Michele Kozubal, PharmD Candidate

Breast cancer continues to affect women globally, with approximately 13% developing invasive disease. New treatment regimens and options are on the horizon for breast cancer therapy. The following therapies highlight the current progression in clinical trials.

Breast cancer, specifically HER2-positive cancer, is typically considered an aggressive cancer, and is associated with poor outcomes. Trastuzumab has been the standard of care for HER2-positive breast cancer and has undoubtedly increased overall survival among patients with this type of disease. 

Due to resistance to HER2-targeted therapies in some patients, research has been directed to this area. There are 7 FDA-approved targeted therapies that are frequently used in combination with endocrine and chemotherapy. Investigators are studying new compounds: HER2-targeted tyrosine kinase inhibitors (TKIs), antibody-drug conjugates (ADCs), and monoclonal antibodies, among others.

These compounds may be more efficient at inhibiting HER2 signaling. In the meantime, combination therapy with HER2-targeted therapy and CD4 and CD6 kinase inhibitors, PIK3 inhibitors, or immunotherapy may be the way of overcoming resistance.

Adjuvant hormone therapy is still favored for up to 10 years in most patients with estrogen receptor (ER)-positive breast cancer. Endocrine therapy aids in preventing recurrence, metastatic disease, and contralateral tumors. Menopausal status aside, tamoxifen is the conventional standard of care. Benefits from hormone treatment are dependent on the extent of ER expression. 

Recently, aromatase inhibitors have been the new therapy of choice, as they can greatly reduce recurrence risk compared with that of 5 years of tamoxifen therapy. However, these agents are contraindicated in premenopausal women. The length of endocrine therapy remains patient specific, but a duration of 5 to 10 years with either an aromatase inhibitor or tamoxifen has shown benefit compared with just 5 years of tamoxifen.

Pembrolizumab (Keytruda) has been very promising against tumor activity with an added plus of a respectable safety profile. Findings from a recent study of patients with a triple-negative breast cancer diagnosis showed a significant difference in complete pathological response in patients who received neoadjuvant chemotherapy with pembrolizumab compared with those who received chemotherapy and placebo.

CDK4 and CDK6 are enzymes that play an essential role in cell division. They partake in the transition from the G1 phase to the S phase in cell division. Blocking this step may be beneficial in treating breast cancer and stopping the growth of cancer cells. The inhibition of CDK4 and CDK6 is considered to be broad spectrum because it inhibits the division of healthy cells as well as tumor cells. 

This drug class is used in patients with HER2-negative metastatic breast cancer specifically as an adjuvant to hormonal therapies. But CDK4/CDK6 inhibitors have some major adverse effects, including bone marrow suppression and an increased risk of infection, because of their effect on immune cells. Agents that belong to this class include ribociclib (Kisqali), abemaciclib (Verzenio), and palbociclib (Ibrance). All of these were FDA approved between 2015 and 2017.

PI3K is an enzyme that plays an important role in the signaling pathways of cells and cancer cells. Many studies are examining how each class plays a specific role in certain types of cancers. However, there is a specific isoform of PI3K found in breast tissues (PI3K-C2γ). Investigators have found that some females may have this mutation in the PIK3CA gene, a breast cancer mutation gene, which affects PI3K function and cancer cell growth.

Alpelisib (Piqray) is an FDA-approved PI3K inhibitor for the treatment of patients with advanced or metastatic breast cancer. It can be used for both HER2-positive and HER2-negative breast cancers, but patients must have 1 or more PIK3CA mutations in the tumor tissues.

Shams Alrubaie and Michele Kozubal are PharmD Candidates at Duquesne University in Pittsburgh, Pennsylvania, anticipated to graduate in spring 2022.

Jonathan Ogurchak, PharmD, CSP, is CEO and cofounder of STACK, a professional information management platform. He also serves as a preceptor at over 15 schools of pharmacy for a virtual advanced pharmacy practice experiential rotation for specialty pharmacy, technology, and entrepreneurship.

Articles

Breast cancer continues to affect women globally, with approximately 13% developing invasive disease. New treatment regimens and options are on the horizon for breast cancer therapy.