Managing Early-Stage Breast Cancer in Your Older Patients
Managing Early-Stage Breast Cancer in Your Older Patients
As the aging population in the United States continues to grow, the incidence of diseases of the elderly, such as breast cancer, are increasing. Many more elderly women are expected to be diagnosed with new breast cancers, most of them in an early stage. Appropriate treatment of these women is important, as they have poorer outcomes when undertreated. In this review, we will discuss the biology and treatment of early breast cancer in elderly women. We will focus on the role of comorbidity and its effect on life expectancy, treatment decisions, current recommendations for primary treatment with surgery, radiation and neoadjuvant strategies, and adjuvant treatment including local radiation therapy and systemic treatment with endocrine therapy, chemotherapy, and newer agents. Finally we will discuss the importance of clinical trials in the elderly.
Mortality from breast cancer is decreasing, yet breast cancer incidence is rising in the United States and, as the population grows and ages, so does the absolute number of new breast cancers diagnosed. The increase in new breast cancers will be particularly dramatic in the elderly, as increasing age remains the greatest risk factor for developing the disease. Breast cancer is the most common cancer diagnosis in US women, with a current median age of 61 years old at diagnosis. Moreover, most women who die of breast cancer are over the age of 65 (Figure 1). It is estimated that by 2030, 20% of Americans will be 65 years and older. If cancer incidence rates continue to rise, it is estimated that absolute numbers of new breast cancer cases will double by 2050, the majority being in older women. It is therefore becoming increasingly important to understand how to treat elderly women with early breast cancer.
Stage at Presentation and Tumor Biology
The biologic characteristics of breast cancer in older women are different from those in younger women, but whether these differences result in tumors with a more indolent prognosis is controversial. Older women are more likely to express estrogen (ER) and progesterone receptors (PR), which improves their prognosis by making them candidates for adjuvant endocrine therapy (Figure 2). As women age, their breast cancers are associated with a decreased expression of markers of tumor growth and aggressiveness, including lower tumor grade, a lower S-phase fraction, more frequent diploidy, normal p53 levels, lack of HER2 (cerbB2) and epidermal growth factor receptor expression, and a lower probability of being node-positive. Regardless of age, infiltrating ductal carcinoma is the most common pathologic subtype.
Diab and colleagues reviewed tumor biology and outcomes from the Surveillance, Epidemiology and End Results (SEER) database in women over 65 years old and found that despite markedly decreased rates of surgery, radiotherapy (RT), and chemotherapy, older women with breast cancer had a good prognosis. Women over the age of 70 with node-negative tumors had an 8-year overall survival equivalent to that of the non-breast cancer age-matched population; women with lymph node-positive tumors had only a modest decrease in overall survival. The authors suggest that older women have more indolent disease and require less screening and treatment, but these conclusions are controversial.[6,7]
Singh et al reviewed outcomes of women with early breast cancer treated with mastectomy alone from 1927 to 1987 at a single institution and found that breast cancer was not more indolent in the 251 women who were over 70 years old. Compared to younger women, the older women were less likely to have lymph node-positive tumors. However, when stage was accounted for, mortality rates were similar across age groups. Women over 70 with node-negative disease had lower distant disease-free survival than patients from 40 to 70 years old (65% vs 81% at 10 years, P = .018). Patients with node-positive disease, however, did not have a significantly different overall survival at 10 years (33% vs 38%).
In treating older women with breast cancer, it is important to account for the increased effect that comorbidity, limitations in functional status, and decreased life expectancy have in balancing the risks and benefits of both primary and adjuvant treatment.
Comorbidity and Mortality
The presence of other, coexisting medical conditions can affect a woman's ability to tolerate specific treatments and decreases the non-breast cancer survival rate, regardless of age. As age increases, the risk of death from causes other than breast cancer increases (Figure 3). Satariano and Ragland noted a significant decrease in 3-year overall survival and an increase in non-breast cancer mortality in women with multiple comorbid conditions. Yancik et al found that six comorbidities—diabetes, renal failure, stroke, prior malignancy, liver disease, and smoking—predicted increased mortality in postmenopausal women with breast cancer.
Carey et al have created a useful prognostic index for 2-year mortality in community dwelling elders over 70 years old. Using a point scale of six items, age, gender, self-report of one activity of daily living, one instrumental activity of daily living, and two measures of physical functioning patients could reliably be divided into low-, intermediate-, and high-risk groups with a 3%-5%, 11%-12%, and 34%-36% 2-year mortality, respectively.
Functional status impacts survival independently of age and comorbidity, and poor performance status (as measured by tools such as the Karnofsky and Eastern Cooperative Oncology Group [ECOG] performance scales) correlates with worse outcomes in cancer patients.
Comprehensive Geriatric Assessment
The National Comprehensive Cancer Network and the International Society of Geriatric Oncology (SIOG) recommend the use of a comprehensive geriatric assessment (CGA) when planning treatment in the elderly. The CGA is a structured evaluation of multiple domains, including physical and functional status (activities of daily living, instrumental activities of daily living, and performance status), comorbidity, socioeconomic issues, polypharmacy, nutritional status, and geriatric syndromes (delirium, dementia, depression, incontinence, falls, spontaneous bone fractures, failure to thrive, neglect, and abuse).
The CGA has been tested in oncologic practice and has been found to detect problems that directly affect cancer treatment. The primary barrier to the routine use of CGA in oncology practice is time, but a short CGA, tailored for use in the outpatient oncology setting, is being tested.[12,15] Regardless of whether a formal CGA is used, when evaluating the elderly patient particular attention should be paid to cognition (memory and orientation), comorbidity (psychiatric, neuropsychiatric, and medical), polypharmacy, social issues (living conditions, caregivers, and transportation), dependence in activities of daily living, and the presence of geriatric syndromes.