Breast Cancer Therapy: Right On Target
Medically reviewed by Leigh Ann Anderson, PharmD. Last updated on Feb 21, 2021.
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. Breast cancer is the most common cancer in American women, except for skin cancers. Numerous lives are saved each year due to early detection.
Overall, breast cancer is still the most common type of cancer in the U.S. based on 2020 statistics, with about 281,550 new cases of invasive breast cancer in women expected in 2021, and an estimated 43,600 breast cancer deaths. In men, roughly 2,650 new cases of invasive breast cancer will be diagnosed in 2021, and 530 men will die.
The good news is groundbreaking targeted treatment may extend survival time in advanced, metastatic disease. And death rates are declining: with rates going down in women over 50 years of age since 2007.
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.
Special treatments for BRCA-gene related (genetic) breast cancers are now approved, too.
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 (sentinel node biopsy) for cancer spread, and they can also be removed, if needed.
Related: Sentinel Node Biopsy Overview
In addition, for many women, breast reconstruction can occur at the same time as surgery, or later on, depending upon the type of surgery, surgeon recommendations, and her preference.
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 may be given 5 days a week for about 5 to 6 weeks. Accelerated radiation approaches are now possible, too, shortening treatment time to 3 to 4 weeks using slightly larger doses. Fewer side effects with shorter radiation schedules may be possible, too. Radiation itself is painless and usually only takes a few minutes after initial set up.
Temporary side effects from radiation can occur such as: swelling in the breast, skin changes or dryness, and fatigue. Side effects tend to worsen towards the end of treatment; it may be several days or weeks before side effects clear up once radiation is completed.
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)
- epirubicin (Ellence)
- taxanes such as paclitaxel (Taxol) and docetaxel (Taxotere).
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 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 or different side effects compared to traditional chemotherapy. However, 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 (HER2+). It is important to target treatment against this protein, as these breast cancers can be more aggressive. Trastuzumab (Herceptin) is commonly used and has been shown to significantly reduce the risk of recurrence in HER2+ breast cancers.
Drugs that specifically target HER2, known as HER2 inhibitors, include:
- Herceptin (trastuzumab)
- Perjeta (pertuzumab)
- Phesgo (hyaluronidase, pertuzumab, and trastuzumab)
- Kadcyla (ado-trastuzumab emtansine)
- Tykerb (lapatinib)
- Tukysa (tucatinib)
- Nerlynx (neratinib)
- Margenza (margetuximab-cmkb)
- Enhertu (fam-trastuzumab deruxtecan-nxki)
Plus, 5 biosimilars to Herceptin are now approved, including: Ogivri (trastuzumab-dkst), Herzuma (trastuzumab-pkrb), Ontruzant (trastuzumab-dttb), Trazimera (trastuzumab-qyyp), and Kanjinti (trastuzumab-anns).
In Dec. 2019, AstraZeneca and Daiichi Sankyo received FDA accelerated approval for Enhertu for the treatment of adults with unresectable or metastatic HER2-positive breast cancer who have received two or more prior anti-HER2-based regimens in the metastatic setting. Enhertu is a HER2-directed antibody and topoisomerase inhibitor conjugate.
In Dec. 2020, the FDA cleared Margenza plus chemotherapy for adults with metastatic HER2-positive breast cancer who have received two or more prior anti-HER2 regimens, at least one of which was for metastatic disease. Margenza, from MacroGenics, is classified as a HER2/neu receptor antagonist.
Nerlynx: An Oral HER2 Agent
In July 2017, the FDA first approved Nerlynx (neratinib), a once-daily oral tyrosine kinase inhibitor. It is used to lower the risk of breast cancer recurrence. Nerlynx is used for breast cancer only if your tumor tests positive for a protein called human epidermal growth factor receptor 2 (HER2) which can speed the growth of the tumor.
- Nerlynx was cleared as a single agent to treat early-stage HER2-positive breast cancer following adjuvant trastuzumab (Herceptin)-based therapy.
- In Feb. 2020, Nerlynx was also approved to be used in combination with capecitabine (Xeloda) to treat advanced or metastatic HER2-positive breast cancer after two prior anti-HER2-based regimens in the metastatic setting.
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 ability of the cancer cells to receive growth signals.
Nerlynx causes diarrhea in almost all patients (about 95%). An over-the-counter (OTC) antidiarrheal called loperamide (brand name: Imodium AD) is recommended for the first 56 days of treatment and then as needed to help lessen this side effect. Loperamide should be started on the same day Nerlynx is started. Your doctor will tell you exactly how to take loperamide.
Tukysa (tucatinib): HER2 Agent
Tukysa was approved in April 2020 to be used with trastuzumab and capecitabine in adults with HER2-positive breast cancer. This combination treatment is used when the cancer has spread to other parts of the body (metastatic) or cannot be removed with surgery (unresectable). This new approval also includes patients with brain metastases.
- In studies, patients who received Tukysa with trastuzumab / capecitabine had a significant 46% reduction in the risk of cancer progression or death (PFS) compared to patients who received trastuzumab and capecitabine alone. The risk of cancer progression or death was also significantly reduced by 52% in patients with brain metastases.
- Serious side effects occurred in 26% of patients who received Tukysa and included diarrhea (4%), vomiting (2.5%), nausea, stomach pain, and seizure (2% each).
- Common side effects (≥20%) included diarrhea, nausea, fatigue, liver toxicity, and vomiting, among others.
Side Effects With HER2 Inhibitors
HER2 inhibitors can have fewer or different effects than traditional chemotherapy, but side effects can still be significant and warrant a discussion with your healthcare provider.
Certain monoclonal antibody drugs such as Herceptin, Ogivri, Perjeta, Kadcyla, and Enhertu can cause a type of heart damage known as congestive heart failure. Patients are monitored for this side effect. If you should develop these signs or symptoms, be sure to alert your doctor right away:
- new or worsening shortness of breath
- irregular heartbeat
- sudden weight gain
- feeling tired
- dizziness or feeling light-headed
- swelling of your ankles or legs
- loss of consciousness
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 common and serious 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 and men; or with the estrogen receptor antagonist Faslodex (fulvestrant) in those 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 or tablet taken once a day for 21 days, with a 7 day break before starting again. When given with hormone blockers such as Femara (letrozole), Femara is taken continuously throughout the 28 days. When Ibrance is taken with Faslodex (fluvestrant), Faslodex is taken on Days 1, 15, 29, and once monthly thereafter. Your doctor will direct your dosing and therapy and follow their instructions exactly.
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.
A tablet formulation of Ibrance was approved in October of 2019.
Side effects for Ibrance.
- 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.
In April of 2019, Ibrance was also approved to treat men with HR+, HER2- metastatic breast cancer in combination with an aromatase inhibitor as initial endocrine based therapy, or with fulvestrant in patients with disease progression following endocrine therapy.
Afinitor: Dosing and Side Effects
Afinitor (everolimus) is another targeted drug that boosts the effect of hormone therapy given to women with advanced hormone receptor-positive, HER2-negative breast cancer.
It is used in women whose cancers have grown while taking the hormone blockers Arimidex (anastrozole) or Femara (letrozole). Afinitor is given as a 10 mg 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 from Novartis
Kisqali (ribociclib) was first approved in 2017.
- Kisqali is a kinase inhibitor, and in the same drug class as Pfizer's Ibrance (palbociclib).
Specifically both agents are classified as CDK4/6 inhibitors used for breast cancer treatment.
In labeling, Kisqali is recommended for use alongside the aromatase inhibitor Femara (letrozole) for the treatment of pre/perimenopausal or postmenopausal women with HR+/HER2- metastatic breast cancer, as the first endocrine-based therapy.
- It is also indicated for use in HR+/HER2 postmenopausal women in combination with the estrogen receptor antagonist fulvestrant as initial endocrine-based therapy or following disease progression on endocrine therapy.
In the pivotal 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%.
The recommended starting dose for Kisqali tablets is a 600 mg dose (three 200 mg film-coated tablets) given once daily for 21 days followed by 7 days off in a 28 day cycle with an aromatase inhibitor. Kisqali can be taken with or without food.
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), also a CDK 4/6 kinase inhibitor, was also cleared by the FDA in 2017. Verzenio comes as a 50, 100, 150, and 200 mg tablet. It can be taken with or without food.
It is used in 3 patient populations:
- either with fulvestrant (Faslodex) in patients with HR+, HER2- advanced or metastatic breast cancer that progressed after endocrine therapy
- as monotherapy for patients with HR+, HER2- advanced or metastatic breast cancer who previously received endocrine therapy and chemotherapy.
- in combination with an aromatase inhibitor (AI) as initial endocrine-based therapy for the treatment of postmenopausal women with HR+, HER2- metastatic breast cancer.
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.
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. It also has uses in prostate cancer and pancreatic 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.
Talzenna and Tecentriq Also Approved for BRCA Mutations
In October 2018, the FDA approved Pfizer's Talzenna (talazoparib). Talzenna is used to treat adults with locally advanced or metastatic HER2- breast cancer with an abnormal inherited BRCA gene.
Like Lynparza, Talzenna is classified as a poly (ADP-ribose) polymerase (PARP) inhibitor.
- In the EMBRACA open-label trial of 431 participants, patients received either talazoparib 1 mg or the clinician's choice of chemotherapy (capecitabine, eribulin, gemcitabine, or vinorelbine).
- The primary outcome was progression-free survival (PFS), the length of time during and after treatment that a patient's disease does not worsen. Results yielded an estimated median 8.6 and 5.6 months PFS in the Talzenna and chemotherapy groups, respectively.
- Common side effects occurring in over 20% of patients included fatigue, anemia, nausea, and headache, among others.
Advances: Triple Negative Breast Cancer (TNBC)
- The combo is used for treatment of adults with unresectable or locally advanced or metastatic triple-negative breast cancer (TNBC) whose tumors express the protein PD-L1. Programmed death-ligand 1 (PD-L1) positive, metastatic triple-negative breast cancer is a disease with high unmet medical need.
In Nov. 2020, Merck's Keytruda was approved in combination with chemotherapy, for the treatment of patients with locally recurrent unresectable or metastatic TNBC.
- It is used in patients whose tumors express PD-L1 [Combined Positive Score (CPS) ≥10] as determined by an FDA approved test. See clinical studies here.
In April 2020, the FDA approved Trodelvy (sacituzumab govitecan-hziy) injection from Immunomedics for the treatment of adults with metastatic triple-negative breast cancer (mTNBC) who have received at least two prior therapies in the metastatic setting. Trodelvy was approved through the FDA’s Accelerated Approval Program.
- Trodelvy is classified as a Trop-2-directed antibody and topoisomerase inhibitor conjugate.
Novartis' Piqray is the First PI3K Inhibitor for Breast Cancer
In May 2019, the FDA approved Novartis' Piqray (alpelisib), an oral tablet kinase inhibitor to be used in combination with the endocrine therapy fulvestrant (Faslodex) to treat postmenopausal women, and men, with HR-positive, human epidermal growth factor receptor 2 (HER2)-negative, PIK3CA-mutated, advanced or metastatic breast cancer.
- In the Phase 3 SOLAR-1 clinical study, 341 patients were enrolled with a PIK3CA mutation.
- Results showed that Piqray + fulvestrant, when compared to placebo + fulvestrant, significantly prolonged progression-free survival (PFS, median of 11 months vs. 5.7 months, respectively) in patients whose tumors had a PIK3CA mutation.
- No PFS benefit was observed in patients whose tumors did not have a PIK3CA tissue mutation.
The recommended dose of Piqray is 300 mg taken orally, once daily with food. Common side effects include high blood sugar levels, elevated creatinine, diarrhea, rash, and hair loss, among others. Severe cutaneous reactions may also occur.
Ongoing Research: The Sister Study
As the many new drug approvals have shown, 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. They come from all walks of life and from all 50 states and Puerto Rico.
- The Sister Study is the only long-term study in the United States and Puerto Rico of women ages 35 to 74 whose sisters had breast cancer.
Researchers believe The Sister Study 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). Enrollment may be ongoing due to additional funding.
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. Know that you do not have to fight alone.
- Lean upon your team of healthcare providers, family and caretakers for support.
- 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
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