Emerging Areas in Chemotherapy, Hormone Therapy and Other Drug Therapies
This is a promising time in breast cancer research. New drugs are becoming available and treatment for breast cancer is improving.
New chemotherapy, hormone therapy and other drug therapies for early breast cancer, as well as some tools for tailoring treatment, are under study in clinical trials. The results of these studies will decide whether these new therapies become part of the standard of care.
After discussing the benefits and risks with your health care provider, we encourage you to consider joining a clinical trial.
If you or a loved one needs information or resources about clinical trials, call the Komen Breast Care Helpline at 1-877 GO KOMEN (1-877-465-6636) or email firstname.lastname@example.org.
This section discusses emerging areas of research in the treatment of early breast cancer.
Learn more about clinical trials.
Some special antibody drugs are designed to target certain cancer cells. For example, the drug trastuzumab (Herceptin) is a specially made antibody that targets HER2-positive cancer cells.
Antibody-drug conjugates are a combination of an antibody therapy and a chemotherapy drug. The combination allows the targeted delivery of chemotherapy to certain cancer cells.
For example, antibody-drug conjugate ado-trastuzumab emtansine (Kadcyla, T-DM1, trastuzumab emtansine) consists of trastuzumab and a chemotherapy called DM1. Ado-trastuzumab emtansine targets the delivery of chemotherapy to HER2-positive cancer cells. It’s FDA-approved for the treatment of HER2-positive breast cancers.
Other antibody-drug conjugates are under study.
Poly(ADP-ribose) polymerase (PARP) is an enzyme that helps repair DNA damage. PARP inhibitor drugs try to keep cancer cells from repairing damaged tumor DNA.
The PARP inhibitors olaparib (Lynparza) and talazoparib (Talzenna) are FDA-approved for the treatment of HER2-negative metastatic breast cancer. Other PARP inhibitors are FDA-approved for other types of cancer.
Studies are now looking at whether adding a PARP inhibitor to treatment for early breast cancer can help lower the risk of recurrence.
The PARP inhibitor olaparib is under study for the treatment of high-risk, HER2-negative early breast cancer in people who have a BRCA1 or BRCA2 inherited gene mutation. Findings show people who got olaparib after completing chemotherapy had a lower risk of breast cancer recurrence than those who didn’t get olaparib .
Olaparib and the PARP inhibitor talazoparib, each in combination with neoadjuvant chemotherapy (given before surgery), are under study for the treatment of early breast cancer in people who have a BRCA1/2 inherited gene mutation [65,280].
PI3 kinase inhibitors
PI3 kinase is an enzyme important in cell growth. The PIK3CA gene helps control PI3 kinase enzyme activity.
Some breast cancers have a mutation in the PIK3CA gene (this mutation is in the genes of breast cancer, not the person). This mutation can affect PI3 kinase and cause the tumor to grow.
PI3 kinase inhibitors are drugs designed to interrupt PI3 kinase signals and stop the growth of cancer cells.
The PI3 kinase inhibitor alpelisib (Piqray) is FDA-approved for the treatment of some metastatic breast cancers that have a PIK3CA gene mutation.
The PI3 kinase inhibitor taselisib in combination with the hormone therapy drug letrozole is under study as neoadjuvant therapy (given before surgery) for estrogen receptor-positive, HER2-negative early breast cancers .
Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors
CDK4 and CDK6 are enzymes important in cell division. CDK4/6 inhibitors are drugs designed to interrupt the growth of cancer cells.
Abemaciclib (Verzenio), palbociclib (Ibrance) and ribociclib (Kisqali) are CDK4/6 inhibitors FDA-approved for metastatic breast cancer treatment. They are used in combination with hormone therapy to treat hormone receptor-positive, HER2-negative metastatic breast cancers.
CDK4/6 inhibitors in combination with hormone therapy are now under study in the neoadjuvant (before surgery) and adjuvant (after surgery) settings .
Recent findings showed hormone therapy plus abemaciclib reduced the risk of breast cancer recurrence better than hormone therapy alone in women with hormone receptor-positive, HER2-negative breast cancers at high risk of recurrence .
However, other findings show no benefit of hormone therapy plus palbociclib compared to hormone therapy alone for women with hormone receptor-positive, HER2-negative breast cancers [69,277].
Bone density medications
Bisphosphonates and the RANK ligand (RANKL) inhibitor drug denosumab are bone density medications used to help prevent bone loss and treat osteoporosis. They are also used as a bone-strengthening treatment for women with breast cancer that has spread to the bones (bone metastases).
Bisphosphonates (including zolendronic acid (Zometa)) may also lower the risk of breast cancer recurrence [7,70-72].
Drugs that help the body’s immune system attack cancer cells are now used to treat many cancers (including melanoma, lung cancer, bladder cancer and kidney cancer).
Immunotherapy drugs for breast cancer haven’t shown results as strong as for other cancers. However, some immunotherapy drugs may be helpful in treating some breast cancers.
Many types of immunotherapy drugs are under study.
“Checkpoint inhibitors” are the most widely used type of immunotherapy drugs. These drugs “take the brakes off” the natural factors that limit how the immune system can control tumor cells.
Atezolizumab (Tecentriq) and pembrolizumab (Keytruda) in the neoadjuvant setting
The checkpoint inhibitor immunotherapy drugs atezolizumab and pembrolizumab are under study for use in neoadjuvant therapy (given before surgery).
Some studies show adding atezolizumab or pembrolizumab to neoadjuvant chemotherapy helps shrink the triple negative breast cancer during neoadjuvant therapy [75-77]. It’s not known whether adding one of these drugs will lower the risk of breast cancer recurrence.
Vaccines are a type of immunotherapy. Like vaccines that protect against the flu or measles, cancer vaccines are designed to build up the body’s immunity against disease.
Breast cancer vaccines are still in early stages of development.
Tyrosine-kinase inhibitors are drugs that target enzymes important for cell functions (called tyrosine-kinase enzymes). These drugs can block tyrosine-kinase enzymes at many points along the cancer growth pathway.
Tyrosine-kinase inhibitors include tucatinib (Tukysa) and lapatinib (Tykerb), which are FDA-approved for the treatment of HER2-positive metastatic breast cancer, and neratinib (Nerlynx), which is FDA-approved for the treatment of HER2-positive early and metastatic breast cancer.
Lapatinib is under study for use in early breast cancer treatment .
Circulating tumor cells and circulating tumor DNA (liquid biopsies) and prognosis
Circulating tumor cell levels and circulating tumor DNA may help predict recurrence and survival in people with early breast cancer [79-82].
Some studies have found women with early breast cancer who had more circulating tumor cells had a worse prognosis than those who had few or no circulating tumor cells [79-83].
Similarly, some findings have shown women with early breast cancer who have circulating tumor DNA after neoadjuvant therapy (given before surgery) or adjuvant therapy (given after surgery) may have a worse prognosis than those with no circulating tumor DNA [82-83].
Circulating tumor cell and circulating tumor DNA tests (sometimes called liquid biopsies) are not used to guide breast cancer treatment. These topics are under study.
Molecular classifications of breast cancer
Molecular and genetic differences in breast cancers may be useful in guiding the development of new drug therapies.
Most studies divide breast cancer into 4 major molecular classifications:
- Luminal A
- Luminal B
- Basal-like/triple negative
Although mainly used in research settings, these classifications may be useful in tailoring treatment in the future.
Learn more about molecular classifications of breast cancer.
Tamoxifen and anti-depressant use
Whether these SSRIs may impact the effectiveness of tamoxifen is under study.
Some SSRIs, including fluoxetine (Prozac), buproprion (Wellbutrin), paroxetine (Paxil) and sertraline (Zoloft), may interfere with tamoxifen. However, it’s not known whether they might affect tamoxifen treatment for breast cancer.
If tamoxifen is part of your treatment plan, talk with your health care provider about potential drug interactions.
CYP2D6 and tamoxifen
CYP2D6 is an enzyme that affects how the body metabolizes (breaks down and uses) certain medications.
In the past, researchers were interested in whether certain forms of the gene related to CYP2D6 function affected the hormone therapy drug tamoxifen.
Large studies found no difference in the risk of breast cancer recurrence in women with genes related to low CYP2D6 function compared to risk in women with genes related to normal or high CYP2D6 function [87-88].
There is no role for routine testing of CYP2D6 in women taking tamoxifen.
Tumor profiling (using gene expression profiling tools) gives information about the genes in cancer cells. Tumor profiling tests look at a set of genes in a sample of the tumor removed during a biopsy or surgery.
The gene profiles of some tumors may help predict whether the cancer is more likely to metastasize (spread to other parts of the body) . Sometimes, this information can be used to guide breast cancer treatment.
The 3 tumor profiling tests recommended by the American Society of Clinical Oncology (ASCO) are Oncotype DX®, PAM50 (Prosigna®), and MammaPrint® [89-90]. These tests may be used to help guide the use of chemotherapy for some people with breast cancer.
Breast Cancer Index
Breast Cancer Index® is a tumor profiling test that looks at a set of 11 genes to give prognostic information for some breast cancers.
Breast Cancer Index may be considered in making treatment decisions for some estrogen receptor-positive, HER2-negative, lymph node-negative breast cancers [7,89].
Other tumor profiling tests are under study.
After talking with your health care provider, we encourage you to consider joining a clinical trial.
Susan G. Komen® Breast Care Helpline
If you or a loved one needs information or resources about clinical trials, call the Komen Breast Care Helpline at 1-877 GO KOMEN (1-877- 465- 6636) or email email@example.com.
The helpline offers breast cancer clinical trial education and support, such as:
BreastCancerTrials.org in collaboration with Susan G. Komen® offers a custom matching service to help find clinical trials that fit your needs.
Learn more about clinical trials and find a list of resources to help you find a clinical trial.
Read our perspective on metastatic breast cancer.*
Our commitment to research
At Susan G. Komen®, we are committed to saving lives by meeting the most critical needs in our communities and investing in breakthrough research to prevent and cure breast cancer. Our Research Program is an essential driving force for achieving this mission.
Since our inception in 1982, Komen has provided funding to support research grants that have greatly expanded our knowledge of breast cancer and helped us understand that breast cancer is not just a single disease but many diseases, unique to each individual.
To date, Komen has provided about $1.1 billion to researchers in 47 states, the District of Columbia and 24 countries to support research that has resulted in a better understanding of breast cancer; earlier detection; personalized, less invasive treatments for what was once a “one-treatment-fits-all” disease; and improvements in both quality of life and survival rates.
Learn more about our continuing investment in research and the exciting research that we are funding, because nothing would make us happier than ending breast cancer forever.
*Please note, the information provided within Komen Perspectives articles is only current as of the date of posting. Therefore, some information may be out of date.