Race, Gene Expression Signatures, and Clinical Outcomes of Patients With High-Risk Early Breast Cancer.

Importance: There has been little consideration of genomic risk of recurrence by breast cancer subtype despite evidence of racial disparities in breast cancer outcomes.

Objective: To evaluate associations between clinical trial end points, namely pathologic complete response (pCR) and distant recurrence-free survival (DRFS), and race and examine whether gene expression signatures are associated with outcomes by race.

Design, Setting, And Participants: This retrospective cohort study used data from the Investigation of Serial Studies to Predict Your Therapeutic Response With Imaging and Molecular Analysis 2 (I-SPY 2) multicenter clinical trial of neoadjuvant chemotherapy with novel agents and combinations for patients with previously untreated stage II/III breast cancer.

Safety and efficacy of HSP90 inhibitor ganetespib for neoadjuvant treatment of stage II/III breast cancer.

HSP90 inhibitors destabilize oncoproteins associated with cell cycle, angiogenesis, RAS-MAPK activity, histone modification, kinases and growth factors. We evaluated the HSP90-inhibitor ganetespib in combination with standard chemotherapy in patients with high-risk early-stage breast cancer. I-SPY2 is a multicenter, phase II adaptively randomized neoadjuvant (NAC) clinical trial enrolling patients with stage II-III breast cancer with tumors 2.

Cardiac mechanisms for low aerobic power in anthracycline treated, older, long-term breast cancer survivors.

Breast cancer survivors have reduced peak aerobic capacity (VO) which may be related to latent or lingering chemotherapy induced cardiac damage. Nine, older (67 ± 3 years), long-term survivors (9.8 years) of anthracycline based chemotherapy and age- and sex-matched healthy controls were recruited and tested to determine whether: i) VO remains reduced in long-term survivorship; and ii) reductions in VO are due to cardiac dysfunction.

Neoadjuvant T-DM1/pertuzumab and paclitaxel/trastuzumab/pertuzumab for HER2 breast cancer in the adaptively randomized I-SPY2 trial.

HER2-targeted therapy dramatically improves outcomes in early breast cancer. Here we report the results of two HER2-targeted combinations in the neoadjuvant I-SPY2 phase 2 adaptive platform trial for early breast cancer at high risk of recurrence: ado-trastuzumab emtansine plus pertuzumab (T-DM1/P) and paclitaxel, trastuzumab and pertuzumab (THP). Eligible women have >2.

A Multicenter Phase II Trial of Ipilimumab and Nivolumab in Unresectable or Metastatic Metaplastic Breast Cancer: Cohort 36 of Dual Anti-CTLA-4 and Anti-PD-1 Blockade in Rare Tumors (DART, SWOG S1609).

Purpose: Metaplastic breast cancer (MpBC) is a rare aggressive subtype that responds poorly to cytotoxics. Median survival is approximately 8 months for metastatic disease. We report results for advanced MpBC treated with ipilimumab + nivolumab, a cohort of S1609 for rare cancers (DART: NCT02834013).

Preliminary Results of Multi-Institutional Phase 1 Dose Escalation Trial Using Single-Fraction Stereotactic Partial Breast Irradiation for Early Stage Breast Cancer.

Purpose: We report on our early experience of our prospective multicenter phase 1 dose- escalation study of single-fraction stereotactic partial breast irradiation (S-PBI) for early stage breast cancer after partial mastectomy using a robotic stereotactic radiation system.

Methods And Materials: Thirty women with in situ or invasive breast cancer stage 0, I, or II with tumor size <3 cm treated with lumpectomy were enrolled in this phase 1 single-fraction S-PBI dose-escalation trial. Women received either 22.

Ganitumab and metformin plus standard neoadjuvant therapy in stage 2/3 breast cancer.

I-SPY2 is an adaptively randomized phase 2 clinical trial evaluating novel agents in combination with standard-of-care paclitaxel followed by doxorubicin and cyclophosphamide in the neoadjuvant treatment of breast cancer. Ganitumab is a monoclonal antibody designed to bind and inhibit function of the type I insulin-like growth factor receptor (IGF-1R). Ganitumab was tested in combination with metformin and paclitaxel (PGM) followed by AC compared to standard-of-care alone.

Assessment of Residual Cancer Burden and Event-Free Survival in Neoadjuvant Treatment for High-risk Breast Cancer: An Analysis of Data From the I-SPY2 Randomized Clinical Trial.

Importance: Residual cancer burden (RCB) distributions may improve the interpretation of efficacy in neoadjuvant breast cancer trials.

Objective: To compare RCB distributions between randomized control and investigational treatments within subtypes of breast cancer and explore the relationship with survival.

Design, Setting, And Participants: The I-SPY2 is a multicenter, platform adaptive, randomized clinical trial in the US that compares, by subtype, investigational agents in combination with chemotherapy vs chemotherapy alone in adult women with stage 2/3 breast cancer at high risk of early recurrence.

Efficacy of Neratinib Plus Capecitabine in the Subgroup of Patients with Central Nervous System Involvement from the NALA Trial.

Background: Neratinib has efficacy in central nervous system (CNS) metastases from HER2-positive metastatic breast cancer (MBC). We report outcomes among patients with CNS metastases at baseline from the phase III NALA trial of neratinib plus capecitabine (N + C) versus lapatinib plus capecitabine (L + C).

Materials And Methods: NALA was a randomized, active-controlled trial in patients who received two or more previous HER2-directed regimens for HER2-positive MBC.

A Phase I/Ib Trial of PD 0332991 (Palbociclib) and T-DM1 in HER2-Positive Advanced Breast Cancer After Trastuzumab and Taxane Therapy.

Background: Preclinical breast cancer models with acquired HER2 resistance exhibit decreased proliferation with CDK4/6 inhibition in tumors with intact Rb and low p16 levels. Adding cytotoxic agents like T-DM1 enhances the inhibitory CDK4/6 cytostatic effect.

Patients And Methods: A phase I/Ib 3+3 dose escalation/expansion trial of palbociclib and T-DM1 identified 150 mg on days 5 to 18 as the palbociclib maximal tolerated dose combined with day 1 intravenous T-DM1 in 21-day treatment cycles.

Electronic Health Records-Based Cardio-Oncology Registry for Care Gap Identification and Pragmatic Research: Procedure and Observational Study.

Background: Professional society guidelines are emerging for cardiovascular care in cancer patients. However, it is not yet clear how effectively the cancer survivor population is screened and treated for cardiomyopathy in contemporary clinical practice. As electronic health records (EHRs) are now widely used in clinical practice, we tested the hypothesis that an EHR-based cardio-oncology registry can address these questions.

Cosmetic Outcomes of a Phase 1 Dose Escalation Study of 5-Fraction Stereotactic Partial Breast Irradiation for Early Stage Breast Cancer.

Purpose: Our purpose was to evaluate cosmetic changes after 5-fraction adjuvant stereotactic partial breast irradiation (S-PBI).

Methods And Materials: Seventy-five women with in situ or invasive breast cancer stage 0, I, or II, with tumor size ≤3 cm, were enrolled after lumpectomy in a phase 1 dose escalation trial of S-PBI into cohorts receiving 30, 32.5, 35, 37.

Neratinib Plus Capecitabine Versus Lapatinib Plus Capecitabine in HER2-Positive Metastatic Breast Cancer Previously Treated With ≥ 2 HER2-Directed Regimens: Phase III NALA Trial.

Purpose: NALA (ClinicalTrials.gov identifier: NCT01808573) is a randomized, active-controlled, phase III trial comparing neratinib, an irreversible pan-HER tyrosine kinase inhibitor (TKI), plus capecitabine (N+C) against lapatinib, a reversible dual TKI, plus capecitabine (L+C) in patients with centrally confirmed HER2-positive, metastatic breast cancer (MBC) with ≥ 2 previous HER2-directed MBC regimens.

Methods: Patients, including those with stable, asymptomatic CNS disease, were randomly assigned 1:1 to neratinib (240 mg once every day) plus capecitabine (750 mg/m twice a day 14 d/21 d) with loperamide prophylaxis, or to lapatinib (1,250 mg once every day) plus capecitabine (1,000 mg/m twice a day 14 d/21 d).

Risk Factors for Fat Necrosis After Stereotactic Partial Breast Irradiation for Early-Stage Breast Cancer in a Phase 1 Clinical Trial.

Purpose: This study reports predictive dosimetric and physiologic factors for fat necrosis after stereotactic-partial breast irradiation (S-PBI).

Methods And Materials: Seventy-five patients with ductal carcinoma-in situ or invasive nonlobular epithelial histologies stage 0, I, or II, with tumor size <3 cm were enrolled in a dose-escalation, phase I S-PBI trial between January 2011 and July 2015. Fat necrosis was evaluated clinically at each follow-up.

Cytogenomic characterization of double minute heterogeneity in therapy related acute myeloid leukemia.

Breast cancer patients treated with adjuvant chemotherapy regimens containing alkylating agents and anthracyclines are at an increased risk for secondary myeloid malignancies, either acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Complex genomic changes (karyotypes and/or gene amplification) accompany the development of the secondary neoplasms. Here we present a unique case of a breast cancer patient who developed secondary AML within 18 months of treatment with trastuzumab, pertuzumab, docetaxel, carboplatin (TCHP) and radiation.

Novel hyaluronan formulation for preventing acute skin reactions in breast during radiotherapy: a randomized clinical trial.

Purpose: We conducted a randomized, double-blind, vehicle-controlled clinical trial to investigate the use of a new proprietary hyaluronan (HA) formulation for the prevention of acute skin toxicity in breast cancer patients undergoing radiotherapy (RT).

Methods: Thirty women with breast cancer undergoing whole breast RT were enrolled. Each patient was randomly assigned to HA formulation (study cream, S) on the medial or lateral half of the irradiated breast and the control cream (placebo, P) on the other half.

Combined Targeting of Estrogen Receptor Alpha and XPO1 Prevent Akt Activation, Remodel Metabolic Pathways and Induce Autophagy to Overcome Tamoxifen Resistance.

A majority of breast cancer specific deaths in women with ERα (+) tumors occur due to metastases that are resistant to endocrine therapy. There is a critical need for novel therapeutic approaches to resensitize recurrent ERα (+) tumors to endocrine therapies. The objective of this study was to elucidate mechanisms of improved effectiveness of combined targeting of ERα and the nuclear transport protein XPO1 in overcoming endocrine resistance.

Blocking Monocytic Myeloid-Derived Suppressor Cell Function via Anti-DC-HIL/GPNMB Antibody Restores the Integrity of T Cells from Cancer Patients.

Purpose: Blocking the function of myeloid-derived suppressor cells (MDSC) is an attractive approach for cancer immunotherapy. Having shown DC-HIL/GPNMB to be the T-cell-inhibitory receptor mediating the suppressor function of MDSCs, we evaluated the potential of anti-DC-HIL mAb as an MDSC-targeting cancer treatment.

Experimental Design: Patients with metastatic cancer ( = 198) were analyzed by flow cytometry for DC-HIL or PDL1 expression on blood CD14HLA-DR MDSCs.

The Promoting Activity in Cancer Survivors (PACES) trial: a multiphase optimization of strategy approach to increasing physical activity in breast cancer survivors.

Background: Despite the significant, empirically supported benefits of physical activity, the majority of breast cancer survivors do not meet recommended guidelines for physical activity. A variety of effective strategies to increase physical activity in breast cancer survivors have been identified. However, it is unknown which of these strategies is most effective or how these strategies might be combined to optimize intervention effectiveness.

Randomized Phase II Trial of Fulvestrant Plus Everolimus or Placebo in Postmenopausal Women With Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer Resistant to Aromatase Inhibitor Therapy: Results of PrE0102.

Purpose The mammalian target of rapamycin inhibitor everolimus targets aberrant signaling through the PI3K/AKT/mammalian target of rapamycin pathway, a mechanism of resistance to anti-estrogen therapy in estrogen receptor (ER)-positive breast cancer. We hypothesized that everolimus plus the selective ER downregulator fulvestrant would be more efficacious than fulvestrant alone in ER-positive metastatic breast cancer resistant to aromatase inhibitor (AI) therapy. Patients and Methods This randomized, double-blind, placebo-controlled, phase II study included 131 postmenopausal women with ER-positive, human epidermal growth factor receptor 2-negative, AI-resistant metastatic breast cancer randomly assigned to fulvestrant (500 mg days 1 and 15 of cycle 1, then day 1 of cycles 2 and beyond) plus everolimus or placebo.

Isolated Contralateral Axillary Lymph Node Involvement in Breast Cancer Represents a Locally Advanced Disease Not Distant Metastases.

Background: Breast cancer metastases to an ipsilateral supraclavicular lymph node is assigned a N3 status in the TNM system and thus classified as stage III disease in the American Joint Commission on Cancer staging manual. Breast cancer metastatic to contralateral axillary lymph node (CAM) without metastases to any other distant organ is currently assigned M1 status (stage IV) instead of N3 (stage III).

Patients And Methods: We retrospectively reviewed the medical records of breast cancer patients diagnosed with CAM for their clinical presentation, pathologic diagnoses, treatment, and follow-up data.

Preliminary Results of a Phase 1 Dose-Escalation Trial for Early-Stage Breast Cancer Using 5-Fraction Stereotactic Body Radiation Therapy for Partial-Breast Irradiation.

Purpose: To evaluate the tolerability of a dose-escalated 5-fraction stereotactic body radiation therapy for partial-breast irradiation (S-PBI) in treating early-stage breast cancer after partial mastectomy; the primary objective was to escalate dose utilizing a robotic stereotactic radiation system treating the lumpectomy cavity without exceeding the maximum tolerated dose.

Methods And Materials: Eligible patients included those with ductal carcinoma in situ or invasive nonlobular epithelial histologies and stage 0, I, or II, with tumor size <3 cm. Patients and physicians completed baseline and subsequent cosmesis outcome questionnaires.