Evidence-Based Oncology

Breast Cancer: Will Treatment Costs Outpace Effectiveness? | Page 1

Published Online: December 06, 2012
Marj P. Zimmerman, MS, BSPharm, RPh; and Stanton R. Mehr
Breast cancer was one of the first disorders to profit from the successful application of targeted therapy, and its treatment has changed dramatically from 20 years ago. Despite these advances, breast cancer is responsible for 14% of cancer deaths among women, second only to lung cancer.1

The death rate has decreased since 1990; however, it is projected that about 40,000 will die in 2012 due to the disease (approximately 39,500 women and 400 men),1 with the most deaths occurring among African Americans, followed by Caucasians (Table 1).2 The overall 5-year survival for 2002 to 2008 was 89%, with the longest survival rate in patients having localized disease (98%) and a much lower survival for those with metastasized disease (24%).2

An estimated 227,000 new cases will be diagnosed in 2012, and it is the most frequently diagnosed cancer in women. The incidence of breast cancer had declined by the year 2000 and has since remained stabilized.1 The highest incidence is seen in Caucasians, followed by African Americans.2 Breast cancer remains a cancer that is most often diagnosed in older women; about onefourth of the cases will be diagnosed in women between the ages of 55 and 64 years, followed closely by women between the ages of 65 and 74 years.2

Factors responsible for the reduction in deaths are reduced utilization of hormone replacement therapy for menopausal women, earlier tumor detection, and improved therapies.1

High Incidence Results in Significant Economic Burden

Direct costs in 2010 for breast cancer care were $16.5 billion, which accounted for about 13% of all direct costs attributed to cancer care in the United States.3 In a review of US cost-of-illness studies for breast cancer, the lifetime perpatient costs ranged from $20,000 to $100,000, with higher costs associated with managing patients with advanced disease.4 The Susan G. Komen Foundation estimated an average cost of $22,000 to manage the early stages of breast cancer, whereas stages 3 and 4 of the disease are associated with treatment costs in excess of $120,000.5 A Medicare analysis revealed a mean $110,000 direct lifetime cost of patients with metastatic breastcancer.6 Average direct costs of breast cancer in a managed care population were calculated to be $2896 per member per month (PMPM), with hospitalization accounting for the greatest share, followed by medications and surgical interventions.7

The indirect costs of productivity loss associated with morbidity and premature mortality are much greater: 89% of all breast cancer costs are indrect costs.8 Another study found, using 2007 data, that patients with metastatic breast cancer cost $12.2 billion, or $98,571 per patient per year (including direct medical, palliative/best supportive care, and lost productivity costs).9 Even though there are discrepancies in cost, the societal costs of breast cancer remain high, pointing to the importance of early detection and cost-effective treatment regimens with a goal of curing the disease.

Current Treatment Guided by Genetic Markers

Breast cancers are classified according to hormone receptors and human epidermal growth factor receptor-2 (HER2) status.10 Approximately 70% of breast cancer tumors express a hormone receptor (estrogen or progesterone), and about 20% demonstrate HER2 overexpression.11,12 Recent research has found that there are 4 distinct types of breast cancer, each with its own genetic pattern (Table 2). Of special interest was that triple-negative breast cancer, also known as basal-like breast cancer, was found to have characteristics similar to ovarian cancer, thus offering new therapeutic options to be used to treat this type of cancer.13 Knowing the type of breast cancer the patient presents with guides the clinician in treating the tumor.

Treatment options include radiation, lumpectomy, mastectomy, chemotherapy, or a combination of these options.14 Chemotherapy for breast cancer includes traditional chemotherapy, hormonal therapy, and targeted therapy. Examples of chemotherapy medications are: anthracyclines (doxorubicin, epirubicin), taxanes (paclitaxel, docetaxel), anti-metabolites (capecitabine, gemcitabine), microtubules inhibitors (vinorelbine, eribulin), and others (5-fluorouracil, cyclophosphamide, mitoxantrone, cisplatin, etoposide, vinblastine, ixabepilone, and methotrexate).

Hormonal therapy includes the agents tamoxifen, toremifene, nonsteroidal aromatase inhibitors (anastrozole and letrozole), steroidal aromatase inactivator (exemestane), fulvestrant, megestrol acetate, fluoxymesterone, and ethinyl estradiol.

Targeted therapies for tumors that test positive for HER2 include lapatinib and trastuzumab.14 The breast cancer indication of another targeted therapy, bevacizumab, was revoked by the US Food and Drug Administration (FDA) in November 2011 owing to concerns about its effectiveness and safety.15

Everolimus, an mTOR inhibitor, was approved by the FDA in July 2012 for use in combination with exemestane to treat postmenopausal women with advanced hormone receptor–positive, HER-2 negative breast cancer after failing treatment with letrozole or anastrozole. The FDA had approved the medication for the treatment of other tumors (eg, advanced renal cell carcinoma, advanced neuroendocrine tumors ofpancreatic origin, and renal angiomyolipoma).16 Results from the phase 3 BOLERO-2 study of 724 patients comparing everolimus plus exemastane versus placebo plus exemastane indicated a plus exemastane group compared with 8 months in the combination therapy group (hazard ratio [HR], 0.45; P <.0001). The response rates were 1.7% and 12.6%, respectively. Fewer deaths were reported in the combination therapy group. However, patients older than 64 years did not experience any benefit of the combination treatment.17,18

Pertuzumab, an anti-HER2 therapy, in combination with trastuzumab and docetaxel to treat patients with HER2- positive late-stage breast cancer who have received previous anti-HER2 therapy or chemotherapy. Patients in the triple-therapy group demonstrated a median PFS of 18.5 months versus 12.4 months in the group that did not receive pertuzumab (only trastuzumabwas approved by the FDA in June 2012 and docetaxel) (HR, 0.62; P <.0002).19 Patients receiving the triple therapy had more neutropenia (199 vs 182 patients, respectively), febrile neutropenia (56 vs 30 patients), and diarrhea (32 vs 20 patients) than those receiving trastuzumab and docetaxel.20

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Issue: December
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