In the United States, an estimated 276,000 new invasive breast cancer cases in women were diagnosed in 2020 (see Figure 1).1,2 Despite early screenings and improved therapy, breast cancer remains a challenging disease, as approximately 42,000 of these patients will succumb to this illness.1 Although uncommon, breast cancer can also be diagnosed in men, with an estimated 2620 new cases of invasive breast cancer in men in 2020.1

Although breast cancer may afflict all segments of the population, there are modifiable risk factors. These include physical inactivity, hormone therapy, and alcohol intake,3 but there are also many unmodifiable risk factors (see Figure 2).1-3

Diagnoses Overview
Breast cancer may present as swelling, thickening, pain, or irritation of any area of the breast; a new lump in the breast or underarm; or abnormal nipple discharge.2,3 Regular breast self-examinations are strongly recommended for all women because the disease initially presents locally.3 However, a mammogram is the preferred method to screen for breast cancer, as abnormalities can be detected prior to symptom presentation. Upon detection of an abnormal mammographic finding, a subsequent diagnostic mammogram should be performed to confirm a diagnosis.2,3

Once breast cancer is diagnosed, the disease stage serves as a template to guide treatment. The widely used TNM staging system, created by the American Joint Committee on Cancer (AJCC), is based on tumor characteristics, lymph node involvement, and metastasis status.2,3

Based on this system, an individual’s malignancy would be categorized into stages. In general, stage 0 refers to noninvasive cancer, where cancer cells have yet to invade normal tissues. Upon malignancy growth into normal tissues, the cancer is considered invasive (stage I, II, or III) and, once it has spread to other parts of the body is considered metastatic (stage IV).2,3

The eighth edition of the AJCC staging manual, published in 2017, now incorporates biomarker evaluation.4

Breast cancer cells are tested for biomarkers based on the presence of hormone receptors (HRs), referring to positive or negative estrogen receptors (ER+/ER–) and positive or negative progesterone receptors (PR+/PR–), and HER2 overexpression.2,5

Based on HR status, termed HR positive (HR+) or HR negative (HR–), and HER2 status, HER2 positive (HER2+) or HER2 negative (HER2–), a patient’s molecular subtype is divided into 1 of 4 categories (see Figure 3).1-3,5

Current Therapy
Breast cancer therapy is divided into local and systemic treatments. Surgery and radiation therapy are considered local treatment. Systemic treatments include chemotherapy, hormone therapy, targeted therapy, and immunotherapy.2 The stage of a patient’s cancer will ultimately determine which type of treatment is most effective. Local treatment is emphasized in less invasive cancer, and as disease progresses, systemic treatment becomes essential (see Figure 4).1,2,6 Overall, a higher stage is associated with a worse prognosis, and stage IV breast cancer is generally considered incurable.2,3

Among multiple chemotherapy options, taxanes and anthracyclines are most commonly used.2,6 The best prognoses are associated with a combination of different chemotherapy classes (see TABLE).2,3,6

In addition to general treatment modalities, patients with HR+ breast cancer should receive hormone therapy, which is used to inhibit intrinsic production of hormones, thereby inhibiting or slowing the growth of these tumors.2,6 This can be done via surgical ovarian ablation or with drug therapy, such as aromatase inhibitors, selective estrogen receptor modulators (SERMs), luteinizing hormone-releasing hormone (LHRH) agonists, and selective estrogen receptor degraders (SERDs) (see Table).2,3,6

The selection of targeted therapy relies on cancer and patient-specific gene expression.2,6 HER2+ targeted therapy includes monoclonal antibodies, antibody-drug conjugates, and tyrosine kinase inhibitors.2,3,6 These medications are designed to attach specifically to the HER2 protein on cancer cells and inhibit growth.2,6 CDK 4/6 inhibitors and mTOR inhibitors are considered HR+ targeted therapy because these agents have been found to inhibit cell division in cells specific to HR+ cancer cells and enhance hormone therapy (see Table).2,3,6

Recent advancements that target HR+ and HER2+ tumors allow a multimodal approach to inhibition of breast cancer.2,6 This is generally why these subsets have a better prognosis than triple-negative breast cancer (TNBC).2,6

On the Horizon
Current cancer research focuses heavily on adjunct immunotherapy in combination with traditional chemotherapy.2,6 In contrast to previously mentioned systemic therapies, immunotherapy involves the restoration of a patient’s own immune system to recognize and target cancer cells.2 In addition, research emphasis has been placed on TNBC, which currently holds the worst prognosis among breast cancer subtypes.7

In March 2019, based upon findings from the IMpassion130 trial (NCT02425891) results, the FDA approved atezolizumab (Tecentriq; Genentech) plus nab-paclitaxel as initial therapy for locally advanced or metastatic TNBC and in tumors that express PD-L1.2 Atezolizumab is an immune checkpoint inhibitor that selectively binds to PD-L1 and ultimately restores the antitumor function of T cells.7

The IMpassion031 phase 3 trial results demonstrated the addition of atezolizumab to nab-paclitaxel followed by doxorubicin (Adriamycin; Pfizer) plus cyclophosphamide in early-stage TNBC significantly improved pathological response rate, even in the PD-L1–negative population.7 Similar results were found in the KEYNOTE-522 trial (NCT03036488), where patients with early-stage TNBC achieved higher response rates with the addition of pembrolizumab (Keytruda; Merck) versus placebo to neoadjuvant chemotherapy, regardless of PD-L1 expression.8 Pembrolizumab exhibits the same mechanism of action as atezolizumab.8

These results suggest that PD-L1 status might play less of a role in early-stage breast cancer versus metastatic disease.7 In this case, more patients with early-stage breast cancer would qualify for and benefit from PD-L1 targeted immunotherapy, regardless of PD-L1 status.

Many breast cancer resources suggest that participation in clinical trials may be an optimal treatment approach for patients with breast cancer because many of these trials focus on novel therapeutic options, prevention of cancer recurrence, and reduction of adverse events.2

Despite a wide array of treatment options and improved screenings, breast cancer continues to be a substantial burden on a large segment of the female population.1 Currently, the emphasis is placed on patient education, early detection, novel drug approaches for treatment, and prevention of recurrence.2 Investigators and patients remain focused on improving breast cancer outcomes, demonstrated by the vast numbers of ongoing clinical trials. 
JERRY BARBEE JR, PHARMD, BCPS, CPH, and GLENN SCHULMAN, PHARMD, MS, BCPS, BCACP, BCGP, BCIDP are clinical pharmacists in Pensacola, Florida.

CAITLIN M. SACCO is a PharmD candidate at Belmont University in Nashville, Tennessee.

  1. Breast cancer statistics. Susan G. Komen. Updated January 4, 2021. Accessed January 7, 2021.
  2. Breast cancer treatment (adult) (PDQ). National Cancer Institute. Updated September 2, 2020. Accessed January 7, 2021. breast-treatment-pdq#_1994_toc
  3. Breast cancer. Centers for Disease Control and Prevention. Reviewed September 14, 2020. Accessed January 7, 2021.
  4. Giuliano, AE, Edge, SB, Hortobagyi, GN. Eighth edition of the AJCC cancer staging manual: breast cancer. Ann Surg Oncol. 2018;25(7):1783-1785. doi:10.1245/ S10434-018-6486-6
  5. Kwa M, Makris A, Esteva FJ. Clinical utility of gene-expression signatures in early stage breast cancer. Nat Rev Clin Oncol. 2018;14(10):595-610. doi:10.1038/nrclinonc.2017.74
  6. Waks AG, Winer EP. Breast cancer treatment: a review. JAMA. 2019;321(3):288-300. doi:10.1001/jama.2018.19323
  7. Mittendorf EA, Zhang H, Barrios CH, et al. Neoadjuvant atezolizumab in combination with sequential nab-paclitaxel and anthracycline-based chemotherapy versus placebo and chemotherapy in patients with early-stage triple-negative breast cancer (IMpassion031): a randomized, double-blind, phase 3 trial. Lancet Oncol. 2020;396(10257):1090-1100. doi:10.1016/S0140-6736(20)31953-X
  8. Schmid P, Cortes J, Pusztai L, et al. Pembrolizumab for early triple-negative breast cancer. N Engl J Med. 2020;382(9):810-821. doi:10.1056/NEJMoa1910549