Comorbidities in the Aging Breast Cancer Population: Are Current Assessments Leading to Improved Outcomes?
Authors: W. McCaskill-Stevens, J. S. Abrams
Journal: JNCI Journal of the National Cancer Institute (2011)

Breast cancer is the most common noncutaneous cancer worldwide among a rapidly growing population of women aged 65 years or older. More than one half of the 2.6 million women who are breast cancer survivors and of the 207 000 women newly diagnosed with breast cancer each year in the United States are older than 65 years. Survival and all-cause mortality clinical outcomes among breast cancer patients are influenced by competing mortality associated with age, race/ethnicity, and comorbid diseases (1). Important questions concerning the development of other diseases commonly associated with aging and coexisting with breast cancer are challenges to its management.

In this issue of the Journal, Patnaik et al. (2) use Surveillance, Epidemiology, and End Results and Medicare data to determine the effect of 13 distinct comorbid conditions on overall survival and all-cause mortality among 64 034 breast cancer patients aged 66 years or older from 1992 to 2000. Inpatient and outpatient visits were reviewed to determine comorbidities 1 year before and 30 days after breast cancer diagnosis and to capture comorbidities not associated with cancer treatment. At the time of diagnosis, relationships between comorbidities and survival were determined by a modified and weighted Charlson Comorbidity Index Score. Comorbidities with the highest prevalence observed by the authors in the study population included previous cancer, diabetes, chronic obstructive pulmonary disease, congestive heart failure, and stroke. When patients were stratified by specific comorbidity, all 13 comorbidities were associated with a statistically significant decreased overall survival and increased mortality compared with patients who had no comorbidities. Also, Patnaik et al. (2) show that stage I breast cancer patients aged 66–74 with comorbid conditions had survival rates similar to patients with stage II cancers who did not have comorbidities; a similar trend was also found among older patients aged 75–84 years and 85 years or older.

Despite evidence for benefits of systemic and local therapy in older breast cancer patients, many physicians do not adhere to existing practice guidelines. Also, inadequate representation of older patients with comorbidities in clinical trials, further impairs a physician’s ability to communicate to this patient subgroup the benefits and risks of systemic vs local therapy. Representation of women aged 65 years or 70 years or older in National Cancer Institute–sponsored breast cancer treatment trials during the past 5 years is 25% and 14%, respectively. Although not representative because one half of breast cancers occur after age 65, it is nonetheless an improvement compared with studies in the 1990s. During the time period studied by Patnaik et al. (2), women aged 65 years or older composed only 18% of breast cancer trial participants and 10% for women aged older than 70. Efforts to continue to enroll older women into clinical trials are essential if evidence-based guidance is to be enhanced for this subset of women.

Fortunately, researchers are increasingly incorporating measures of specific comorbidities along with summary measures such as the Charlson Comorbidity Index. The findings by Patnaik et al. (2) support this trend and indicate that measures of specific comorbidities may more clearly reflect outcome than do summary measures in which the same weight is often given to all morbidities despite their differing impact on outcome. Yet, predicting outcome is complex because multiple variables must be taken into account. Whereas performance status is clinically the most compelling factor for deciding on a treatment plan, the predictive potential of a more broadly based functional status for survival (including activities of daily living, instrumental activities of daily living, comorbidity, cognitive status, and depression) has been demonstrated in several studies (J. S. Abrams, unpublished data) (3) and is an approach that is increasingly promoted by geriatric oncologists. This broadly based functional approach is thought to be superior to performance status alone, which is captured in most clinical trials (4). To date, support for this approach has come primarily from population-based or longitudinal observational studies. Hopefully, comorbidities will be incorporated more commonly into prospective randomized treatment trials so that their translation to general practice can become more routine.

As the need for more multidimensional evaluations gains support by increasing data from research, the challenge will be to develop convenient assessment tools for practical application to facilitate more rapid adoption of multidimensional approaches. Efforts to educate providers on the interpretation of these tools will be required. Owusu et al. (5) reported the effects of discontinuation of tamoxifen and found that in their study, 14% of women with breast cancer aged 65 years or older had Charlson Comorbidity Index Scores that increased from the baseline measurements and 8% had increases in the number of cardiopulmonary comorbidities after 3 years of taking tamoxifen (6). These observed changes in geriatric assessments were associated with tamoxifen discontinuation during the next 2 years of prescribed therapy. It was not reported whether the new morbidities were related to treatment or age. It is important to note that within the large study by Patnaik et al. (2) of older breast cancer patients (n = 64 034), 58% of patients had none of the comorbidities studied. However, if age is a confounding factor and is known to be an independent predictor of increased mortality, then these women are at increased risk of developing other diseases. It is possible that serial assessments of such patients would detect changes in their health status that could influence survival. When a more multidimensional evaluation with more frequent assessments is instituted, the implications of the study results from Patnaik et al. (2), which has identified conditions that may have a differential influence on mortality, could be considered in clinical practice and may help to improve treatment strategies for older breast cancer patients.

The key finding in the report by Patnaik et al. (2) is that patients with serious comorbidities have outcomes that are comparable to those seen with later-stage tumors, resulting in the practical equivalent of a stage shift for individual tumors. The causes for this stage shift are likely to be multifactorial. Physicians may reduce treatment or diminish its intensity in patients with comorbidities. Patients with comorbidities may be less able to comply with treatment regimens or tolerate their side effects. And finally, there is a biological interplay among cancer and other diseases that may diminish the effect of anticancer treatments. Whether these considerations should lead to different treatment selections, tighter assessments of compliance, and/or efforts to more closely monitor and treat the comorbidity remain to be determined. Future researchers should plan to address these potential reasons for poorer outcomes and should consider including obesity and hypertension in the list of comorbidities. Although this study has some limitations related to the databases used for analysis (eg, lack of data on hormonal therapy use and duration and quality of care for existing diseases), the findings are provocative, suggesting that care should be individualized in patients with comorbidities and the diseases should be comanaged between the oncologist and primary care physicians. Research efforts in older patients should focus on modifying the eligibility and management guidelines in clinical trials to encourage the inclusion of older breast cancer patients with treatable diseases. The results presented by Patnaik et al. (2) underscore the importance of specifically studying the large population of older breast cancer patients with comorbidities, because they currently face a poorer outcome than do their counterparts without such conditions.