Breast Cancer Armamentarium Offers New Options for Patients

In In The News by Barbara Jacoby

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By: Sagar Shah, PharmD candidate; and Saro Arakelians, PharmD



Breast cancer is the second-leading cause of cancer-related death among women in the United States.1 Each year, about 250,000 cases of breast cancer are diagnosed in the United States.2 According to the American Cancer Society, about 276,480 cases of breast cancer will be diagnosed in women in 2020. About 42,000 women die from breast cancer annually in the United States.1

Several genetic, endocrine, and lifestyle factors are associated with the development of breast cancer. The common symptoms include thickening or swelling of the breast, lump in the breast or underarm, change in the size or the shape of the breast, and pain in any area of the breast.1

Breast cancer is diagnosed though multiple tests, such as a mammogram, ultrasound, MRI, and biopsy. In this patient population, clinicians may use a biopsy to determine whether a tissue is cancerous. The good news is that breast cancer is highly curable if diagnosed in its early stages.1

Breast cancer staging is based on the primary tumors, the lymph node involvement, and the presence or absence of distant metastases. The treatment of breast cancer is based on TNM staging, estrogen receptor (ER)/progesterone receptor (PR) status, and HER2 receptor status to estimate the prognosis and personalize the therapy.3

Most women undergo surgery for breast cancer and receive additional treatment post surgery, such as chemotherapy, hormone therapy, and radiation. In some cases, chemotherapy may also be used before surgery.1 Two main types of surgical procedures can be used to remove breast cancer: breast-conserving surgery, in which only the part of the breast containing the cancer is removed, and mastectomy, in which the entire breast is removed.1

Chemotherapy is an option before surgery (neoadjuvant) or after surgery (adjuvant). Chemotherapy drugs may include anthracyclines such as doxorubicin and epirubicin, taxanes such as paclitaxel and docetaxel, 5-fluorouracil (5-FU) or capecitabine, cyclophosphamide (Cytoxan), and carboplatin (Paraplatin).4

Hormone therapy is often used after surgery to help reduce the risk of the recurrence and is usually taken for at least 5 to 10 years. Most cancer cells have receptors for the hormones estrogen (ER-positive cancers) and/or progesterone (PR-positive cancers), which help the cancer cells grow and spread. Drugs, such as tamoxifen, that block the estrogen receptors are called selective estrogen receptor modulators. Tamoxifen is used in patients who have not gone through menopause.5 Fulvestrant (Faslodex), a selective estrogen receptor degrader, works by blocking and damaging ERs and is approved for postmenopausal women. Aromatase inhibitors such as letrozole (Femara), anastrozole (Arimidex), and exemestane (Aromasin) work by blocking aromatase from making estrogen and are used in postmenopausal women.6

Targeted therapy, on the other hand, is useful against cancers that have spread to distant parts of the body. The HER2/neu gene is overexpressed in about 25% to 30% of patients with breast cancer.1 HER2-positive breast cancers tend to grow and spread more aggressively in the body. Treatment for HER2-positive breast cancer may include trastuzumab (Herceptin) and the pertuzumab, trastuzumab and hyaluronidase-zzxf combination (Phesgo).7

Approved by the FDA on June 29, 2020,8 the pertuzumab, trastuzumab, and hyaluronidase-zzxf combination comprises a pair of HER2/neu receptor antagonists and an endoglycosidase that is injected subcutaneously into the thigh over several minutes.4 This combination has been approved for use in patients with HER2-positive, locally advanced, or early-stage breast cancer prior to surgery. It is also approved for patients with HER2-positive early breast cancer who have a high likelihood of coming back after surgery. The FDA’s approval was based on the results of the phase 3 FeDeriCa study (NCT03493854), which evaluated the pharmacokinetics, efficacy, and safety of subcutaneous injection of the combination drug in combination with chemotherapy compared with intravenous infusion of pertuzumab and trastuzumab with chemotherapy.4

Additional targeted therapies are lapatinib (Tykerb), neratinib (Nerlynx), and tucatinib (Tukysa). These agents are tyrosine kinase inhibitors that prevent cell growth. Palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio) block CDK4/6 proteins in the cell. The blocking of these proteins in hormone receptor (HR)–positive breast cancer stops the cells from dividing. These drugs are approved for women with advanced HR-positive, HER2-negative breast cancer.1

Everolimus (Afinitor) is a targeted mTOR inhibitor and is approved for use in women who have gone through menopause and have advanced HR-positive, HER2-negative breast cancer. Alpelisib (Piqray) is a targeted PI3K inhibitor that blocks a form of the PI3K protein in cancer cells.5

Olaparib (Lynparza) and talazoparib (Talzenna) are PARP inhibitors. PARP proteins normally help repair damaged DNA inside cells. Olaparib and talazoparib can be used to treat metastatic, HER2-negative breast cancer.7

Patients with triple-negative breast cancers have limited treatment options because they lack ERs or PRs and do not express the HER2 protein in the body. Hormone therapy and drugs that target HER2 are not beneficial in these patients, so chemotherapy is the main treatment option.1

When detected in its early stages, breast cancer is highly curable, with a 5-year survival of 98.7%.9 Several factors increase the risk of developing breast cancer, but following a healthy diet, exercising, keeping a healthy weight, and controlling alcohol consumption can lower women’s risk of developing cancer long term. Continued research on breast cancer will bring new horizons, new therapies, and new hope for these patients.