Parp Inhibitors In Breast Cancer Research
PARP inhibitors appear under a variety of names and are used to treat several different forms of cancer. Recent breast cancer research has indicated the usefulness of PARP inhibitors in aiding the effectiveness of associated chemotherapy treatments. In advanced breast cancer cases, stronger cancer cells can often successfully combat chemotherapy drugs. PARP inhibitors may be able to reduce the ability of cancer cells to develop this resistance. Two new drugs, talazoparib and olaparib , recently passed FDA approval to treat HER2-negative breast cancer in a small set of patients with BRCA1 or BRCA2 gene mutations. Current research is being performed into PARP inhibitors for treating additional instances of metastatic breast cancer and triple-negative breast cancer, as well as reducing recurrence in early-stage patients.
Rabia Cattie Md Of Ochsner Health Spoke To The Utility Of Cdk4/6 Inhibitors In Hr
I have been most with the lack of uniformity of the data in that setting. The positive results with abemaciclib , albeit clearly in a higher-risk subgroup of patients, the negative results of the PALLAS study . Even in the subgroup analysis of PALLAS, the higher-risk subgroup didnt seem to benefit from . That certainly speaks to a potential difference in those 2 drugs. We are waiting for the results of the NATALEE trial ribociclib , which will go a long way toward telling us whether there is a group effect or not. If is a positive trial, the people at Pfizer will be scratching their heads about why didnt succeed.
Its great to have other drugs in the high-risk subgroup of patients. We treat a lot of patients neoadjuvantly with aggressive ER-positive tumors that are probably luminal B if we look at them from a genomic perspective. higher Ki-67. They are often ER-positive and progesterone receptor negative. They often have significant residual tumor burden at the time of surgery. Being able to offer them more than just single-agent endocrine therapy is a big plus. We have certainly been doing that routinely in our practice. In the adjuvant setting, that is important.
We have not yet brought genomics into the equation in terms of whether there are patients who have higher-risk genomic scores who would benefit from not just chemotherapy but CDK4/6 inhibitors in the adjuvant setting. I dont know the answer to that question.
What Causes Her2+ Breast Cancer
Breast cancer starts when the cells in the ducts or the lobules of the breast begin to grow uncontrollably, due to the DNA in the cell becoming abnormal.
As part of this abnormal process, sometimes these cells have too many HER2 proteins on the outside of the cells. This extra HER2 protein tells the cells to keep growing, even though they shouldnt be. As this process continues, a mass in the breast forms, and over time, it can begin to grow and spread into other areas of the body.
It is not often known what the trigger is that alters the DNA inside the cell to become abnormal. There are, however, some gene mutations that have been shown to increase someones risk of developing cancer. Though not the only ones, two of these genes are BRCA1 and BRCA2. These genes can be passed down through family members, and the person who gets them has a higher risk of getting breast cancer.
Besides genetics, there are other factors that have been found to increase the risk of developing breast cancer. These risk factors include:
- Increasing age
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What Is Metastatic Cancer
Cancer that spreads from where it started to a distant part of the body is called metastatic cancer. For many types of cancer, it is also called stage IV cancer. The process by which cancer cells spread to other parts of the body is called metastasis.
When observed under a microscope and tested in other ways, metastatic cancer cells have features like that of the primary cancer and not like the cells in the place where the metastatic cancer is found. This is how doctors can tell that it is cancer that has spread from another part of the body.
Metastatic cancer has the same name as the primary cancer. For example, breast cancer that spreads to the lung is called metastatic breast cancer, not lung cancer. It is treated as stage IV breast cancer, not as lung cancer.
Sometimes when people are diagnosed with metastatic cancer, doctors cannot tell where it started. This type of cancer is called cancer of unknown primary origin, or CUP. See the Carcinoma of Unknown Primary page for more information.
What Is The Treatment For Metastatic Breast Cancer
Treatments include many of the same treatments as other stages of breast cancer:
- Radiation therapy
- Hormone therapy For patients diagnosed with Stage IV breast cancer that is hormone receptor positive, hormonal therapy may be the first line of defense against the disease. As long as the drugs are keeping the cancer from progressing, the patient may be kept on the medication for some time. If scans show the progression of the cancer, the medical oncologist may switch to another form of hormonal therapy or possibly stop this therapy and pursue a different line of systemic treatment, such as chemotherapy or biologic targeted therapy.
- Biologic targeted therapy
- Breast surgery It is controversial whether surgery should be done on the breast in the presence of known metastatic disease. In most cases, however, the knowledge of metastasis is discovered after the breast cancer surgery and other treatment has been performed. The cancer returns as a distant recurrence.
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Phase Ii Studies In Breast Cancer
Collectively, these Phase I studies showed that eribulin was well tolerated. Subsequently, the activity of eribulin, mostly in a weekly schedule, was investigated in MBC in a series of Phase II studies ., Most of these studies included patients who had been extensively pretreated with chemotherapy., Given the potential concerns about neurotoxicity from microtubule agents, one study examined the incidence of peripheral neuropathy as the primary endpoint in a second-line treatment setting. More recently, two other studies have evaluated the activity of eribulin in the first-line setting for MBC.,
Metastatic Breast Cancer: Treatments And Possible Consequences
When breast cancer is diagnosed, the aim of treatment is usually to remove all of the tumor. But this is no longer possible if it has spread to other parts of the body. Then the aim of treatment is to keep your overall health and quality of life as good as possible for as long as possible.
The goal of treatment for metastatic breast cancer is to stop or slow down the growth of the tumor. It is also possible to reduce the symptoms and possible side effects of treatment and to treat associated medical conditions. Cancer-related pain can be treated with well-managed pain relief therapy. If treatment is carefully planned and tailored to a person’s specific situation, and if their overall health is good, it is often possible to keep the disease under control for years, even if they have metastatic tumors, and have a good quality of life despite the symptoms.
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Breast Cancer Metastasis: Secondary Sites
Over the years there have been significant improvements and advancements in the diagnosis and treatment of breast cancer. Indeed, breast cancer is now considered to be a manageable disease.
However, there are still over half a million deaths worldwide from breast cancer and over 90% of these women die of metastasis. Consequently, research into metastasis is of vital importance in overcoming deaths from metastatic breast cancers.
Stage IV or metastatic breast cancer, as mentioned earlier, are cancer cells that have spread from the breast to distant sites around the body. Common secondary sites are:-
- Bone: .
Chemotherapy For Metastatic Breast Cancer
Chemotherapy is used as a treatment for most people who have metastatic breast cancer. Whether it is used first-line or not depends on your receptor status, previous treatments, and other factors.
Chemotherapy is a systemic treatment that attacks cancer cells wherever they happen to be in the body. One exception to this is the brain, where the passage of many of these drugs is limited by the protective blood-brain barrier.
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Side Effects And Complications
Anti-estrogens can increase the risk of thrombosis and cause changes in the lining of the womb. Aromatase inhibitors can cause muscle and joint problems, among other things. They can also lower bone density, which increases the risk of bone fractures.
Younger women who are having hormone therapy stop getting their periods. They cannot get pregnant during treatment. The treatment often leads to problems that can also arise during menopause, such as hot flashes, sleep problems, dry skin and dry mucous membranes.
Side Effects And Mental Health
Cancer treatment can be difficult to go through. It often has severe side effects and sometimes leads to complications. The side effects vary depending on the kind of treatment, but they can often be effectively treated themselves. The treatment of side effects is part of what is known as supportive care. If the treatment is too distressing, though, there may be good reasons for deciding not to have treatment.
One common side effect is . The word ‘fatigue’ describes paralyzing physical and mental exhaustion and tiredness that can be accompanied by increased irritability. People may be affected by fatigue the whole time they are having treatment, and sometimes even longer. It is most likely caused by physical and psychological reactions to the disease and the treatment. Fatigue can be very distressing and make people feel down. Even small tasks may become impossible or very difficult to perform. It is important to talk to your doctor and find your own personal way of dealing with fatigue.
Any life-threatening disease that requires repeated courses of physically draining treatment will inevitably end up affecting your mental health too. Almost everyone in this situation will feel down from time to time. If these feelings last for a longer period of time, may develop. It is then important to get treatment because depression is in itself a serious disease.
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What Are Targeted Treatments And How Do They Work In The Body
The tumor profile determines the targeted therapies for which a person with MBC may be a suitable candidate. In those with HER2-positive breast cancer, doctors prescribe medications such as trastuzumab to counteract the HER2 receptor.
Pertuzumab is another MBC agent focused on blocking the HER2 receptor. Doctors often prescribe it in combination with trastuzumab and chemotherapy.
T-DM1 is also an option when treatment has already involved trastuzumab and chemotherapy.
When multiple therapeutic options have not worked, oncologists can weigh up other targeted options specific to a persons condition.
Other HER2 targeted therapies include lapatinib and neratinib
For people with cancer that is negative for the HER2 receptor and positive for the estrogen or progesterone receptors, additional options include palbociclib , which inhibits the enzymes cyclin-dependent kinase 4 and 6, and letrozole or fulvestrant, which are anti-hormone receptor therapies for postmenopausal hormone blockade.
Other CDK4/6 inhibitors include ribociclib and abemaciclib .
What Are The Chances Of Breast Cancer Recurring
Despite huge advancements in breast cancer screening, early detection and treatment, a percentage of breast cancers will recur and spread to distant sites.
Although at the moment, it is almost impossible to say which cancers will recur and at what time period from diagnosis, there are a few factors that are known to increase the risk for recurrence.
These risk factors include:-
- Lymph node involvement and number of lymph nodes affected at the time of diagnosis
- Tumor Size at the time of diagnosis
- A subtype of Breast Cancer and hormonal receptor Status
- The time span from the initial diagnosis to recurrence of breast cancer
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What Does It Mean When Breast Cancer Metastasizes To Bones
As mentioned earlier, metastatic breast cancer is when cancer has spread beyond the breast and the surrounding lymph nodes to other parts of the body. This can happen either because a cancer has come back after treatment or because a cancer did not respond to treatment or wasn’t treated in time, allowing it to spread. In the case of metastatic breast cancer in the bones, cancer cells take up residence in parts of a person’s bone, causing lesions that replace healthy tissue with cancer cells.
Modern science still doesn’t quite understand exactly how cancers metastasize, Nancy Lin, MD, a medical oncologist who specializes in breast cancer treatment at Dana-Farber Cancer Institute in Boston, Massachusetts, tells Health. “We know that at some point the cancer manages to find its way into the bloodstream and then through that is able to get to other parts of the body,” she says. Beyond that, it’s unclear why certain cancers tend to spread to specific spots in the body like the bones, but there are some theories.
Any part of your skeletal system can be impacted by metastatic cancer, but per the American Cancer Society , the spine is the most common site of bone metastasis. Other areas include the hip, femur, upper arm, ribs, and skull.
What About Clinical Trials
Its important that patients know they may be eligible for clinical trials of new, experimental agents when needed. A number of drugs are currently being investigated, including those that block the protein kinases CDK4/6, PIK3CA, and AKT, and drugs that block a mutated estrogen receptor. We are studying drugs that work against the androgen receptor in breast cancer these are typically used in the treatment of prostate cancer. There are also new agents being tested for patients with HER2-positive cancer and immunotherapies that are being evaluated in patients with metastatic breast cancer.
Patients being treated for advanced disease at MSK also can undergo IMPACT testing, which looks for hundreds of cancer genes that may be mutated. Some of these mutations may play a role in cancer growth. We are actively studying drugs that target these mutations.
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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.
When Do People Get A Metastatic Breast Cancer Diagnosis
Metastatic breast cancer can occur at different points:
- De novo metastatic breast cancer: About 6% of women and 9% of men have metastatic breast cancer when theyre first diagnosed with breast cancer.
- Distant recurrence: Most commonly, metastatic breast cancer is diagnosed after the original breast cancer treatment. A recurrence refers to the cancer coming back and spreading to a different part of the body, which can happen even years after the original diagnosis and treatment.
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Everolimus And Hormone Therapy
Everolimus is an mTOR inhibitor. mTOR inhibitors are a class of drugs that may increase the benefit of hormone therapy.
Everolimus is FDA-approved for the treatment of hormone receptor-positive, HER2-negative metastatic breast cancers in postmenopausal women. The combination of everolimus and the aromatase inhibitor exemestane can slow the growth of such cancers better than exemestane alone .
Everolimus is a pill.
Some possible side effects include mouth ulcers, infections, rash, fatigue, diarrhea and decreased appetite.
In rare cases, it can cause lung inflammation, which can cause death. Tell your health care provider right away if you have shortness of breath or other breathing problems while taking this drug.
Adapted from select sources .
Treatment As Part Of A Clinical Study
Clinical studies test medications and non-drug treatments and compare them with other kinds of treatment. For example, participants might be given new drugs, the effects of which are not yet completely known, or for which more experiences with larger patient groups are needed in order for them to be approved. But this does not mean that patients are exposed to incalculable risks. Clinical studies are thoroughly planned following strict quality standards, reviewed by expert committees and carried out by specialists. The effects and side effects of the drugs used are closely monitored. Patients can drop out of the study at any time.
Under certain conditions it might be possible to receive treatment as part of a clinical study. Patients receive particularly intensive care during their participation in clinical studies. But they also have to be prepared to deal with the treatment more intensively and, in many cases, to have more check-ups than usual. In order to weigh up the pros and cons of participating in a clinical study, it is important to get all the information you need and consult and coordinate things with your doctors.
In Germany, the German Society of Senology and the German Clinical Trials Register provide further information and help looking for clinical trials of breast cancer treatments.
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What Can I Expect While Living With Metastatic Breast Cancer
Your care team will monitor you every few months to check if the cancer is responding to treatment, and also to see if you are having any side effects. The process of restaging the cancer includes:
- History/physical exam.
- Blood tests.
- Imaging tests, including CTs and bone scan or PET scan.
Before your scans or tests, its normal to feel anxiety. It may help to bring a friend or family member to the appointment with you.