Exploring the impact of exercise and mind-body prehabilitation interventions on physical and psychological outcomes in women undergoing breast cancer surgery.

PURPOSE: To compare the impact of exercise and mind-body prehabilitation interventions on changes in quality of life and cancer treatment-related symptoms in women with newly diagnosed breast cancer. METHODS: The following describes a secondary analysis of a randomized window of opportunity trial (The Pre-Operative Health and Body Study). Forty-nine women were randomized to participate in either an exercise prehabilitation intervention or a mind-body prehabilitation intervention from the time of enrollment to surgery. Participants (N = 47) completed measures of quality of life, anxiety, depression, and stress at the time of enrollment (T1), post-intervention/surgery (T2), and one-month post-surgery (T3). Changes in outcome measures between groups were compared over time using longitudinal models. RESULTS: Mind-body group participants experienced significant improvements in cognitive functioning in comparison to exercise group participants between T1 and T3 (difference in average change: -9.61, p = 0.04, d = 0.31), otherwise, there were no significant differences between groups. Within group comparisons demonstrated that both groups experienced improvements in anxiety (exercise: average change = -1.18, p = 0.03, d = 0.34; mind-body: average change = -1.69, p = 0.006, d = 0.43) and stress (exercise: average change = -2.33, p = 0.04, d = 0.30; mind-body: average change = -2.59, p = 0.05, d = 0.29), while mind-body group participants experienced improvements in insomnia (average change = -10.03, p = 0.04, d = 0.30) and cognitive functioning (average change = 13.16, p = 0.0003, d = 0.67). CONCLUSIONS: Both prehabilitation interventions impacted cancer treatment-related symptoms. Further work in larger groups of patients is needed to evaluate the efficacy of prehabilitation interventions on quality of life in women with breast cancer. Pre-operative exercise and mind-body interventions may impact physical and/or psychological effects of cancer diagnosis and treatment in women with breast cancer. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01516190. Registered January 24, 2012.

Oncotype DX testing in node-positive breast cancer strongly impacts chemotherapy use at a comprehensive cancer center.

PURPOSE: In 2016, we initiated standardized "reflex" Oncotype DX Recurrence Score (RS) testing for patients ≤ 65 years with pT1-2N0-1 HR+/HER2- breast cancer. Here, we examine RS testing patterns, RS distribution, and factors associated with chemotherapy use in patients with pN1 breast cancer. METHODS: Patients with stage I-III HR+/HER2- pN1 breast cancer treated with upfront surgery from February 2016 to March 2019 were identified. Clinical characteristics were compared between patients meeting reflex RS testing criteria, those with RS ordered outside of reflex criteria, and those without RS testing. RS was categorized as low (< 18), intermediate (18-30), and high (≥ 31). Multivariate logistic regression was performed to identify factors associated with adjuvant chemotherapy receipt. We examined 3-year recurrence-free survival (RFS) and overall survival (OS) stratified by chemotherapy use. RESULTS: We identified 347 HR+/HER2- pN1 patients; 272 (78.4%) received RS testing, and 194 (71.3%) met reflex criteria. RS was < 18 in 164 (61.4%) patients, 18-30 in 89 (32.7%) patients, and ≥ 31 in 16 (5.9%) patients. On multivariate analysis, RS < 18 (OR 0.47, 95% CI 0.24-0.92) was associated with lower odds of chemotherapy use, whereas presence of lymphovascular invasion (OR 1.77, 95% CI 1.03-3.07) and lobular subtype (OR 2.40, 95% CI 1.21-4.78) were associated with higher odds. No differences in 3-year RFS (p = 0.97) or OS (p = 0.19) based on chemotherapy receipt were observed. CONCLUSION: Most RS-tested HR+/HER2- pN1 patients at our center had low genomic risk. A low RS independently influenced chemotherapy omission and in RS-tested patients, short-term outcomes were excellent. Our study demonstrates increased use of RS in guiding adjuvant treatment decisions in node-positive disease.

Randomized Trial of Standard Adjuvant Chemotherapy Regimens Versus Capecitabine in Older Women With Early Breast Cancer: 10-Year Update of the CALGB 49907 Trial.

PURPOSE: Older women with breast cancer remain under-represented in clinical trials. The Cancer and Leukemia Group B 49907 trial focused on women age 65 years and older. We previously reported the primary analysis after a median follow-up of 2.4 years. Standard adjuvant chemotherapy showed significant improvements in recurrence-free survival (RFS) and overall survival compared with capecitabine. We now update results at a median follow-up of 11.4 years. PATIENTS AND METHODS: Patients age 65 years or older with early breast cancer were randomly assigned to either standard adjuvant chemotherapy (physician's choice of either cyclophosphamide, methotrexate, and fluorouracil or cyclophosphamide and doxorubicin) or capecitabine. An adaptive Bayesian design was used to determine sample size and test noninferiority of capecitabine. The primary end point was RFS. RESULTS: The design stopped accrual with 633 patients at its first sample size assessment. RFS remains significantly longer for patients treated with standard chemotherapy. At 10 years, in patients treated with standard chemotherapy versus capecitabine, the RFS rates were 56% and 50%, respectively (hazard ratio [HR], 0.80; P = .03); breast cancer-specific survival rates were 88% and 82%, respectively (HR, 0.62; P = .03); and overall survival rates were 62% and 56%, respectively (HR, 0.84; P = .16). With longer follow-up, standard chemotherapy remains superior to capecitabine among hormone receptor-negative patients (HR, 0.66; P = .02), but not among hormone receptor-positive patients (HR, 0.89; P = .43). Overall, 43.9% of patients have died (13.1% from breast cancer, 16.4% from causes other than breast cancer, and 14.1% from unknown causes). Second nonbreast cancers occurred in 14.1% of patients. CONCLUSION: With longer follow-up, RFS remains superior for standard adjuvant chemotherapy versus capecitabine, especially in patients with hormone receptor-negative disease. Competing risks in this older population dilute overall survival benefits.

Drug Resistance in HER2-Positive Breast Cancer Brain Metastases: Blame the Barrier or the Brain?

The brain is the most common site of first metastasis for patients with HER2-positive breast cancer treated with HER2-targeting drugs. However, the development of effective therapies for breast cancer brain metastases (BCBM) is limited by an incomplete understanding of the mechanisms governing drug sensitivity in the central nervous system. Pharmacodynamic data from patients and in vivo models suggest that inadequate drug penetration across the "blood-tumor" barrier is not the whole story. Using HER2-positive BCBMs as a case study, we highlight recent data from orthotopic brain metastasis models that implicate brain-specific drug resistance mechanisms in BCBMs and suggest a translational research paradigm to guide drug development for treatment of BCBMs. Clin Cancer Res; 24(8); 1795-804. ©2018 AACR.

Lymphedema, musculoskeletal events and arm function in older patients receiving adjuvant chemotherapy for breast cancer (Alliance A171302).

PURPOSE: Musculoskeletal events (MEs) resulting from breast cancer treatment can significantly interfere with the quality of life (QOL) of older adults. We evaluated the incidence of MEs in women 65 years and older who had surgery and adjuvant chemotherapy for breast cancer, and the impact of treatment on MEs and arm function. PATIENTS AND METHODS: Patient-reported data in Alliance/CALGB 49907 were collected using the EORTC QLQ-BR23 and physician-reported adverse events to characterize self-reported MEs and incidence of lymphedema. EORTC QLQ-BR23 items related to musculoskeletal events were analyzed in this study and data collected at study entry (post-operative) and 12 and 24 months post-entry. RESULTS: Lymphedema, arm function, and ME data were available for 321 patients. One or more MEs were reported by 87% (median number = 3) and 64% (median number = 1) of patients post-operatively and at 24 months. At 24 months 2% had persistence of six MEs. Seventy-four percent experienced at least ≥3/6 types of MEs over the 24-month period. Detection of lymphedema at any time during the study was noted in 7.5% of the patients and appeared to be associated with the type of chemotherapy given: CMF 16.4%, capecitabine 5.8%, and AC 4%. Mastectomy and axillary node dissection were associated with the most MEs. LROM correlated with poorer arm function at all time periods. CONCLUSION: Potentially debilitating MEs occur in three-fourths of elderly women undergoing standard therapy for breast cancer. Emphasis should be placed on prevention, identification, and treatment of these MEs to improve QOL.

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.

Randomized trial of a physical activity intervention in women with metastatic breast cancer.

BACKGROUND: Exercise interventions improve fitness, functional capacity, and quality of life in patients with early-stage breast cancer, but to the authors' knowledge there are few data regarding the feasibility or potential benefits of exercise in women with metastatic breast cancer. METHODS: Individuals with metastatic breast cancer were randomized 1:1 to a 16-week moderate-intensity exercise intervention or wait-list control group. Intervention goals included 150 minutes of moderate-intensity aerobic exercise per week. The baseline and 16-week evaluations included a modified Bruce Ramp treadmill test, 7-day Physical Activity Recall interview, and European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ C-30) questionnaire. RESULTS: A total of 101 participants were randomized (48 to the intervention group and 53 to the control group). The median age of the participants was 49 years, the median time since the diagnosis of metastatic breast cancer was 1.1 years, and approximately 42% of participants were undergoing chemotherapy at the time of enrollment. Study attrition was higher in the intervention arm (14 participants vs 8 participants; P = .15). Women randomized to the exercise intervention experienced a nonsignificant increase with regard to minutes of weekly exercise (62.4 minutes vs 46.0 minutes; P = .17) and physical functioning (EORTC QLQ C30: 4.79 vs 0.93 [P = .23] and Bruce Ramp Treadmill test: 0.61 minutes vs 0.37 minutes [P = .35]) compared with control participants. CONCLUSIONS: Participation in an exercise intervention did not appear to result in significant improvements in physical functioning in a heterogeneous group of women living with advanced breast cancer. Given the significant benefits of exercise in women with early-stage breast cancer, more work is needed to explore alternative interventions to determine whether exercise could help women with metastatic disease live more fully with fewer symptoms from disease and treatment.

Trends in the use of mastectomy in women with small node-negative breast cancer treated at US academic centers.

Breast-conserving surgery (BCS) provides equivalent survival outcomes to unilateral mastectomy. There is no survival advantage to bilateral mastectomy in average risk breast cancer. Among a cohort of breast cancer patients expected to be candidates for BCS, we examined choice of surgery and factors associated with it. A prospective cohort study of unilateral clinical Stage I breast cancer patients treated at National Comprehensive Cancer Network centers from 2000 to 2009 was performed. The proportion of patients who initially underwent mastectomy versus BCS and time to definitive surgery and chemotherapy were examined. Of 10,249 patients, 23 % underwent mastectomy as an initial surgery. No decline in the use of mastectomy as initial surgery was found. There was significant institutional variation, with rates of initial mastectomy ranging from 14 to 30 % (adjusted odds ratio: 0.42-1.38). Tumor characteristics were associated with surgical option, but with small absolute differences. Of those who received initial mastectomy, 22 % had bilateral mastectomy, with an increase over time (2000:13 % vs. 2009:30 %) and substantial institutional variation (11-34 %). Women treated with initial mastectomy had longer median times from diagnosis to complete definitive surgery (6 vs. 4 weeks) and to start of adjuvant chemotherapy (12 vs. 11 weeks). Among Stage I breast cancer, the overall use of mastectomy did not change significantly over 10 years; however, an increasing proportion of women with unilateral cancer had bilateral mastectomy, and there was wide variation in type of surgery by institution. Further studies to assess reasons for the observed wide variation are warranted.

Tailoring adjuvant chemotherapy regimens for patients with triple negative breast cancer.

Cytotoxic chemotherapy remains the systemic therapy of choice for triple-negative breast cancer (TNBC), a poor-prognosis subtype of breast cancer. Growing data focusing on TNBC provides an opportunity to assess if we can tailor adjuvant chemotherapy based on patient and tumor characteristics. The standard of care for moderate-to-high risk TNBC remains a sequential anthracycline-taxane combination, with the potential for shorter and less toxic regimens in stage I disease. Platinums are promising in the neoadjuvant and metastatic settings but we await long-term outcome data before incorporation into standard regimens in the adjuvant setting. Specific subgroups within TNBC, such as BRCA mutation carriers, require special attention, and the role of platinums in these patients warrants further consideration. There is hope that in the future, further subdividing TNBC by gene expression profile, mutation, immune infiltrate, and others will reveal novel susceptibilities.

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.

Variation in type of adjuvant chemotherapy received among patients with stage I breast cancer: A multi-institutional study.

BACKGROUND: Among patients with stage I breast cancer, there is significant uncertainty concerning the optimal threshold at which to consider chemotherapy, and when considered, there is controversy regarding whether to consider non-intensive versus intensive regimens. The authors examined the types and costs of adjuvant chemotherapy received among patients with stage I breast cancer. METHODS: The current study was a prospective cohort study including patients with stage I breast cancer who were treated at a National Comprehensive Cancer Network center from 2000 through 2009. Stage was defined according to the version of the American Joint Committee on Cancer Staging Manual applicable at the time of diagnosis. Stratifying by human epidermal growth factor receptor 2 (HER2), the authors examined the percentage of patients receiving intensive versus non-intensive chemotherapy regimens and the factors associated with type of chemotherapy administered using multivariable logistic regression. Costs of the most common regimens were estimated. RESULTS: Of 8907 patients, 33% received adjuvant chemotherapy. Among those individuals, there was an increase in the use of intensive chemotherapy within the last decade, from 31% in 2000 through 2005 to 63% in 2008 through 2009 (including an increase in the use of the combination of docetaxel, carboplatin, and trastuzumab) among patients with HER2-positive disease and from 15% in 2000 through 2005 to 41% in 2008 through 2009 among patients with HER2-negative disease (32% of patients with hormone receptor-positive and 59% of patients with triple-negative disease). Among patients treated with non-intensive regimens, there was an increase in the use of the combination of docetaxel and cyclophosphamide noted, with a decrease in the use of the doxorubicin and cyclophosphamide combination. The choice of regimen varied significantly by institution. The major drivers of cost variation were the incorporation of biologics (eg, trastuzumab) and growth factors, with significant variation even within non-intensive and intensive regimens. CONCLUSIONS: Over time, there was an increase in use of intensive regimens among Stage I breast cancer, with striking institutional and cost variations.

Comorbidity, chemotherapy toxicity, and outcomes among older women receiving adjuvant chemotherapy for breast cancer on a clinical trial: CALGB 49907 and CALGB 361004 (alliance).

PURPOSE: We evaluated associations among comorbidity, toxicity, time to relapse (TTR), and overall survival (OS) in older women with early-stage breast cancer receiving adjuvant chemotherapy. METHODS: Cancer and Leukemia Group B 49907 (Alliance) randomly assigned women ≥ 65 years old with stages I-III breast cancer to standard adjuvant chemotherapy or capecitabine. We reviewed data from 329 women who participated in the quality of life companion study CALGB 70103 and completed the Physical Health Subscale of the Older American Resources and Services Questionnaire. This questionnaire captures data on 14 comorbid conditions and the degree to which each interferes with daily activities. A comorbidity burden score was computed by multiplying the total number of conditions by each condition's level of interference with function. Outcomes were grade 3 to 5 toxicity, TTR, and OS. Logistic regression was used to evaluate associations between comorbidity and toxicity, and Cox proportional hazards models for TTR and survival. RESULTS: Number of comorbidities ranged from 0 to 10 (median 2); the comorbidity burden score ranged from 0 to 25 (median 3). The most common conditions were arthritis (58%) and hypertension (55%). Comorbidity was associated with shorter OS, but not with toxicity or TTR. The hazard of death increased by 18% for each comorbidity (hazard ratio [HR] = 1.18, 95% CI = 1.06 to 1.33) after adjusting for age, tumor size, treatment, node and receptor status. Comorbidity burden score was similarly associated with OS (HR = 1.08; 95% CI, 1.03 to 1.14). CONCLUSIONS: Among older women enrolled onto a clinical trial, comorbidity was associated with shorter OS, but not toxicity or relapse.

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.

A phase II study of preoperative capecitabine in women with operable hormone receptor positive breast cancer.

Conventional preoperative chemotherapy regimens have only limited efficacy in hormone receptor positive (HR+) breast cancer and new approaches are needed. We hypothesized that capecitabine, which is effective in metastatic breast cancer, may be an active preoperative treatment for HR+ breast cancer. Women with HR+, HER2-negative operable breast cancer received capecitabine, 2000 mg/m(2) daily in divided doses for 14 days, followed by a 7-day rest period. Treatment was repeated every 21 days for a total of four cycles. The primary endpoint of the study was to determine the rate of pathological complete response (pCR). Because of slow accrual, the study was closed after 24 patients were enrolled. Three patients had a complete clinical response, and eight patients had a partial clinical response, for an overall clinical response rate of 45.8%. There were no cases of pCR. Of the 22 patients who had pathological response assessment by the Miller-Payne grading system, there were six grade 3 responses, and no grade 4 or 5 responses. Toxicity was manageable: the only grade 3 toxicities observed were one case each of diarrhea, palmar plantar erythrodysesthesia, hypokalemia, and mucositis. There was no association between baseline levels, or change in level from baseline to cycle 1, or from baseline to time of surgery, of thymidine phosphorylase (TYMP), thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD), or Ki67 and pathological, clinical, or radiographic response. Preoperative capecitabine is a well-tolerated regimen, but appears not lead to pCR when used as monotherapy in HR+ breast cancer.

Cognitive function in older women with breast cancer treated with standard chemotherapy and capecitabine on Cancer and Leukemia Group B 49907.

Cognitive changes in older women receiving chemotherapy are poorly understood. We examined self-reported cognitive function for older women who received adjuvant chemotherapy on Cancer and Leukemia Group B (CALGB) 49907. CALGB 49907 randomized 633 women aged ≥65 with stage I-III breast cancer to standard adjuvant chemotherapy (cyclophosphamide-methotrexate-5-fluorouracil or doxorubicin-cyclophosphamide) versus capecitabine. We examined self-reported cognitive function in 297 women (CALGB 361002) who enrolled on the quality of life substudy and had no gross impairment on cognitive screening. Women were evaluated using an 18-item instrument at six time points (baseline through 24 months). At each time point for each patient, we calculated a cognitive function score (CFS) defined as the mean response of items 1-18 and defined impairment as a score >1.5 standard deviations above the overall average baseline score. Differences in scores by patient characteristics were evaluated using a Kruskal-Wallis test. A linear mixed-effects model was used to assess CFSs by treatment over time. Among 297 women, the median age was 71.5 (range 65-85) and 73 % had performance status of 0. Baseline depression and fatigue were reported in 6 and 14 % of patients, respectively. The average CFS at baseline was 2.08 (corresponding to "normal ability"), and baseline cognitive function did not differ by treatment regimen (p = 0.350). Over 24 months, women reported minimal changes at each time point and insignificant differences by treatment arm were observed. In a healthy group of older women, chemotherapy was not associated with longitudinal changes in self-reported cognitive function.

PAM50 proliferation score as a predictor of weekly paclitaxel benefit in breast cancer.

To identify a group of patients who might benefit from the addition of weekly paclitaxel to conventional anthracycline-containing chemotherapy as adjuvant therapy of node-positive operable breast cancer. The predictive value of PAM50 subtypes and the 11-gene proliferation score contained within the PAM50 assay were evaluated in 820 patients from the GEICAM/9906 randomized phase III trial comparing adjuvant FEC to FEC followed by weekly paclitaxel (FEC-P). Multivariable Cox regression analyses of the secondary endpoint of overall survival (OS) were performed to determine the significance of the interaction between treatment and the (1) PAM50 subtypes, (2) PAM50 proliferation score, and (3) clinical and pathological variables. Similar OS analyses were performed in 222 patients treated with weekly paclitaxel versus paclitaxel every 3 weeks in the CALGB/9342 and 9840 metastatic clinical trials. In GEICAM/9906, with a median follow up of 8.7 years, OS of the FEC-P arm was significantly superior compared to the FEC arm (unadjusted HR = 0.693, p = 0.013). A benefit from paclitaxel was only observed in the group of patients with a low PAM50 proliferation score (unadjusted HR = 0.23, p < 0.001; and interaction test, p = 0.006). No significant interactions between treatment and the PAM50 subtypes or the various clinical-pathological variables, including Ki-67 and histologic grade, were identified. Finally, similar OS results were obtained in the CALGB data set, although the interaction test did not reach statistical significance (p = 0.109). The PAM50 proliferation score identifies a subset of patients with a low proliferation status that may derive a larger benefit from weekly paclitaxel.

High performance teamwork training and systems redesign in outpatient oncology.

BACKGROUND: Oncology care is delivered largely in ambulatory settings by interdisciplinary teams. Treatments are often complex, extended in time, dispersed geographically and vulnerable to teamwork failures. To address this risk, we developed and piloted a team training initiative in the breast cancer programme at a comprehensive cancer centre. METHODS: Based on clinic observations, interviews with key staff and analyses of incident reports, we developed interventions to address four high-risk areas: (1) miscommunication of chemotherapy order changes on the day of treatment; (2) missing orders on treatment days without concurrent physician appointments; (3) poor follow-up with team members about active patient issues; and (4) conflict between providers and staff. The project team developed protocols and agreements to address team members' roles, responsibilities and behaviours. RESULTS: Using a train-the-trainer model, 92% of breast cancer staff completed training. The incidence of missing orders for unlinked visits decreased from 30% to 2% (p<0.001). Patient satisfaction scores regarding coordination of care improved from 93 to 97 (p=0.026). Providers, infusion nurses and support staff reported improvement in efficiency (75%, 86%, 90%), quality (82%, 93%, 93%) and safety (92%, 92%, 90%) of care, and more respectful behaviour (92%, 79%, 83%) and improved relationships among team members (91%, 85%, 92%). Although most clinicians reported a decrease in non-communicated changes, there was insufficient statistical power to detect a difference. CONCLUSIONS: Team training improved communication, task coordination and perceptions of efficiency, quality, safety and interactions among team members as well as patient perception of care coordination.

Time to diagnosis and breast cancer stage by race/ethnicity.

We examined differences in time to diagnosis by race/ethnicity, the relationship between time to diagnosis and stage, and the extent to which it explains differences in stage at diagnosis across racial/ethnic groups. Our analytic sample includes 21,427 non-Hispanic White (White), Hispanic, non-Hispanic Black (Black) and non-Hispanic Asian/Pacific Islander (Asian) women diagnosed with stage I to IV breast cancer between January 1, 2000 and December 31, 2007 at one of eight National Comprehensive Cancer Network centers. We measured time from initial abnormal mammogram or symptom to breast cancer diagnosis. Stage was classified using AJCC criteria. Initial sign of breast cancer modified the association between race/ethnicity and time to diagnosis. Among symptomatic women, median time to diagnosis ranged from 36 days among Whites to 53.6 for Blacks. Among women with abnormal mammograms, median time to diagnosis ranged from 21 days among Whites to 29 for Blacks. Blacks had the highest proportion (26 %) of Stage III or IV tumors. After accounting for time to diagnosis, the observed increased risk of stage III/IV breast cancer was reduced from 40 to 28 % among Hispanics and from 113 to 100 % among Blacks, but estimates remained statistically significant. We were unable to fully account for the higher proportion of late-stage tumors among Blacks. Blacks and Hispanics experienced longer time to diagnosis than Whites, and Blacks were more likely to be diagnosed with late-stage tumors. Longer time to diagnosis did not fully explain differences in stage between racial/ethnicity groups.

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.

Clinicopathologic features, patterns of recurrence, and survival among women with triple-negative breast cancer in the National Comprehensive Cancer Network.

BACKGROUND: The objective of this study was to describe clinicopathologic features, patterns of recurrence, and survival according to breast cancer subtype with a focus on triple-negative tumors. METHODS: In total, 15,204 women were evaluated who presented to National Comprehensive Cancer Network centers with stage I through III breast cancer between January 2000 and December 2006. Tumors were classified as positive for estrogen receptor (ER) and/or progesterone receptor (PR) (hormone receptor [HR]-positive) and negative for human epidermal growth factor receptor 2 (HER2); positive for HER2 and any ER or PR status (HER2-positive); or negative for ER, PR, and HER2 (triple-negative). RESULTS: Subtype distribution was triple-negative in 17% of women (n = 2569), HER2-positive in 17% of women (n = 2602), and HR-positive/HER2-negative in 66% of women (n = 10,033). The triple-negative subtype was more frequent in African Americans compared with Caucasians (adjusted odds ratio, 1.98; P < .0001). Premenopausal women, but not postmenopausal women, with high body mass index had an increased likelihood of having the triple-negative subtype (P = .02). Women with triple-negative cancers were less likely to present on the basis of an abnormal screening mammogram (29% vs 48%; P < .0001) and were more likely to present with higher tumor classification, but they were less likely to have lymph node involvement. Relative to HR-positive/HER2-negative tumors, triple-negative tumors were associated with a greater risk of brain or lung metastases; and women with triple-negative tumors had worse breast cancer-specific and overall survival, even after adjusting for age, disease stage, race, tumor grade, and receipt of adjuvant chemotherapy (overall survival: adjusted hazard ratio, 2.72; 95% confidence interval, 2.39-3.10; P < .0001). The difference in the risk of death by subtype was most dramatic within the first 2 years after diagnosis (overall survival for 0-2 years: OR, 6.10; 95% confidence interval, 4.81-7.74). CONCLUSIONS: Triple-negative tumors were associated with unique risk factors and worse outcomes compared with HR-positive/HER2-negative tumors.