Background
More than 50 years of research has guided the development of evidence-based treatment guidelines for breast cancer, including those published by NCCN.1,2 Although the course of treatment for each woman is primarily determined by her tumor characteristics and extent of disease, multiple treatment pathways exist that are dependent on patient characteristics and preferences. However, not all patients receive guideline-concordant care (GCC). Vulnerable populations, such as racial and ethnic minorities or those who are socioeconomically disadvantaged, are more likely to experience treatment disparities.3–7 Independent of these characteristics, older women are less likely to receive GCC due to increasing age and declining health and functional status associated with older age.6,8,9 The NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Breast Cancer contain 2 age-based treatment concessions. The first is the omission of radiation therapy (RT) following breast-conserving surgery (BCS) for patients aged ≥70 years with stage I, estrogen receptor (ER)–positive breast cancer and that they should receive adjuvant endocrine therapy (AET) based on the CALGB C9343 trial findings.2,10,11 The second is the recommendation that the decision to treat women aged >70 years with chemotherapy be made on a case-by-case basis, considering patient preferences, health, and risks, citing insufficient evidence for this age group.2,12 Guidelines note that older women who received chemotherapy in trial studies experienced similar survival outcomes but had an increased risk for side effects and treatment-related mortality.13,14
Despite flexibility in treatment guidelines, treatment disparities reported by previous studies raise concern that older women are undertreated more frequently than warranted. Recent studies have reported that among women aged ≥65 years, 21% to 29% did not receive RT following BCS for early-stage breast cancer regardless of their ER status,4,15 67% with lymph node–positive disease did not receive chemotherapy,9 50% did not receive trastuzumab,16 and 17% to 40% did not receive AET when indicated.5 Moreover, age and comorbidity have been found to be the strongest predictors of treatment, irrespective of clinical indications.17–20 These findings are of particular concern considering that women aged ≥65 years represent 43% of newly diagnosed breast cancer cases,21 and that undertreatment is associated with worse disease-specific survival for many older patients.15,17,20
Although undertreatment is commonly reported among older women with breast cancer, it is difficult to discern how inappropriate or problematic this is if the treatment is in accordance with evidence-based treatment guidelines that provide age-based treatment considerations, depending on individual circumstances. Therefore, the extent to which older women with invasive breast cancer receive GCC, considering all available treatment options, remains unknown. Bearing these thoughts in mind, the goal of this study was to determine US population-based estimates of the prevalence and associations with GCC for breast cancer among older women, as well as receipt of specific types of treatments using the US population-based SEER-Medicare data.
Patients and Methods
Data Source and Cohort Definition
The SEER-Medicare linked database was created in a collaborative effort by the NCI and Centers for Medicare & Medicaid Services. SEER data are collected from 17 tumor registries representing 26% of the US population, and are successfully matched to Medicare enrollment records for 94% of patients aged ≥65 years.22 SEER-Medicare data contains information about date of diagnosis, cancer site, stage, tumor characteristics, treatment, healthcare use, patient enrollment and eligibility, selected demographic characteristics, and vital status information. Medicare claims are available for Part A (inpatient), Part B (outpatient), and Part D (prescription drug) services.23 County and state identifiers were used to link SEER-Medicare data to the US Department of Health & Human Service's 2009 Area Resource File (ARF) to identify the area-level health resources.24
We identified 431,212 women aged ≥66 years diagnosed with breast cancer as their first or only primary tumor between January 1, 2007, and December 31, 2011. We excluded women without a pathologic diagnosis (n=9,954) and those diagnosed with breast cancer at death or autopsy (n=30); who died within 366 days of diagnosis (n=23,729); diagnosed with stage 0 or stage IV disease (n=105,189); not continuously enrolled in Medicare Parts A and B fee-for-service programs for 12 months before and after diagnosis (n=9,469); not continuously enrolled in Medicare Part D services for 4 months before diagnosis and 12 months after diagnosis (n=124,231); enrolled in a health maintenance organization plan during the 12 months before and after diagnosis (n=14,542); and whose records were missing tumor size (n=484) and surgeon specialty (n=1,151). The final analytic cohort consisted of 142,433 patients (Figure 1).
Dependent Variables
The primary outcome was receipt of GCC, defined as treatment, including surgery, RT, chemotherapy, and AET, received according to the NCCN Guidelines for Breast Cancer, Version 1.2009.25 Measures assessed by this study remained unchanged in previous and later versions of the guidelines published during the cohort study period. Initiation of chemotherapy within 120 days of diagnosis, when indicated, as specified by the joint ASCO/NCCN quality measures,26 and receipt of ER and progesterone receptor (PR)
Flow diagram for study cohort selection.
Abbreviation: HMO, health maintenance organization.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 16, 6; 10.6004/jnccn.2018.7004
Flow diagram for study cohort selection.
Abbreviation: HMO, health maintenance organization.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 16, 6; 10.6004/jnccn.2018.7004
Flow diagram for study cohort selection.
Abbreviation: HMO, health maintenance organization.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 16, 6; 10.6004/jnccn.2018.7004
Guideline-concordant treatment options by tumor size and lymph node status.
Abbreviations: AET, adjuvant endocrine therapy; BCS, breast-conserving surgery; CT, chemotherapy; ER, estrogen receptor; ERT, estrogen receptor testing; N, nodal status; PR, progesterone receptor; PRT, progesterone receptor testing; RT, radiation therapy; T, tumor size.
aAET recommended when breast tumors are ER- and/or PR-positive.
bRecommended that, for women aged >70 years, the decision to treat with chemotherapy should be made on an individual patient basis.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 16, 6; 10.6004/jnccn.2018.7004
Guideline-concordant treatment options by tumor size and lymph node status.
Abbreviations: AET, adjuvant endocrine therapy; BCS, breast-conserving surgery; CT, chemotherapy; ER, estrogen receptor; ERT, estrogen receptor testing; N, nodal status; PR, progesterone receptor; PRT, progesterone receptor testing; RT, radiation therapy; T, tumor size.
aAET recommended when breast tumors are ER- and/or PR-positive.
bRecommended that, for women aged >70 years, the decision to treat with chemotherapy should be made on an individual patient basis.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 16, 6; 10.6004/jnccn.2018.7004
Guideline-concordant treatment options by tumor size and lymph node status.
Abbreviations: AET, adjuvant endocrine therapy; BCS, breast-conserving surgery; CT, chemotherapy; ER, estrogen receptor; ERT, estrogen receptor testing; N, nodal status; PR, progesterone receptor; PRT, progesterone receptor testing; RT, radiation therapy; T, tumor size.
aAET recommended when breast tumors are ER- and/or PR-positive.
bRecommended that, for women aged >70 years, the decision to treat with chemotherapy should be made on an individual patient basis.
Citation: Journal of the National Comprehensive Cancer Network J Natl Compr Canc Netw 16, 6; 10.6004/jnccn.2018.7004
The secondary outcome was receipt of individual tests and treatments: ER testing, PR testing, BCS, mastectomy, RT, chemotherapy, initiation of chemotherapy within 120 days of diagnosis, and AET when indicated.
Independent Variables
Independent variables included year of diagnosis, age, preexisting chronic conditions, frequency of primary care provider (PCP) visits, clinical prognostic factors, oncology care resources, and demographic characteristics. Specific preexisting chronic conditions prevalent among older individuals examined were anxiety, depression, dementia, arthritis, osteoporosis, diabetes, hypertension, hyperlipidemia, heart disease, stroke, and chronic obstructive pulmonary disease, identified using methods described by the Working Group on Health Outcomes for Older Persons With Multiple Chronic Conditions.28 Frequency of PCP visits was calculated by counting the number of unique PCP claim dates recorded 1 year before diagnosis in the physician claims file and dividing by the lower and upper 50th percent median cutoff (low, high). Clinical prognostic factors examined were stage at diagnosis, tumor size, lymph node status, ER status, PR status, and tumor grade. Measures of oncology care resources were the density (low vs high) of area-level mammography screening centers and oncology treatment centers relative to each woman's location of residence using data from the ARF, and were then categorized by the lower and upper 50th percent median cutoff. Surgeon specialty was assessed using provider specialty claims codes 02 and 49 (general) and 83, 90, 91, and 98 (oncology) from the physician claims file variable “hcfaspec” to determine the type of surgeon seen (general only, oncology only, both). Demographic characteristics examined were race/ethnicity, marital status, 2010 Census measure of education and annual income, and metropolitan status.
Statistical Analysis
Pearson and Mantel-Haenszel chi-square tests were used to compare the proportions of patients receiving GCC. Multivariable logistic regression models estimated the adjusted odds of receiving GCC (yes vs no), adjusting for all covariates. A secondary analysis was performed to further investigate the association of age of receipt of GCC and specific tests and treatments, controlling for all other covariates using multivariable logistic regression models. Age was dichotomized by women aged ≥75 years versus 66 to 74 years, because findings from the primary analysis showed a significant decrease in GCC after 74 years of age. Parameter estimates are presented as adjusted odds ratios (AORs) with their corresponding 95% CIs; P ≤.05 was considered statistically significant. All analyses were conducted using SAS 9.4 (SAS Institute Inc.). This study was approved for exemption by the West Virginia Institutional Review Board.
Results
Cohort Characteristics
Patient characteristics are presented in supplemental eTable 2. Most were aged >80 years at diagnosis, white, diagnosed at stage I, lymph node–negative, ER-positive, and diagnosed with hypertension and hyperlipidemia. Most patients received BCS (60.8%), RT (57.4%), and AET (49.7%). Overall, 39.7% received GCC.
Receipt of GCC
Rates of GCC were highest among women aged 70 to 74 years and lowest for those aged ≥80 years (50.5% vs 28.1%; P<.001; supplemental eTable 2). Lower rates of GCC were observed among women with preexisting depression, dementia, arthritis, diabetes, or heart disease compared with those without these conditions. Women diagnosed at stage I had higher rates of GCC than those diagnosed at stages II and III (42.0% vs 37.2% and 36.9%, respectively; P<.001), as did women with hormone-negative and higher-grade tumors. Women treated by an oncology surgeon or both an oncology and general surgeon had higher rates of GCC than women treated by a general surgeon (37.9% and 43.3% vs 19.2%; P<.001). White women had higher rates of GCC than those who were black, Hispanic/Latino, and other races (41.8% vs 32.5%, 36.5%, 37.2%, respectively; P<.001). Multivariable regression analyses confirmed findings of the bivariate analysis (Table 1). Compared with women aged 66 to 69 years, those aged ≥80 years were approximately half as likely to receive GCC (AOR, 0.52; 95% CI, 0.51–0.54). Women with hypertension (AOR, 1.15; 95% CI, 1.12–1.19) and stroke (AOR, 1.45; 95% CI, 1.38–1.52) were more likely to receive GCC than those
Multivariable Logistic Regression of Guideline-Concordant Care
Receipt of Tests and Treatments
Compared with women aged 66 to 74 years at diagnosis, those aged ≥75 years were more than 40% less likely to receive GCC (AOR, 0.59; 95% CI, 0.57–0.60) or AET (AOR, 0.63; 95% CI, 0.61–0.65), almost 80% less likely to have any type of surgery (AOR, 0.22; 95% CI, 0.20–0.24), approximately half as likely to have RT (AOR, 0.53; 95% CI, 0.52–0.54), and approximately 61% less likely to have chemotherapy (AOR, 0.39; 95% CI, 0.38–0.40) and 34% less likely to experience an appropriate time to chemotherapy (AOR, 0.66; 95% CI, 0.63–0.69) (Table 2).
Discussion
This study evaluated the extent to which older women with invasive breast cancer receive GCC in accordance with NCCN and ASCO evidence-based guidelines using the large, population-based SEER-Medicare database. Findings showed that only 40% received GCC, and rates were lowest among the oldest women (aged ≥80 years). A recent study of women of all ages with breast cancer reported an 80% GCC rate, but also found that GCC decreased with age.29 The difference in rate of GCC reported between these studies is likely attributable to the difference in age composition of the study populations.
Interestingly, women between ages 70 and 74 years were more likely to receive GCC. A probable explanation for this finding is that RT is not recommended for a subset of women aged ≥70 years with
Multivariable Logistic Regression of Treatment in Women Aged ≥75 Versus 66–74 Years
The increasing prevalence of chronic conditions and multimorbidity among elderly patients with cancer presents additional treatment challenges, and is often associated with undertreatment.4,20,37 This study found that the presence of specific conditions, such as diabetes and heart disease, decreased the likelihood of GCC. Diabetes can decrease the likelihood of GCC by having a more severe impact on patient health, creating competing health demands and increasing the risk of treatment complications, intolerance, and adverse reactions,38–40 whereas certain other chronic conditions may increase the likelihood of GCC through increased contact with healthcare providers, without creating competing health demands and treatment complications. In fact, patients with breast cancer with a greater frequency of PCP visits were more likely to receive GCC.
This study has several strengths, including a comprehensive examination of the association between GCC among older women with breast cancer and health, clinical, oncology resource, and demographic characteristics using a large population-based data set. Complex algorithms were used to determine receipt of GCC by calculating the correct course of care according to each patient's tumor characteristics and comparing that with the actual care received.
However, several limitations should be kept in mind when interpreting the results of this study. This study did not measure completion of RT or chemotherapy, only the initiation of therapy. It also did not distinguish between the receipt of neoadjuvant and adjuvant chemotherapy. Neoadjuvant chemotherapy is given to some women to shrink larger tumors and provide an opportunity for BCS after clinical staging but before pathologic staging. Although tumor size was used to determine the need for postmastectomy RT, the number of positive lymph nodes was not. This study only accessed the presence of positive or negative nodes. Because the SEER program only began recording information about the status of HER2/neu breast cancer cases in 2011, this study did not assess treatment for HER2/neu-positive tumors. Nor does SEER-Medicare collect information regarding results of any Oncotype testing that may influence treatment choices.
Conclusions
A little more than half of older women received GCC for breast cancer, even after incorporating age-based considerations into the definition of GCC. Variations in GCC by age group likely reflect the differing definitions of GCC by age, given than women aged ≥75 years were less likely to receive certain treatments. However, patients with more aggressive breast cancer characteristics were more likely to receive GCC. Given that older women represent close to half of all newly diagnosed breast cancers, and many are diagnosed at stages that require RT or chemotherapy, increasing rates of earlier-stage diagnosis and the development of less toxic treatments could help to improve GCC and survival while preserving quality of life.
The authors have disclosed that they have no financial interests, arrangements, affiliations, or commercial interests with the manufacturers of any products discussed in this article or their competitors.
See JNCCN.org for supplemental online content.
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