Laurel A. Habel, PhD

A 21-gene test that predicts recurrence risk among women with hormone receptor positive (HR+), localized breast cancer was nationally recommended in 2007, but we know little about its subsequent impact. We evaluated: a) patient characteristics associated with test use, b) correlations between Recurrence Score (RS) and chemotherapy, and c) whether test introduction was associated with a reduction in chemotherapy use.

The Kaiser Permanente Northern California tumor registry and electronic health records from 2005 to 2012 were used to identify HR+, human epidermal growth factor receptor 2 negative, node-negative cancers. Analyses used logistic regression with propensity score matching and 2-level logistic regression.

Of the 7004 patients who met guidelines for testing, 22% were tested and 26% had chemotherapy. Test use was more likely in younger women (for ages 40-49 years vs 50-64 years: odds ratio [OR], 1.22; 95% CI, 1.04-1.44), in women with tumors sized 1.0 to 2.0 cm versus >2 cm (OR, 1.20; 95% CI, 1.03-1.40), and in women from higher-income neighborhoods (for each $10,000 increase in area median income: OR, 1.05; 95% CI, 1.03-1.07). Among patients with low RS, 8% had chemotherapy versus 72% among patients with high RS (

 <.01). In propensity score-matched analyses, testing was associated with an absolute reduction of 6.2% in the proportion of women receiving chemotherapy (95% CI, 2.9%-9.5%); the 2-level model showed a similar but nonsignificant (

The 21-gene test is used in a minority of eligible patients in this integrated plan. Its use appears to be associated with a modest decrease in overall chemotherapy use.

	In this retrospective cohort study, we evaluated the use of a multigene test that predicts recurrence risk in localized breast cancer, and associated trends in chemotherapy use in eligible patients.

		The multigene test was used in fewer than 1 in 3 eligible patients, with use plateauing in 2010 through 2012.

		Recurrence risk scores on the test were highly, but not perfectly, correlated with the use of chemotherapy. 

		Introduction of the test was associated with a modest decrease in overall chemotherapy use.

Genetic testing of tumor cells has the potential to revolutionize the care of patients with breast cancer and to accelerate the benefits of personalized medicine.

 Several studies have observed that these tests have been incorporated into clinical practice and seem to influence chemotherapy decisions.

 Recent US studies of claims data and the National Cancer Institute’s Surveillance Epidemiology and End Results (SEER) data found that only 20% to 30% of eligible women were being tested, with the claims data study observing that reimbursement by insurers has increased slowly.

 It is unknown whether acceptance and use of this test have been more complete in integrated, fully capitated systems where the costs of care are covered and decisions are less likely to be affected by financial incentives for or against test or chemotherapy use. These tests are potentially costly, and may be marketed directly to patients, as well as physicians.

 As genetic testing in cancer grows more common, healthcare systems need to systematically evaluate how consistently such tests are being used, and how much incremental benefit they add to baseline clinical practices.

Breast cancer genetic testing provides a useful paradigm for evaluating the impact of such tests at a population level. Decisions about the use of adjuvant chemotherapy, for women with early-stage breast tumors that are estrogen or progesterone receptor positive (ER/PR+), can be especially difficult, as most will never experience a recurrence, even without adjuvant chemotherapy. Currently, several gene-expression profiling tests are being marketed to clinicians and patients as tools to enhance the accuracy of predicting recurrence risk and the likelihood of realizing benefit from adjuvant chemotherapy. The 21-gene Oncotype DX (Genomic Health, Inc, Redwood City, California) breast cancer assay has been validated in clinical trials to predict risk of distant recurrence in patients with early-stage, node-negative, ER/PR+, human epidermal growth factor receptor 2 negative (HER2—) cancers.

 Guidelines for incorporating Oncotype DX testing into treatment decisions were published in 2007

; however, little is known about how this test and other genomic tests are being incorporated into real-world oncology practice and how they affect patterns of care.

This study’s overall objective was to assess how the 21-gene test is being used among patients with early-stage breast cancer in a large integrated health delivery system. Among patients who met current guidelines for use of this test, our aims were to: a) compare the demographic and clinical characteristics of patients who had the test with those who did not; b) describe chemotherapy use among women with test results that indicate low, intermediate, and high risk of recurrence; and c) evaluate whether the introduction of the test was associated with a change in chemotherapy use.

Kaiser Permanente Northern California (KPNC) is a nonprofit integrated healthcare delivery system that currently provides care to more than 3.9 million members. Within KPNC, essentially all primary and specialty care, and the vast majority of emergency and hospital care, is delivered by providers working within a single care system for patients of a single health plan.

Identification of Breast Cancers and Cancer Characteristics

The KPNC tumor registry—a contributor to the SEER program of cancer registries&mdash;was used to identify all female KPNC members diagnosed with invasive, nonmetastatic, incident breast cancer between September 1, 2005 (when significant use of Oncotype DX began at KPNC), and June 30, 2012. A member’s first, newly diagnosed breast cancer during this period was included. The tumor registry includes patient age, sex, diagnosis date, tumor size, node involvement, ER/PR status, stage, and initial chemotherapy treatment. HER2 status was determined using the results of Immunohistochemistry and Fluorescence In Situ Hybridization tests.

In 2007, both the National Comprehensive Cancer Network (NCCN) and the American Society of Clinical Oncology included Oncotype DX testing in their guidelines.

 Following NCCN guidelines, we selected women for whom Oncotype DX was to be considered: those with ER/PR+, HER2—, stage I and stage II breast cancers having primary tumors ≥0.51 cm with either no lymph node involvement or only ≤2 mm axillary node micro-metastases.

 The Oncotype DX assay analyzes the expression of 21 genes to provide a Recurrence Score (RS) corresponding to the risk of distant recurrence at 10 years among tamoxifen-treated patients not treated with chemotherapy.

 The RS is classified into 3 categories based on likelihood of distant recurrence: low risk (RS <18), intermediate risk (RS 18-30), and high risk (RS ≥31). Low RS has been shown to predict little benefit from chemotherapy, whereas high RS predicts greater benefit.

 The routine approach in this medical group was to follow NCCN recommendations; thus, other genetic tests for breast cancer were not commonly used.

Due to the timing of SEER registry reporting requirements, there is some underascertainment of the chemotherapy treatment status in the tumor registry. As part of an ongoing prospective study of newly diagnosed cases of breast cancer,

 a subset of cases were reviewed to validate the chemotherapy treatment status. Of 7004 eligible cancers, 62% were reviewed. Of 1071 patients validated to have used chemotherapy, 86.18% were correctly classified as such in the registry, and of 3240 patients validated not to have used chemotherapy, 99.97% were correctly classified in the registry. The chemotherapy status used was the validated one, if it existed; otherwise, the registry status was used.

Patients were assigned to a census block group (defined by the US 2010 Census) based on their home address at the time of cancer diagnosis. Block group income and education were based on the 2006 to 2010 American Community Survey.

 We used data from the year before the cancer diagnosis to create a modified Deyo version of the Charlson comorbidity index.

 From administrative databases, we extracted (from the year before the cancer diagnosis) the following additional variables for each patient for use in the propensity score matching: primary medical center used for care, number of clinic visits and hospital days, and their associated cost.

To identify the predictors of receiving 21-gene testing, we used logistic regression, in which receipt of the test was the dependent variable. Independent variables were calendar year of cancer diagnosis (as a categorical variable), age group (5 categories: aged <40, 40 to <50, 50 to <65, 65 to <75, and ≥75 years), race/ethnicity (Asian, black, white Hispanic, white non-Hispanic, and other/unknown), tumor size (3 categories: 0.5 cm to ≤1.0 cm, >1.0 cm to ≤2.0 cm, and >2.0 cm), comorbidity (3 categories: 0, 1-2, and ≥3 comorbidities), census block group median income, and proportion of adults in the block group with less than a high school degree.

To assess the potential impact of 21-gene testing on receipt of chemotherapy, we used 2 different analytic approaches. The first approach directly evaluated whether women who received the test were more or less likely to receive chemotherapy compared with women who were not tested. We ran a logistic regression in which the dependent variable was whether the woman was tested, and the independent variables were the same as those listed above, plus the following (to increase further the similarity of the matched cohorts): primary medical center for care, patient’s age-squared (for potential nonlinear age effects), costs of clinic and hospital services, as well as the number of clinic visits and hospital days in the year before cancer diagnosis. Model calibration and discrimination were good (C statistic = 0.81; Hosmer-Lemeshow goodness of fit test: 

= .32, with nonsignificance reflecting adequate fit). The resulting predicted probability of receiving the test was the patient’s propensity score.

We selected patients who received the 21-gene test and matched them 1-to-1 to patients who were not tested. Matching was performed using the Mahalanobis metric matching within calipers, defined as one-fourth of the standard deviation of the logit of the propensity score.

 Using this methodology, 93% (n = 1462) of tested women were matched to a nontested woman, and after matching, there were no significant differences between the cohorts with regard to the variables used in the propensity score calculation. However, women in the matched cohorts were younger and had fewer comorbidities than the general pool of women from whom they were drawn. This reflects the fact that among the entire cohort of patients with cancer, tested women tended to be different from nontested women.

Using the propensity-matched samples, we calculated the percent of women in each sample receiving chemotherapy, and the corresponding ratio of the odds of receiving chemotherapy among women tested, to the odds of receiving chemotherapy among matched women not tested. As a sensitivity analysis, the matched analysis was repeated among the subset of patients with validated chemotherapy use.

The second analytical approach was to treat the overall percent of women who received testing as a predictive variable for receiving chemotherapy. This approach is similar to “ecological” regression, wherein aggregates are used either in place of, or in addition to, individual-level predictors.

 Unlike an interrupted time-series analysis in which differences before and after some change in practice are assessed, this approach does not require us to arbitrarily define time periods as “before” or “after” the introduction of the test, given that testing was phased in over time. We started with an analytic data set with 1 record per woman. For each calendar year and age group, we calculated the percent of women who received the test, and added this variable to the analytic data set. Thus, a woman diagnosed with cancer in 2011 who was aged 50 to <65 years, had a variable added to her record that reflected the percent of women in her age group in 2011 who were tested. Using these patient-level records, we ran a logistic regression in which receipt of chemotherapy was the dependent variable, and the independent variable of interest was the percent of women in the strata who were tested. The woman’s own test status is not included in the model. Other independent variables included in the model were the same as those used in the model identifying predictors of testing. The results of this model were then used to predict the percent of women receiving chemotherapy, assuming 1 of 2 scenarios: 1) 0% of women in her age group and year were tested, and 2) 30% were tested (which was about the maximum percent of women who received the 21-gene test in any given year).

The first approach has been called an “individual-level analysis” and the second approach a “2-level analysis.”

 Each of these approaches has distinct advantages and disadvantages. The individual-level analysis has the advantage of directly measuring the relationship between the individual’s use of the test and their use of chemotherapy, but does not account for certain aspects associated with self-selection of testing. For example, women with a strong predilection for or against chemotherapy may choose not to be tested—a problem similar to “confounding by indication.” The 2-level “ecologic” analysis factors out some of the potential unmeasured confounders related to which women choose to be tested.

 However, that approach is prone to bias if there are other unmeasured factors that may have increased or decreased use of chemotherapy at the same time as the increase in the use of testing.

We identified 7004 women diagnosed with cancers meeting our inclusion criteria, who met guidelines for 21-gene testing (

). The majority of women were under 65 years of age (57%) and 71% were non-Hispanic white. Three-fourths of cancers were stage I, and 70% of tumors were >1.0 cm in size. Overall, 21-gene testing was performed for 22% of women. In adjusted analyses, compared with women aged 50 to <65 years, women aged 40 to <50 years were more likely to be tested (OR, 1.22; 95% CI, 1.04-1.44), whereas women aged 65 to <75 years and ≥75 years were less likely to be tested (OR, 0.42; 95% CI, 0.36 to 0.49; and OR, 0.04; 95% CI, 0.02-0.06, respectively) (

). Compared with women with tumors >2.0 cm, women with tumors 0.5 cm to ≤1.0 cm were less likely to be tested (OR, 0.51; 95% CI, 0.42-0.61), whereas women with tumors >1.0 to ≤2.0 cm were more likely to be tested (OR, 1.20; 95% CI, 1.03-1.40). Each $10,000 increase in block group median income was associated with increased odds of testing (OR, 1.05; 95% CI, 1.03-1.07).

Among women with 21-gene testing, 52%, 39%, and 9% had low-risk, intermediate-risk, and high-risk RS values, respectively (

). Among women who had the test, a slightly higher percentage (26%) received chemotherapy compared with those who did not (22%; 

 <.01). Among women with low-, intermediate-, and high-risk RS, 8%, 40%, and 72%, respectively, received chemotherapy.

Between 2005 and 2012, the percent of eligible women receiving 21-gene testing rose from 8% to more than 25%, while the percent of women receiving chemotherapy decreased modestly from 26% to 22% (

). Younger women were much more likely to receive chemotherapy, and the 2 age groups with the most women receiving chemotherapy had the most pronounced downward trends in chemotherapy use from 2005 to 2012 (from 59% to 47% for those aged 40 to <50 years, and from 35% to 24% for those aged 50 to <65 years) (

In analyses with individual-level propensity score matching (n = 2924), receipt of the 21-gene testing was associated with decreased odds of chemotherapy (OR, 0.74; 95% CI, 0.63-0.87), corresponding to a reduction in the percent of women receiving chemotherapy from 32.7% to 26.5%, or an absolute reduction of 6.2% (95% CI, 2.9%-9.5%). When including only women with validated chemotherapy treatment status, 21-gene testing was associated with lower odds of chemotherapy (OR, 0.64; 95% CI, 0.53-0.78) than in the primary analysis, corresponding to an absolute reduction of 9.5% (95% CI, 5.3%-13.6%). Among this matched cohort, women who had received Oncotype DX testing and went on to receive chemotherapy were older, and were more likely to have stage I cancer and smaller tumors, than women who had not received Oncotype DX testing and went on to receive chemotherapy.

In the 2-level multivariable (ecological) analysis, each 10% increase in the absolute percent of women tested was associated with a 0.92 decreased odds of chemotherapy, but this result was not statistically significant (95% CI, 0.83-1.03; 

 = .14). The point estimates of this model imply that 26% of women in the study would have received chemotherapy in the absence of any testing, while 23% would receive chemotherapy if 30% of women were tested.

This is among the first large investigations of the use and impact of the 21-gene test for breast cancer recurrence risk in a managed care population. In this integrated system, we found that although rates of use increased over time, only 20% to 25% of patients meeting guidelines received testing. In adjusted analyses, use of testing was differential by age, tumor size, and neighborhood-level income. Patterns of chemotherapy use were generally consistent with test results, with those having a low RS far less likely to have chemotherapy than those with a high RS. When used, the test was associated with a modest reduction in overall chemotherapy use.

The rates of testing we observed were similar to other reports from US populations,

 including those of a large, for-profit oncology network.

 One difference from past studies is that we found no racial/ethnic differences in use of the test. For example, Guth et al found that women treated at municipal hospitals—who were more likely to be of low income and nonwhite&mdash;were less likely to have the 21-gene test than socioeconomically similar women seen in tertiary care settings (3% vs 30%).

 The fact that the test was fully covered by insurance in our setting removed patient-level financial barriers and may have mitigated racial/ethnic variation in test use. However, patients living in higher-income areas were more likely to have the test than those living in lower-income areas.

The other clinical and demographic correlates of nonuse of 21-gene testing that we identified, such as smaller tumor size and older age, have also been observed in other settings.

 For these subgroups, clinicians and/or their patients may have decided that chemotherapy was not indicated, so that testing would not change treatment decisions. Clinicians may also feel that standard clinicopathologic prognostic factors, existing decision tools (eg, Adjuvant!),

 and/or a patient’s health status or preferences are more important in treatment decision making than 21-gene test results.

 However, it has been reported that, when obtained, the 21-gene results can change pre-testing treatment decisions in about 30% to 50% of cases.

 A survey of KPNC oncologists, completed in spring 2015, suggests that among those patients who have the 21-gene test, the results cause changes in chemotherapy decisions in approximately 40%—and that these changes are equally divided among changes away from having chemotherapy and changes toward having chemotherapy (Lieu et al [unpublished data from a survey of 85 KPNC oncologists via mail and e-mail, as part of the overall project that produced this paper]).

This 21-gene test and other multigene tests have been promoted as likely to be cost-effective since test costs are expected to be offset by decreases in chemotherapy use among women with low recurrence risk, and, hence, low predicted benefits of chemotherapy.

 In our matched analysis, we found that testing was associated with a 6% to 10% reduction in chemotherapy use. A recent meta-analysis estimated a somewhat higher percent reduction of 12%.

 Our “ecologic” analysis indicated that an increase in testing in the KPNC setting, from 0% to 30%, resulted in approximately a 3% absolute decrease in the percent of women getting chemotherapy. The 2-level analysis is a more indirect (and conservative) approach, with fewer observations due to the summarized nature of the analysis, and, therefore, has less power. Nevertheless, the direction of the result was the same as that of the propensity score-matched analysis. Regardless of approach, our estimated reductions in chemotherapy were far lower than the 31% reduction in chemotherapy observed in a smaller study of a younger cohort in Ireland.

 The lower reduction in chemotherapy we observed relative to other studies was most likely due to our patient population being older and having a lower baseline percent of women receiving chemotherapy, as well as a lower percentage of eligible women being tested, compared with the study from Ireland.

Our results should not be construed as suggesting that the 21-gene test is being underused, as the study only evaluated chemotherapy in relation to current levels of testing. Our results cannot be extrapolated to project whether, or by how much, chemotherapy use would decrease if the test were used for a higher percentage of patients. The current level of testing may reflect clinicians’ judgments that the nontested patients would not benefit from testing because the decision about chemotherapy is already clear in their cases.

Chemotherapy treatment decisions in our study were not always in accord with the RS. Among women with low RS, 8% received chemotherapy anyway, and 28% of those with high RS did not receive chemotherapy. Similar discordant use patterns were noted in a recent meta-analysis.

 Our data did not enable us to determine the reasons for these conflicting choices; however, based on other reports,

 it seems that discordant use patterns are not unexpected since multigene testing is only 1 factor in complex chemotherapy decisions, and test results are not an absolute mandate for or against chemotherapy. For instance, doctors may sometimes use the test to discourage a low-risk (based on tumor size, histology, grade) or unhealthy patient who wants chemotherapy from having it, or to encourage treatment in a high-risk, healthy patient who does not want it. In the latter situation, a patient may continue to refuse chemotherapy even after receiving a high-risk test result. Genomic testing may increase anxiety and impair decision making or results may be poorly understood.

This study has many strengths, including its fully enumerated managed care population, inclusion of only those cases with clinical indications for 21-gene testing, and ability to relate test results to chemotherapy use. Although these findings from an integrated health plan population in California may not be representative of all practice settings, the testing and treatment patterns we found were remarkably similar to those reported from other settings.

 This suggests that clinical norms, randomized controlled trial evidence, and national recommendations may be more important to physicians’ ordering behavior than the costs of the test or who is covering those costs. That chemotherapy is sometimes discordant from therapy suggested by the RS indicates that patient factors may be as, or more important than the healthcare structure. These hypotheses will need to be tested explicitly in future research across diverse healthcare systems and populations.

Overall, this study suggests that in a large integrated healthcare system, the 21-gene test is used in a minority of eligible patients, but when used, it is leading to clinically appropriate patterns of chemotherapy use. Optimizing the benefit and efficiency of this and other genomic tests for cancer patients will require additional research on the factors that drive test use and subsequent decisions about chemotherapy. 

Articles

A multigene test for breast cancer recurrence risk was used in a minority of eligible patients, yet was associated with a decrease in chemotherapy use.

Breast Cancer Multigene Testing Trends and Impact on Chemotherapy Use

Human epidermal growth factor receptor 2 (HER2) expression is amplified in about 20% of breast cancer tumors, and evaluation of HER2 status should influence therapy selection. A critical gap in our knowledge is the real-world implementation of HER2 testing and its impact on treatment decisions for women diagnosed with breast cancer.

To assess use of HER2 testing, to describe characteristics of patients who do or do not receive HER2 testing, to describe which HER2 tests were used (fluorescence in situ hybridization or immunohistochemistry), and to evaluate trastuzumab use as a function of HER2 results.

The population included 6460 women diagnosed with invasive breast cancer between 1999 and 2007 at 8 geographically distributed Cancer Research Network healthcare delivery systems in the United States.

Electronic records were used to identify patient and tumor characteristics and treatment with trastuzumab. Chart abstraction was performed for 400 women (50 per site) to identify receipt of HER2 testing and results.

More than 90% of study participants received HER2 testing. Everyone who received trastuzumab had a HER2 test, and nearly all (>95%) who received trastuzumab had a positive HER2 test result recorded in their medical chart. Most (77%) eligible patients with a positive HER2 test result diagnosed after 2005 received trastuzumab. This study expands upon previous work in individual health plans.

HER2 status has been successfully incorporated into medical practice to guide treatment decisions for breast cancer patients in diverse integrated healthcare delivery settings.

We evaluated real-world implementation of human epidermal growth factor receptor 2 (HER2) testing and its impact on treatment decisions for women diagnosed with breast cancer between 1999 and 2007 at 8 US integrated delivery systems. There was consistent success in implementation of HER2-guided treatment decisions for breast cancer patients in these settings.

More than 90% of study participants received HER2 testing.

Everyone who received trastuzumab had a HER2 test, and more than 95% of these women had a positive HER2 test result.

Most (77%) eligible patients with a positive HER2 test result diagnosed after 2005 received trastuzumab.

In 2011, about 230,000 women in the United States were newly diagnosed with invasive breast cancer.

About 40,000 of these women are expected to die of this disease. Recent advances in medicine utilizing genetic-based technologies better predict cancer recurrence or response to various treatments and present an important opportunity for patients and their physicians to individualize therapy. However, there are limited reports in the literature about how such technologies are being incorporated into clinical practice and whether they are being used appropriately.

 As genetic-based technologies proliferate, understanding how and when these applications should be used in clinical practice becomes increasingly important.

One such genetic technology targets human epidermal growth factor receptor 2 (HER2). HER2 is a gene that influences cell growth, division, and repair. A normal cell has 2 copies of HER2. About 18% to 20% of breast cancers have HER2 gene amplification (more than 2 copies of this gene).

 HER2 amplification is associated with rapid tumor proliferation, shorter disease-free survival, and poorer overall survival.

The drug trastuzumab (Herceptin, Genentech Inc, San Francisco, California) is indicated for individuals with breast cancer that either overexpresses the HER2 protein or amplifies the HER2 gene to prevent the growth of HER2-positive cancer cells.

 It was approved by the US Food and Drug Administration (FDA) for use in the treatment of metastatic breast cancer in 1998 based on the findings from 2 clinical trials, which showed improvement in the median time to progression of 3 to 5 months, and an increase in the overall response rate of 10% to 30%.

 Despite the fact that trastuzumab is also well established as a highly efficacious (adjuvant) antineoplastic agent for HER2-positive breast cancer, it is expensive ($44,000-$65,000 per year

) and may have serious cardiotoxic effects.

 Because of these factors, selecting patients for whom trastuzumab treatment is appropriate remains vital. Trastuzumab treatment should be cautiously used for patients with preexisting cardiac dysfunction or deteriorating cardiac function even if they have a positive HER2 test result, especially older women with prior cardiac history or prior cardiotoxic therapies.

Two types of tests are FDA approvedto select patients for treatment with trastuzumab. The first test is a based on immunohistochemistry (IHC) (eg, Dako HercepTest, Ventana PATHWAY), which measures membrane expression of HER2 receptor protein. The second type of test (eg, Vysis PathVysion, Ventana INFORM HER2 probe) is based on the fluorescence in situ hybridization (FISH) technology to measure the underlying gene amplification in tumor cells. In this approach, fluorescent probes are used to quantify the number of HER2 gene copies in a tumor cell. If there are 2 or more copies of the HER2 gene per chromosome 17, then a gene amplification has occurred, and the breast cancer is considered HER2 positive.

The American Society of Clinical Oncology and College of American Pathologists HER2 testing guidelines currently recommend initial testing by IHC testing and reflex testing of equivocal result (2+) by FISH testing.

 Although some reports have suggested that the FISH technology more accurately predicts response to trastuzumab than IHC technology,

 a recent summary report indicates that both technologies perform equally well if carefully validated testing is performed.

 Cost may also be a factor in the selection of test modality, because the FISH test is generally more expensive to perform than the IHC test. For both testing methods, underlying quantitative measures can be translated into a dichotomous positive/negative finding. Both tests are considered equivocal when the quantitative measures are near the threshold for a positive result. Retesting might resolve these equivocal findings.

 Increased error rates and inconsistent results are also introduced by decentralized testing, particularly for centers with a low volume of testing. Thus, Wolff and colleagues

 recommend a quality assurance program for HER2 testing, and suggest various accreditation, proficiency, and competency measures for laboratories conducting HER2 testing.

Trastuzumab was initially approved by the FDA in 1998 for use in breast cancer patients with metastatic cancer. In November 2006, the FDA approved the use of trastuzumab in the adjuvant setting for women with lymph node—positive and HER2-positive breast cancer, following several major trials.

 Professional organizations, including a joint guideline from the American Society of Clinical Oncologists and College of American Pathologists, currently recommend that HER2 testing should be performed for all invasive breast cancers regardless of lymph node disease status.

The National Comprehensive Cancer Network has also issued physician practice guidelines endorsing HER2 testing.

 Despite these evidence-based practice guidelines, there are few reports on how HER2 testing has been utilized in realworld settings. In particular, Phillips and colleagues

 highlighted the fact that little is known about how many patients are tested for HER2, which testing methods are used, whether patients are retested to confirm indeterminate results, and how many patients with negative or equivocal results receive trastuzumab. Additionally, it is not clear how trastuzumab is utilized across important subgroups such as patient age, race, and cancer stage.

To answer these questions, we conducted a large, multiinstitutional study in 8 Cancer Research Network (CRN) integrated healthcare delivery systems across the United States. The organizations participating in this study provide a unique resource to address this research question by providing access to longitudinal and comprehensive electronic medical record data for populations totaling more than 6 million covered lives. We describe the real-world implementation of HER2 testing and trastuzumab prescribing in this setting.

The study population included 6460 women who were diagnosed with an invasive breast cancer that was 2+ cm in size or who had positive nodes at diagnosis from January 1, 1999, to December 31, 2007, and who were enrolled at one of the 8 participating CRN study sites for at least 12 months prior to diagnosis. These tumor size and lymph node status criteria were used to restrict the population to women similar to those in the adjuvant trastuzumab clinical trials. Subjects were followed for up to 12 months following diagnosis. Follow-up periods of less than 12 months were due to death or disenrollment during that period. The 8 participating study sites are geographically distributed within the United States and represent diverse populations: Group Health Cooperative (Washington), Kaiser Permanente Northwest (Oregon and Washington), Kaiser Permanente Northern California, Kaiser Permanente Colorado, Kaiser Permanente Georgia, Marshfield Clinic (Wisconsin), Henry Ford Health System (Michigan), and Harvard Pilgrim Health Care Institute with clinical data from Harvard Vanguard Medical Associates (Massachusetts). The study population included all eligible subjects at each site except for Kaiser Permanente Northern California, which contributed data on a 10% random sample of their eligible population.

A subset of 400 cases (50 from each site) was sampled from the original cohort for detailed chart review using stratified sampling (

) to ensure adequate numbers of subjects with chemotherapy exposure and the outcome of heart failure. Weights were used for some analyses, and were calculated as 1 over the probability of being sampled (ie, 1/(1/N), where N is the number of subjects in that stratum; N 

1, since at minimum the sampled subject belongs to the stratum). The primary purpose of the chart review was to validate electronic administrative data for chemotherapy exposure to anthracyclines or trastuzumab and the outcome of heart failure, as measured by clinical criteria and measurement of left ventricular ejection fraction, which was previously reported in a separate publication.

 However, the availability of data on HER2 genetic testing from the chart abstraction allowed us to conduct this secondary analysis. This study was approved by the institutional review boards (IRBs) at Group Health Cooperative, Marshfield Clinic Research Foundation, and Henry Ford Health System, and did not require written informed consent. The IRBs for the remaining sites ceded authority to the Group Health Cooperative IRB. A small number of health system members at each site have elected not to participate in anonymous or unconsented research protocols, and these subjects were excluded from this research study.

All genetic test results used in this study are from testing that occurred as part of routine medical care at each of the 8 participating sites. The laboratory performing the testing varied by site; however, the interpretation was similar. IHC testing for HER2 was classified as negative (0 or 1+), equivocal (2+), or positive (3+), except at Henry Ford Health System where 2+ was considered positive. FISH testing for HER2 was classified as negative (HER2/CEP 17 ratio <1.8), equivocal (HER2/CEP 17 ratio between 1.8 and 2.2), or positive (HER2/CEP 17 ratio >2.2). At Kaiser Permanente Northern California, the cutoff for FISH positive was a HER2/CEP 17 ratio of >2.0 for all but the last year of this study, following the American Society of Clinical Oncology and College of American Pathologists recommendation to change the cut point to 2.2 in January 2007.

We identified the internal practice guidelines for HER2 testing at each site. Since 2000, guidelines for all sites specify that all new invasive breast cancer patients are automatically ordered a HER2 test using IHC testing. Reflex testing is performed using FISH to clarify or confirm equivocal IHC findings (at all sites) plus additional subsets including all positive IHC findings at 2 sites, cases at the discretion of the treating oncologist at 2 other sites, or cases with an IHC test result of 1+ or more positive at 1 additional site. At 1 site, the protocol was changed in October 2007 to initially test all invasive tumors for HER2 by FISH.

We used stratified sampling to ensure adequate representation of the chemotherapy exposures and outcomes in the chart-reviewed sample (eAppendix). Identification of prevalent heart failure at the time of diagnosis (a possible contraindication for trastuzumab use) was also obtained exclusively from chart abstraction. The method used to define heart failure is described elsewhere.

 We used standardized abstraction forms and abstractor training protocols to ensure uniform data recording across sites and abstractors. The lead project manager rereviewed 10% of charts from each CRN site for inconsistencies, inaccuracies, and missing data, and questions were referred back to the originating site for clarification. During chart review, both qualitative and quantitative descriptions of HER2 results were collected from the medical record. Any apparent discrepancies were resolved by rereview at the originating site.

Each CRN site maintains electronic health record information on its member population including membership, diagnoses, pharmacy data, and a tumor registry. From these records, we extracted electronic data on patient characteristics (age at diagnosis, sex, race, ethnicity, year of diagnosis), tumor characteristics (stage, lymph node involvement, tumor size), and chemotherapy treatment. The Charlson Comorbidity Index is a quantitative variable that was computed using diagnosis codes as previously described anchored at the date of diagnosis.

Patients were classified as receiving trastuzumab using a dichotomous indicator variable if any of the following national drug codes were in the pharmacy records after their date of diagnosis: 50242013460, 50242013468, 50242005656, or 63552047001, or if procedure code J9355 was in the procedures database. This definition was validated against data from chart abstraction and demonstrated to have high predictive value.

Lymph node status was a dichotomous indicator variable defined as positive (1 or more positive nodes) or negative. Tumor size was a quantitative trait defined as the size of the largest qualifying tumor (a small number of patients had more than 1 primary tumor during the study period). We defined invasive breast cancer using Surveillance Epidemiology and End Results (SEER) staging criteria

 as patients diagnosed with localized, regional, or distant metastatic breast cancer. The primary dependent variable was receipt of HER2 testing, which was treated as a dichotomous indicator variable. Data on receipt of HER2 testing and the test result (categorical variable) were obtained exclusively from chart abstraction of the medical record.

All analyses, including descriptive statistics, summaries, and multivariate linear regression, were produced using R (version 2.11.1; R Foundation for Statistical Computing, www.r-project.org) and SAS version 9.2 (SAS Institute Inc, Cary, North Carolina). We used a Bonferroni correction to adjust the simultaneous confidence intervals. The multivariate model used a generalized linear model with receipt of HER2 testing as the dependent variable and the following independent variables: diagnosis year, race, lymph node status, SEER stage, site, age, presence of heart failure, and Charlson Comorbidity Index.

Of the entire cohort of 6460 women, 7.5% (n = 483) received trastuzumab. Trastuzumab use varied by year of diagnosis and stage of disease. Although the 

 of subjects who received trastuzumab was highest among women with distant stage breast cancer (

), women with distantstage breast cancer represented the smallest 

 who received trastuzumab in every year (

), because most women are diagnosed at an earlier stage of disease. The proportion of subjects who received trastuzumab increased for all stages of disease after 2004 when professional guidelines changed (Figure 1). The proportion of women in the chart review population who received trastuzumab was 18% (72/400), which is higher than the proportion of women who received trastuzumab in the entire study population, because we intentionally overselected trastuzumab recipients for review. However, after adjustment using the weights described above, 6.4% of the chart review population received trastuzumab.

All of the sites performed IHC testing in-house, and most sites used the HercepTest kit (Dako, Carpenteria, California). All except 1 site used a reference laboratory to perform FISH testing, and all sites used the Vysis PathVysion test (Abbott Molecular, Abbott Park, Illinois). Among the 400 subjects in the chart review population, 367 had tumors tested by IHC and 94 had tumors tested by FISH. Only 30 women (7.5%) received neither test.

Consistent with practice guidelines at the 8 sites, nearly everyone who was tested received IHC testing, with only 4 women receiving FISH testing alone. FISH testing occurred more frequently in the latter years of the study, possibly reflecting a phasing in of FISH testing during this time frame. Of those who received both tests, 74% had a positive or borderline IHC test result, whereas the majority of patients (69%) who received IHC testing alone had a negative HER2 result. A substantial proportion (40%) of subjects with a borderline IHC test result had no evidence of receiving FISH testing, contrary to most site practice guidelines. Among 17 patients with a borderline IHC test result, 3 received trastuzumab. There was also large variation among sites in the proportion of subjects with a borderline IHC test who did not receive FISH testing (range 0%-63%; 

Of those who did not receive either test, 50% (n = 14) were diagnosed in 1999, around the time that testing was initiated at most of the sites (

). Excluding the 28 patients diagnosed in 1999, 96% (356/372) of patients received some form of HER2 testing. The remaining 16 patients who were not tested were more likely to be older than 70 years (

 = .026), to have distant-stage disease (

 = .0032), to have negative lymph nodes (

 = .013), or to have been diagnosed in 2005. We also detected differences in the proportion who did not receive testing across sites ranging from 0% to 14% (

 = .0003), although about one-third of the women had missing data for race/ethnicity.

Trastuzumab Use as a Function of HER2 Status

As expected based on the sampling criteria, a higher proportion (32% [119/373]) of women in the chart review sample who received HER2 testing were HER2 positive compared with population estimates.

Trastuzumab was primarily used by patients with a HER2- positive test result (

). None of the patients in this sample who were not tested for HER2 status used trastuzumab. Of patients with only a HER2-negative or borderline result, 1.6% (4/255) used trastuzumab, and 35% (9/26) of patients with HER2 discordant results used trastuzumab. In these 9 discordant cases, 7 patients had positive FISH tests and 2 had a positive IHC test. Of the 17 who did not receive trastuzumab, 10 had positive FISH tests and 7 had positive IHC tests. Overall, 64% (61/96) of patients with HER2-positive results received trastuzumab; however, this use was dependent on year of diagnosis and stage of disease. In 1999-2005 (when trastuzumab was primarily recommended for patients with distant metastatic disease) only 52% of HER2-positive patients used trastuzumab, whereas in 2006-2007 (by which time recommendations had been adopted for use of trastuzumab in all cases of invasive cancer), 84% of HER2-positive patients used trastuzumab.

Some subjects with positive HER2 status did not receive trastuzumab. Of the 6 subjects with localized or regional disease who were diagnosed after 2005 and who did not receive trastuzumab, one had heart failure at diagnosis. For the remainder, a rationale was not readily apparent based on our assessment of the comorbidity index, age at diagnosis, or other patient characteristics. In addition, 2 subjects with distant metastatic disease who were HER2 positive did not receive trastuzumab. One of these patients had heart failure at diagnosis, while the other case could not be readily explained based on patient characteristics in our data set. Other factors such as patient preference, physician opinion, unrecorded negative or borderline HER2 test results, or treatment outside of the reporting sites could explain these observations.

Evaluation of real-world implementation of HER2 testing showed that uptake was high (>90%) and trastuzumab treatment was targeted to patients with positive HER2 status.

Utilization of HER2 Genetic Testing in a Multi-Institutional Observational Study

 To examine whether use of adjuvant therapy varies by race/ethnicity among patients with ductal carcinoma in situ (DCIS) at 3 integrated health plan delivery sites based in California and Massachusetts.

Cross-sectional study nested within a cohort of women diagnosed as having DCIS between 1990 and 2001.

We reviewed medical records of 3000 non-Hispanic white (69%), black (10%), Hispanic (9%), and Asian or Pacific Islander (12%) women diagnosed as having DCIS between 1990 and 2001 and treated with breast-conserving therapy. 

 Test and multinomial logistic regression analysis were used to examine the association between race/ethnicity and use of adjuvant treatments after controlling for patient and clinical variables, including certain pathologic factors.

We found no significant differences in DCIS adjuvant treatment among racial/ethnic groups in bivariate or multinomial analyses after adjusting for demographic characteristics, comorbidity, and clinical factors. Minority women were as likely to undergo adjuvant radiation therapy as non-Hispanic white women. However, women 70 years or older (odds ratio, 0.40; 95% confidence interval, 0.31-0.51) and women who lived in areas with low geocoded median family income (odds ratio, 0.65; 95% confidence interval, 0.48-0.89) were less likely to receive adjuvant radiation therapy. Tumor size and comedo histologic growth pattern were associated with increased likelihood of receiving radiation therapy.

Use of adjuvant therapy by minority women in these managed care plans is similar to that by non-Hispanic white women, although use was less among older women and among women who lived in poorer neighborhoods.

The lack of differences in the treatment of ductal carcinoma in situ by race/ethnicity observed in these integrated healthcare delivery systems may be due to coordinated clinical guidelines and multidimensional approaches to reduce barriers in care by educating physician leaders, nurse practitioners, case managers, and disease management program managers in these organizations.

However, older women (>70 years) and women who lived in census tracts with low median family incomes were less likely to receive adjuvant radiation therapy.

Such groups of women may have different functionality, comorbidity burden, and treatment preferences, all of which need to be considered in the treatment decision-making process.

The diagnosis of ductal carcinoma in situ (DCIS) has increased markedly because of enhanced screening mammography efforts and constitutes more than 20% of newly diagnosed breast cancer cases in the United States.

 Despite improvements in detection, determining the most appropriate treatment strategy remains a challenge owing to the heterogeneity of DCIS lesions.

 While racial/ ethnic differences have been reported for the detection, diagnosis, evaluation, and treatment of invasive breast cancer, data are limited on whether there are similar disparities in the treatment of DCIS.

 of women with invasive disease have found that racial/ ethnic minority women undergo breast-conserving surgery (BCS) more frequently than white women; however, black women are at twice the risk of white women for failing to receive postsurgery chemotherapy and hormonal therapy. This racial/ethnic disparity in the receipt of adjuvant therapy for invasive disease has been reported in many settings.

In contrast, less information on treatment disparity exists for DCIS than for invasive disease.

 Because DCIS can progress to invasive disease, it is critical to determine whether modifiable and nonmodifiable factors are associated with receipt of therapy. While controversy exists regarding optimal treatment for DCIS, research indicates that women treated with BCS and subsequent radiation therapy have significantly reduced recurrence versus women treated with surgery alone.

 The risk of recurrence can be further reduced by combining radiation therapy with adjuvant tamoxifen citrate treatment.

 Breast-conserving surgery with adjuvant tamoxifen treatment alone is generally not a recommended option.In addition, neither cytotoxic chemotherapy nor any of the newer biologic agents are recommended for DCIS.

 that have examined breast cancer treatment differences were based on claims data from fee-for-service settings; however, these sources offer a limited understanding of utilization. Tumor registries reliably capture information on surgery and race/ethnicity but less reliably capture adjuvant radiation therapy or hormonal treatment data.

 Such databases generally also lack data on socioeconomic status, which may contribute to treatment differences.

 Medical record review is resource intensive but enables more comprehensive insight into treatments used. The objective of this study was to use information abstracted from medical records to examine whether use of adjuvant therapy varied by race/ethnicity among a diverse cohort of 3000 women diagnosed as having DCIS between 1990 and 2001 and treated with BCS in 3 geographically diverse integrated healthcare delivery systems. A key advantage of this study is the additional information we captured on pathologic features and socioeconomic factors that vary by race/ethnicity and may influence treatment  decisions.

This study was conducted at 3 sites participating in the Cancer Research Network, a consortium of research organizations affiliated with nonprofit integrated healthcare delivery systems and the National Cancer Institute. Study participantsincluded women enrolled at Kaiser Permanente Northern California, Kaiser Permanente Southern California, and Harvard Pilgrim Health Care. The sites care for more than 6 million members in California and Massachusetts. We examined patient and healthcare factors associated with utilization of adjuvant cancer treatment (radiation therapy and hormonal therapy). This study was part of a retrospective cohort study of women diagnosed as having DCIS between 1990 and 2001. The study was approved by the institutional review boards at all 3 study sites.

Women with DCIS were identified through the Kaiser Permanente health plans’ electronic cancer registries in California. These health plans report cancer cases in specific geographic regions to the SEER (Surveillance, Epidemiology and End Results) program. At Harvard Pilgrim Health Care, claims and electronic outpatient medical records were used to identify women with DCIS.

The cohort included women from Kaiser Permanente Northern California, Kaiser Permanente Southern California, and Harvard Pilgrim Health Care who were aged 20 to

84 years at diagnosis of DCIS, were diagnosed between 1990 and 2001, had unilateral disease, were treated with BCS, had no history of DCIS or invasive cancer (breast or other site), and remained enrolled within the health plans for at least 6 months after diagnosis.

Of 3668 patients identified as potentially eligible by our cancer registries or electronic medical records, 602 were deemed ineligible for 1 or more of the following reasons based on medical record review: unavailability of medical records (n = 82), miscoding of DCIS in the cancer registry (n = 63), prior breast or other cancer (n = 216), bilateral breast cancer at diagnosis (n = 29), mastectomy for the index DCIS (n = 96), age 85 years or older at diagnosis (n = 15), or lack of follow-up in the health plan for 6 consecutive months (n = 101). Of 3066 remaining patients, 29 women had unknown treatment and 37 women had missing race/ethnicity, leaving 3000 patients for this study.

We used standardized medical record abstraction forms to capture information on treatment (surgery, radiation therapy, chemotherapy, and hormonal therapy), history of breast cancer among first-degree relatives, year of diagnosis, and height, weight, and age at index DCIS diagnosis. Family history of breast cancer was history of the disease in a first-degree blood relative (including mother, sisters, half sisters, or daughters) of the study patient. We recorded information on family history if it appeared in the medical record within 6 months of the study patient’s DCIS diagnosis.

We also collected information on the presence of diabetes mellitus around the time of DCIS diagnosis as a surrogate measure of comorbidity because findings from studies

suggest that patients with diabetes are treated less aggressively for cancer. The analysis presented herein examines the initial course of treatment documented in the medical records in the 6 months after DCIS diagnosis. Because detection methods can vary by race/ethnicity and influence treatment decisions, we abstracted information as to whether the breast lesion was identified through palpation or screening mammography. Because prevalence of pathologic features may vary by race/ethnicity and may influence treatment decisions, we conducted a subset analysis involving 1 study site (n = 986). At this study site, we abstracted key features from the pathology reports such as surgical margins, tumor size, comedo histologic growth pattern, necrosis, and nuclear grade. Because the health plan tumor registries in California did not uniformly capture pathologic variables during the study period, we assessed these factors based on review of the original pathology

report and specimens by a single study pathologist rather than through the SEER program. In this way, the pathologic variables were measured in a standard manner for all patients at this study site whether or not the patients lived in a geographic area covered by the SEER program during the study period (1990-2001).

Information on race/ethnicity was captured from the medical records or the electronic SEER-affiliated cancer registries (in California). The SEER data are based on medical records and administrative information. We grouped race/ethnicity as non-Hispanic white, black, Hispanic, or Asian or Pacific Islander. Because the health plans do not uniformly collect members’ income or educational attainment, information on these factors was obtained from geocoding files based on California’s 1990 census (which was closest to the DCIS diagnosis dates). In this approach, the women in the cohort were classified according to the socioeconomic characteristics of their census tract at the time of diagnosis.

 Geocoded educational attainment and median family income were based on the distribution of the women in our sample (the cohort’s census tract). Geocoded educational attainment was divided into 2 groups (high vs low). High geocoded educational attainment means that the percentage of women in the sample with at least some college education is greater than the percentage of women in the cohort with at most a high school diploma. Geocoded median family income was divided into quartiles. Analyses considering median family income and educational attainment were restricted to patients in California (93% of

the study cohort). Similar information was not feasible to ascertain for patients in Massachusetts.

We first conducted stratified analyses and examined the distribution of patient characteristics by race/ethnicity and DCIS treatment regimens. Two-sided P values were based on

 test for heterogeneity. Unknown and missing values were excluded in the calculation of 

 values. The levels of treatment examined included BCS alone (reference group), BCS with adjuvant radiation therapy, BCS with adjuvant tamoxifen therapy, and BCS with both adjuvant treatments. Finally, adjusted odds ratios (ORs) were estimated using multinomial logistic regression analysis, which is an extension of the binary logistic regression technique in which the dependent variable (DCIS treatment regimens) has unordered multiple levels.

 Variables examined in the models were race/ethnicity, age at diagnosis, year of diagnosis, study site, body mass index (BMI), family history of breast cancer, comorbidity (history of diabetes), geocoded educational attainment, and median family income. Cut points for BMI were based on categories of the National Heart, Lung, and Blood Institute.

 For the subset of patients for whom we had pathologic data, the model for receipt of adjuvant radiation therapy also included tumor characteristics. All analyses were conducted using commercially available statistical software (SAS, version 9.1; SAS Institute Inc, Cary, NC35).

Participants included 292 black (10%), 263 Hispanic (9%), 370 Asian or Pacific Islander (12%), and 2075 (69%) non-Hispanic white women. We identified only 1 woman as being non-white Hispanic (this patient was included in the black category). Asian or Pacific Islanders tended to be younger at the time of DCIS diagnosis, and 38% of those women were diagnosed before age 50 years (

). Within each racial/ethnic group, the percentage of women diagnosed as having DCIS increased over time, with the sharpest rise occurring after 1997 among Asian or Pacific Islanders. Within this group, the rate of diagnosis increased from 14% in1996-1997 to 29% in 1998-1999. The percentage of women with a known family history (first-degree blood relative) of breast cancer was similar in black, Hispanic, and white women (19% in each group) and was lower in Asian or Pacific Islanders (11%).

For participants with known addresses, 77% lived in census tracts where the geocoded educational attainment included some college. Geocoded educational attainment varied by race/ethnicity, with Asian or Pacific Islander women and white women representing the highest proportions of women who lived in census tracts with higher educational attainment (

 <.001). Similarly, geocoded median family income varied by race/ethnicity, with higher percentages of black and Hispanic women living in census tracts with lower median family income (

 <.001). Among participants with known weight, 58% of Asian or Pacific Islanders were of normal weight. A considerable percentage of white women were of normal weight (41%), although 57% were in the overweight and obese categories.

Detection method of DCIS was associated with race/ ethnicity (

 = .02) and varied by age, with more younger women having palpable lesions (

 <.001). Although most lesions (83%) were detected by screening mammography, 17% were detected by palpation. Among Asian or Pacific Islanders, almost one-fourth of the lesions were detected by palpation, whereas among white women 16% were detected by palpation.

gives adjusted ORs from the multinomial logistic regression models for the association of patient and tumor factors with DCIS treatment regimens. The reference group for each treatment regimen (the dependent variable) comprised women who underwent BCS alone. The reference group for race/ethnicity (the main independent variable) was white women. Of 3000 women, 43% (n = 1284) underwent BCS alone, whereas 57% (n = 1716) underwent adjuvant radiation therapy or tamoxifen treatment. As expected, none of the women in our cohort were treated with chemotherapy. Radiation therapy alone was the most common adjuvant regimen. About 4% (n = 129) of women underwent adjuvant tamoxifen treatment only, while 11% (n = 337) underwent a combination of adjuvant radiation therapy and tamoxifen treatment.

Race/ethnicity was not strongly associated with use of adjuvant treatments; variation differed little by these subgroups of women, as the confidence intervals (CIs) were wide and included the null. Treatment regimens also did not vary by family history of breast cancer, geocoded educational attainment, BMI, or history of diabetes. Year of diagnosis was the strongest correlate of adjuvant radiation therapy use. For example, compared with women who underwent BCS alone, the oddsof adjuvant radiation therapy receipt increased over the years; adjusted ORs varied from 2.55 (95% CI, 1.75-3.71) in 1992- 1993 to 4.08 (95% CI, 2.86-5.83) in 2000-2001. Women who lived in census tracts with a low geocoded median family income were significantly less likely to receive adjuvant radiation therapy (OR, 0.65; 95% CI, 0.48-0.89). Older women (

70 years) were 2.5 times more likely to receive adjuvant tamoxifen therapy (without radiation therapy) than younger women (<50 years) (OR, 2.52; 95% CI, 1.29-4.90). However, older women were dramatically less likely to receive adjuvant radiation therapy (OR, 0.40; 95% CI, 0.31-0.51). The ORs for all treatment regimens increased over the years, with the sharpest rise occurring for combined radiation therapy and tamoxifen treatment.

Of the subset of women with pathologic data (n = 986), patients with large tumors (OR, 2.45; 95% CI, 1.23-4.88) and comedo histologic growth pattern (OR, 1.89; 95% CI, 1.35-2.64) were more likely to receive adjuvant radiation therapy than BCS alone. We did not have a large enough sample size to examine the association of pathologic factors and other treatment combinations (ie, BCS with tamoxifen treatment or BCS with radiation therapy and tamoxifen treatment). During the study period (1990-2001), estrogen receptor testing was not routinely performed. Therefore, this information was not captured in relation to tamoxifen use.

Our findings suggest that receipt of adjuvant radiation therapy (with or without tamoxifen treatment) was not related to race/ethnicity in these managed care plans. However, we found that older women (

70 years) and women who lived in census tracts with low median family incomes were substantially less likely to receive adjuvant radiation therapy, despite potential equal access to care.

Although we found no DCIS treatment disparities by race/ethnicity, use of adjuvant radiation therapy was less among older women and among residents of poorer neighborhoods.


Laurel A. Habel, PhD

Articles

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