Treatment interruption and discontinuation of hormonal therapy in hormone receptor-positive breast cancer patients.

PURPOSE: To investigate predictors of treatment interruption and early discontinuation of adjuvant hormonal therapy (HT) in a retrospective cohort of women with newly diagnosed hormone receptor-positive (HR +) breast cancer. METHODS: Eligible cases were identified from a single institutional tumor registry from 2009 to 2015. Patients were followed from initiation of adjuvant HT for a minimum of one year through December 1, 2016. Predictors of treatment interruption or early discontinuation were analyzed with Cox proportional hazards regression models. RESULTS: With a median follow-up time of 3.0 years (IQR 1.5-4.5), 22 women (10.9%) discontinued HT early and 47 (23.4%) had at least one treatment interruption of > 14 days. Adjusted Cox proportional hazards regression models showed that women with pre-existing affective disorders were more likely to discontinue therapy early (HR 3.15; 95% CI 1.35-7.37), while those with pre-existing chronic pain disorders were at increased risk for treatment interruption (HR 2.24; 95% CI 1.20-4.19). HT-related symptoms were the most commonly reported reason for HT interruption or discontinuation. Women who experienced severe treatment-related symptoms were at increased risk for both HT interruption (HR 2.64; 95% CI 1.07-6.50) and HT discontinuation (HR 3.48; 95% CI 1.20-10.1). CONCLUSIONS: This study showed that HT interruptions and discontinuation were common, often associated with HT-related symptoms. Clinicians caring for breast cancer patients on HT should monitor closely for treatment-emergent symptoms, especially women with pre-existing disorders, and support them to continue therapy through aggressive symptom management and other patient-centered approaches.

Standardized activities for lay patient navigators in breast cancer care: Recommendations from a citywide implementation study.

BACKGROUND: There is a need for guidelines on patient navigation activities to promote both the quality of patient navigation and the standards of reimbursement for these services because a lack of reimbursement is a major barrier to the implementation, maintenance, and sustainability of these programs. METHODS: A broad community-based participatory research process was used to identify the needs of patients for navigation. A panel of stakeholders of clinical providers was convened to identify specific activities for navigators to address the needs of patients and providers with the explicit goal of reducing delays in the initiation of cancer treatment and improving adherence to the care plan. RESULTS: Specific activities were identified that could be generalized to all patient navigation programs for care during active cancer management to address the needs of vulnerable communities. CONCLUSIONS: Oncology programs that seek to implement lay patient navigation may benefit from the adoption of these activities for quality monitoring. Such activities are necessary as we consider reimbursement strategies for navigators without clinical training or licensure.

Longer therapy, iatrogenic amenorrhea, and survival in early breast cancer.

BACKGROUND: Chemotherapy regimens that combine anthracyclines and taxanes result in improved disease-free and overall survival among women with operable lymph-node-positive breast cancer. The effectiveness of concurrent versus sequential regimens is not known. METHODS: We randomly assigned 5351 patients with operable, node-positive, early-stage breast cancer to receive four cycles of doxorubicin and cyclophosphamide followed by four cycles of docetaxel (sequential ACT); four cycles of doxorubicin and docetaxel (doxorubicin-docetaxel); or four cycles of doxorubicin, cyclophosphamide, and docetaxel (concurrent ACT). The primary aims were to examine whether concurrent ACT was more effective than sequential ACT and whether the doxorubicin-docetaxel regimen would be as effective as the concurrent-ACT regimen. The secondary aims were to assess toxic effects and to correlate amenorrhea with outcomes in premenopausal women. RESULTS: At a median follow-up of 73 months, overall survival was improved in the sequential-ACT group (8-year overall survival, 83%) as compared with the doxorubicin-docetaxel group (overall survival, 79%; hazard ratio for death, 0.83; P=0.03) and the concurrent-ACT group (overall survival, 79%; hazard ratio, 0.86; P=0.09). Disease-free survival was improved in the sequential-ACT group (8-year disease-free survival, 74%) as compared with the doxorubicin-docetaxel group (disease-free survival, 69%; hazard ratio for recurrence, a second malignant condition, or death, 0.80; P=0.001) and the concurrent-ACT group (disease-free survival, 69%; hazard ratio, 0.83; P=0.01). The doxorubicin-docetaxel regimen showed noninferiority to the concurrent-ACT regimen for overall survival (hazard ratio, 0.96; 95% confidence interval, 0.82 to 1.14). Overall survival was improved in patients with amenorrhea for 6 months or more across all treatment groups, independently of estrogen-receptor status. CONCLUSIONS: Sequential ACT improved disease-free survival as compared with doxorubicin-docetaxel or concurrent ACT, and it improved overall survival as compared with doxorubicin-docetaxel. Amenorrhea was associated with improved survival regardless of the treatment and estrogen-receptor status. (ClinicalTrials.gov number, NCT00003782.)

Comparative Effectiveness of Adjuvant Chemotherapy in Early-Stage Breast Cancer: A Network Meta-analysis.

BACKGROUND: There are several regimens recommended by the National Comprehensive Cancer Network (NCCN) for HER2-negative operable breast cancer. To our knowledge, no trials have yet been performed comparing these regimens head to head. We performed a network meta-analysis comparing the efficacy of NCCN-recommended chemotherapy regimens. METHODS: We searched Medline, Embase, Web of Science, the Cochrane Central Register of Controlled Trials, and World Health Organization (WHO) International Clinical Trials Registry Platform from inception to February 2020. We included randomized clinical trials comparing adjuvant regimens in predominantly node-positive operable breast cancer patients. We compared (1) DDACT, (2) TCx4 cycles, (3) TAC, and (4) ACWKT. Common comparators were (5) AC, (6) ACT, and (7) ACD. Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines were followed. The Cochrane risk of bias tool assessed quality of the studies. Odds ratios (ORs) were calculated as measures of treatment effects with AC as reference. We used Bayesian hierarchical random-effects models with noninformative priors for mixed multiple treatment comparisons. Effectiveness was estimated by disease-free and overall survival using ORs. Sensitivity analyses were performed. Safety outcomes included febrile neutropenia. RESULTS: We identified 7 randomized controlled trials with 16,332 patients. TC (odds ratio [95% confidence interval], 0.71 [0.36-1.40]), TAC (0.77 [0.37-1.57]), ACWKT (0.68 [0.34-1.38]), and DDACT (0.72 [0.35-1.42]) were similar for overall survival. TC (0.64 [0.36-1.14]), TAC (0.67 [0.39-1.15]), ACWKT (0.63 [0.37-1.07]), and DDACT (0.59 [0.35-1.01]) had similar disease-free survival benefit. With regard to toxicity, TAC (2.67 [0.30-21.04]) had the highest odds of febrile neutropenia. CONCLUSION: The current generation of regimens are similar in efficacy. Given the lower toxicity of TCx4 comparatively, it is an acceptable alternative for lower-risk early-stage HER2-negative breast cancers.

Niraparib for Advanced Breast Cancer with Germline BRCA1 and BRCA2 Mutations: the EORTC 1307-BCG/BIG5-13/TESARO PR-30-50-10-C BRAVO Study.

PURPOSE: To investigate the activity of niraparib in patients with germline-mutated BRCA1/2 (gBRCAm) advanced breast cancer. PATIENTS AND METHODS: BRAVO was a randomized, open-label phase III trial. Eligible patients had gBRCAm and HER2-negative advanced breast cancer previously treated with ≤2 prior lines of chemotherapy for advanced breast cancer or had relapsed within 12 months of adjuvant chemotherapy, and were randomized 2:1 between niraparib and physician's choice chemotherapy (PC; monotherapy with eribulin, capecitabine, vinorelbine, or gemcitabine). Patients with hormone receptor-positive tumors had to have received ≥1 line of endocrine therapy and progressed during this treatment in the metastatic setting or relapsed within 1 year of (neo)adjuvant treatment. The primary endpoint was centrally assessed progression-free survival (PFS). Secondary endpoints included overall survival (OS), PFS by local assessment (local-PFS), objective response rate (ORR), and safety. RESULTS: After the pre-planned interim analysis, recruitment was halted on the basis of futility, noting a high degree of discordance between local and central PFS assessment in the PC arm that resulted in informative censoring. At the final analysis (median follow-up, 19.9 months), median centrally assessed PFS was 4.1 months in the niraparib arm (n = 141) versus 3.1 months in the PC arm [n = 74; hazard ratio (HR), 0.96; 95% confidence interval (CI), 0.65-1.44; P = 0.86]. HRs for OS and local-PFS were 0.95 (95% CI, 0.63-1.42) and 0.65 (95% CI, 0.46-0.93), respectively. ORR was 35% (95% CI, 26-45) with niraparib and 31% (95% CI, 19-46) in the PC arm. CONCLUSIONS: Informative censoring in the control arm prevented accurate assessment of the trial hypothesis, although there was clear evidence of niraparib's activity in this patient population.

Timeliness of Treatment Initiation in Newly Diagnosed Patients With Breast Cancer.

BACKGROUND: Evidence-based timeliness benchmarks have been established to assess quality of breast cancer care, as delays in treatment are associated with poor clinical outcomes. However, few studies have evaluated how current breast cancer care meets these benchmarks and what factors may delay the timely initiation of treatment. PATIENTS AND METHODS: Demographic and disease characteristics of 377 newly diagnosed patients with breast cancer who initiated treatment at Tufts Medical Center (2009-2015) were extracted from electronic medical records. Time from diagnosis to initial surgery and time from diagnosis to initiation of hormone therapy were estimated with Kaplan-Meier curves. Multivariable regression analysis was used to identify factors associated with treatment delays. Thematic analysis was performed to categorize reasons for delay. RESULTS: Of 319 patients who had surgery recommended as the first treatment, 248 (78%) met the 45-day benchmark (median, 28 days; 25th-75th %, 19-43). After adjusting for potential confounders, multivariable regression analysis revealed that negative hormone receptor status (odds ratio, 3.48; 95% confidence interval, 1.44-8.43) and mastectomy (odds ratio, 4.07; 95% confidence interval, 2.10-8.06) were significantly associated with delays in surgery. Delays were mostly owing to clinical complexity or logistical/financial reasons. Of 241 patients eligible for hormone therapy initiation, 232 (96%) met the 1-year benchmark (median, 147 days; 25th-75th %, 79-217). CONCLUSION: Most patients met timeliness guidelines for surgery and initiation of hormone therapy, although risk factors for delay were identified. Knowledge of reasons for breast cancer treatment delay, including clinical complexity and logistical/financial issues, may allow targeting interventions for patients at greatest risk of care delays.

Development of Phase-Specific Breast Cancer Survivorship Care Plans.

INTRODUCTION: Phase-specific survivorship care plans (SCPs) have the potential to be powerful tools in providing individualized, comprehensive survivorship care, particularly in terms of care coordination and transition, if used as dynamic documents. MATERIALS AND METHODS: We designed an initial follow-up care plan (FCP) to be used at the conclusion of curative therapy, as well as distinct, phase-specific FCPs for periodic use at 5-year and 10-year time points in the survivorship course. These FCPs incorporate the 4 essential components of survivorship care outlined by the Institute of Medicine: prevention, surveillance, intervention for consequences of cancer treatment, and coordination among health care providers. RESULTS: Phase-specific SCPs were designed by a multidisciplinary team with expertise in breast health, survivorship, and cancer care delivery across diverse practice settings. The FCPs were formulated to align with national guidelines and emergent, peer-reviewed literature, and reflect evolving recommendations regarding the duration of adjuvant hormone therapy. The SCPs were pilot-tested and successfully integrated into the existing work flow of the electronic medical records at each practice site. CONCLUSION: Phase-specific SCPs were developed to incorporate new knowledge about evolving treatment recommendations, screening guidelines, and updated genetic information to encourage timely discussions relevant to the specific stage of survivorship.

Vitamin D supplementation for prevention of cancer: The D2d cancer outcomes (D2dCA) study.

Evidence on biological plausibility from mechanistic studies and data from observational studies suggest that vitamin D may be linked to risk of several types of cancer. However, evidence from clinical trials evaluating the effect of vitamin D supplementation on cancer risk is limited. The Vitamin D and Type 2 Diabetes (D2d) study is a multi-center, randomized, placebo-controlled clinical trial conducted to examine the causal relationship between oral vitamin D supplementation and development of diabetes among overweight adults with prediabetes. The D2d study provides a unique opportunity to assess the effect of vitamin D supplementation at a higher dose (4000 IU/day) than has been used in other clinical trials with cancer outcomes, in a population at higher than average risk for cancer. This paper provides: Krishnan and Feldman (2011) a) baseline characteristics of the D2d population included in the D2d cancer outcomes secondary study (D2dCA) and comparison to other large trials of vitamin D supplementation and cancer risk; Leyssens et al. (2013) b) description of data that are being collected during the trial and the planned statistical analyses to test whether vitamin D supplementation at a dose of 4000 IU/day has an effect on incident cancer overall, on incidence of certain types of cancer, and on incidence of precancerous lesions. Results of D2dCA will help guide future research and clinical recommendations related to vitamin D and cancer risk.

Personalized Decision Making in Early Stage Breast Cancer: Applying Clinical Prediction Models for Anthracycline Cardiotoxicity and Breast Cancer Mortality Demonstrates Substantial Heterogeneity of Benefit-Harm Trade-off.

BACKGROUND: Anthracycline agents can cause cardiotoxicity. We used multivariable risk prediction models to identify a subset of patients with breast cancer at high risk of cardiotoxicity, for whom the harms of anthracycline chemotherapy may balance or exceed the benefits. PATIENTS AND METHODS: A clinical prediction model for anthracycline cardiotoxicity was created in 967 patients with human epidermal growth factor receptor-negative breast cancer treated with doxorubicin in the ECOG-ACRIN study E5103. Cardiotoxicity was defined as left ventricular ejection fraction (LVEF) decline of ≥ 10% to < 50% and/or a centrally adjudicated clinical heart failure diagnosis. Patient-specific incremental absolute benefit of anthracyclines (compared with non-anthracycline taxane chemotherapy) was estimated using the PREDICT model to assess breast cancer mortality risk. RESULTS: Of the 967 women who initiated therapy, 51 (5.3%) developed cardiotoxicity (12 with clinical heart failure). In a multivariate model, increasing age (odds ratio [OR], 1.04; 95% confidence interval [CI], 1.01-1.08), higher body mass index (OR, 1.06; 95% CI, 1.02-1.10), and lower baseline LVEF (OR, 0.93; 95% CI, 0.89-0.98) at baseline were significantly associated with cardiotoxicity. The concordance statistic of the risk model was 0.70 (95% CI, 0.63-0.77). In patients with low anticipated treatment benefit (n = 176) from the addition of anthracycline (< 2% absolute risk difference of breast cancer mortality at 10 years), 16 (9%) of 176 had a > 10% risk of cardiotoxicity and 61 (35%) of 176 had a 5% to 10% risk of cardiotoxicity at 1 year. CONCLUSION: Older age, higher body mass index, and lower baseline LVEF were associated with increased risk of cardiotoxicity. We identified a subgroup with low predicted absolute benefit of anthracyclines but with high predicted risk of cardiotoxicity. Additional studies are needed incorporating long-term cardiac outcomes and cardiotoxicity model external validation prior to implementation in routine clinical practice.

Efficacy and Effectiveness Too Trials: Clinical Trial Designs to Generate Evidence on Efficacy and on Effectiveness in Wide Practice.

Efficacy trials, designed to gain regulatory marketing approval, evaluate drugs in optimally selected patients under advantageous conditions for relatively short time periods. Effectiveness trials, designed to evaluate use in usual practice, assess treatments among more typical patients in real-world conditions with longer follow-up periods. In "efficacy-to-effectiveness (E2E) trials," if the initial efficacy trial component is positive, the trial seamlessly transitions to an effectiveness trial component to efficiently yield both types of evidence. Yet more time could be saved by simultaneously addressing efficacy and effectiveness in an "efficacy and effectiveness too (EE2) trial." Additionally, hybrids of the E2E and EE2 approaches with differing degrees of overlap of the two components could allow flexibility for specific drug development needs. In planning EE2 trials, each stakeholder's current and future needs, incentives, and perspective must be considered. Although challenging, the ultimate benefits to stakeholders, the health system, and the public should justify this effort.

Open-label Clinical Trial of Niraparib Combined With Pembrolizumab for Treatment of Advanced or Metastatic Triple-Negative Breast Cancer.

IMPORTANCE: Poly(adenosine diphosphate-ribose) polymerase inhibitor and anti-programmed death receptor-1 inhibitor monotherapy have shown limited clinical activity in patients with advanced triple-negative breast cancer (TNBC). OBJECTIVE: To evaluate the clinical activity (primary) and safety (secondary) of combination treatment with niraparib and pembrolizumab in patients with advanced or metastatic TNBC. DESIGN, SETTING, AND PARTICIPANTS: This open-label, single-arm, phase 2 study enrolled 55 eligible patients with advanced or metastatic TNBC irrespective of BRCA mutation status or programmed death-ligand 1 (PD-L1) expression at 34 US sites. Data were collected from January 3, 2017, through October 29, 2018, and analyzed from October 29, 2018, through February 27, 2019. INTERVENTIONS: Patients were administered 200 mg of oral niraparib once daily in combination with 200 mg of intravenous pembrolizumab on day 1 of each 21-day cycle. MAIN OUTCOMES AND MEASURES: The primary end point was objective response rate (ORR) per the Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points were safety, disease control rate (DCR; complete response plus partial response plus stable disease), duration of response (DOR), progression-free survival (PFS), and overall survival. RESULTS: Within the full study population of 55 women (median age, 54 years [range, 32-90 years]), 5 patients had confirmed complete responses, 5 had confirmed partial responses, 13 had stable disease, and 24 had progressive disease. In the efficacy-evaluable population (n = 47), ORR included 10 patients (21%; 90% CI, 12%-33%) and DCR included 23 (49%; 90% CI, 36%-62%). Median DOR was not reached at the time of the data cutoff, with 7 patients still receiving treatment at the time of analysis. In 15 evaluable patients with tumor BRCA mutations, ORR included 7 patients(47%; 90% CI, 24%-70%), DCR included 12 (80%; 90% CI, 56%-94%), and median PFS was 8.3 months (95% CI, 2.1 months to not estimable). In 27 evaluable patients with BRCA wild-type tumors, ORR included 3 patients (11%; 90% CI, 3%-26%), DCR included 9 (33%; 90% CI, 19%-51%), and median PFS was 2.1 months (95% CI, 1.4-2.5 months). The most common treatment-related adverse events of grade 3 or higher were anemia (10 [18%]), thrombocytopenia (8 [15%]), and fatigue (4 [7%]). Immune-related adverse events were reported in 8 patients (15%) and were grade 3 in 2 patients (4%); no new safety signals were detected. CONCLUSIONS AND RELEVANCE: Combination niraparib plus pembrolizumab provides promising antitumor activity in patients with advanced or metastatic TNBC, with numerically higher response rates in those with tumor BRCA mutations. The combination therapy was safe with a tolerable safety profile, warranting further investigation. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02657889.

Rapid Change in Mental Status in a Patient with Hypereosinophilia.

We present the case of a 48-year-old female with acute onset altered mental status, who was found to have eosinophilia, elevated troponin, and embolic strokes. Extensive testing for autoimmune, infectious, and coronary artery etiologies was unremarkable. After a cardiac MRI revealed focal myocardial hyperenhancement, the patient underwent an endomyocardial biopsy with findings consistent with eosinophilic myocarditis. The patient was diagnosed of idiopathic hypereosinophilic syndrome and started on prednisone and apixaban. Our case highlights the importance of considering hypereosinophilic syndrome when eosinophilia is associated with multisystem impairments, as tissue biopsy is usually required to diagnose this rare condition.

Neoadjuvant therapy for treatment of breast cancer: the way forward, or simply a convenient option for patients?

The complexity of managing early stage breast cancer is well known. Optimal treatment is increasingly multidisciplinary and in the modern era informed by sophisticated molecular tools to help select and guide therapy. Major phase III trials have determined that the order of systemic therapy relative to surgery does not influence important endpoints such as event free survival and overall survival (OS), but questions remain as to how best to utilize these most essential services. For example, there is still uncertainty regarding the ideal timing, intensity, and duration of proposed therapy. For treating physicians, evidence based standardization of these practices is both possible and critically important. Optimization of care will increasingly rely on well-designed studies that have addressed the choice as well as the timing of the steps involved in multidisciplinary breast cancer treatment. Understanding when factors under the oncologist's control will influence outcome, cost and convenience is essential in the era of quality and value-based medical decision making. The timing of surgery before or after chemotherapy for breast cancer is one such factor. Investigators are to be commended for addressing these questions, which may generate additional hypotheses concerning the biology of metastasis and the nature of recurrence.

Weight Management: Perception, Interest, and Preferences in Adult Cancer Survivors.

BACKGROUND: Obesity in cancer survivors has been recognized as a growing crisis in cancer care, but cancer survivors may not perceive weight status as important and may not be motivated to manage weight. OBJECTIVES: This study aims to evaluate survivors' perception, interest, and preferences for weight management and to identify characteristics that may affect attitudes toward weight management. METHODS: This cross-sectional survey assessed cancer survivors' attitudes toward weight management with patients attending oncology outpatient clinics at Tufts Medical Center in Boston, Massachusetts. FINDINGS: Among 209 respondents who completed the survey, 35% were overweight and 27% were obese. Most participants indicated that they would like to lose weight or were interested or very interested in participating in weight management programs. The results reinforce the need for the oncology team to provide weight management support to cancer survivors.

Lack of uniform diagnostic criteria for inflammatory breast cancer limits interpretation of treatment outcomes: a systematic review.

PURPOSE: Inflammatory breast cancer (IBC) is the most aggressive type of breast cancer. No randomized controlled trial or systematic review with an IBC-only cohort that evaluates interventions has been published. We conducted a systematic review of the literature to characterize the reporting of clinical criteria and response to neoadjuvant therapy for IBC. PATIENTS AND METHODS: We searched MEDLINE and other sources for the following: previously untreated patients with IBC without metastasis in cohort studies; utilized chemotherapy; and reported clinical outcomes. The following 4 groups were analyzed: no anthracycline induction, low-dose anthracycline induction, moderate-dose anthracycline induction, and high-dose chemotherapy requiring stem cell support. Weighted averages for the overall response rates were calculated using a random effects model. RESULTS: Twenty-seven studies met all criteria, totaling 1232 patients. Clinical description of IBC eligibility criteria and reported response assessments varied significantly among studies. The response rates and 3- and 5-year overall survival for all 27 studies ranged from 14% to 100%, 22% to 84%, and 32% to 75%, respectively. Pathologic complete response rates after no anthracycline induction, low-dose anthracycline induction, moderate-dose anthracycline induction, and neoadjuvant high-dose chemotherapy subgroups were 4% (95% confidence interval [CI], 1%-18%), 11% (95% CI, 7%-17%), 14% (95% CI, 8%-22%), and 32% (95% CI, 24%-41%), respectively. CONCLUSION: The criteria and reporting of IBC and treatment response was notably variable, with significant potential for subject heterogeneity. Pathologic complete response rates appear to be related to intensity of neoadjuvant treatment; however, this analysis is not based on randomized data. Future clinical trials should define and report the criteria for IBC diagnosis and response assessment to enhance interstudy comparisons.

Phase II study of neoadjuvant docetaxel/ vinorelbine followed by surgery and adjuvant doxorubicin/cyclophosphamide in women with stage II/III breast cancer.

BACKGROUND: The purpose of this study was to evaluate the combination of docetaxel plus vinorelbine as neoadjuvant chemotherapy for stage II/III locally advanced breast cancer. PATIENTS AND METHODS: Eligible women with stage IIA-IIIB or locoregional stage IV breast cancer were treated before surgery with 6 cycles of docetaxel 60 mg/m2 and vinorelbine 45 mg/m2, repeated every 2 weeks with granulocyte colony-stimulating factor and quinolone prophylaxis. Pathologic complete response (pCR), viewed as an early surrogate for disease-free and overall survival, was the primary efficacy endpoint. Sixty patients were enrolled; 60% had T3 or T4 lesions, 67% had clinically palpable lymph nodes, and 52% were hormone receptor positive. RESULTS: Fifty-nine patients were evaluable for pathologic response; 16 (27%) exhibited pCR in the breast alone (T0 Tis NX), 20% exhibited a pCR in the breast and lymph nodes (T0 Tis N0), 24 (41%) had < 5 mm of residual tumor, and 28 (47%) had node-negative disease at surgery. Relative dose intensity was 96% for docetaxel and 95% for vinorelbine. The clinical response rate was 98% (59 of 60 patients), including 38 complete responses (63%). Grade 3/4 neutropenia (95%), neutropenic fever (22%), mucositis (5%), and pulmonary toxicity (5%) occurred in >or= 5% of patients. Constipation was seen early but became insignificant after incorporating a prophylactic laxative regimen. Other toxicities have been minimal. CONCLUSION: With a clinical response rate of 98% and an in-breast pCR rate of 27%, docetaxel/vinorelbine is among the most active neoadjuvant regimens reported for locally advanced breast cancer. Docetaxel/vinorelbine can be administered in a dose-dense fashion while maintaining relative dose intensity. However, there was a significant incidence of fever and neutropenia despite the use of prophylactic growth factors and quinolones, indicating that lower doses of docetaxel/vinorelbine should be evaluated in future studies.

Selective loss of heterozygosity in multiple breast cancers from a carrier of mutations in both BRCA1 and BRCA2.

Carriers of one mutant allele of either BRCA1 or BRCA2 are at risk for somatic loss of the second wild-type allele, leading to the initiation of breast tumorigenesis. We identified a patient of Ashkenazi Jewish heritage with germ-line heterozygous mutations in both BRCA1 (5382insC) and BRCA2 (6174delT), who had developed three independent breast cancers by age 47. Two breast cancers demonstrated inactivation of both BRCA2 alleles but retention of the wild-type BRCA1 allele, and the third showed loss of heterozygosity for BRCA1 but not BRCA2. The observation that breast tumors arising in a double heterozygote show biallelic inactivation of either BRCA1 or BRCA2, but not both, suggests that these genetic events are functionally equivalent in initiating tumorigenesis. The distinct histopathological features of these tumors may reflect the acquisition of subsequent genetic events.

Promoting High-Quality Cancer Care and Equity Through Disciplinary Diversity in Team Composition.

Disciplinary diversity in team composition is a valuable vehicle for oncology care teams to provide high-quality, person-centered comprehensive care. Such diversity facilitates care that effectively addresses the complex needs (biologic, psychosocial, and spiritual) of the whole person. The concept of professional or disciplinary diversity centers on differences in function, education, and culture, reflecting variety and heterogeneity in the perspectives of team members contributing to care. Thorough understanding of the skills, knowledge, and education related to each team member's professional or lay expertise is critical for members to be able to optimize the team's potential. Furthermore, respect and appreciation for differences and similarities across disciplinary cultures allow team members to create a positive collaboration dynamic that maintains a focus on the care of the person with cancer. We present a case study of one oncology team's provision of care to the patient, a Chinese immigrant woman with breast cancer. The case illuminates the strengths and challenges of disciplinary diversity in team composition in assessing and addressing potential barriers to care. Coordinated sharing of information among the varied team members facilitated understanding and care planning focused on the patient's concerns, needs, and strengths. Importantly, collaboration across the disciplinarily diverse set of team members facilitated high-quality oncology care and promoted equity in access to the full range of care options, including enrollment on a National Cancer Institute-sponsored clinical trial. Further implications of disciplinary diversity in oncology care teams are considered for both clinical practice and research.