Targeted Therapy for Breast Cancer

Biologic treatment or targeted therapy employs the body’s immunological or hormonal systems to combat breast cancer cells. The adverse effects are often not as severe as those from more well-known therapies like chemotherapy since it causes less damage to good cells.

Biological drug treatment involves administering drugs that are intended to (target) proteins in breast cancer cells that support their ability to proliferate, disseminate, and develop.

Drugs that are specifically targeted either kill cancer cells or inhibit their development. They can be administered intravenously (IV), subcutaneously (under the skin), or as a tablet.

Because they strengthen the immune system, some biological treatment medications, such as monoclonal antibodies, have many mechanisms of action against cancer cells. These medications may also be referred to as immunotherapy.

Biological Therapy for HER2-Positive Breast Cancer

The cancer cells overproduce the growth-promoting protein HER2 in 15% to 20% of breast tumors.

These malignancies sometimes referred to as HER2-positive breast cancers, have a propensity for faster growth and metastasis than HER2-negative breast cancers. [ref]

Monoclonal Antibodies: Cancer Cell Binding Agent

Monoclonal antibodies are one sort of biological treatment that is currently being researched. These lab-made proteins have a binding affinity for specific cancers.

Trastuzumab (Herceptin and other brand names)

Breast cancer in both its early and late stages can be treated with trastuzumab. This medication may be used alone or in conjunction with chemotherapy.

This medication is often administered for 6 months to a year whether used before (neoadjuvant) or after (adjuvant) surgery to treat early breast cancer.

Treatment is frequently continued for as long as the medicine is effective in treating advanced breast cancer. This medication can be injected beneath the skin or administered intravenously (IV).

Trastuzumab was first marketed under the trade name Herceptin, however, there are now several biosimilars.

Pertuzumab (Perjeta):

Pertuzumab is a HER2 monoclonal antibody that is used to treat to treat early-stage breast cancer or metastatic breast cancer when combined with trastuzumab and chemotherapy. It’s injected into a vein (IV).

Trastuzumab, pertuzumab, and hyaluronidase injection (Phesgo)

Phesgo is a combination of all these drugs and is administered as a shot under the skin (subcutaneously) for several minutes.

Margetuximab (Margenza)

This HER2 monoclonal antibody is used in conjunction with chemotherapy to treat advanced breast cancer when at least two other HER2 inhibitors have been tried. The drug is administered through venous injection (IV).

Antibody-Drug Conjugates

This is considered a biological missile for biological cancer therapy. [ref]

A monoclonal antibody joined to a chemotherapeutic medication is known as an antibody-drug conjugate (ADC).

In this instance, the anti-HER2 antibody binds to the HER2 protein on cancer cells, acting as a homing signal to deliver the chemotherapy to the cancer cells.

Trastuzumab deruxtecan (Enhertu)

Deruxtecan, a chemotherapy treatment, is combined with the HER2 antibody in this antibody-drug combination.

It can be used on its own to treat breast cancer that cannot be surgically removed or has metastasized (spread to another region of the body) after at least one more anti-HER2 targeted drug has been attempted. The medication is given intravenously (IV).

Trastuzumab deruxtecan may be used to address HER2-low breast tumors that cannot be surgically repaired or that have disseminated to other regions of the body when chemotherapy has failed or if the tumor reappears within six months of finishing adjuvant chemotherapy.

Trastuzumab emtansine (Kadcyla)

The HER2 antibody is linked to the chemotherapy medication emtansine through this antibody-drug conjugate.

Trastuzumab is used on its own to cure early-stage breast cancer that has spread or to treat advanced breast cancer in women who have previously received trastuzumab and chemotherapy when chemotherapy and trastuzumab were given prior to surgery and there was still disease present. The medication is given intravenously (IV).

Kinase Inhibitors

An example of a kinase protein is HER2. Proteins called kinases are often used by cells to convey messages (such as telling the cell to grow). Kinase inhibitors are medications that stop kinases from working.

Tucatinib (Tukysa)

This kinase inhibitor is typically taken twice daily as a tablet. Tucatinib is used to treat advanced breast cancer after at least one other anti-HER2 targeted drug has been tried. It is typically used alongside the chemo medication capecitabine and trastuzumab.

Lapatinib (Tykerb)

This medication is a daily tablet. Advanced breast cancer is treated with lapatinib. It is frequently used alongside the chemotherapy medication capecitabine and trastuzumab.

Neratinib (Nerlynx)

This kinase inhibitor is a tablet that is taken every day. Neratinib is used to treat early-stage breast cancer, and it is typically given for a year after a woman has received trastuzumab treatment for a year.

It can also be given to patients with metastatic cancer along with the chemotherapy drug capecitabine, usually after the administration of at least two additional anti-HER2 drugs.

Biological treatment for triple-negative breast cancer

Estrogen and progesterone receptors are absent, and the HER2 protein is produced infrequently or not at all by the cancer cells in triple-negative breast cancer (TNBC).

Sacituzumab govitecan (Trodelvy)

In the instance of this particular antibody-drug conjugate, its antibody part attaches itself to the Trop-2 proteins present in the cells of breast cancer and delivers the chemotherapeutic drug directly to the cancerous cells.

This antibody-drug mixture can be used on its own to treat advanced TNBC following the administration of at least two different chemotherapy regimens.

Sacituzumab Govitecan is infused intravenously (IV) once every two weeks for 2 weeks, with a one-week break in between infusions.

Some common side effects of this medicine include nausea, vomiting, diarrhea, constipation, fatigue, rashes, loss of appetite, loss of hair, low red blood cell counts, and stomach pain.

Extremely low white blood cell counts, severe diarrhea, and adverse medication injection responses are all possible side effects. Prior to using this medication, medications to reduce the risk of an allergic response are often administered.

Biological Therapy For Hormone Receptor-Positive Breast Cancer

Hormone (estrogen or progesterone) receptor-positive breast tumors account for about 3 out of 4 cases.

Hormone therapy is frequently beneficial for treating these tumors in female patients. While certain targeted therapy medications may increase the negative effects of hormone therapy, they can also increase the effectiveness of the treatment.

mTOR inhibitor

mTOR is a protein that typically aids in cell growth and division. It is blocked by the drug everolimus (Afinitor).

Everolimus may also prevent tumors from growing new blood vessels, which may assist to slow down the development of the tumors. It improves the effect of hormone treatment medications and it is administered once daily.

It commonly causes mouth sores, rashes, diarrhea, nausea, feelings of weakness or exhaustion, low blood counts, shortness of breath, and coughing.

Everolimus can also raise blood sugar levels and blood lipids (cholesterol and triglycerides), therefore your doctor will monitor your blood work frequently while you take it.

CDK4/6 inhibitors

CDK4/6 inhibitors like palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio) block proteins called cyclin-dependent kinases (CDKs), especially CDK4 and CDK6. Breast cancer cells that have hormone receptors can be prevented from proliferating by blocking these proteins. This may inhibit the spread of cancer.

These drugs can be used by women with advanced hormone receptor-positive, and HER2-negative breast cancer. These are typically taken as pills once or twice a day.

Fatigue and low blood counts are known to be the most frequent side effects.

PI3K inhibitor

Approximately 30%-40% of breast tumors contain a PIK3CA gene mutation. [ref]

Alpelisib (Piqray) blocks a version of the P13K protein that assists cancer cells in ceasing their growth.  This medication is administered orally once a day.

This medication can be used to treat post-menopausal women who have:

• Advanced hormone receptor-positive, HER2-negative breast cancer
• Greatly expanded PIK3CA gene mutation.

Biological therapy for women with BRCA gene mutations

BRCA genes like BRCA1 and BRCA2 support DNA repair. However, changes to these genes inhibit these functions.  PARP inhibitors, olaparib (Lynparza) and talazoparib (Talzenna) work by preventing the PARP proteins from assisting cancer cells in rebuilding themselves. As a result, the cancer cells are unable to repair and end up dying.

Both of these drugs come in the form of pills and can be taken twice a day.

Olaparib (Lynparza)

Olaparib may be administered to women with early-stage, HER2-negative breast cancer. Especially, those who have had surgery or received chemotherapy (either before or after surgery), and are at a high risk of the condition recurring.

Usually, it is granted for a full year. Some women may live longer when it is administered in this manner.

Talazoparib (Talzenna)

Talzenna is an oral medication and its recommended beginning dose is one 1-mg tablet, taken once a day with or without meals.

It is used to treat locally advanced or metastatic HER2-negative breast cancer in those with a genetic BRCA1 or BRCA2 mutation.

Moreover, Talzenna therapy is only done after genetic testing that confirms a BRCA1 or BRCA2 mutation. Genetic testing involves providing a blood or saliva sample for examination to search for genetic abnormalities.

Summary:

Here is a summary of the targeted therapy for breast cancer: