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Purpose: Racial disparity in breast cancer outcomes exists between African American and white women in the United States. We have evaluated the impact of genetically determined ancestry on disparity in efficacy and therapy-induced toxicity for patients with breast cancer in the context of a randomized, phase III adjuvant trial. Methods: This study compared outcomes between 386 patients of African ancestry (AA) and 2,473 patients of European ancestry (EA) in a randomized, phase III breast cancer trial, ECOG-ACRIN-5103. The primary efficacy end point, invasive disease–free survival (DFS), and clinically significant toxicities were compared, including anthracycline-induced congestive heart failure, taxane-induced peripheral neuropathy (TIPN), and bevacizumab-induced hypertension. Results: Overall, AAs had significantly inferior DFS (P =.002; hazard ratio, 1.5) compared with EAs. This was significant in the estrogen receptor–positive subgroup (P =.03), with a similar, nonsignificant trend for those who had triple-negative breast cancer (P =.12). AAs also had significantly more grades 3 to 4 TIPN (odds ratio [OR], 2.9; P = 2.4 × 10−11) and grades 3 to 4 bevacizumab-induced hypertension (OR, 1.6; P =.02), with a trend for more congestive heart failure (OR, 1.8; P =.08). AAs had significantly more dose reductions in paclitaxel (P = 6.6 × 10−6). In AAs, dose reductions in paclitaxel had a significant negative impact on DFS (P =.03), whereas in EAs, dose reductions did not have an impact on outcome (P =.35). Conclusion: AAs had inferior DFS, with more clinically important toxicities, in ECOG-ACRIN-5103. The altered risk-to-benefit ratio for adjuvant breast cancer chemotherapy should lead to additional research with the focus on the impact of genetic ancestry on both efficacy and toxicity. Strategies to minimize dose reductions in paclitaxel, especially as the result of TIPN, are warranted for this population. [ABSTRACT FROM AUTHOR]

Purpose: Identification of single-gene biomarkers that are prognostic of outcome can shed new insights on the molecular mechanisms that drive breast cancer and other cancers. Methods: Exploratory analysis of 20,464 single-gene messenger RNAs (mRNAs) in the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC) discovery cohort indicates that low expression of FGD3 mRNA is prognostic for poor outcome. Prognostic significance of faciogenital dysplasia 3 (FGD3), SUSD3, and other single-gene proliferation markers was evaluated in breast cancer and The Cancer Genome Atlas (TCGA) cohorts. Results: A meta-analysis of Cox regression of FGD3 mRNA as a continuous variable for overall survival of estrogen receptor (ER)–positive samples in METABRIC discovery, METABRIC validation, TCGA breast cancer, and Combination Chemotherapy in Treating Women With Breast Cancer (E2197) cohorts resulted in a combined hazard ratio (HR) of 0.69 (95% CI, 0.63 to 0.75), indicating better outcome with high expression. In the ER-negative samples, the combined meta-analysis HR was 0.72 (95% CI, 0.63 to 0.82), suggesting that FGD3 is prognostic regardless of ER status. The potential of FGD3 as a biomarker for freedom from recurrence was evaluated in the Breast International Group 1-98 (BIG 1-98; Letrozole or Tamoxifen in Treating Postmenopausal Women With Breast Cancer) study (HR, 0.85; 95% CI, 0.76 to 0.93) for breast cancer–free interval. In the Hungarian Academy of Science (HAS) breast cancer cohort, splitting on the median had an HR of 0.49 (95% CI, 0.42 to 0.58) for recurrence-free survival. A comparison of the Stouffer P value in five ER-positive cohorts showed that FGD3 (P = 3.8E-14) outperformed MKI67 (P = 1.06E-8) and AURKA (P = 2.61E-5). A comparison of the Stouffer P value in four ER-negative cohorts showed that FGD3 (P = 3.88E-5) outperformed MKI67 (P =.477) and AURKA (P =.820). Conclusion: FGD3 was previously shown to inhibit cell migration. FGD3 mRNA is regulated by ESR1 and is associated with favorable outcome in six distinct breast cancer cohorts and four TCGA cancer cohorts. This suggests that FGD3 is an important clinical biomarker. [ABSTRACT FROM AUTHOR]

The article discusses the impact of community-based patient assistance programs on treating patients with breast cancer. It examines patients who engaged with the patient-assistance program, and determine that the intervention, and usual care patients gained high rates of adjuvant treatment. It adds that the community-based program assist patients to receive the required informational and psychosocial therapy.

Purpose: Black women experience higher rates of taxane-induced peripheral neuropathy (TIPN) compared with White women when receiving adjuvant once weekly paclitaxel for early-stage breast cancer, leading to more dose reductions and higher recurrence rates. EAZ171 aimed to prospectively validate germline predictors of TIPN and compare rates of TIPN and dose reductions in Black women receiving (neo)adjuvant once weekly paclitaxel and once every 3 weeks docetaxel for early-stage breast cancer., Methods: Women with early-stage breast cancer who self-identified as Black and had intended to receive (neo)adjuvant once weekly paclitaxel or once every 3 weeks docetaxel were eligible, with planned accrual to 120 patients in each arm. Genotyping was performed to determine germline neuropathy risk. Grade 2-4 TIPN by Common Terminology Criteria for Adverse Events (CTCAE) v5.0 was compared between high- versus low-risk genotypes and between once weekly paclitaxel versus once every 3 weeks docetaxel within 1 year. Patient-rated TIPN and patient-reported outcomes were compared using patient-reported outcome (PRO)-CTCAE and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity., Results: Two hundred and forty of 249 enrolled patients had genotype data, and 91 of 117 (77.8%) receiving once weekly paclitaxel and 87 of 118 (73.7%) receiving once every 3 weeks docetaxel were classified as high-risk. Physician-reported grade 2-4 TIPN was not significantly different in high- versus low-risk genotype groups with once weekly paclitaxel (47% v 35%; P = .27) or with once every 3 weeks docetaxel (28% v 19%; P = .47). Grade 2-4 TIPN was significantly higher in the once weekly paclitaxel versus once every 3 weeks docetaxel arm by both physician-rated CTCAE (45% v 29%; P = .02) and PRO-CTCAE (40% v 24%; P = .03). Patients receiving once weekly paclitaxel required more dose reductions because of TIPN (28% v 9%; P < .001) or any cause (39% v 25%; P = .02)., Conclusion: Germline variation did not predict risk of TIPN in Black women receiving (neo)adjuvant once weekly paclitaxel or once every 3 weeks docetaxel. Once weekly paclitaxel was associated with significantly more grade 2-4 TIPN and required more dose reductions than once every 3 weeks docetaxel.

Purpose: Patients with triple-negative breast cancer (TNBC) and residual invasive disease (RD) after completion of neoadjuvant chemotherapy (NAC) have a high-risk for recurrence, which is reduced by adjuvant capecitabine. Preclinical models support the use of platinum agents in the TNBC basal subtype. The EA1131 trial hypothesized that invasive disease-free survival (iDFS) would not be inferior but improved in patients with basal subtype TNBC treated with adjuvant platinum compared with capecitabine., Patients and Methods: Patients with clinical stage II or III TNBC with ≥ 1 cm RD in the breast post-NAC were randomly assigned to receive platinum (carboplatin or cisplatin) once every 3 weeks for four cycles or capecitabine 14 out of 21 days every 3 weeks for six cycles. TNBC subtype (basal v nonbasal) was determined by PAM50 in the residual disease. A noninferiority design with superiority alternative was chosen, assuming a 4-year iDFS of 67% with capecitabine., Results: Four hundred ten of planned 775 participants were randomly assigned to platinum or capecitabine between 2015 and 2021. After median follow-up of 20 months and 120 iDFS events (61% of full information) in the 308 (78%) patients with basal subtype TNBC, the 3-year iDFS for platinum was 42% (95% CI, 30 to 53) versus 49% (95% CI, 39 to 59) for capecitabine. Grade 3 and 4 toxicities were more common with platinum agents. The Data and Safety Monitoring Committee recommended stopping the trial as it was unlikely that further follow-up would show noninferiority or superiority of platinum., Conclusion: Platinum agents do not improve outcomes in patients with basal subtype TNBC RD post-NAC and are associated with more severe toxicity when compared with capecitabine. Participants had a lower than expected 3-year iDFS regardless of study treatment, highlighting the need for better therapies in this high-risk population., Competing Interests: Ingrid A. MayerConsulting or Advisory Role: Novartis, AstraZeneca, Lilly, Genentech, GlaxoSmithKline, Immunomedics, Macrogenics, Pfizer, AbbVie, Seattle Genetics, Puma Biotechnology, Cyclacel, Blueprint MedicinesResearch Funding: Novartis, Pfizer, Genentech Carlos L. ArteagaLeadership: American Association for Cancer ResearchStock and Other Ownership Interests: Provista Diagnostics, Y-Trap IncConsulting or Advisory Role: Novartis, Lilly, Sanofi, Radius Health, Taiho Pharmaceutical, Puma Biotechnology, Merck, H3 Biomedicine, Symphogen, Origimed, Petra Pharma, Third Rock Ventures, Immunomedics, Daiichi Sankyo, Athenex, G1 Therapeutics, Clovis OncologyResearch Funding: Puma Biotechnology, Pfizer, Lilly, Radius Health, Takeda, BayerOther Relationship: Susan G. Komen for the Cure William F. SymmansStock and Other Ownership Interests: ISIS Pharmaceuticals, Nuvera Biosciences, Delphi Diagnostics, Eiger BioPharmaceuticalsConsulting or Advisory Role: Merck, Almac DiagnosticsPatents, Royalties, Other Intellectual Property: Intellectual Property, Intellectual Property (expired)Travel, Accommodations, Expenses: Luminex, MerckUncompensated Relationships: Delphi Diagnostics Ben H. ParkLeadership: LoxoStock and Other Ownership Interests: Loxo, CelcuityHonoraria: AstraZenecaConsulting or Advisory Role: Horizon Discovery, Foundation Medicine, Loxo, Casdin Capital, H3 Biomedicine, Jackson Laboratory for Genomic Medicine, Lilly, Celcuity, Sermonix Pharmaceuticals, PathovaxResearch Funding: AbbVie, Pfizer, GE Healthcare, LillyPatents, Royalties, Other Intellectual Property: Royalties paid through inventions at Johns Hopkins University by Horizon Discovery LtdTravel, Accommodations, Expenses: Lilly, LoxoUncompensated Relationships: Tempus Amye J. TevaarwerkOther Relationship: Epic Systems Karen L. SmithStock and Other Ownership Interests: AbbVie, Abbott LaboratoriesHonoraria: ASiM CMEResearch Funding: Pfizer Margaret BlockConsulting or Advisory Role: Theranostics Health Bernard TawfikOther Relationship: Ipsen Lisa E. FlaumConsulting or Advisory Role: Seattle Genetics, NovartisSpeakers' Bureau: Seattle Genetics, Novartis, AstraZeneca Erica L. MayerConsulting or Advisory Role: Lilly, Novartis, Sanofi, Eisai, AstraZenecaResearch Funding: Pfizer William M. SikovHonoraria: UpToDateSpeakers' Bureau: Lilly, Daiichi Sankyo, Eisai, Seagen Lynne I. WagnerStock and Other Ownership Interests: Johnson & Johnson, Lilly, Gilead SciencesConsulting or Advisory Role: Celgene, AthenexTravel, Accommodations, Expenses: Celgene Angela M. DeMicheleResearch Funding: Pfizer, Genentech, Calithera Biosciences, Novartis Joseph A. SparanoStock and Other Ownership Interests: MetastatConsulting or Advisory Role: Genentech/Roche, Novartis, AstraZeneca, Celgene, Lilly, Celldex, Pfizer, Prescient Therapeutics, Juno Therapeutics, Merrimack, Adgero Biopharmaceuticals, Cardinal Health, GlaxoSmithKline, CStone Pharmaceuticals, Epic Sciences, Daiichi Sankyo, BMSiSpeakers' Bureau: Eisai, CertaraResearch Funding: Prescient Therapeutics, Deciphera, Genentech/Roche, Merck, Novartis, Merrimack, Radius Health, Olema PharmaceuticalsTravel, Accommodations, Expenses: Menarini Silicon Biosystems, Roche/Genentech, Adgero Biopharmaceuticals, Myriad Genetics, Pfizer, AstraZeneca, Rhenium Medical Antonio C. WolffConsulting or Advisory Role: Ionis PharmaceuticalsPatents, Royalties, Other Intellectual Property: Antonio Wolff has been named as inventor on one or more issued patents or pending patent applications relating to methylation in breast cancer, and has assigned his rights to JHU, and participates in a royalty sharing agreement with JHUOpen Payments Link: https://openpaymentsdata.cms.gov/physician/357301/summary Kathy D. MillerConsulting or Advisory Role: Merck, Genentech/Roche, Athenex, AstraZeneca, Bristol Myers Squibb/CelgeneResearch Funding: Taiho Pharmaceutical, Novartis, Seattle Genetics, Pfizer, Astex Pharmaceuticals, British Biotech, CytomX TherapeuticsNo other potential conflicts of interest were reported.

Purpose: The aim of this study was to review the current status of clinical trials for HIV-associated malignancies in people living with HIV in sub-Saharan Africa (SSA) and efforts made by the AIDS Malignancy Consortium (AMC) to build capacity in SSA for HIV malignancy research., Methods: All malignancy-related clinical trials in 49 SSA countries on ClinicalTrials.gov were reviewed and evaluated for inclusion and exclusion criteria pertaining to HIV status. Additional studies by AMC in SSA were compiled from Web-based resources, and narrative summaries were prepared to highlight AMC capacity building and training initiatives., Results: Of 96 cancer trials identified in SSA, only 11 focused specifically on people living with HIV, including studies in Kaposi sarcoma, cervical dysplasia and cancer, non-Hodgkin lymphoma, and ocular surface squamous neoplasia. Recognizing the increasing cancer burden in the region, AMC expanded its clinical trial activities to SSA in 2010, with 4 trials completed to date and 6 others in progress or development, and has made ongoing investments in developing research infrastructure in the region., Conclusion: As the HIV-associated malignancy burden in SSA evolves, research into this domain has been limited. AMC, the only global HIV malignancy-focused research consortium, not only conducts vital HIV-associated malignancies research in SSA, but also develops pathology, personnel, and community-based infrastructure to meet these challenges in SSA. Nonetheless, there is an ongoing need to build on these efforts to improve HIV-associated malignancies outcomes in SSA., Competing Interests: The opinions expressed in this article are the authors own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States Government. The other authors report no proprietary or commercial conflicts of interest with respect to any product mentioned or concept discussed in the present work.

Purpose: Racial disparity in breast cancer outcomes exists between African American and Caucasian women in the United States. We have evaluated the impact of genetically determined ancestry on disparity in efficacy and therapy-induced toxicity for breast cancer patients in the context of a randomized, phase III adjuvant trial., Patients and Methods: This study compared outcomes between 386 patients of African ancestry (AA) and 2473 patients of European ancestry (EA) in a randomized, phase III breast cancer trial; ECOG-ACRIN-E5103. The primary efficacy endpoint, invasive disease free survival (DFS) and clinically significant toxicities were compared including: anthracycline-induced congestive heart failure (CHF), taxane-induced peripheral neuropathy (TIPN), and bevacizumab-induced hypertension., Results: Overall, AAs had significantly inferior DFS (p=0.002; HR=1.5) compared with EAs. This was significant in the estrogen receptor-positive subgroup (p=0.03); with a similar, non-significant trend for those who had triple negative breast cancer (TNBC; p=0.12). AAs also had significantly more grade 3-4 TIPN (OR=2.9; p=2.4 ×10 -11 ) and grade 3-4 bevacizumab-induced hypertension (OR=1.6; p=0.02), with a trend for more CHF (OR=1.8; p=0.08). AAs had significantly more dose reductions for paclitaxel (p=6.6 ×10 -6 ). In AAs, dose reductions in paclitaxel had a significant negative impact on DFS (p=0.03); whereas in EAs, dose reductions did not impact outcome (p=0.35)., Conclusion: AAs had inferior DFS with more clinically important toxicities in ECOG-ACRIN-E5103. The altered risk to benefit ratio for adjuvant breast cancer chemotherapy should lead to additional research with the focus centered on the impact of genetic ancestry on both efficacy and toxicity. Strategies to minimize dose reductions for paclitaxel, especially due to TIPN, are warranted for this population.

Breast cancer is a heterogeneous disease associated with variable clinical outcomes despite standard local therapy for the primary tumor and systemic adjuvant therapy to prevent distant recurrence. Management decisions are typically made using classical prognostic and predictive clinicopathologic factors, and more recently gene expression profiling assays are commonly used in practice. Recent advances in genomic sequencing-often referred to collectively as next-generation sequencing (NGS)-have facilitated more in-depth evaluation of the cancer genome than could be afforded by the initial generation of gene expression studies, including DNA single nucleotide variants, small insertions and deletions, structural alterations, and copy number alterations (CNAs). In addition, this information has been integrated with other molecular profiling methods of processes that affect gene transcription (e.g., epigenetic, microRNA) and protein expression-the ultimate readout of the genetic code. Although NGS has provided new insights on the classification of breast cancer and identified potential predictive biomarkers and novel targets, there are formidable logistical and scientific obstacles that must be addressed before the promise of this technology is fully realized.

Purpose: We sought to determine whether the combination of ixabepilone plus capecitabine improved overall survival (OS) compared with capecitabine alone in patients with metastatic breast cancer (MBC) previously treated with anthracyclines and taxanes., Patients and Methods: A total of 1,221 patients with MBC previously treated with anthracycline and taxanes were randomly assigned to ixabepilone (40 mg/m(2) intravenously on day 1) plus capecitabine (2,000 mg/m(2) orally on days 1 through 14) or capecitabine alone (2,500 mg/m(2) on the same schedule) given every 21 days. The trial was powered to detect a 20% reduction in the hazard ratio (HR) for death., Results: There was no significant difference in OS between the combination and capecitabine monotherapy arm, the primary end point (median, 16.4 v 15.6 months; HR = 0.9; 95% CI, 078 to 1.03; P = .1162). The arms were well balanced with the exception of a higher prevalence of impaired performance status (Karnofsky performance status 70% to 80%) in the combination arm (32% v 25%). In a secondary Cox regression analysis adjusted for performance status and other prognostic factors, OS was improved for the combination (HR = 0.85; 95% CI, 0.75 to 0.98; P = .0231). In 79% of patients with measurable disease, the combination significantly improved progression-free survival (PFS; median, 6.2 v 4.2 months; HR = 0.79; P = .0005) and response rate (43% v 29%; P < .0001). Grade 3 to 4 neuropathy occurred in 24% treated with the combination, but was reversible., Conclusion: This study confirmed a previous trial demonstrating improved PFS and response for the ixabepilone-capecitabine combination compared with capecitabine alone, although this did not result in improved survival.

Purpose: Diffuse large B-cell lymphoma (DLBCL) represents a clinically heterogeneous disease. Models based on immunohistochemistry predict clinical outcome. These include subdivision into germinal center (GC) versus non-GC subtypes; proliferation index (measured by expression of Ki-67), and expression of BCL-2, FOXP1, or B-lymphocyte-induced maturation protein (Blimp-1)/PRDM1. We sought to determine whether immunohistochemical analyses of biopsies from patients with DLBCL having HIV infection are similarly relevant for prognosis., Patients and Methods: We examined 81 DLBCLs from patients with AIDS in AMC010 (cyclophosphamide, doxorubicin, vincristine, and prednisone [CHOP] v CHOP-rituximab) and AMC034 (etoposide, doxorubicin, vincristine, prednisone, and dose-adjusted cyclophosphamide plus rituximab concurrent v sequential) clinical trials and compared the immunophenotype with survival data, Epstein-Barr virus (EBV) positivity, and CD4 counts., Results: The GC and non-GC subtypes of DLBCL did not differ significantly with respect to overall survival or CD4 count at cancer presentation. EBV could be found in both subtypes of DLBCL, although less frequently in the GC subtype, and did not affect survival. Expression of FOXP1, Blimp-1/PRDM1, or BCL-2 was not correlated with the outcome in patients with AIDS-related DLBCL., Conclusion: These data indicate that with current treatment strategies for lymphoma and control of HIV infection, commonly used immunohistochemical markers may not be clinically relevant in HIV-infected patients with DLBCL. The only predictive immunohistochemical marker was found to be Ki-67, where a higher proliferation index was associated with better survival, suggesting a better response to therapy in patients whose tumors had higher proliferation rates.

Purpose: To determine whether the combination of pegylated liposomal doxorubicin (PLD) and docetaxel significantly prolongs time to disease progression compared with docetaxel alone without an increase in cardiac toxicity in women with advanced breast cancer who had experienced relapse at least 1 year after prior adjuvant or neoadjuvant anthracycline therapy., Patients and Methods: This international, phase III study randomly assigned 751 patients to receive either docetaxel 75 mg/m(2) (n = 373) or PLD 30 mg/m(2) followed by docetaxel 60 mg/m(2) every 21 days (n = 378) and continued until disease progression or prohibitive toxicity. The primary end point was time to progression (TTP). Secondary end points were overall survival (OS), objective response rate (ORR), cardiac toxicity, and safety., Results: Treatment with PLD-docetaxel significantly improved median TTP from 7.0 to 9.8 months (hazard ratio [HR] = 0.65; 95% CI, 0.55 to 0.77; P = .000001) and the ORR from 26% to 35% (P = .0085). OS was similar between the two groups (HR = 1.02; 95% CI, 0.86 to 1.22). The incidence of grade 3 or 4 adverse events were similar (78% v 72%), although a higher incidence of hand-foot syndrome (24% v 0%) and mucositis/stomatitis (12% v 1%) were observed in the PLD-docetaxel combination. Protocol-defined left ventricular ejection fraction decreases and congestive heart failure were reported in 5% and 1% in both treatment arms, respectively., Conclusion: The PLD-docetaxel combination was more effective than docetaxel alone in women with metastatic breast cancer who had experienced relapse at least 1 year after prior adjuvant anthracycline therapy without an increase in cardiac toxicity, although mucocutaneous toxicity was more common.

Purpose: Adjuvant! is a standardized validated decision aid that projects outcomes in operable breast cancer based on classical clinicopathologic features and therapy. Genomic classifiers offer the potential to more accurately identify individuals who benefit from chemotherapy than clinicopathologic features., Patients and Methods: A sample of 465 patients with hormone receptor (HR) -positive breast cancer with zero to three positive axillary nodes who did (n = 99) or did not have recurrence after chemohormonal therapy had tumor tissue evaluated using a 21-gene assay. Histologic grade and HR expression were evaluated locally and in a central laboratory., Results: Recurrence Score (RS) was a highly significant predictor of recurrence, including node-negative and node-positive disease (P < .001 for both) and when adjusted for other clinical variables. RS also predicted recurrence more accurately than clinical variables when integrated by an algorithm modeled after Adjuvant! that was adjusted to 5-year outcomes. The 5-year recurrence rate was only 5% or less for the estimated 46% of patients who have a low RS (< 18)., Conclusion: The 21-gene assay was a more accurate predictor of relapse than standard clinical features for individual patients with HR-positive operable breast cancer treated with chemohormonal therapy and provides information that is complementary to features typically used in anatomic staging, such as tumor size and lymph node involvement. The 21-gene assay may be used to select low-risk patients for abbreviated chemotherapy regimens similar to those used in our study or high-risk patients for more aggressive regimens or clinical trials evaluating novel treatments.

Purpose: Central and local laboratory concordance for hormone receptor measurement is therapeutically important. This study compares estrogen receptor (ER) and progesterone receptor (PR) measured by local laboratory immunohistochemistry (IHC), central IHC, and central reverse-transcriptase polymerase chain reaction (RT-PCR) using a proprietary 21-gene assay., Patients and Methods: A case-control sample of 776 breast cancer patients from Eastern Cooperative Oncology Group (ECOG) study E2197 was evaluated. Central IHC Allred score for ER and PR was obtained using tissue microarrays and 1D5 ER antibody and 636 PR antibody. Quantitative RT-PCR for ER and PR in whole sections was performed using the 21-gene assay., Results: For ER, the concordance between local and central IHC was 90% (95% CI, 88% to 92%), between local IHC and central RT-PCR was 91% (95% CI, 89% to 93%), and between central IHC and central RT-PCR was 93% (95% CI, 91% to 95%). For PR, the concordance between local IHC and central IHC was 84% (95% CI, 82% to 87%), between local IHC and central RT-PCR was 88% (95% CI, 85% to 90%), and between central IHC and central RT-PCR was 90% (95% CI, 88% to 92%). Although concordance was high, IHC ER-negative cases that were RT-PCR positive were more common than IHC ER-positive cases that were RT-PCR negative. In ER-positive patients, ER expression by central IHC Allred score was marginally associated with recurrence (P = .091), and ER expression by central RT-PCR was significantly associated with recurrence (P = .014). However, recurrence score, which incorporates additional genes/pathways, was a highly significant predictor of recurrence (P < .0001)., Conclusion: There is a high degree of concordance among local IHC, central IHC, and central RT-PCR by the proprietary gene assay for ER and PR status. Although ER expression is marginally associated with relapse in ER-positive patients treated with chemohormonal therapy, recurrence score is a highly significant predictor of recurrence.

Several multigene markers that predict relapse more accurately than classical clinicopathologic features have been developed. The 21-gene assay was developed specifically for patients with estrogen receptor (ER)-positive breast cancer, and has been shown to predict distant recurrence more accurately that classical clinicopathologic features in patients with ER-positive breast cancer and negative axillary nodes treated with adjuvant tamoxifen; validation studies in this population led to its approval as a diagnostic test. In a similar population, it also may be used to assess the benefit of adding chemotherapy to hormonal therapy. Other validation studies indicate that it also predicts the risk of distant and local recurrence in other populations with ER-positive disease, including node-negative patients receiving no adjuvant therapy and patients with positive axillary nodes treated with doxorubicin-containing chemotherapy. The Trial Assigning Individualized Options for Treatment (TAILORx) is multicenter trial that integrates the 21-gene assay into the clinical decision-making process and is designed to refine the utility of the assay in clinical practice and to provide a resource for evaluating additional molecular markers as they are developed in the future.

Purpose: This study examines the impact of yoga, including physical poses, breathing, and meditation exercises, on quality of life (QOL), fatigue, distressed mood, and spiritual well-being among a multiethnic sample of breast cancer patients., Patients and Methods: One hundred twenty-eight patients (42% African American, 31% Hispanic) recruited from an urban cancer center were randomly assigned (2:1 ratio) to a 12-week yoga intervention (n = 84) or a 12-week waitlist control group (n = 44). Changes in QOL (eg, Functional Assessment of Cancer Therapy) from before random assignment (T1) to the 3-month follow-up (T3) were examined; predictors of adherence were also assessed. Nearly half of all patients were receiving medical treatment., Results: Regression analyses indicated that the control group had a greater decrease in social well-being compared with the intervention group after controlling for baseline social well-being and covariates (P < .0001). Secondary analyses of 71 patients not receiving chemotherapy during the intervention period indicated favorable outcomes for the intervention group compared with the control group in overall QOL (P < .008), emotional well-being (P < .015), social well-being (P < .004), spiritual well-being (P < .009), and distressed mood (P < .031). Sixty-nine percent of intervention participants attended classes (mean number of classes attended by active class participants = 7.00 +/- 3.80), with lower adherence associated with increased fatigue (P < .001), radiotherapy (P < .0001), younger age (P < .008), and no antiestrogen therapy (P < .02)., Conclusion: Despite limited adherence, this intent-to-treat analysis suggests that yoga is associated with beneficial effects on social functioning among a medically diverse sample of breast cancer survivors. Among patients not receiving chemotherapy, yoga appears to enhance emotional well-being and mood and may serve to buffer deterioration in both overall and specific domains of QOL.

Purpose: Standardized definitions of breast cancer clinical trial end points must be adopted to permit the consistent interpretation and analysis of breast cancer clinical trials and to facilitate cross-trial comparisons and meta-analyses. Standardizing terms will allow for uniformity in data collection across studies, which will optimize clinical trial utility and efficiency. A given end point term (eg, overall survival) used in a breast cancer trial should always encompass the same set of events (eg, death attributable to breast cancer, death attributable to cause other than breast cancer, death from unknown cause), and, in turn, each event within that end point should be commonly defined across end points and studies., Methods: A panel of experts in breast cancer clinical trials representing medical oncology, biostatistics, and correlative science convened to formulate standard definitions and address the confusion that nonstandard definitions of widely used end point terms for a breast cancer clinical trial can generate. We propose standard definitions for efficacy end points and events in early-stage adjuvant breast cancer clinical trials. In some cases, it is expected that the standard end points may not address a specific trial question, so that modified or customized end points would need to be prospectively defined and consistently used., Conclusion: The use of the proposed common end point definitions will facilitate interpretation of trial outcomes. This approach may be adopted to develop standard outcome definitions for use in trials involving other cancer sites.

Purpose: To determine the recommended phase II dose (RPTD) of the farnesyltransferase (FTase) inhibitor tipifarnib when combined with doxorubicin and cyclophosphamide (AC) in patients with advanced breast cancer, the pathologic complete response (pCR) rate after preoperative treatment with four cycles of the combination in locally advanced breast cancer (LABC), and the effect of tipifarnib on primary tumor FTase enzyme activity in vivo., Patients and Methods: Thirty-two patients with metastatic breast cancer (n = 11) or LABC (n = 21) received AC (doxorubicin 60 mg/m2 and cyclophosphamide 600 mg/m2) administered intravenously on day 1 plus tipifarnib (100, 200, or 300 mg bid for 6 to 14 days) without (n = 2) or with (n = 30) granulocyte colony-stimulating factor (G-CSF) for up to four cycles. Patients with LABC underwent surgery after up to four cycles of the combination., Results: When combined with AC every 2 weeks plus G-CSF, the RPTD of tipifarnib was 200 mg bid administered on days 2 to 7. Seven (33%) of 21 patients (95% CI, 15% to 55%) with LABC treated with up to four cycles of the combination at the RPTD had a pCR in the breast at surgery. The five patients had serial biopsies that demonstrated at least 50% FTase enzyme inhibition in the primary tumor (median, 100%; range, 55% to 100%) after tipifarnib., Conclusion: Tipifarnib may be safely combined with dose-dense AC using a dose and schedule that significantly inhibits FTase enzyme activity in human breast cancer in vivo and may enhance the pCR rate after four cycles of preoperative dose-dense AC.

Purpose: To determine whether a matrix metalloproteinase inhibitor improves progression-free survival (PFS) in patients with metastatic breast cancer who have responding or stable disease after first-line chemotherapy., Patients and Methods: One hundred seventy-nine eligible patients were randomly assigned to receive oral marimastat (10 mg bid; n = 114) or a placebo (n = 65) within 3 to 6 weeks of completing six to eight cycles of first-line doxorubicin- and/or taxane-containing chemotherapy for metastatic disease. Patients were evaluated every 3 months until disease progression., Results: When comparing placebo with marimastat, there was no significant difference in PFS (median, 3.1 months v 4.7 months, respectively; hazard ratio, 1.26; 95% CI, 0.91 to 1.74; P = .16) or overall survival (median, 26.6 months v 24.7 months, respectively; hazard ratio, 1.03; 95% CI, 0.73 to 1.46; P = .86). Patients treated with marimastat were more likely to develop grade 2 or 3 musculoskeletal toxicity (MST), a known complication of the drug indicative of achieving a biologic effect, compared with patients administered placebo (63% v 22%, respectively; P < .0001). Patients with grade 2 or 3 MST had significantly inferior survival compared with patients who had grade 0 or 1 MST (median, 22.5 months v 28.2 months; P = .04). In addition, patients who had a marimastat plasma concentration of at least 10 ng/mL at month 1 and/or 3 were significantly more likely to have grade 2 to 3 MST (P < .0001)., Conclusion: Marimastat does not prolong PFS when used after first-line chemotherapy for metastatic breast cancer. Patients with higher marimastat levels exhibited MST, and MST was associated with inferior survival.

Purpose: To determine the effectiveness of an infusional chemotherapy regimen in patients with HIV-associated lymphoma treated before and after the use of highly active antiretroviral therapy (HAART) in routine clinical practice., Patients and Methods: Ninety-eight assessable patients with HIV-associated intermediate- or high-grade non-Hodgkin's lymphoma received cyclophosphamide 200 mg/m(2)/d, doxorubicin 12.5 mg/m(2)/d, and etoposide 60 mg/m(2)/d (CDE) given by continuous intravenous infusion for 4 days (96 hours) every 4 weeks plus filgrastim. Concurrent antiretroviral treatment consisted of the nucleoside analog didanosine in the first 43 patients enrolled before December 1996 (pre-HAART group), or HAART in the remaining 55 patients enrolled after that time (HAART group)., Results: Complete response occurred in 44 patients (45%; 95% CI, 35% to 55%). Failure-free survival and overall survival (OS) at 2 years was 36% (95% CI, 26% to 46%) and 43% (95% CI, 33% to 53%), respectively. At the time of the analysis, 30% in the pre-HAART group were alive compared with 47% in the HAART group; when adjusted for varying length of follow-up, patients in the HAART group had improved OS (P =.039). Patients in the HAART group experienced less grade 4 nonhematologic toxicity (22% v 42%; P =.037), thrombocytopenia (31% v 52%; P =.033), and anemia (9% v 27%; P =.021), and had fewer treatment-associated deaths (0% v 10%; P =.013)., Conclusion: Infusional CDE is an effective and potentially curative regimen for patients with HIV-associated lymphoma. Patients treated in the HAART era have less chemotherapy-associated toxicity and improved survival.