Breast Cancer: Treatment and Prevention Options
Overview: Treatment of Breast Cancer
Breast cancer is the most common female cancer in the U.S. with the exception of skin cancer. The primary risk factors for having breast cancer diagnosis include being a woman and older age, with most breast cancers occurring after the age of 50.
Currently, the average risk of developing breast cancer over 80 years of life is 12.5%. However, today, 90% of women with breast cancer are still alive five years after their diagnosis due to earlier detection and advanced treatment options.
Treatment of breast cancer often requires a multifactorial approach, using surgery, radiation and medications. Breast cancer may be treated with local therapy, systemic therapy, or both.
Local therapies, such as surgery and radiation, are used to remove or destroy breast cancer in a specific area. If the breast cancer has spread to other parts of the body, local therapy may also be used to control cancer in those specific areas, such as in the lung or bone.
Systemic therapies, such as chemotherapy, hormonal therapy and biologic or targeted treatments are used to destroy or control cancer throughout the body. Sometimes, systemic therapy is used to shrink the tumor before local therapy like surgery. Systemic therapy is also used to prevent the cancer from coming back, or to treat cancer that has spread.
Chemotherapy and HER2 inhibitors, if indicated, are often the selected agents used prior to surgery; however, most people will not need chemotherapy before surgery.
Surgery and Radiation
Surgery is the most common treatment for breast cancer, and there are several types:
Breast-sparing (or breast-conserving) surgery removes the cancer but not the breast. Examples are lumpectomy and segmental (partial) mastectomy. Radiation therapy is usually given after breast-sparing surgery to destroy remaining cancer cells in the area.
Mastectomy is an operation to remove the breast (or as much of the breast as possible).
Breast reconstruction is often an option at the same time or after the mastectomy.
In most cases, the surgeon also removes lymph nodes under the arm to help determine whether cancer cells have entered the lymphatic system. This is called an axillary lymph node biopsy.
In certain cases, a sentinel lymph node biopsy may be needed, where the lymph node closest to the tumor is removed to determine if cancer has spread to other places in your body. By knowing this information, your doctor can better select your best treatment.
Risks of surgery
Breast cancer surgery causes short-term pain and tenderness in the area of the operation and also carries a risk of infection, poor wound healing, bleeding, or a reaction to the anesthesia used during surgery.
Removal of a breast can cause a weight imbalance, which can result in discomfort in the neck and back. Skin in the area where the breast was removed may be tight, the muscles of the arm and shoulder may feel stiff, and nerves that may be injured or cut during surgery can cause numbness and tingling in the chest, underarm, shoulder, and upper arm. These feelings usually go away within a few weeks or months.
Your surgeon will outline the specific risks associated with your surgery, the timelines for recovery, and follow-up appointments.
Radiation therapy
Radiation therapy (radiotherapy) is the use of high-energy rays to kill cancer cells. The radiation may be directed at the breast by a machine (external radiation), or may come from radioactive material placed in thin plastic tubes that are placed directly in the breast (implant radiation). Sometimes, both types of radiation therapy are used.
Before surgery, radiation therapy, alone or with chemotherapy or hormonal therapy, is sometimes used to destroy cancer cells and shrink tumors. This approach is most often used in cases in which the breast tumor is large or not easily removed by surgery.
Radiation side effects can occur. During radiation therapy, patients may become extremely tired, especially after several treatments. It is also common for the skin in the treated area to become red, dry, tender, and itchy. The breast may feel heavy and hard, but these conditions will clear up with time. Toward the end of treatment, the skin may become moist and weepy but exposing this area to air as much as possible will help the healing process.
Chemotherapy
Chemotherapy is the use of drugs to kill cancer cells. Chemotherapy for breast cancer is usually a combination of drugs given in a pill or by injection.
The side effects of chemotherapy depend mainly on the specific drugs and the dose. These include:
infections or bleeding: blood cells, which fight infection, help the blood to clot, and carry oxygen to all parts of the body. When blood cells are affected, patients are more likely to get infections, anemia, may bruise or bleed easily, and may feel unusually weak and very tired.
hair loss, mouth sores, stomach upset: rapidly dividing cells in hair roots and cells that line the digestive tract may also be affected. As a result, side effects may include loss of hair, poor appetite, nausea and vomiting, diarrhea, or mouth and lip sores.
In general, anti-cancer drugs affect rapidly dividing cells. Many of these side effects can now be controlled, thanks to other new or improved medications. Side effects generally are short-term and gradually go away. Hair almost always grows back, but it may be different in color and texture.
Hormone therapy
Hormonal (endocrine) therapy prevents the growth of hormone dependent cancer cells. This treatment may include the use of drugs, or surgery to remove the ovaries and possibly the fallopian tubes (oophorectomy or salpingo-oophorectomy). Hormone therapy is not the same thing as hormone-replacement therapy to lessen symptoms from menopause such as hot flashes and vaginal dryness.
Medications used in this type of adjuvant treatment are typically the selective estrogen receptor modulators (SERMs) or aromatase inhibitors (AIs). These agents block estrogen’s ability to fuel breast cancer. This treatment has been shown to reduce the risk of recurrence and death from breast cancer in hormone receptor-positive women. These are usually oral medications taken daily for 5 to 10 years.
The side effects of hormonal therapy depend largely on the specific drug or type of treatment. For example, tamoxifen, one of the most common hormonal treatments, may cause hot flashes, vaginal discharge or irritation, nausea, mood changes, and irregular periods.
Biologics
Biologic therapy is a treatment designed to enhance the body's natural defenses against cancer. For example, monoclonal antibodies can target breast cancer cells that have too much of a protein known as human epidermal growth factor receptor-2 (HER-2). Blocking HER-2 slows or stops the growth of these cells.
The side effects of biological therapy differ with the types of substances used, and from patient to patient. Rashes or swelling where the biological therapy is injected are common. Flu-like symptoms also may occur.
Common Drugs Used in the Treatment of Breast Cancer
Hormone (Endocrine) Therapy
Estrogen or progesterone, naturally occurring female hormones, can fuel breast cancers known as hormone receptor (HR+) positive cancers. These cancers are often treated with a type of hormone therapy that blocks the cancer from getting the estrogen or progesterone or slows down the production. Most breast cancers, about 80%, are hormone receptor-positive.
Endocrine therapy include aromatase inhibitors (AIs), selective estrogen receptor modulators (SERMs), and the estrogen receptor antagonist fulvestrant (Faslodex), also called an anti-estrogen or a selective estrogen receptor degrader (SERD). AIs and SERMs are all given orally, while fulvestrant (Faslodex) is given by intramuscular injection.
Hormone therapy is used for most HR+ breast cancers and is often the first treatment given. It may be prescribed before surgery, after surgery, or if the cancer returns later. Selection of which drug is based on whether you are pre- or postmenopausal. They are usually taken for 5 to 10 years.
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Brand name examples |
Use |
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Postmenopausal; early/locally advanced or metastatic disease |
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Postmenopausal; early/locally advanced or metastatic disease |
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Postmenopausal; advanced or metastatic disease |
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Postmenopausal; metastatic disease |
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Postmenopausal; early/locally advanced or metastatic disease |
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Nolvadex, Soltamox |
Pre- and postmenopausal; early/locally advanced or metastatic disease |
How do aromatase inhibitors work?
Aromatase inhibitors (AIs) are used to treat HR+ early, locally advanced and metastatic (spread to other parts of the body) breast cancers. Aromatase inhibitors (AIs) work by blocking estrogen production in postmenopausal women with HR+ breast cancer. After menopause, estrogen can still be made in fat cells, adrenal glands and the liver.
AIs in women with HR+ breast cancer can:
lower the risk of breast cancer recurrence
lower the risk of breast cancer occurring in the opposite breast
lower the risk of death from breast cancer
AIs do not block estrogen production from the ovaries, so they must be used with ovarian suppression in premenopausal women. Ovarian suppression can occur with surgery by removing the ovaries, which is permanent, or by using a medication for ovarian suppression, which is temporary.
How do selective estrogen receptor agents work?
SERMs or SERDs work to either block the receptors so that estrogen cannot have an effect to fuel the cancer, or both block and destroy the estrogen receptor.
SERMS can be used in premenopausal women with breast cancer who are HR positive, HER2 negative.
SERMs or SERDs can be used in postmenopausal women who are HR positive, HER2 negative.
Chemotherapy
Chemotherapy (“chemo”) drugs work in breast cancer by disrupting the life cycle of the cancer cell. Most people receive chemotherapy for breast cancer after they’ve had surgery, but you might receive it before surgery to help shrink your tumor in some cases. Chemotherapy is a treatment option for most forms of breast cancer. It can be used for treating early and locally advanced breast cancer as well as metastatic disease. Chemotherapy might also be called antineoplastic or cytotoxic therapy.
Neoadjuvant chemotherapy is chemotherapy given before surgery to shrink the tumor size. Adjuvant chemotherapy is therapy given after surgery, but before radiation treatment, and helps to kill any remaining cancer cells.
How are chemotherapy drugs given?
Chemotherapy drugs are typically given by mouth (oral) or by injection into the vein. You may receive treatment daily, weekly, or every few weeks. They are often used in two or three drug regimens, either together or one after another, so you might received both an oral and an injected drug. Chemotherapy is usually given in cycles over a period of 3 to 6 months. You will have several days or weeks off between treatments, which will help you to recover.
There are many classes of chemotherapy used in breast cancer treatment. Your combination of drugs determines your treatment schedule. Your doctor may call these regimens by abbreviations such as “AC” (Adriamycin and Cytoxan) or “CAF” (Cytoxan, Adriamycin, and fluorouracil), or TAC (docetaxel, doxorubicin and cyclophosphamide). Targeted drugs, such as trastuzumab (Herceptin), pertuzumab (Perjeta) or neratinib (Nerlynx) may also be used in HER2+ breast cancer regimens along with chemotherapy agents
Your physician will explain your treatment plan and schedule for you. The choice is very individualized and based on your specific circumstances. Your treatment plan will be based upon the stage and characteristics of the cancer, your previous treatments, your age, your preferences, and other patient specific information, such as interactions with other medications you take or health conditions you might have.
Anthracyclines
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Anthracycline agents are a class of antibiotic antineoplastics drugs that block cancer growth in several different ways. They are derived from microorganisms like bacteria, and some drugs in this class are used to treat breast cancer.
Anthracyclines work by inhibiting the synthesis of DNA, promoting free radical creation, and blocking the action of certain enzymes. Heart toxicity is a major drawback when using anthracyclines.
Alkylating agents and Platinum Analogs
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Paraplatin, Carboplatin Novaplus |
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Cytoxan (brand discontinued) |
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Tepadina |
Alkylating agents were one of the first classes of chemotherapy, dating back to the 1940's. These agents work by causing breakage of the DNA, RNA, disrupting protein synthesis. This action affects the ability of the cancer cell to multiply, which leads to cell death.
Carboplatin is further classified as a platinum analog, cyclophosphamide as a nitrogen mustard, and thiotepa as an ethylenimine.
Antimetabolites
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Generic name |
Brand name examples |
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fluorouracil (5-FU) |
Adrucil (brand discontinued) |
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methotrexate (MTX) |
Antimetabolites are a class of drug that interfere with enzymes needed for DNA synthesis. These drugs are similar to normal substances found in the cell already. When the breast cancer cells incorporate these substances into their cellular metabolism at a very specific phase of cell replication, they cannot divide.
These agents are further classified based on substances they affect in the cells needed for growth. For example, folic acid antagonists like methotrexate interfere with the use of the B vitamin folic acid to exert their cancer-killing effect. This leads to a folic acid deficiency in the cells, both cancer cells and healthy cells, and causes their death. Your doctor can give you special medication to treat the vitamin deficiency.
Mitotic Inhibitors
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paclitaxel, protein-bound |
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Mitotic inhibitors come from natural plant sources, and these drugs are used to treat particular types of cancer, such as leukemia, lung cancer, or breast cancer. Mitotic inhibitors affect cancer cells more than healthy cells because cancer cells divide more rapidly.
These drugs work by inhibiting cell division (mitosis) where a single cell divides into two genetically identical cells. Mitotc inhibitors block the formation of microtubules, which are structures needed to pull the cell apart whein it divides.
HER2 Inhibitors
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Brand name examples |
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ado-trastuzumab emtansine |
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hyaluronidase and trastuzumab |
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trastuzumab-anns (biosimilar) |
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traztuzumab-dkst (biosimilar) |
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trastuzumab-dttb (biosimilar) |
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traztuzumab-pkrb (biosimilar) |
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trastuzumab-qyyp (biosimilar) |
In roughly 20% of women with breast cancer, the HER2 protein is found on the surface of the cancer cell. All women are screened for this protein when they are first diagnosed.
HER2-targeted therapy, known as HER2 inhibitors, are a standard treatment for HER2-positive breast cancers, which can be more aggressive. They are often used with other cancer drugs for early and locally advanced tumors, metastatic disease, and in neoadjuvant treatment before surgery.
These medications are given by injection or orally. HER2 therapy is not used for HER2 negative breast cancer.
Side effects vary by drug given, but may include serious heart effects such as congestive heart failure, diarrhea, skin or liver toxicity.
Herceptin (trastuzumab) is commonly used and has been shown to lower the chance for a recurrence of HER2+ breast cancer.
CDK 4/6 Inhibitors
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CDK (cyclin-dependent kinase) is a protein enzyme that supports growth and division of cells. CDK 4/6 inhibitors are targeted therapies for hormone positive, HER2-negative advanced or metastatic breast cancers (MBCs). MBCs have spread to other areas in the body. These drugs block the cyclin-dependent kinase (CDK) 4/6 proteins to slow cell division and breast cancer growth.
These agents are used in various ways: they might be combined with an aromatase inhibitor (AI) or fulvestrant in women; used as first-line or second-line treatment for MBC. When used in pre/perimenopausal women, they are used along with an LHRH analog. Ibrance is also approved for use in men with breast cancer. They are given as oral pills, typically once or twice a day.
Side effects vary by drug, but may include heart rhythm problems, diarrhea, low white blood cell counts, nausea, tiredness, mouth sore, infections, vomiting, hair loss, rash, or cough, among others.
In 2019, the FDA reported that a severe lung side effect (interstitial lung disease (ILD) and/or pneumonitis) can occur in patients treated with CDK4/6 inhibitors. This is a rare side effect, but one you should discuss with your doctor prior to treatment.
Mammalian Target of Rapamycin (mTOR) Inhibitors
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Mammalian target of rapamycin (mTOR) inhibitors: Everolimus is a targeted therapy used for hormone positive, HER2-negative breast cancers. They are given to postmenopausal women in combination with exemestane, after treatment failure with letrozole or anastrozole.
Mammalian target of rapamycin (mTOR) inhibitors block the activity of the mammalian target of rapamycin. mTOR is a protein kinase enzyme that affects cell growth and blood vessel development. In certain cancers the mTOR pathway is more active.
Common side effects of Afinitor include: infection, decreased hemoglobin, increased blood glucose, low white blood cells, and mouth sores.
Phosphatidylinositol-3-Kinase (PI3K) Inhibitor
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Phosphatidylinositol-3-Kinase (PI3K) inhibitors are a newer class of cancer drug. Alpelisib (Piqray) is the first approved PI3K inhibitor and is used only if your cancer has a specific genetic marker (an abnormal "PIK3CA" gene). Your doctor will test you for this gene.
Alpelisib (Picray) is given in combination with the hormonal therapy fulvestrant (Faslodex) for men and postmenopausal women with hormone receptor-positive, HER2-negative metastatic breast cancer (with the PIK3CA gene mutation) that has worsened during or after hormonal therapy. Metastatic breast cancer has spread to other parts of the body, like the bones, brain, or lungs.
Common side effects may include: increased blood sugar levels, diarrhea, rash, low white blood cells, nausea, ALT increased, fatigue, kidney or liver toxicity, hair loss, anemia, decreased appetite, and mouth sores, among others.
Poly (ADP-ribose) polymerase (PARP) inhibitors
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Poly (ADP-ribose) polymerase (PARP) inhibitors, also called PARP inhibitors, are used to treat cancers that have errors in their DNA repair genes.
Olaparib (Lynparza) is used for the treatment of metastatic HER2-negative breast cancer and BRCA1 or BRCA2 gene mutation in patients who have previously received chemotherapy.
Talazoparib (Talzenna) is used to treat BRCA1 or BRCA2 gene mutation, triple negative breast cancer, meaning it is hormone (ER/PR) negative and HER2-negative but has abnormal BRCA genes, as determined by a specific test. Your healthcare provider may test you for these genes.
Side effects vary among individual drugs, but may include: anemia, low white blood cell counts, nausea and vomiting, hair loss, cough, and diarrhea, among others.
Tropomyosin receptor kinase (TRK) Inhibitor
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Larotrectinib (Vitrakvi) is an oral selective tropomyosin receptor kinase (TRK) inhibitor. Multikinase inhibitors such as larotrectinib work by blocking certain TRK proteins in the cell or on the cell surface, which may cause tumor growth and more aggressive cancer.
Larotrectinib (Vitrakvi) is used for solid tumors (such as breast cancer) with an NTRK fusion protein without a known acquired resistance mutation that is metastatic or cannot be removed with surgery and has worsened with other treatments.
Side effects can include fatigue, nausea, vomiting, cough, constipation, diarrhea, liver toxicity, and dizziness.
Anti-PD-1 Monoclonal Antibodies
Immunotherapy or biologic therapy such as anti-PD-1 monoclonal antibodies are some of the latest advances in breast cancer treatment and cancer treatment overall. These drugs may also be called immune checkpoint inhibitors. Some of these checkpoints are called PD-1, PD-L1, and CTLA-4 receptors, which are protein receptors or ligands on cell surfaces. By blocking these receptor sites, immunotherapy can help boost the body's own immune system to further fight many types of cancer.
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Atezolizumab (Tecentriq) was FDA approved in 2019 to be used in combination with protein-bound paclitaxel (Abraxane), a chemotherapy agent, for the treatment of metastatic triple-negative breast cancer (HER2 negative and ER/PR negative breast cancer). Atezolizumab targets PD-L1.
Pembrolizumab (Keytruda) was approved in 2017 for unresectable or metastatic solid tumors (which may include breast cancer) with a biomarker referred to as microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR). This indication covers patients with solid tumors that have progressed following prior treatment and who have no satisfactory alternative treatment options. Pembrolizumab targets PD-1 ligands.
Side effects with anti-PD-1 therapies vary based on drug and other combined treatments: common side effects can include: fatigue, muscle or joint pain, decreased appetite, itching, diarrhea, nausea, rash, fever, cough, shortness of breath, constipation, and stomach pain, among others.
Breast Cancer Prevention in Women at High Risk
Some women who have not previously been diagnosed with breast cancer may be determined to be at higher risk for developing breast cancer. This can be determined by an assessment done by your doctor looking at your risk factors. A discussion of options for breast cancer risk reduction may be warranted with your physician.
However, risk factor assessment cannot predict with 100% accuracy if you will, or will not, develop breast cancer. It is important to discuss your possible risk factors with your doctor. It is also important to weigh the risk of taking a medication long-term versus the predicted risk for getting breast cancer.
Factors that affect breast cancer risk include:
Age - women 35 years of age or older
Women with a history of lobular carcinoma in situ (LCIS) or atypical hyperplasia
Genetic profile (presence of BRCA mutation)
Other factors such as age at first menstrual period, age at first live birth, number of 1st degree relatives with breast cancer, the results of past breast biopsies, if any.
Women with a 5-year calculated risk of breast cancer over a certain percentage, using tools such as the Breast Cancer Risk Assessment Tool. Always discuss the results of any health tool with your doctor for a better understanding of the results as they pertain to you.
All of the preventive agents recommended by the American Society of Clinical Oncology (ASCO) as of September 2019 work to prevent only estrogen receptor (ER) positive tumors.
Medications Used to Help Prevent Invasive Breast Cancer in Women at High Risk
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Brand name examples |
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Postmenopausal |
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Postmenopausal |
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Postmenopausal |
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Nolvadex, Soltamox |
Premenopausal; Postmenopausal |
These include the selective estrogen receptor modulators (SERMs) tamoxifen or raloxifene, or the aromatase inhibitors (AIs) anastrozole or exemestane. Raloxifene (Evista) is given to lower the risk of invasive breast cancer in postmenopausal women with osteoporosis, or other postmenopausal women at risk of invasive breast cancer. Evista is not a cancer medication and will not treat breast cancer.
These medications are typically given for 5 years or longer, and can lower the risk of breast cancer development by 40% to 65%. The cancer prevention effects last long-term, even after the medication is stopped.
The choice of which agent you use will depend upon if you have been through menopause, the side effect profile of each medication, past medical history, and cost concerns or insurance coverage.
Premenopausal women typically use tamoxifen, while postmenopausal women can use either tamoxifen or the aromatase inhibitors (AIs). AIs are not used in premenopausal women with ovaries as they may elevate estrogen production, which can further increase risk for breast cancer.
The side effects of these drugs used over 5 years or longer should be discussed with your doctor. Depending upon which drug you use, these effects may include:
menopausal symptoms: hot flashes, night sweats, possible weight gain
vaginal dryness
blood clots in the legs
uterine cancer
weakened bones (with aromatase inhibitors)
In some women at high risk, a breast MRI may be used as a preventive tool for breast cancer detection. A breast MRI is used with a mammogram to image your breasts, not as a replacement for a mammogram.
Triple-negative breast cancer is the most common type of breast cancer found in women with BRCA1 mutations. Triple negative breast cancer is hormone negative (estrogen receptor/progesterone receptor negative) and HER2-negative but has abnormal BRCA genes, as determined by a genetic test.
Women with a very high risk of breast cancer, for example with BRCA gene mutations, may decide to have their breasts and/or ovaries surgically removed to help prevent the occurrence of breast cancer and ovarian cancer. This is a significant decision that should only be made in conjunction with a genetic specialist, oncologist and surgeon.
Learn More: Genetic testing for breast cancer: Psychological and social impact
Lifestyle Changes for Breast Cancer Prevention
The primary risk factors for developing breast cancer include being a woman and older age, as most breast cancers are found in women over 50 years of age. Currently, the average risk of developing breast cancer over an 80-year lifespan is about 1-in-8 (a 12.5% chance). Even if you are not at a higher than average risk for breast cancer development, there are lifestyle changes that you can implement to help maintain a normal risk for breast cancer.
limit or avoid alcohol consumption, no more than 1 alcoholic drink a day; even low levels of alcohol use are linked with breast cancer.
don't smoke
maintain a healthy weight
stay active and exercise regularly (150 minutes per week of moderate activity)
breast feed
limit use of systemic hormone therapies for menopausal symptoms (local, vaginal estrogen does not increase the risk for breast cancer).
avoid unnecessary radiationon
eat a healthy, plant-based diet, through imaging tests like a CT scan
avoid environmental polluti supplemented with healthy nuts, olive oil, and avoidance of excessive red meat
Latest Research in the Treatment of Breast Cancer
Many studies of new approaches for patients with breast cancer are underway. Current areas of research and treatment advances include:
Research evaluating best practice with genetic testing and treatments for BRCA1 and BRCA2 mutations
Research looking at environmental causes of breast cancer
Prevention with aromatase inhibitors
Investigation into certain dietary supplements to reduce the risk of breast cancer although published data is scarce.
Further studies evaluating immunotherapy and targeted drugs for treatment of breast cancer
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