Breast Cancer Therapy: Right On Target
Medically reviewed on Feb 11, 2018 by L. Anderson, PharmD.
In the Pink: Breast Cancer Death Rates Are Declining
Breast cancer is meeting it's match, and it's encouraging to look at the novel advances in treatments and drug therapy. Numerous lives are saved each year due to early detection. Groundbreaking targeted treatment may extend time in women with advanced, metastatic disease. This truly gives us something to celebrate.
In fact, according to the American Cancer Society, death rates from breast cancer have been declining since 1989. Since 2007, breast cancer death rates have been steady in women younger than 50, but have continued to decrease in older women. These statistics are believed to be the result of earlier detection through screening, increased awareness, lower post-menopausal estrogen hormone use, and improved cancer treatment.
Nonetheless, breast cancer is still the most common type of cancer in the U.S., with more than 255,000 new cases expected in 2017.
Treatment is Always Individualized
A diagnosis of breast cancer is scary and leaves many questions about how to proceed.
But there is no single "best" treatment regimen for breast cancer -- it's always an individual plan. Usually a combination of surgery and medicine is used. Many factors come into play for treatment decisions:
How Is Breast Cancer Treated?
Common types of treatment for breast cancer include:
- Radiation therapy
- Endocrine (anti-estrogen) therapy
- Targeted therapy
Local therapy treats a tumor at the site; surgery and radiation therapy are examples of local therapies.
Systemic therapy are drugs given by mouth or injection to reach cancer cells in the body.
Chemotherapy, endocrine (hormone) therapy, and targeted therapy are "adjuvant" systemic therapies. Adjuvant therapy for breast cancer is given after primary treatment to increase the chance of long-term survival and may include chemotherapy, radiation or hormonal therapy.
Surgery: Often the First Step
Most women with breast cancer usually have some type of surgery. Removing as much of the tumor as possible is key.
Depending upon the stage of the cancer at diagnosis, options include breast-conserving surgery (lumpectomy) or removing one or both breasts (mastectomy). Surgery is also used to check the lymph nodes under the arm for cancer spread, which may also be removed.
In addition, for many women, breast reconstruction can occur at the same time as surgery, or later on, depending upon her preference, the type of surgery, and surgeon experience.
Radiation Therapy: Often Used in Addition to Surgery
Radiation to the breast may be used after breast-conserving surgery or after a mastectomy. Radiation is directed to the cancer area using a large machine that emits high-powered energy to destroy the cancer cells. Radiation therapy will help lower the chance that the cancer will come back after surgery.
Breast radiation is most commonly given 5 days a week for about 5 to 6 weeks. Radiation itself is painless and usually only takes a few minutes after initial set up. Temporary side effects such as swelling in the breast, skin changes or dryness, and fatigue may occur.
Chemotherapy: Often Added to Surgery
Chemotherapy ("chemo") is when oral or injectable drugs are used to kill the cancer cells. Chemo can help prevent a cancer recurrence, limit spreading, or kill cancer cells that have already spread. Chemo is given in cycles, with rest periods, over several months. Treatment will depend, in part, upon the stage at diagnosis.
Common treatments used in breast cancer diagnosed in the earlier stages include the anthracyclines, such as doxorubicin (Adriamycin) and epirubicin (Ellence), and taxanes such as paclitaxel (Taxol) and docetaxel (Taxotere). These may be combined with fluorouracil (5-FU), cyclophosphamide, and carboplatin.
Estrogen and Hormone Blockers
Estrogen can fuel some breast cancers known as estrogen receptor (ER) positive cancers. Roughly 80% of all diagnosed breast cancers are ER-positive. These cancers are hormone sensitive and may be treated with medicines known as hormone therapy, which block estrogen or prevent production.
Hormone therapy may be prescribed to women after surgery to prevent a recurrence of breast cancer, before surgery, or if the cancer returns later. However, a 2017 study in JAMA Oncology noted that many eligible breast cancer survivors are not receiving life-extending hormonal therapies such as tamoxifen or the aromatase inhibitors.
Let's Get Personal: Targeted Therapy
Researchers have developed newer medicines that work only on certain cancers with specific genetic traits. For example, some cancer cells have proteins, like CDK, HER2 or mTOR, that promote rapid or unusual growth. Your doctor can test you to see if you have the kind of cancer that would respond to "targeted" drug therapy.
There are several targeted therapies doctors might use for more advanced cases of breast cancer. Because these drugs are "targeted", they may be linked with fewer side effects, but risks are still present, so be sure to discuss each option with your physician.
Drugs That Target the HER2 Protein
All women are screened for the HER2 protein when they are first diagnosed with breast cancer. In roughly 1 out of 5 women (20%), the HER2 protein is found on the surface of the cancer cell. These cancers are known as HER2 positive. It is important to target treatment against this protein, as these breast cancers can be more aggressive.
Drugs that specifically target this protein, known as HER2 inhibitors, include:
- Herceptin (trastuzumab)
- Perjeta (pertuzumab)
- Kadcyla (ado-trastuzumab emtansine)
- Tykerb (lapatinib)
- [Nerlynx](https://www.drugs.com/history/nerlynx.html) (neratinib)
- [Ogivri](https://www.drugs.com/history/ogivri.html) (trastuzumab-dkst), a biosimilar to Herceptin (not an interchangeable product)
Ogivri is the first biosimilar approved in the U.S. for the treatment of breast cancer.
When Are HER2 Inhibitors Used?
These drugs are often used with other breast cancer drugs in women who are considered HER2 positive. Herceptin, Ogivri, Perjeta and Kadcyla are all intravenous targeted drugs and are considered monoclonal antibodies, an immune protein that is man-made.
Herceptin, Ogiviri, and Perjeta can both be used to treat early and more advanced breast cancer; Perjeta may be used before surgery in early cancer. Trastuzumab (Herceptin) is commonly used and has been shown to significantly reduce the risk of breast cancer returning in HER2-positive breast cancers.
Kadcyla is used in advanced, metastitic breast cancer in women who have already received Herceptin. Tykerb, a tyrosine kinase inhibitor, is also used in advanced breast cancer and is given as a pill. Tykerb may be used if trastuzumab (Herceptin), trastuzumab-dkst (Ogivri) or (ado-trastuzumab emtansine) Kadcyla are no longer working.
Nerlynx: A Newer HER2 Agent
In July 2017, the FDA approved Nerlynx (neratinib), a once-daily oral tyrosine kinase inhibitor for the extended adjuvant treatment (for an extended period of time after surgery) of early stage HER2-positive breast cancer, following adjuvant trastuzumab (Herceptin) based therapy. It is used to lower the risk of breast cancer recurrence.
Nerlynx is considered targeted therapy but is not an "immune" targeted therapy such as Herceptin or Kadcyla. It works by blocking several enzymes and the cancer cells’ ability to receive growth signals. You take Nerlynx once a day by mouth for up to one year. It can cause severe diarrhea, and an antidiarrheal called loperamide (e.g., Imodium) is recommended for the first 56 days of treatment and then as needed to help lessen this side effect.
Side Effects With HER2 Inhibitors
HER2 inhibitors can have fewer effects than traditional chemotherapy. However, the antibody drugs Herceptin, Ogivri, Perjeta, and Kadcyla can cause a type of heart damage known as congestive heart failure, but patients are monitored for this side effect, which can improve if the drug is stopped.
Tykerb and Nerlynx can lead to severe diarrhea and liver toxicity. Tykerb also can cause a side effect known as "hand-foot syndrome" (palmar-plantar erythrodysesthesia) where hands and feet may turn red, sore, blister and peel.
Women who are pregnant should not take targeted therapies. There are many other possible side effects with these drugs; always discuss side effects with your doctor prior to starting treatment.
Ibrance and Afinitor: Boosting Hormone Therapy
Targeted drugs can be used along with certain hormone therapies to fight advanced hormone receptor-positive (HR+) breast cancer in women who are also determined to be HER2-negative.
Ibrance (palbociclib) blocks proteins in the cell called CDK4 and CDK6. Blocking these proteins helps to slow down cell division that leads to new cancer cell growth. Ibrance is used two ways: either with the aromatase inhibitor Femara (letrozole) as initial endocrine-based therapy in postmenopausal women; or with the estrogen receptor antagonist Faslodex (fulvestrant) in women with disease progression following endocrine therapy. Pre/perimenopausal women treated with the combination of Ibrance plus fulvestrant therapy should be treated with luteinizing hormone-releasing hormone (LHRH) agonists according to current clinical practice standards.
Afinitor (everolimus) blocks the mTOR protein to limit cancer cell growth and is used with the hormone therapy Aromasin (exemestane) after failure of treatment with letrozole or anastrozole. Afinitor is taken by mouth as a tablet once daily at the same time every day. Take with food OR without food consistently.
Ibrance: Dosing and Side Effects
Ibrance is an oral capsule taken once a day for 21 days, with a 7 day break before starting again. When given with the hormone blocker Femara, Femara is taken continuously throughout the 28 days. When Ibrance is taken with Faslodex, Faslodex is taken on Days 1, 15, 29, and once monthly thereafter. Your doctor will direct your dosing and therapy.
Ibrance should be taken with food at the same time each day. Avoid grapefruit and grapefruit juice while taking Ibrance, as these can increase the blood levels of Ibrance, possibly leading to side effects. Be sure not to open or crush the capsule before taking it.
Side effects tend to be mild. Ibrance can lower the body's ability to fight off infections and lead to anemia (low red blood cell counts). Other common side effects include fatigue, nausea, hair loss, diarrhea and mouth sores. If the patient vomits or misses a dose, an additional dose should NOT be taken. The next prescribed dose should be taken at the usual time.
Afinitor: Dosing and Side Effects
Afinitor is another targeted drug that boosts the effect of hormone therapy given to women with breast cancer. It is used in women whose cancers have grown while taking the hormone blockers Arimidex or Femara. Afinitor is given as a tablet taken at the same time each day and is given with Aromasin (exemestane).
The tablet should be swallowed whole, and should be taken either with or without food consistently. Grapefruit and grapefruit juice should be avoided. Common side effects with Afinitor may include mouth sores, diarrhea, nausea, diarrhea, fatigue, infections, increased cholesterol, and shortness of breath. Your blood work will be monitored regularly.
Kisqali: Approved March 2017
Kisqali (ribociclib) from Novartis was FDA-approved on March 13, 2017. Kisqali is a kinase inhibitor, and in the same drug class as Pfizer's Ibrance (palbociclib) - specifically both agents are CDK4/6 inhibitors for breast cancer. In labeling, Kisqali is recommended for use alongside the aromatase inhibitor Femara (letrozole) for the treatment of postmenopausal women with HR+/HER2- metastatic breast cancer. The new drug became commercially available on March 14, 2017.
In the MONALEESA-2 Phase III, randomized studies, 668 postmenopausal women with HR+/HER2- metastatic breast cancer received either Kisqali plus letrozole, or placebo plus letrozole. The patients who received Kisqali plus letrozole reduced their risk of disease worsening or death by 44% over letrozole alone, and 53% of the women saw their tumors shrink by at least 30%.
Kisqali tablets are given as a 600 mg dose once daily for 21 days followed by 7 days off in a 28 day cycle with an aromatase inhibitor. Common side effects include low white blood cells (neutropenia, leukopenia), upset stomach (nausea), vomiting, fatigue, diarrhea, hair loss (alopecia), headache and back pain. Kisqali also has numerous drug and food interactions due to CYP3A4 metabolism in the liver, and requires ECG monitoring due to prolongation of the QT interval, a type of abnormal heart rhythm.
Verzenio: Approved September 2017
Lilly’s Verzenio (abemaciclib), a CDK 4/6 kinase inhibitor breast cancer treatment, was FDA-approved in September 2017. It too is a targeted treatment and is used in 2 patient populations:
- either with fulvestrant (Faslodex) in patients with HR-positive, HER2-negative advanced or metastatic breast cancer that progressed after endocrine therapy
- as monotherapy for patients with HR-positive, HER2-negative advanced or metastatic breast cancer who previously received endocrine therapy and chemotherapy.
In studies In combination with fulvestrant, the median progression-free survival was 16.4 months compared to 9.3 months for the fulvestrant/placebo group. In monotherapy trials, 19.7% of patients taking Verzenio experienced complete or partial shrinkage of their tumors for a median 8.6 months. Palbociclib (Ibrance) and ribociclib (Kisqali) are other kinase inhibitors approved for metastatic breast cancer.
Verzenio comes as a tablet of 50, 100, 150, and 200 mg strength. It is taken with or without food.
- The recommended starting dose in combination with fulvestrant is 150 mg twice daily.
- The recommended starting dose when used as monotherapy is 200 mg twice daily.
The most common adverse reactions (incidence ≥20%) included: diarrhea, low white blood cells, nausea, stomach pain, infections, fatigue, anemia, decreased appetite, vomiting, headache, and low blood platelet counts.
Lynparza for Breast Cancer with BRCA Mutations
About 5% to 10% of patients with any type of breast cancer have a breast cancer susceptibility gene (BRCA) gene mutation. BRCA genes normally work to repair damaged DNA and prevent tumor development.
In January 2018, the FDA approved the expanded use of Lynparza (olaparib tablets) as the first approved treatment for patients with metastatic breast cancer with a BRCA mutated, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer, who have been previously treated with chemotherapy. Patients with hormone receptor (HR)-positive breast cancer should have been treated with a prior hormonal (endocrine) therapy or be considered inappropriate for endocrine treatment.
Lynparza, also approved to treat BRCA ovarian cancer, is the first PARP inhibitor approved to treat breast cancer.
In clinical studies, the median progression-free survival for patients taking Lynparza was 7 months compared to 4.2 months for patients using chemotherapy only.
Future Research: The Sister Study
Genetics can play a large role in breast cancer. To gain a better understanding of genetic variables, the National Institute of Environmental Health Sciences has recruited over 50,000 women between the ages of 35 to 74 for The Sister Study and The Two Sister Study. These women, whose sister had breast cancer, will provide data for identifying risk factors that may boost breast cancer prevention.
Researchers believe The Sister Studies will help us better understand genetic and environmental factors linked with breast cancer. To learn more, you can call toll-free at 877-4SISTER (877-474-7837). If you or your sister, or any other loved one, are breast cancer survivors, take time out to celebrate your special bond and paint the town pink.
Share Your Experience to Discover Others
Breast cancer treatment can be a long and trying process for many women. Lean upon your team of healthcare providers, family and caretakers for support. Know that you do not have to fight alone. It's always good to have the support of similar women with common fears, questions -- and yes -- triumphs, too!
Consider joining the Drugs.com Breast Cancer Support Group. Here, you can voice opinions, raise concerns, and follow along with the groundbreaking medical news that is occurring almost daily in the area of breast cancer research. Empower yourself with the knowledge you need.
Finished: Breast Cancer Therapy: Right On Target
- FDA Approves Lynparza (olaparib tablets) for Germline BRCA-Mutated Metastatic Breast Cancer. Drugs.com. Jan 12, 2018. Accessed Feb 5, 2018 at https://www.drugs.com/newdrugs/fda-approves-lynparza-olaparib-germline-brca-mutated-metastatic-breast-cancer-4678.html
- Ogivri Product Labeling. 2017. Mylan Pharmaceuticals. Accessed Dec. 11, 2017 at https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/761074s000lbl.pdf
- Verzenio Product Label. Eli Lilly and Co. Indianapolis, IN. Accessed October 29, 2017 at http://uspl.lilly.com/verzenio/verzenio.html#pi
- FDA Approves Nerlynx. New Drugs. Drugs.com. Accessed July 31, 2017 at https://www.drugs.com/newdrugs/fda-approves-nerlynx-neratinib-extended-adjuvant-early-stage-her2-positive-breast-cancer-4561.html
- Ibrance Product Labeling. Pfizer. Feb. 2016. Accessed Feb. 7, 2017 at http://labeling.pfizer.com/ShowLabeling.aspx?id=2191
- Helfand C. With Novartis' Kisqali, Pfizer faces its first in-class threat for Ibrance. FierePharma. March 14, 2017. Accessed March 14, 2017 at http://www.fiercepharma.com/marketing/novartis-kisqali-pfizer-has-its-first-class-competition-for-ibrance-but-how-much-does-it
- Afinitor Product Labeling. Novartis. June 2016. Accessed Feb. 6, 2017. https://www.pharma.us.novartis.com/sites/www.pharma.us.novartis.com/files/afinitor.pdf
- Kisqali Product Label. Novartis. March 2014. Accessed March 14, 2017 at http://www.accessdata.fda.gov/drugsatfda_docs/label/2017/209092s000lbl.pdf
- American Cancer Society. Breast Cancer. Targted therapy for breast cancer. Last Revised: March 14, 2017. Accessed July 31, 2017 at http://www.cancer.org/cancer/breastcancer/detailedguide/breast-cancer-treating-targeted-therapy
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