Breast Cancer (BC)

Types of treatment

Surgery

For most women with breast cancer surgery is required as part of their treatment. There are different types of surgery:

• Removal of the tumor focus (breast-conserving surgery or mastectomy).
• Surgery to find out if the cancer has spread to the axillary lymph nodes (sentinel lymph node biopsy or axillary lymph node dissection).
• Breast reconstruction after removal of the tumor.
• Surgery to relieve symptoms of advanced cancer (pressure on the spinal cord or other organs of the spreading breast cancer).

Radiation therapy

Indications:

• after breast-conserving surgery to reduce the chance of cancer recurring in the same breast or in nearby lymph nodes;
• after a mastectomy, especially if the tumor was larger than 5 cm, if the tumor is detected in many lymph nodes, or if there are tumor cells in some areas of the surgical intervention, such as skin or muscles;
• if the cancer has spread to other parts of the body, such as the bones, spinal cord, or brain.

Types:

Remote radiation therapy

It is the most common type of radiation therapy for women with breast cancer. An equipment outside the body focuses the radiation on the affected area.

Brachytherapy Internal Irradiation

A device containing radioactive pellets is placed in the breast tissue for a short time in the area where the cancer was removed (tumor bed). Relevant for organ-preserving surgery.

Hormone therapy

Cells of some types of breast cancer (about 2/3 of cases) have receptors (proteins) on the surface, to which estrogen and progesterone are attached, what helps them grow. Treatment that prevents these hormones from binding to their receptors is called hormone therapy.

Hormone therapy can affect tumor cells almost anywhere in the body, not just in the breast. It is recommended for women with hormone receptor positive tumors.

Hormone therapy is more commonly used after surgery to reduce the risk of cancer recurrence. Sometimes it is prescribed as neoadjuvant therapy. Usually it lasts at least for 5 years.

Estrogen receptor blocking drugs

Selective estrogen receptor modulators

In other tissues (bones, ovaries) drugs do not block estrogen receptors, but act like estrogen.

• Tamoxifen
• Toremifene (Fareston)

Selective estrogen receptor degraders

They bind to estrogen receptors and destroy them. SERD acts as an antiestrogen throughout the body. When given to premenopausal women, it must be combined with a luteinizing hormone-releasing hormone agonists to supress the ovaries. Only for the treatment of advanced breast cancer that has not been treated with other hormone therapy.

• Fulvestrant (Faslodex)

Estrogen lowering drugs

Aromatase inhibitors

Before menopause, most estrogen is produced by the ovaries. Estrogen is also produced in fatty tissues by an enzyme called aromatase. Aroma inhibitors prevent aromatase from producing estrogen.

• Letrozole (Femara)
• Anastrozole (Arimidex)
• Exemestane (Aromasin)

Chemotherapy

Indicated only in certain cases.

Adjuvant chemotherapy may be given if there is a possibility that tumor cells may have remained or spread to reduce the risk of breast cancer recurrence.

Before surgery neoadjuvant chemotherapy may be given to reduce the tumor size for later surgical removal, particularly when the tumor is very large, many lymph nodes are involved, or in inflammatory BC.

If, after neoadjuvant chemotherapy, tumor cells are still found during surgery (residual disease), additional chemotherapy (adjuvant chemotherapy) may be offered to reduce the chance of recurrence.

In the case of triple negative or HER2+, neoadjuvant therapy is often prescribed.

It is used as the main treatment for metastatic BC.

Chemo drugs:

• Taxanes: paclitaxel, docetaxel, and albumin-bound paclitaxel (abraxane)
• Ixabepylon
• Eribulin
• Anthracyclines: doxorubicin, liposomal doxorubicin and epirubicin
• Platinum-based therapy (cisplatin, carboplatin)
• Vinorelbine
• Capecitabine
• Gemcitabine
• Antibody-drug conjugates (ado-trastuzumab emtansine, fam-trastuzumab derustecan)

Targeted Therapy

Monoclonal antibodies for binding to the HER2 receptor

In about 20% of breast cancer cases, the cells make too much of a growth-promoting protein known as HER2. In such cases, there is a tendency to grow and spread more aggressively than in HER2-negative breast cancer.

• Trastuzumab (Herceptin and analogues)
• Pertuzumab (Perjeta)
• Trastuzumab, pertuzumab + hyaluronidase (Fesgo)
• Margetuximab (Margenza)
• Ado-trastuzumab emtansine (Kadcyla) (HER2 antibody-drug conjugate with emtansine chemotherapy)
• Fam-trastuzumab deruxtecan (Enhertu) (HER2 antibody-drug conjugate with deruxtecan chemotherapy)

HER2 kinase inhibitors (the kinase part of the HER2 protein provides signals into the cell)

• Lapatinib (Tikerb)
• Neratinib (NERLINKS)
• Tucatinib (TUKISA)

CDK4/6 inhibitors

• Palbociclib (IBRANCE)
• Ribociclib (KISKALI)
• Abemaciclib (VERZENIO)

mTOR inhibitor

Everolimus (Afinitor) is prescribed for progressive hormone-receptor-positive, HER2-negative BC.

PI3K inhibitor

About 30-40% of breast cancers have a mutated PIK3CA gene. It is prescribed for progressive hormone-receptor-positive, HER2-negative breast cancer with a mutation in the PIK3CA gene.

• Alpelisib (Pikrey)

PARP inhibitors

PARP proteins usually help repair damaged DNA. BRCA genes are also involved in DNA repair processes. Since tumor cells with a mutated BRCA gene already have problems to repair damaged DNA, blocking PARP proteins often leads to the death of these cells.

It is indicated for the treatment of advanced or metastatic HER2-negative breast cancer in women with a BRCA mutation after chemotherapy.

• Olaparib (Linparza)

A monoclonal antibody conjugates targeting Trop-2 and chemotherapy

A conjugate of a monoclonal antibody and a chemotherapy drug attaches to the Trop-2 protein on breast cancer cells due to the monoclonal antibody and delivers the chemotherapy drug govitecan to the cell. It is prescribed for triple-negative breast cancer after several chemotherapy regimens.

• Sacituzumab govitecan (Trodelvy)

Immunotherapy

It is prescribed for triple-negative breast cancer, possibly in conjunction with chemotherapy.

• Pembrolizumab (Keytruda)