Rebecca A. Ottesen

A Multi-Institutional Analysis of the Socioeconomic Determinants of Breast Reconstruction: A Study of the National Comprehensive Cancer Network

Objective:To determine the rate of postmastectomy reconstruction and investigate the impact of socioeconomic status on the receipt of reconstruction. Summary Background Data:The National Comprehensive Cancer Network (NCCN) Outcomes Project is a prospective, multi-institutional database that contains data on all newly diagnosed breast cancer patients treated at one of the participating comprehensive cancer centers. Methods:The study cohort consisted of 2174 patients with DCIS and stage I, II, and III invasive breast cancer who underwent mastectomy at one of 8 NCCN centers. Rates of reconstruction were determined. Logistic regression analyses were used to evaluate whether socioeconomic characteristics are associated with breast reconstruction. Results:Overall, 42% of patients had breast reconstruction following mastectomy. Patients with Medicaid and Medicare were less likely to undergo reconstruction than those with managed care insurance; however, there was no difference for indemnity versus managed care insurance. Homemakers and retired patients had fewer reconstructions than those employed outside the home. Patients with a high school education or less were less likely to have reconstruction than those with more education. Race and ethnicity were not significant predictors of reconstruction. Conclusions:The reconstruction rate in this study (42%) is markedly higher than those previously reported. The type of insurance, education level, and employment status of a patient, but not her race or ethnicity, appear to influence the use of breast reconstruction. Because all patients were treated at an NCCN institution, these socioeconomic differences cannot be explained by access to care.

Outcomes by Tumor Subtype and Treatment Pattern in Women With Small, Node-Negative Breast Cancer: A Multi-Institutional Study

PURPOSE Treatment decisions for patients with T1a,bN0M0 breast cancer are challenging. We studied the time trends in use of adjuvant chemotherapy and survival outcomes among these patients. PATIENTS AND METHODS This was a prospective cohort study within the National Comprehensive Cancer Network Database that included 4,113 women with T1a,bN0M0 breast cancer treated between 2000 and 2009. Tumors were grouped by size (T1a, T1b), biologic subtype defined by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status, and receipt of chemotherapy with or without trastuzumab. RESULTS Median follow-up time was 5.5 years. Eight percent of patients with HR-positive/HER2-negative tumors were treated with chemotherapy. Fifty-two percent of those with HER2-positive or HR-negative/HER2-negative breast cancers received chemotherapy, with an increase over the last decade. Survival outcomes diverged by subtype and size, but the 5-year distant relapse-free survival (DRFS) did not exceed 10% in any subgroup. The 5-year DRFS for patients with T1a tumors untreated with chemotherapy ranged from 93% to 98% (n = 49 to 972), and for patients with T1b tumors, it ranged from 90% to 96% (n = 17 to 2,005). Patients with HR-positive/HER2-negative disease had the best DRFS estimates, and patients with HR-negative/HER2-negative tumors had the lowest. In this observational, nonrandomized cohort study, the 5-year DRFS for treated patients with T1a tumors was 100% for all subgroups (n = 12 to 33), and for patients with T1b tumors, it ranged from 94% to 96% (n = 88 to 241). CONCLUSION Women with T1a,b tumors have an excellent prognosis without chemotherapy. Size and tumor subtype may identify patients in whom the rate of recurrence justifies consideration of chemotherapy. These patients represent an optimal group for evaluating less toxic adjuvant regimens to maintain efficacy while minimizing short- and long-term risks.

The use of radiation as a component of breast conservation therapy in national comprehensive cancer network centers

PURPOSE Benchmark data regarding quality measures of breast cancer management are needed. We investigated rates of radiation use after breast conservation therapy (BCT) for patients treated for ductal carcinoma-in-situ (DCIS) or invasive breast cancer at National Comprehensive Cancer Network (NCCN) centers. PATIENTS AND METHODS We studied 3,333 consecutive patients treated between 1997 and 2002 with BCT for DCIS (n = 587) or for stage I or II breast cancer (n = 2,746) in eight NCCN centers. RESULTS The overall rate of radiation therapy use was 91%, with a lower frequency of radiation use in DCIS versus invasive breast cancers (82% v 94%; odds ratio [OR] = 0.31; P < .0001). In a multivariable analysis of the patients with DCIS, the only factor significantly associated with lower rates of radiation use was low/intermediate grade (OR = 0.19; P = .0003). For patients with invasive breast cancer, significant factors were presence of comorbidity (OR = 0.53; P = .0005), tubular histology (OR = 0.39; P = .02), type of health insurance (P = .0072), and the NCCN institution (P = .0005). The model also showed lower rates of radiation use in patients with stage II disease who did not receive systemic therapy (OR = 0.01; P = .0001), younger patients who did not receive systemic therapy (P = .003); and older patients with stage I disease (P < .0001). CONCLUSION Radiation use as a component of BCT was high for patients seen at NCCN centers; however, there was variability in practice patterns noted across institutions. Radiation was most commonly omitted in patients with favorable disease characteristics, patients with comorbidities, and patients who also did not receive guideline-recommended systemic treatment.

Impact of hormone receptor status on patterns of recurrence and clinical outcomes among patients with human epidermal growth factor-2-positive breast cancer in the National Comprehensive Cancer Network: a prospective cohort study

IntroductionIn gene expression experiments, hormone receptor (HR)-positive/human epidermal growth factor-2 (HER2)-positive tumors generally cluster within the luminal B subset; whereas HR-negative/HER2-positive tumors reside in the HER2-enriched subset. We investigated whether the clinical behavior of HER2-positive tumors differs by HR status.MethodsWe evaluated 3,394 patients who presented to National Comprehensive Cancer Network (NCCN) centers with stage I to III HER2-positive breast cancer between 2000 and 2007. Tumors were grouped as HR-positive/HER2-positive (HR+/HER2+) or HR-negative/HER2-positive (HR-/HER2+). Chi-square, logistic regression and Cox hazard proportional regression were used to compare groups.ResultsMedian follow-up was four years. Patients with HR-/HER2+ tumors (n = 1,379, 41% of total) were more likely than those with HR+/HER-2+ disease (n = 2,015, 59% of total) to present with high histologic grade and higher stages (P <0.001). Recurrences were recorded for 458 patients. HR-/HER2+ patients were less likely to experience first recurrence in bone (univariate Odds Ratio (OR) = 0.53, 95% Confidence Interval (CI): 0.34 to 0.82, P = 0.005) and more likely to recur in brain (univariate OR = 1.75, 95% CI: 1.05 to 2.93, P = 0.033). A lower risk of recurrence in bone persisted after adjusting for age, stage and adjuvant trastuzumab therapy (OR = 0.53, 95% CI: 0.34 to 0.83, P = 0.005) and when first and subsequent sites of recurrence were both considered (multivariable OR = 0.55, 95% CI: 0.37 to 0.80, P = 0.002).As compared with patients with HR+/HER2+ disease, those with HR-/HER2+ disease had significantly increased hazard of early, but not late, death (hazard ratio of death zero to two years after diagnosis = 1.92, 95% CI: 1.28 to 2.86, P = 0.002, hazard ratio of death two to five years after diagnosis = 1.55, 95% CI: 1.19 to 2.00, P = 0.001; hazard ratio of death more than five years after diagnosis = 0.81, 95% CI: 0.55 to 1.19, P = 0.285, adjusting for age, race/ethnicity, stage at diagnosis, grade and year of diagnosis).ConclusionsPresenting features, patterns of recurrence and survival of HER2-positive breast cancer differed by HR status. These differences should be further explored and integrated in the design of clinical trials.

Racial and Ethnic Differences in Breast Cancer Survival: Mediating Effect of Tumor Characteristics and Sociodemographic and Treatment Factors

PURPOSE To evaluate the relationship between race/ethnicity and breast cancer-specific survival according to subtype and explore mediating factors. PATIENTS AND METHODS Participants were women presenting with stage I to III breast cancer between January 2000 and December 2007 at National Comprehensive Cancer Network centers with survival follow-up through December 2009. Cox proportional hazards regression was used to compare breast cancer-specific survival among Asians (n = 533), Hispanics (n = 1,122), and blacks (n = 1,345) with that among whites (n = 14,268), overall and stratified by subtype (luminal A like, luminal B like, human epidermal growth factor receptor 2 type, and triple negative). Model estimates were used to derive mediation proportion and 95% CI for selected risk factors. RESULTS In multivariable adjusted models, overall, blacks had 21% higher risk of breast cancer-specific death (hazard ratio [HR], 1.21; 95% CI, 1.00 to 1.45). For estrogen receptor-positive tumors, black and white survival differences were greatest within 2 years of diagnosis (years 0 to 2: HR, 2.65; 95% CI, 1.34 to 5.24; year 2 to end of follow-up: HR, 1.50; 95% CI, 1.12 to 2.00). Blacks were 76% and 56% more likely to die as a result of luminal A-like and luminal B-like tumors, respectively. No disparities were observed for triple-negative or human epidermal growth factor receptor 2-type tumors. Asians and Hispanics were less likely to die as a result of breast cancer compared with whites (Asians: HR, 0.56; 95% CI, 0.37 to 0.85; Hispanics: HR, 0.74; 95% CI, 0.58 to 0.95). For blacks, tumor characteristics and stage at diagnosis were significant disparity mediators. Body mass index was an important mediator for blacks and Asians. CONCLUSION Racial disparities in breast cancer survival vary by tumor subtype. Interventions are needed to reduce disparities, particularly in the first 2 years after diagnosis among black women with estrogen receptor-positive tumors.

Subtype-Dependent Relationship Between Young Age at Diagnosis and Breast Cancer Survival.

PURPOSE Young women are at increased risk for developing more aggressive subtypes of breast cancer. Although previous studies have shown a higher risk of breast cancer recurrence and death among young women with early-stage breast cancer, they have not adequately addressed the role of tumor subtype in outcomes. METHODS We examined data from women with newly diagnosed stage I to III breast cancer presenting to one of eight National Comprehensive Cancer Network centers between January 2000 and December 2007. Multivariable Cox proportional hazards models were used to assess the relationship between age and breast cancer-specific survival. RESULTS A total of 17,575 women with stage I to III breast cancer were eligible for analysis, among whom 1,916 were ≤ 40 years of age at diagnosis. Median follow-up time was 6.4 years. In a multivariable Cox proportional hazards model controlling for sociodemographic, disease, and treatment characteristics, women ≤ 40 years of age at diagnosis had greater breast cancer mortality (hazard ratio [HR], 1.4; 95% CI, 1.2 to 1.7). In stratified analyses, age ≤ 40 years was associated with statistically significant increases in risk of breast cancer death among women with luminal A (HR, 2.1; 95% CI, 1.4 to 3.2) and luminal B (HR 1.4; 95% CI, 1.1 to 1.9) tumors, with borderline significance among women with triple-negative tumors (HR, 1.4; 95% CI, 1.0 to 1.8) but not among those with human epidermal growth factor receptor 2 subtypes (HR, 1.2; 95% CI, 0.8 to 1.9). In an additional model controlling for detection method, young age was associated with significantly increased risk of breast cancer death only among women with luminal A tumors. CONCLUSION The effect of age on survival of women with early breast cancer seems to vary by breast cancer subtype. Young age seems to be particularly prognostic in women with luminal breast cancers.

The Effect of Age on Delay in Diagnosis and Stage of Breast Cancer

BACKGROUND Young women with breast cancer are more likely to present with more advanced disease and are more likely to die as a result of breast cancer than their older counterparts. We sought to examine the relationship among young age (≤40 years), the likelihood of a delay in diagnosis, and stage. METHODS We examined data from women with newly diagnosed stage I-IV breast cancer presenting to one of eight National Comprehensive Cancer Network centers in January 2000 to December 2007. Delay in diagnosis was defined as time from initial sign or symptom to breast cancer diagnosis >60 days. RESULTS Among 21,818 women with breast cancer eligible for analysis, 2,445 were aged ≤40 years at diagnosis. Young women were not more likely to have a delay in diagnosis >60 days (odds ratio [OR], 1.08; 95% confidence interval [CI], 0.98-1.19) after adjustment for type of initial sign or symptom. Young women were only modestly more likely to present with higher stage disease after a similar adjustment (OR, 1.18; 95% CI, 1.07-1.31). Women presenting with symptomatic disease, more common in younger women, were more likely to have a delay in diagnosis (OR, 3.31; 95% CI, 3.08-3.56) and higher stage (OR, 4.31; 95% CI 4.05-4.58). CONCLUSION Young age is not an independent predictor of delay in diagnosis of breast cancer and only modestly is associated with higher stage disease. Presenting with symptoms of breast cancer predicts delay and higher stage at diagnosis.

The impact of breast reconstruction on the delivery of chemotherapy.

The purpose of this study was to evaluate the impact of postmastectomy breast reconstruction on the timing of chemotherapy.

Selecting high priority quality measures for breast cancer quality improvement.

Background:Although many quality measures have been created, there is no consensus regarding which are the most important. We sought to develop a simple, explicit strategy for prioritizing breast cancer quality measures based on their potential to highlight areas where quality improvement efforts could most impact a population. Methods:Using performance data for 9019 breast cancer patients treated at 10 National Comprehensive Cancer Network institutions, we assessed concordance relative to 30 reliable, valid breast cancer process-based treatment measures. We identified 4 attributes that indicated there was room for improvement and characterized the extent of burden imposed by failing to follow each measure: number of nonconcordant patients, concordance across all institutions, highest concordance at any 1 institution, and magnitude of benefit associated with concordant care. For each measure, we used data from the concordance analyses to derive the first 3 attributes and surveyed expert breast cancer physicians to estimate the fourth. A simple algorithm incorporated these attributes and produced a final score for each measure; these scores were used to rank the measures. Results:We successfully prioritized quality measures using explicit, objective methods and actual performance data. The number of nonconcordant patients had the greatest influence on the rankings. The highest-ranking measures recommended chemotherapy and hormone therapy for hormone-receptor positive tumors and radiation therapy after breast-conserving surgery. Conclusions:This simple, explicit approach is a significant departure from methods used previously, and effectively identifies breast cancer quality measures that have broad clinical relevance. Systematically prioritizing quality measures could increase the efficiency and efficacy of quality improvement efforts and substantially improve outcomes.

Impact of Randomized Clinical Trial Results in the National Comprehensive Cancer Network on the Use of Tamoxifen After Breast Surgery for Ductal Carcinoma in Situ

PURPOSE The National Surgical Adjuvant Breast and Bowel Project B-24 trial, published in June 1999, demonstrated that tamoxifen after breast-conserving surgery (BCS) and radiotherapy for ductal carcinoma in situ (DCIS) reduced the absolute occurrence of ipsilateral and contralateral breast cancer. We assessed the impact of B-24 on practice patterns at selected National Comprehensive Cancer Network (NCCN) centers. PATIENTS AND METHODS Tamoxifen use after surgery was examined among 1,622 patients presenting for treatment of unilateral DCIS between July 1997 and December 2003 at eight NCCN centers. Associations of clinicopathologic and treatment factors with tamoxifen use were assessed in univariate and multivariable logistic regression analyses. RESULTS Overall, 41% of patients (665 of 1,622) received tamoxifen. The proportion increased from 24% before July 1, 1999, to 46% on or after July 1, 1999. Factors significantly associated with receipt of tamoxifen included diagnosis on or after July 1, 1999 (odds ratio [OR], 3.85; P < .0001), BCS in patients younger than 70 years (OR, 3.21; P = .0073), no history of cerebrovascular or peripheral vascular disease (OR, 3.13; P = .0071), receipt of radiotherapy (OR, 1.82; P = .0009), and previous hysterectomy (OR, 1.34; P = .0459). Tamoxifen use varied significantly by center, from 34% to 74% after BCS and 17% to 53% after mastectomy (P < .0001). CONCLUSION Tamoxifen use after surgery for DCIS at NCCN centers increased after presentation of the B-24 results. Rates varied substantially by institution, suggesting that physicians differ in how they weigh the modest reduction in breast cancer risk with tamoxifen against its potential adverse effects in this population.