Emerging Areas in Drug Therapy Research for Early Breast Cancer

If you or a loved one needs information or resources about clinical trials, call the Komen Patient Care Center at 1-877 GO KOMEN (1-877-465-6636) or email clinicaltrialinfo@komen.org.

Learn about promising treatments under study for metastatic breast cancer.

Learn more about clinical trials.

Antibody-drug conjugates

Some 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. This combination allows the targeted delivery of chemotherapy to certain cancer cells.

The antibody-drug conjugate ado-trastuzumab emtansine (Kadcyla, T-DM1, trastuzumab emtansine) is FDA-approved for the treatment of early and metastatic HER2-positive breast cancers.

Other antibody-drug conjugates used in treatment for metastatic breast cancer are under study for use in early breast cancer treatment, including trastuzumab deruxtecan (Enhertu) and sacituzumab govitecan (Trodelvy).

Tyrosine-kinase inhibitors

Tyrosine-kinase inhibitors are drugs that target tyrosine-kinase enzymes, which are important for cell functions. These drugs can block tyrosine-kinase enzymes at many points along the cancer growth pathway.

The tyrosine-kinase inhibitors tucatinib (Tukysa), lapatinib (Tykerb) neratinib (Nerlynx) are FDA-approved for the treatment of HER2-positive metastatic breast cancer. Neratinib is also FDA-approved for the treatment of early breast cancer.

Tucatinib is under study for use in early breast cancer treatment [78].

PARP inhibitors

Poly(ADP-ribose) polymerase (PARP) is an enzyme that helps repair DNA damage. PARP inhibitor drugs work by keeping cancer cells from repairing damaged tumor DNA.

PARP inhibitors appear to hold the most promise for people who have a BRCA1, BRCA2 or PALB2 inherited gene mutation [79-80].

The PARP inhibitors olaparib (Lynparza) and talazoparib (Talzenna) are FDA-approved for the treatment of some metastatic breast cancers in people who have a BRCA1, BRCA2 or PALB2 inherited gene mutation. Olaparib is also FDA-approved for the treatment of some early breast cancers.

Talazoparib is under study for early breast cancer treatment [81-82].

Selective estrogen receptor degraders (SERDs)

Selective estrogen receptor degraders (SERDs) are a type of hormone therapy. These anti-estrogen drugs bind to the estrogen receptor in a tumor cell. They cause the receptor to be broken down by the cell.

The SERDs elacestrant (Orserdu) and fulvestrant (Faslodex) are FDA-approved to treat some hormone receptor-positive metastatic breast cancers.

Some SERDs are under study for the treatment of hormone receptor-positive early breast cancers.

Immunotherapy

Immunotherapy drugs help your body’s immune system attack cancer cells.

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.

The checkpoint inhibitor immunotherapy drug pembrolizumab (Keytruda) is FDA-approved for the treatment of some early breast cancers and some metastatic breast cancers.

Other immunotherapy drugs, such as durvalumab, are under study for use in the treatment of early breast cancer [85].

Vaccines

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 the early stages of development.

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 bone metastases (breast cancer that has spread to the bones).

For some people with early breast cancer, bisphosphonates may lower the risk of breast cancer recurrence and may be recommended [11,86-87].

Most studies show denosumab does not lower the risk of breast cancer recurrence in people with early breast cancer [88-89].

Circulating tumor DNA and circulating tumor cells (liquid biopsies)

Circulating tumor DNA and circulating tumor cells may help predict recurrence and survival in people with early breast cancer [90-94].

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 [93-94].

Similarly, some studies have found women with early breast cancer who had more circulating tumor cells had worse breast cancer outcomes than those who had few or no circulating tumor cells [90-92].

Circulating tumor DNA and circulating tumor cell tests (sometimes called liquid biopsies) are not standard tests at this time and 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
• HER2-enriched

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.

Tumor profiling

Tumor profiling tests give information about the genes in cancer cells. Tumor profiling tests look at patterns of expression for 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 or not the cancer is likely to metastasize (spread to other parts of the body) in the future [95]. Sometimes, this information can be used to guide breast cancer treatment.

Oncotype DX® and MammaPrint® are tumor profiling tests recommended by the American Society of Clinical Oncology (ASCO) to help guide the use of chemotherapy for some people with breast cancer [95].

Tumor profiling may also be called genomic testing, molecular profiling or genetic signature testing.

Other tumor profiling tests that may help guide the use of chemotherapy are under study.

Learn more about tumor profiling.

Tamoxifen and antidepressant use

Some types of antidepressants called selective serotonin reuptake inhibitors (SSRIs) can interfere with the metabolism of tamoxifen (how tamoxifen works in the body) [96].

Some SSRIs, including fluoxetine (Prozac), paroxetine (Paxil) and sertraline (Zoloft), may interfere with tamoxifen. However, it’s not known whether they might impact the effectiveness of tamoxifen. This topic is under study. Results to date are mixed.

If you’re taking an SSRI to treat depression or menopausal symptoms, talk with your health care provider about possible drug interactions and other treatment options.

Learn about SSRI antidepressants for the treatment of menopausal symptoms.

CYP2D6 and tamoxifen

CYP2D6 is an enzyme that affects how the body metabolizes (breaks down and uses) certain medications.

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 [97-98].

There is no role for routine testing of CYP2D6 in women taking tamoxifen [11].

Clinical trials

After talking with your health care provider, we encourage you to consider joining a clinical trial if there’s one right for you.

Susan G. Komen® Patient Care Center

If you or a loved one needs information or resources about clinical trials, the Patient Care Center can help. Contact the Komen Breast Care Helpline at 1-877-465-6636 or email clinicaltrialinfo@komen.org. The Patient Care Center navigators offer breast cancer clinical trial education and support, such as: Knowing when to consider a trial How to find a trial How to decide which trial is best for you What to expect during a trial Information about clinical trial resources Se habla español.

BreastCancerTrials.org in collaboration with Komen offers a custom matching service to help find clinical trials that fit your needs.

Learn what else Komen is doing to help people find and participate in breast cancer clinical trials, including trials supported by Komen.

Learn more about clinical trials and find a list of resources to help you find a clinical trial.

 

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 nearly $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, including earlier detection Personalized, less invasive treatments for what was once a “one-treatment-fits-all” disease 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.

Susan G. Komen research spotlight

Komen-funded research led by Dr. Daniel Stover is using liquid biopsy, a blood test that looks for circulating tumor cells or pieces of DNA from tumor cells, to improve breast cancer treatment in the clinic.

Learn more in our blog, Dr. Daniel Stover Leverages Lab Learnings to Improve His Patients’ Care.

*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.