Managing Breast Cancer in the Older Patient

Tracey O’Connor, MD, Arvind Shinde, MD, MBA, MPH, Caroline Doan, BS, Vani Katheria, BS, MS, and Arti Hurria, MD

Clinical Advances in Hematology & Oncology

June 2013, Volume 11, Issue 6


Tracey O’Connor, MD, Arvind Shinde, MD, MBA, MPH, Caroline Doan, BS, Vani Katheria, BS, MS, and Arti Hurria, MD

Dr. O’Connor is an Associate Professor of Oncology in the Department of Medicine at the Roswell Park Cancer Institute in Buffalo, New York. Dr. Shinde is a Fellow of Hematology and Oncology, Ms. Doan is a Clinical Research Assistant, Ms. Katheria is an Administrative Analyst, and Dr. Hurria is the Director of the Cancer and Aging Research Program at City of Hope in Duarte, California

Address correspondence to: Arti Hurria, MD, Director, Cancer and Aging Research Program, City of Hope, 1500 E. Duarte Road, Duarte, CA 91010; Phone: 626-256-4673 x 62821; E-mail:


Breast cancer is largely a disease of older women, with almost half of all new breast cancer cases diagnosed annually in the United States occurring in women ages 65 and older.1 While there have been improvements in breast cancer survival for the population as a whole, these improvements are much smaller in older patients than in younger patients. Treatment decisions for early-stage breast cancer in an older patient must consider the reduction in recurrence risk that would be gained by specific therapies, and balance that risk with the potential for treatment-related toxicity. Older patients have been underrepresented in prospective clinical trials, and there are therefore fewer data to guide treatment decisions, particularly at the extremes of age. However, research regarding the treatment of older patients with breast cancer has increased over the past decade, and we review that evidence here.

Tumor Characteristics Versus Outcomes

When compared with cancer in younger women, breast cancers in older women are less likely to exhibit aggressive tumor characteristics. For example, the percentage of breast cancers that are estrogen receptor (ER)–positive increases with age,2 from less than 60% in patients aged 30–34 years to as high as 85% in patients aged 80–84 years.3 Older women are also more likely to have tumors with lower proliferative indices and are less likely to have overexpression of human epidermal growth factor receptor 2 (HER2).4 Despite the fact that older patients with breast cancer are more likely to have favorable tumor characteristics, outcomes in older women do not reflect this apparent advantage. Instead, a recent report found that the 5-year relative survival of patients aged 70 years and older was lower than that of patients aged 15–70 years.5 Older patients are also significantly less likely to be treated according to guidelines, potentially increasing their risk of disease recurrence and mortality.6 Recent data suggest that although breast cancer outcomes in younger women have shown substantial improvement as a result of advances in treatment and screening, the improvements in outcomes of older women (particularly the oldest 20% of patients with breast cancer) have been much more modest.7

Treatment of Early-Stage Breast Cancer


The gold standard treatment for patients of any age with early-stage breast cancer is surgery. The surgical mortality rate in older women with breast cancer in reasonable health is negligible (<1%).8-10 The main factor influencing surgical morbidity and mortality is not age, but the presence of significant comorbidity.11 In the frail or debilitated patient who cannot tolerate surgery, treatment should be individualized, and a primary endocrine approach (without planned surgery) could be considered in patients with hormone receptor–positive disease. It should be noted, however, that a Cochrane meta-analysis reported that primary endocrine treatment with tamoxifen is inferior to surgery (with or without hormonal treatment) in terms of local control and progression-free survival in medically-fit women aged 70 years and older. However, a significant difference in overall survival was not demonstrated. Because the average response to tamoxifen is between 18 and 24 months, those patients who do progress will have to consider additional endocrine treatment or choose surgery or radiotherapy (RT) at an older age. Therefore, based on the results of the meta-analysis, this approach is only recommended for patients who refuse surgery or who are otherwise unfit for it.12 Current recommendations from the International Society of Geriatric Oncology (SIOG) strongly recommend the involvement of a geriatrician to optimize management of the patient’s comorbidities and to aid with the assessment of life expectancy if primary endocrine treatment is being considered without surgery.13

Because most older women tolerate breast-conserving surgery (BCS) and mastectomy just as well as younger patients, they should be offered the same surgical options.14 If given a choice, women aged 70 years and older are more likely to choose breast conservation over mastectomy.15 Importantly, older women treated with BCS (partial mastectomy and radiation) in comparison to total or modified mastectomy are less likely to report functional limitations following treatment.16 However, despite these data, older women are more likely to be treated with mastectomy than younger women,17 and are less likely to be offered or to undergo breast reconstruction.18 As body image remains important for many older women, and older women treated with BCS report a better body image than those treated with mastectomy, BCS should be offered if the patient meets clinical criteria.19

Axillary Lymph Node Dissection 

Proper management of the axilla in all patients with breast cancer has been an evolving area of active investigation. An axillary lymph node dissection (ALND) is no longer a routine part of the surgical management of breast cancer when the axilla is clinically negative, having been replaced with the less morbid sentinel lymph node biopsy (SLNB). SLNB is feasible and well tolerated in older patients, and is associated with lower rates of arm disabilities than ALND.20,21 However, studies conducted in patients aged 65 and older with early-stage breast cancer showed underutilization of SLNB among patients who were eligible for the procedure.22,23 Although ALND remains standard for women with at least 3 positive sentinel nodes, the need for ALND in patients of all ages has been questioned for those with T1 disease and 1 or 2 positive sentinel nodes (clinically node-negative) based on the results of the American College of Surgeons Oncology Group (ACOSOG) Z0011 trial.24,25

Some suggest that older patients do not need axillary lymph node assessment if the information gained will not influence treatment or outcome. This is particularly true for those patients who have comorbid conditions that preclude adjuvant chemotherapy. This approach has been investigated in trials of older women with ER-positive breast cancer and a clinically negative axilla. The International Breast Cancer Study Group Trial 10-93 randomly assigned 473 women aged 60 years and older to primary surgery and tamoxifen with or without ALND. Although the endpoint of the study was quality of life (QOL), at a median follow-up of 6.6 years, the rates of disease-free survival (DFS; 67% vs 66%) and overall survival (75% vs 73%) were similar.26 Additional studies have reported comparable results.27,28 It is reasonable to discuss these data in older women with small (≤2 cm) ER-positive tumors with a clinically negative axilla who will receive adjuvant endocrine therapy, if the finding of lymph node–positive disease would not influence adjuvant treatment decisions. However, the standard of care is to apply the usual surgical approaches, including SLNB, for fit older patients with breast cancer.

Adjuvant Radiotherapy

For healthy older patients, as with younger patients, breast irradiation is considered a standard component of BCS. Breast irradiation is generally well tolerated, with good-to-excellent cosmesis in older women, and chronologic age alone should not be a limiting factor in its inclusion.29,30 However, the rate of ipsilateral breast cancer recurrence decreases with age, and although RT after BCS is associated with similar proportional reductions in local recurrence across age groups, the absolute benefits of treatment are lower in older women, since their risk of local recurrence is less.31 This has prompted the re-evaluation of the role of RT for selected older patients with breast cancer. One large randomized trial specifically examined the role of adjuvant RT following BCS in women aged 70 years and older. In this study from the Cancer and Leukemia Group B (CALGB 9343), older patients with ER-positive tumors (≤2 cm) treated with tamoxifen were randomized to treatment with or without RT.27

The most recent update (at a median follow-up of 10.5 years) reported a significant difference in the rate of local recurrence in the patients treated without RT (9% vs 2%; P=.0125). However, there were no significant differences in breast cancer–specific survival or overall survival.32 The majority of deaths to date were due to reasons other than breast cancer. Thus, adjuvant RT may reasonably be omitted in patients aged 70 years or older who received endocrine therapy for small (≤2 cm) ER-positive, clinically node-negative breast cancers. Few data exist that reliably predict whether or not RT can be omitted in older patients who do not fit these highly selective criteria, and determining the specific indications for RT in older patients is an issue that will continue to grow in significance with the aging of the population.33

Despite the compelling data from CALGB 9343, a recent article by Soulos and associates examined the effect of the CALGB 9343 trial on the Medicare population.34 They determined that the reporting of the trial had minimal impact on the use of RT in the studied population, with the use of RT remaining high in clinical practice. Additionally, they found no evidence of differential uptake among patients with limited life expectancy or among the oldest women, with the use of RT among patients with the shortest life expectancy still exceeding 40% after publication of the article, suggesting that increased dissemination of these results is needed.34

Postmastectomy Radiation

Clinical trials indicate that postmastectomy radiotherapy (PMRT) is associated with improved survival and decreased local regional recurrence for women with high-risk breast cancer.31 As women older than 70 years were underrepresented in these clinical trials, PMRT decisions in these individuals are extrapolated from the trials conducted primarily in younger women. Evidence from population-based cohort studies supports the assertion that older women with high-risk cancer may also benefit from PMRT. In one study of 939 women aged 70 years and older who were treated with mastectomy without PMRT, only patients with tumor sizes 5 cm or greater and/or at least 4 positive nodes experienced a risk of local regional recurrence similar to the control arms of the PMRT clinical trials, suggesting that the intervention might only show a survival benefit in high-risk patients.35 One large population-based cohort study of women aged 70 years and older who were treated with mastectomy for newly diagnosed breast cancer reported that PMRT was associated with a survival benefit for high-risk (T3/T4 primary tumor and/or N2/N3 nodal involvement) patients, but not for low-risk (T1/T2, N0) or intermediate-risk (T1/T2, N1) patients. However, only 38% of the high-risk patients in this cohort (treated between 1992 and 1999) actually received PMRT.36 For women with high-risk disease, PMRT should be offered. Future clinical trials in this age group are needed in order to clarify treatment strategies for patients with lower-risk disease.

Adjuvant Endocrine Therapy

In general, because of its favorable toxicity profile and confirmed effectiveness in improving relapse-free and overall survival, adjuvant endocrine therapy is recommended for older women with ER-positive breast cancer. For most postmenopausal women, aromatase inhibitors (AIs) are the preferred agent, as they offer improved DFS and lower rates of thrombosis and endometrial cancer compared with tamoxifen.37 The benefits of endocrine therapy are preserved across age groups. In the Breast International Group (BIG) 1-98 trial, which compared 5 years of letrozole (Femara, Novartis) versus tamoxifen, there was an age-independent DFS benefit reported for letrozole, including in patients aged 75 years and older.37 The National Cancer Institute of Canada Clinical Trials Group MA.17 trial compared 5 years of letrozole versus placebo following 5 years of tamoxifen; a subgroup analysis of older women revealed a statistically significant benefit in DFS from letrozole only in women younger than 60 years of age.38 However, there was no interaction between age and treatment, indicating a similar effect of letrozole among all age groups. Additionally, there was no difference in toxicity or QOL at 24 months in the group of patients aged 70 years and older who were treated with letrozole or placebo, making extended letrozole an option for fit older women.

Despite the benefits of AI therapy in older women, side effects such as musculoskeletal discomfort, accelerated bone loss, and fracture risk are important to monitor in older patients, who have higher rates of osteopenia and osteoporosis than their younger counterparts. Although the studies were not designed to determine fracture rates as the primary outcome, in a meta-analysis of 7 trials comparing AIs to tamoxifen in postmenopausal women with early-stage breast cancer, AIs significantly increased the risk of bone fractures.39 Monitoring bone density and instituting appropriate antiresorptive therapies as indicated is especially important in this population. Furthermore, studies have reported a potential association between aromatase inhibition and cardiovascular risk; however, further research is needed to clarify these findings.

A Danish Breast Cancer Cooperative Group study identified a subgroup of patients with such a favorable prognosis that omission of adjuvant endocrine therapy could be considered. They reported that in the absence of systemic therapy, women aged 60–74 years with small (<1 cm), node-negative, ER-positive, grade 1 ductal carcinoma or grade 1 or 2 lobular carcinoma had the same mortality as age-matched women in the general population. These findings suggest that there may be a population in which no endocrine therapy could be considered.40

Adjuvant Chemotherapy 

Older adults have been underrepresented in adjuvant chemotherapy trials to date; however, a landmark randomized trial specifically focused on older adults has recently been reported. In this prospective randomized study, women aged 65 years and older were randomized to standard polychemotherapy (cyclophosphamide, methotrexate, and fluorouracil [CMF], or doxorubicin and cyclophosphamide [AC]) or capecitabine (Xeloda, Genentech, a member of the Roche Group) alone. At a median follow-up of 2.4 years, patients treated with capecitabine were twice as likely to suffer a relapse and almost twice as likely to die as patients randomly assigned to standard chemotherapy. The benefit was greatest in the subgroup of women with hormone receptor–negative cancer (hazard ratio [HR], 2.62; P=.001). These data suggest that standard adjuvant chemotherapy has a role in the treatment of fit older women.41 Treatment guidelines from the National Comprehensive Cancer Network do not set an upper age limit for the utilization of chemotherapy, acknowledging that both life expectancy and comorbidity must be taken into account.42 Two large international randomized trials (CASA [Chemotherapy Adjuvant Studies for Women at Advanced Age] and ACTION [Adjuvant Cytotoxic Chemotherapy in Older Women]) comparing adjuvant chemotherapy with no chemotherapy in older women closed prematurely because of insufficient accrual, thus highlighting the challenges of conducting randomized trials with a no-chemotherapy arm in this population.13

Data from cooperative group studies enrolling women across all age-groups demonstrate that older women in good general health derive similar benefits from systemic chemotherapy as younger adults; however, they are at increased risk of treatment toxicity. A retrospective analysis of 4 CALGB trials for node-positive breast cancer reported that older patients derived similar benefits to younger patients from the experimental arm (which gave more aggressive chemotherapy), with improved relapse-free and overall survival.43 However, women aged 65 years and older experienced greater treatment-related mortality and hematologic toxicity.44

An Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) meta-analysis of randomized trials initiated in 1995 showed statistically significant reductions in recurrence and breast cancer–specific mortality with polychemotherapy in both older and younger women, with a larger absolute magnitude of benefit in younger women.45 The trials examined in this overview involved too few patients aged 70 years and older to achieve statistical significance, although a 13% reduction in all-cause mortality was reported in women treated with adjuvant chemotherapy. The exact reason for these findings is unclear; however, potential etiologies include the increasing risk of death from competing causes in older women, differences in tumor biology (an increased percentage of ER-positive cancers), or an age-related increased risk of treatment toxicity precluding the ability to deliver adequate dose intensity of adjuvant chemotherapy in older patients.

Weighing the Risk of Chemotherapy Toxicity in Older Adults: Integrating Geriatrics and Oncology

Similar principles guide the use of adjuvant chemotherapy in older and younger patients, with judicious weighing of available tumor prognostic and predictive factors. However, with older patients, a more comprehensive evaluation of patient characteristics (captured in a geriatric assessment) can assist in weighing the potential risks of therapy. A comprehensive geriatric assessment (CGA) includes an evaluation of functional status, comorbidities, polypharmacy, nutritional status, cognitive function, social support, psychological state, and geriatric syndromes (dementia, delirium, depression; Table 1). Components of the CGA have been associated with cancer-specific survival in older patients with cancer.46-49 When used to evaluate the older patient with cancer, the value of the CGA is twofold. First, components of the CGA can be predictive of morbidity and mortality for older patients. Secondly, the CGA can identify deficits that may be addressed prior to initiating cancer-directed therapies, thereby potentially minimizing morbidity.

Predictive models for the risk of chemotherapy toxicity in older adults (incorporating geriatric assessment variables) have been developed (Table 2). The Chemotherapy Risk Assessment Scale for High-Age Patients (CRASH) score utilizes an individual’s clinical, laboratory, and functional variables, with chemotherapy regimen–specific toxicity criteria in order to develop risk categories for grade 3/4 nonhematologic or grade 4 hematologic toxicity.50 The Cancer and Aging Research Group developed a predictive model and scoring algorithm for the risk of grade 3–5 chemotherapy toxicity in patients aged 65 years and older, consisting of tumor and treatment variables, laboratory data, and geriatric assessment questions.51 Both of these studies included patients across tumor types. A study specifically evaluating the clinical and biologic risk factors for adjuvant chemotherapy toxicity is under way (R01 AG037037-01A1, ID: NCT01472094).52

To compensate for the resource and time restraints imposed by a typical oncologic consultation, a brief but comprehensive geriatric assessment for older patients with cancer that is mostly patient-administered and evaluates multiple domains of the standard CGA has been developed. Prospective studies have found that most older patients can complete this questionnaire without assistance, and that it identifies deficits which have been shown to affect the risk of chemotherapy toxicity in older adults.53,54


The number of breast cancer cases in the United States is rising, due to the growing aging population, rises in life expectancy, and the association of cancer with aging. There is emerging data regarding the benefits and risks of breast cancer treatment in older adults; however, more research is needed to inform evidence care, particularly at the extremes of age. Chronologic age alone provides inadequate information when it comes to formulating treatment decisions for an older patient with breast cancer. Melding the fields of geriatrics and oncology research and practice is essential to inform both research and clinical care.


The authors would like to thank Carol A. Pearce, MFA, for her editorial assistance in the preparation of this manuscript. Research Support: Dr. Hurria’s salary is supported by R01AG037037-01A1 (PI: Arti Hurria, MD), the William Randolph Hearst Foundation, and the Breast Cancer Research Foundation.


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