The Who, What, Where, When and Sometimes, Why.

Emerging Areas in Chemotherapy, Hormone Therapy and Other Drug Therapies

This section discusses emerging areas of research in the treatment of early breast cancer, including some tools for tailoring treatment.

This is a promising time in breast cancer research. New drugs are becoming available and treatment for breast cancer is improving.

Learn about promising, new treatments for metastatic breast cancer.

Improving chemotherapy, hormone therapy and other drug therapies

New chemotherapy, hormone therapy and other drug therapies for early breast cancer are under study in clinical trials. The results of these studies will decide whether these new therapies become part of standard 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 our Clinical Trial Information Helpline at 1-877 GO KOMEN (1-877- 465- 6636) or email clinicaltrialinfo@komen.org.

Learn more about clinical trials.

Capecitabine

Capecitabine is a chemotherapy drug used to treat metastatic breast cancer. It’s now under study for early breast cancer treatment.

A randomized clinical trial studied women with HER2-negative early breast cancer who had cancer remaining in their breast after neoadjuvant (before surgery) chemotherapy. Standard treatment after surgery included radiation therapy and/or hormone therapy [54].

Women with triple negative breast cancer who got capecitabine after neoadjuvant chemotherapy had a lower risk of breast cancer recurrence and better overall survival at 5 years compared to women who got standard treatment alone [54].

Antibody-drug conjugates (antibody therapy-chemotherapy drug combinations)

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.

PARP inhibitors

Poly(ADP-ribose) polymerase (PARP) inhibitors are a class of drugs under study for many types of cancer, including breast cancer.

PARP is an enzyme involved in DNA repair. Some chemotherapy drugs damage DNA.

Adding a PARP inhibitor to some chemotherapy regimens may lower the chances the cancer cells will become resistant to the chemotherapy. This is most often a problem for those with metastatic breast cancer.

PARP inhibitors appear to hold the most promise for people who have a BRCA1 or BRCA2 gene mutation [55].

The PARP inhibitors olaparib (Lynparza) and talazoparib (Talzenna) are FDA-approved for the treatment of HER2-negative metastatic breast cancer in people who have a BRCA1 or BRCA2 gene mutation.

Studies are now looking at whether adding PARP inhibitors to treatment for early breast cancer in women with BRCA1/2 gene mutations can help lower the risk of breast cancer recurrence [56].

The PARP inhibitor velaparib in combination with neoadjuvant chemotherapy is under study for the treatment of triple negative breast cancer [56].

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 a class of 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 for the treatment of estrogen receptor-positive, HER2-negative early breast cancers in the neoadjuvant (before surgery) setting [57].

Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors

CDK4 and CDK6 are enzymes important in cell division. CDK4/6 inhibitors are a class of 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 for the treatment of hormone receptor-positive, HER2-negative early breast cancers in the neoadjuvant (before surgery) and adjuvant therapy (after surgery) settings [58].

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 [6,59-61].

The use of denosumab to lower the risk of breast cancer recurrence is under study [62-63].

Immunotherapy/vaccines

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 (including vaccines) for breast cancer haven’t shown results as strong as have been seen for other cancers. However, they may be effective in treating some breast cancers.

Many types of immunotherapy drugs are under study.

Some immunotherapy drugs “take the brakes off” the natural factors that limit how the immune system can control tumor cells. For this reason, they are sometimes called “checkpoint inhibitors.” The checkpoint inhibitor atezolizumab (Tecentriq) is FDA-approved for the treatment of some metastatic breast cancers.

Other immunotherapies include vaccines. Like vaccines that protect against the flu or measles, cancer vaccines are designed to build up the body’s immunity against disease.

Cancer vaccines may be made up of cancer cells or parts of cancer cells. These cells stimulate the body’s natural defenses, helping it attack and kill cancer cells.

Still in early stages of development, cancer vaccines could one day be used to prevent breast cancer recurrence in people with early breast cancer [64]. Clinical trials are underway.

Pembrolizumab

The checkpoint inhibitor immunotherapy drug pembrolizumab in combination with neoadjuvant chemotherapy is under study for the treatment of triple negative breast cancer [65-66].

Tyrosine-kinase inhibitors

Tyrosine-kinase inhibitors are a class of 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 neratinib (Nerlynx), which is FDA-approved for the treatment of HER2-positive early and metastatic breast cancer, and lapatinib (Tykerb), which is FDA-approved for the treatment of HER2-positive metastatic breast cancer.

Other tyrosine-kinase inhibitors are under study.

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 [67-69].

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 [67-70].

Similarly, some findings have shown women with circulating tumor DNA after treatment for early breast cancer may have a worse prognosis than those with no circulating tumor DNA [70].

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.

Circulating tumor cell levels and circulating tumor DNA are also under study for use in treatment for metastatic breast cancer [71-72].

Molecular subtypes 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 subtypes:

  • Luminal A
  • Luminal B
  • Basal-like/triple negative
  • HER2-enriched

Although mainly used in research settings, these subtypes may be useful in tailoring treatment in the future.

Learn more about molecular subtypes of breast cancer.

Tamoxifen and anti-depressant use

Some types of anti-depressants called selective serotonin reuptake inhibitors (SSRIs) can interfere with the metabolism of tamoxifen (how tamoxifen works in the body) [73].

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.

Learn about SSRI anti-depressants 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.

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 [74-75].

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

Tumor profiling

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) [76]. 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® [76-77].

Other tumor profiling tests are under study.

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 [76].

Clinical trials

After talking with your health care provider, we encourage you to consider joining a clinical trial.

Susan G. Komen® Breast Cancer Clinical Trial Information Helpline

If you or a loved one needs information or resources about clinical trials, call our Clinical Trial Information Helpline at 1-877 GO KOMEN (1-877- 465- 6636) or email clinicaltrialinfo@komen.org.

The helpline offers 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
  • What to expect during a trial
  • Information about clinical trial resources

 

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.

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Komen Perspectives

Read our perspective on clinical trials.*

 

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.

Going forward, our commitment to research will contribute significantly to our ability to achieve our Bold Goal of reducing the current number of breast cancer deaths in the U.S. by 50 percent.

To date, Komen has provided more than $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.