The approaches to local therapy are similar between younger and older adults. The surgical treatment of early stage breast cancer is an integral part of therapy, given a low risk of surgical morbidity in all age groups. A key consideration in many older adults is whether to recommend breast radiation after breast-conserving surgery. Radiation is known to decrease the risk of local recurrence; however, its overall benefit must be considered in the context of competing comorbidities and life expectancy. This question was studied among patients age ≥70 who were treated with breast-conserving therapy and endocrine therapy for stage I disease and tumors that were hormone receptor positive and node negative. In patients randomized to radiation therapy or none, after 12 years of follow-up the omission of radiation was associated with a modest increase in the risk of a local recurrence (10 % versus 2 %) but no difference in overall survival. The majority of deaths were caused by comorbidities other than breast cancer (Hughes et al. 2010). However, gaps in knowledge remain regarding this approach in older patients with larger tumors. Of note, despite the results of this randomized trial, translation into clinical care has been limited, and most women continue to receive postoperative radiation (Soulos et al. 2012). Additional studies are needed to determine how to expedite the translation of research findings into practice, and to pinpoint the barriers to translation.

Among those where radiation therapy is warranted, barriers and challenges to receipt of radiation need to be considered including whether the patient has transportation, and whether a caregiver is needed to accompany the patient. These challenges can be amplified in an older adult who is dependent on others for transportation or who has difficulty attending a daily appointment because they are the primary caregiver for another family member such as a spouse. Randomized studies have evaluated the role of hypofractionated breast radiation therapy, and demonstrate the efficacy of such an approach (Haviland et al. 2013; Eblan et al. 2014). Additional studies are needed to identify which older patients truly need radiation therapy and whether shorter courses could yield similar benefits with less resource requirement.

There were several unique components in this study, including the consideration of drug dosing based on organ function, additional safety parameters to decrease the risk of toxicity, and a rich correlative component evaluating the impact of therapy on quality of life, adherence, and geriatric assessment parameters (such as function, comorbidity, and cognition) (Partridge et al. 2010; Kornblith et al. 2011; Freedman et al. 2013).

A novel component in the design of CALGB 49907 was the development of a parallel registry study, CALGB 366901, led by Dr. Jeanne Mandelblatt. The rationale for this observational cohort study was to understand the factors, including patient preferences, that influenced adjuvant treatment decisions in older adults with breast cancer. This study demonstrated that patient preference for chemotherapy and a higher rating of physician communication were associated with chemotherapy receipt (Mandelblatt et al. 2010). Furthermore, physician decision styles also influenced the treatment chosen. In particular, the oncologists’ preference for chemotherapy was associated with patients’ subsequent receipt of chemotherapy treatment. Those patients who preferred to have more of the oncologist’s input in treatment decisions were more likely to receive chemotherapy. Both patient and physician decision styles were independently associated with chemotherapy use (Mandelblatt et al. 2012). The measures included in CALGB 49907 were similar to those utilized in 369901, allowing for a comparison of characteristics and outcomes of patients who enrolled in these two studies with inclusion of detailed geriatric assessment measures.

Additional studies of adjuvant chemotherapy for breast cancer in older adults are needed. This is particularly true because the risks of adjuvant breast cancer treatment are greater in older adults. An evaluation of four adjuvant breast cancer trials performed in the Cancer and Leukemia Group B over a quarter of a century demonstrated that although patients age 65 and older received the same benefits as younger patients from more versus less aggressive chemotherapy regimens, older women had a higher risk of treatment toxicity, a greater likelihood of not being able to complete the treatment course, and an increased risk of treatment-related mortality (Crivellari et al. 2000; Muss et al. 2007). These risks must be weighed in the decision-making process, and studies of novel regimens are needed. CALGB 49907 can serve as a model for future studies in terms of design, implementation, and successful execution of an adjuvant treatment trial in older adults. Trials designed specifically for older patients should be expanded.

Overall, the goals of treatment for metastatic disease are the same across all age groups. Since breast cancer is treatable but not curable, the goals of treatment include preserving function, minimizing symptoms, maintaining quality of life, and prolonging survival. Just as with younger patients, there is an overall desire to integrate new therapies, but the challenge is the low representation of older adults on FDA registration trials, and therefore limited guidelines on how to dose these medications in the geriatric population (Talarico et al. 2004; Scher and Hurria 2012). Furthermore, there have been almost no studies performed in frail older adults, leading to a major gap in knowledge.

As with most cancers, older adults continue to be underrepresented on clinical research studies; as a result there is scant evidence-based data regarding treatment and survivorship issues facing older adults with breast cancer (Lewis et al. 2003; Murthy et al. 2004; Unger et al. 2006). This is particularly true among older patients with breast cancer enrolling in adjuvant treatment trials. Among four cooperative group adjuvant trials for node-positive breast cancer conducted over a quarter of a century, only 8 % of participants were age ≥65, and only 2 % were age ≥70 (Muss et al. 2005). Furthermore older adults are underrepresented on FDA registration trials, so there is inadequate evidence-based data available on how to dose these drugs in older patients (Talarico et al. 2004; Scher and Hurria 2012).

A study performed in Cancer and Leukemia Group B evaluated the barriers to clinical trial enrollment in a matched sample of patients (older vs. younger adults) with breast cancer who had the same treating physician. This study demonstrated that older adults were less likely to be offered a clinical trial but were as likely to accept enrollment if offered (Kemeny et al. 2003). A survey of treating physicians highlighted concerns regarding treatment-related toxicity and the need for specific trials in older adults with safety parameters in place (Kornblith et al. 2002). Education regarding the potential benefits of clinical trial enrollment in older adults is needed, but a multicenter study showed that education alone will not increase clinical trial enrollment, and a multifaceted approach is necessary (Kimmick et al. 2005).

Traditional clinical trials focus on metrics of disease-free and overall survival. For an older adult, the impact of treatment on functional status and cognition may be as, if not more, important to their decision-making process (Braithwaite et al. 2010; Dale et al. 2012; Mandelblatt et al. 2013; Sehl et al. 2013). Measures of functional status, as captured in a geriatric assessment pre-treatment, predict cancer treatment toxicity and survival. Furthermore, among older adults with breast cancer, a decline in functional status in the 2 years following diagnosis has been associated with poorer overall survival (Sehl et al. 2013).

There is a biologic rationale for concern that cancer treatment may accelerate the aging process. Aging and chemotherapy, in particular, are associated with a variety of similar biologic changes including DNA damage, inflammation, oxidative stress, and cellular senescence. A cross-sectional study of breast cancer survivors demonstrated that prior chemotherapy was associated with an increase in p16 ^INK4a expression, a potential molecular marker of aging, which equated to approximately 10 years of chronological aging (Muss et al. 2009; Sanoff et al. 2014). The potential medical, functional, and social impact of these biologic findings is unknown, and further research is needed to address this knowledge gap (Pallis et al. 2014).

There is emerging data suggesting that receipt of cancer therapy may be associated with decrements in cardiopulmonary function, which persist throughout the survivorship years. A study of breast cancer survivors, who were on average 7 years post diagnosis demonstrated reductions in cardiovascular fitness in comparison to a non-cancer control group (mean 55 years; SD 10 years) (Lakoski et al. 2013). Furthermore, another study demonstrated that patients with breast cancer have a marked impairment in peak oxygen consumption (a measure of aerobic consumption) in the survivorship years (Jones et al. 2012). These data demonstrate that adjuvant chemotherapy is likely associated with aging of the cardiopulmonary system. These findings are seen across the aging spectrum and are especially germane to older patients.

There is a dearth of knowledge regarding cancer treatment impact on cognitive aging, as the majority of studies to date have been performed in younger adults (Hurria et al. 2006; Yamada et al. 2010; Koppelmans et al. 2012; Mandelblatt et al. 2013). Studying the cognitive effects of cancer therapy in older adults is complex because breast cancer is only one of many other factors (such as comorbid medical conditions, lifestyle, and genetics) that can affect cognitive function. However, emerging literature is demonstrating an interaction of cancer treatment, aging, and cognitive function/reserve which highlights the importance of studying the cognitive effects of cancer therapy in older adults (Ahles et al. 2010). The age at which an individual is treated (i.e., the more vulnerable brain with decreased cognitive reserve) may also have an impact on the risk of cognitive decline. Research is needed to understand how cancer therapy affects cognitive aging both during the acute post-treatment phase and in the survivorship years. Interventions to maintain or minimize therapy’s potential harm to cognition are needed.

Clinical and biological markers of functional age and cognition (as captured in a geriatric assessment) are vital components to be included in breast cancer trial design, at baseline as well as longitudinally. Interventions to maintain function and independence, such as home-based exercise interventions, have proven efficacious, and additional research is needed to understand both the physical and cognitive impact of such interventions and to evaluate the “dose” of the intervention that is needed to obtain and sustain a positive effect (Demark-Wahnefried, et al. 2006).

There are unique social considerations for the older adult with breast cancer. Questions that arise during the treatment planning process usually include: If the older adult lives alone, who would bring them to the hospital in the event of an emergency? Can the patient and family afford caregiver support? Is the patient a caregiver for someone else (spouse, children, grandchildren)? Who would provide that care if the patient is unable to do so? Does the patient still drive? If not, who will provide transportation for treatment-related visits? These questions are not necessarily unique to patients with breast cancer, and need to be considered when caring for any older adult with cancer. However, studies are needed among patients with breast cancer to more accurately quantify the potential impact of a treatment course on both the patient’s and caregiver’s well-being, and on patients and families planning for treatment.