains Generose. Decreasing your intake of saturated fats, like those in red meats, butter and baked goods, can decrease fat levels and inflammation in your body.
In small or moderate quantities, alcohol namely red wine does have some health benefits, such as lowering stress, lowering the risk of heart disease and reducing the risk of Type 2 diabetes.
In large quantities, however, alcohol is directly linked to breast cancer . Women should keep it to no more than one drink per day, as there is strong evidence that consuming large amounts of alcohol daily increases your risk of breast cancer, says Generose.
In all meal plans, its recommended that you limit your intake of red meats, like beef, lamb and pork, and processed meats, like bacon and hot dogs.
You dont need to swear off all red meat for good, but reducing your intake can have positive effects on your health and may reduce your risk of cancer, says Generose.
The recommended amount of red meat is three portions per week, or a total of 12 to 18 ounces or less.
Try to choose lean cuts of meat or poultry, and add more fish to your diet, adds Generose.
Hormone Therapy For Postmenopausal Women
After menopause, hormone therapy for women with metastatic breast cancer can be an aromatase inhibitor, tamoxifen, fulvestrant or other hormone therapy drug.
If the first hormone therapy stops working and the cancer starts to grow again, a second hormone therapy can be used. If the second drug stops working, another can be tried.
Ovarian suppression isnt helpful for postmenopausal women because their ovaries have already stopped producing large amounts of estrogen.
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The Best Diet For Her2 Positive Breast Cancer
Image source: rgbstock / AI71
The Best Diet For HER2 Positive Breast Cancer
Continuing my series of articles on dietary recommendations for particular types of breast cancer, this one is for those of you who have been diagnosed with HER2 Positive breast cancer.
What Exactly is HER2 Positive Breast Cancer?
HER2 positive refers to a type of breast cancer that overexpresses the HER2/neu gene. About 15-20% of breast cancers are HER2+, meaning the cancer is fueled by over-production of the human epidermal growth factor receptor 2 protein. HER2+ breast cancers contain excess copies of this gene, leading to dramatically more HER2 protein on the surface of cancer cells. Because of this protein, which produces signals that tell the cells to grow, they do so out of control, causing this form of breast cancer.
Many women are told that a HER2+ diagnosis is associated with a significantly higher chance of local breast cancer recurrence . Before the late 1990s, women with HER2+ breast cancer had poorer survival rates. Today, however, because of targeted therapies like Herceptin, this is no longer the case and it is a much more treatable disease. Herceptin works by attaching to HER2 receptors on cancer cells, blocking signals that cause growth, and alerting the immune system to destroy the cancer.
Can Diet Make A Difference?
Please know that there are plenty of things you can eat and supplements you can take which will make a big difference for you and will assist your return to wellness.
Treatment Options For Her2+ Breast Cancer
If breast cancer is HER2-positive, there are targeted medications that can treat that type of breast cancer specifically. The order in which these medications are used may be different for each person, depending on any previous therapy the patient has had.
These medications may also be used in combination with each other or with chemotherapy medications, including those in the list that follows.
Tests To Detect Spread
If you notice signs that your HER2-positive breast cancer may have spread, talk to your doctor. This is especially important if your symptoms are new, wonât go away, or you canât tell why they may be happening.
But itâs important not to panic. Keep in mind that symptoms such as bone pain can happen from arthritis, getting older, or even from your breast cancer treatment. Meanwhile, a cough and shortness of breath could just mean you have a cold or the flu. And itâs normal to feel tired and to not be hungry after youâve had cancer treatment.
To figure out if your breast cancer has spread, your doctor might do a variety of tests. These can include:
- Blood tests, some of which may look for tumor âmarkersâ
- Bone scan
Targeted Therapy For Her2
In about 1 in 5 women with breast cancer, the cancer cells make too much of a growth-promoting protein known as HER2 . These cancers, known as HER2-positive breastcancers, tend to grow and spread more aggressively than HER2-negative breast cancers. Different types of drugs have been developed that target the HER2 protein.
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Personal Genetic Testing For Inherited Gene Mutations
The National Comprehensive Cancer Network recommends everyone diagnosed with metastatic breast cancer get genetic testing for BRCA1 and BRCA2 inherited gene mutations . If you have a mutation in one of these genes, a PARP inhibitor may be included in your treatment plan.
Learn more about genetic testing.
Hormone Therapy For Premenopausal Women
For premenopausal women with metastatic breast cancer, hormone therapy almost always begins with ovarian suppression and either an aromatase inhibitor, tamoxifen or other hormone therapy drug.
Ovarian suppression lowers hormone levels in the body so the tumor cant get the estrogen it needs to grow. This may involve surgery to remove the ovaries or, more often, drugs to stop the ovaries from producing hormones.
Combining ovarian suppression and a hormone therapy drug improves survival over either treatment alone .
If breast cancer progressed during past treatment with a hormone therapy drug, the same hormone therapy drug may not be an option for treatment.
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What Is Targeted Therapy For Her2
When a cancer is HER2-positive, it means that the cancer cells make too much HER2 protein, which can cause tumors to grow more rapidly than with other forms of breast cancer.
Drugs that target the HER2 proteins are the primary treatment for this type of breast cancer, given along with chemotherapy. Your oncology team may refer to these medications as targeted therapy or HER2-directed therapy.
Herceptin and Perjeta are given at the same time as chemotherapy through an IV. HER2-directed therapy is usually given over a longer period of months than chemotherapy.
Herceptin alone is usually continued after chemotherapy has finished, every three weeks for a total of one year.
Side effects for HER2-targeted therapies may include:
- sleep problems
- redness at the IV site
Prognosis For Metastatic Her2+ Cancer
Generally, when breast cancer becomes metastatic, it is not possible to cure the cancer. This does not mean that the cancer isnt treatable, though. Data from the National Cancer Institute estimates that for those diagnosed with metastatic breast cancer, 29% have a five-year survival rate. This means that 29% of the people with that cancer are still alive in five years.
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Current Targeted Therapy Drugs
Among all of the drugs that target HER2 and HER2 TK, trastuzumab, pertuzumab, trastuzumab emtansine and lapatinib have been proven to be effective in treating HER2+ BC in several clinical trials compared with chemotherapy drugs alone . Trastuzumab, the first-generation targeted therapy drug, is a humanized monoclonal antibody targeting the extracellular domain of HER-2 and has the ability to downregulate the signaling pathways involving PI3K/Akt and MAPK , which in turn inhibits the proliferation of BC cells that overexpress HER2. Trastuzumab, both administered as a single agent or injected in combination with a series of chemotherapy agents , showed anti-tumor effects and remarkably improved time to progression, response and survival rate . Furthermore, several randomized control trials have revealed that trastuzumab plus chemotherapy drugs significantly reduce the risk of recurrence and death and promote survival incidence compared to chemotherapy drugs alone , making trastuzumab the cornerstone of adjuvant treatments for HER2+ BC.
Lapatinib is a reversible HER2 TK inhibitor that reacts with the ATP binding site, which in turn improves PFS and clinical benefit rate by inhibiting the autophosphorylation of ErbB1 and ErbB2 and downstream proliferative signaling pathways . Similarly, in some neoadjuvant clinical trials, lapatinib has been used in dual blockade with trastuzumab to treat patients with HER2+ BC .