Impact of the 21-Gene Recurrence Score Assay on Treatment Decisions and Cost in Patients with Node-Positive Breast Cancer: A Multicenter Study in Quebec.

Background: The 21-gene Breast Recurrence Score (RS) assay, "the assay", has led to a paradigm shift for patients with hormone receptor-positive, node-negative early breast cancer and is emerging as an important tool to assist physician-patient decisions in foregoing chemotherapy in node-positive patients. We wanted to better understand the impact of the RS assay in node-positive patients upon physician treatment decisions and treatment cost in Quebec, Canada.

Patients And Methods: We conducted a multicenter, prospective observational trial for Estrogen/Progesterone Receptor (ER/PR)- positive, Human Epidermal Growth Factor Receptor 2 (HER2)-negative breast cancer patients with 1-3 positive lymph nodes.

Behavioral and health outcomes from the NRG Oncology/NSABP B-36 trial comparing two different adjuvant therapy regimens for early-stage node-negative breast cancer.

Background: The NSABP B-36 compared four cycles of doxorubicin and cyclophosphamide (AC) with six cycles of 5-fluorouracil, epirubicin, and cyclophosphamide (FEC-100) in node-negative early-stage breast cancer. A sub-study within B-36, focusing on symptoms, quality of life (QOL), menstrual history (MH), and cardiac function (CF) was conducted.

Patients And Methods: Patients completed the QOL questionnaire at baseline, during treatment, and every 6 months through 36 months.

Amplification and Adjuvant Clodronate Outcomes in Early-Stage Breast Cancer in NSABP B-34 and Potential Impact on Clinical Practice.

Background: The Adjuvant Zoledronic Acid (ZA) study in early breast cancer (AZURE) showed correlation between a nonamplified gene in the primary tumor and benefit from adjuvant ZA. Adverse ZA outcomes occurred in MAF-amplified patients. NSABP B-34 is a validation study.

Prognostic and predictive value of circulating tumor DNA during neoadjuvant chemotherapy for triple negative breast cancer.

Response to neoadjuvant chemotherapy (NAC) in triple negative breast cancer (TNBC) is highly prognostic and determines whether adjuvant chemotherapy is needed if residual tumor is found at surgery. To evaluate the predictive and prognostic values of circulating tumor DNA (ctDNA) in this setting, we analyzed tumor and serial bloods from 26 TNBC patients collected prior, during, and after NAC. Individual digital droplet PCR assays were developed for 121 variants (average 5/patient) identified from tumor sequencing, enabling ctDNA detection in 96% of patients at baseline.

NSABP B-41, a Randomized Neoadjuvant Trial: Genes and Signatures Associated with Pathologic Complete Response.

Purpose: In NSABP B-41, pathologic complete response (pCR) was associated with prolonged survival among women with HER2-positive operable breast cancer treated with neoadjuvant chemotherapy and lapatinib, trastuzumab, or the combination. We used a large human breast cancer gene expression panel to select candidate prognostic biomarkers for pCR among women treated with trastuzumab in NSABP B-41.

Patients And Methods: Eligible patients had a baseline preadjuvant treatment core biopsy sample, known pCR status, and no withdrawal of consent.

The LISA randomized trial of a weight loss intervention in postmenopausal breast cancer.

Obesity has been associated with poor breast cancer (BC) outcomes. We investigated whether a standardized, telephone-based weight loss lifestyle intervention in the adjuvant setting would impact BC outcomes. We conducted a multicenter trial randomizing women 1:1 to mail-based educational material alone (control) or combined with a standardized, telephone-based lifestyle intervention that focused on diet, physical activity, and behavior and involved 19 calls over 2 years to achieve up to 10% weight loss.

Correction to: NSABP FB-7: a phase II randomized neoadjuvant trial with paclitaxel + trastuzumab and/or neratinib followed by chemotherapy and postoperative trastuzumab in HER2+ breast cancer.

After the publication of this work [1] the authors have reported that in Table 3 The letter "T" in columns 5 and 7 should not be there.

Wage losses among spouses of women with nonmetastatic breast cancer.

Background: The aim of this study was to evaluate the wage losses incurred by spouses of women with nonmetastatic breast cancer in the 6 months after the diagnosis.

Methods: A prospective cohort study of spouses of women diagnosed with nonmetastatic breast cancer who were recruited in 8 hospitals in the province of Quebec (Canada) was performed. Information for estimating wage losses was collected by telephone interviews conducted 1 and 6 months after the diagnosis.

NSABP B-47/NRG Oncology Phase III Randomized Trial Comparing Adjuvant Chemotherapy With or Without Trastuzumab in High-Risk Invasive Breast Cancer Negative for HER2 by FISH and With IHC 1+ or 2.

Purpose: Adjuvant trastuzumab reduces invasive breast cancer (IBC) recurrence and risk for death in patients with HER2-amplified or overexpressing IBC. A subset of patients in the landmark trastuzumab adjuvant trials who originally tested HER2-positive but were HER2-negative by central HER2 testing appeared to possibly benefit from trastuzumab. The objective for the NSABP B-47 trial was to determine whether the addition of trastuzumab to adjuvant chemotherapy (CRx) would improve invasive disease-free survival (IDFS) in patients with HER2-negative breast cancer.

NSABP FB-7: a phase II randomized neoadjuvant trial with paclitaxel + trastuzumab and/or neratinib followed by chemotherapy and postoperative trastuzumab in HER2 breast cancer.

Purpose: The primary aim of NSABP FB-7 was to determine the pathologic complete response (pCR) rate in locally advanced HER2-positive (HER2) breast cancer patients treated with neoadjuvant trastuzumab or neratinib or the combination and weekly paclitaxel followed by standard doxorubicin plus cyclophosphamide. The secondary aims include biomarker analyses.

Experimental Design: pCR was tested for association with treatment, gene expression, and a single nucleotide polymorphism (SNP) in the Fc fragment of the IgG receptor IIIa-158V/F (FCGR3A).

Axillary Lymph Node Ultrasound Following Neoadjuvant Chemotherapy in Biopsy-Proven Node-Positive Breast Cancer: Results from the SN FNAC Study.

Background: The sentinel node biopsy following neoadjuvant chemotherapy (SN FNAC) study has shown that in node-positive (N+) breast cancer, sentinel node biopsy (SNB) can be performed following neoadjuvant chemotherapy (NAC), with a low false negative rate (FNR = 8.4%). A secondary endpoint of the SN FNAC study was to determine whether axillary ultrasound (AxUS) could predict axillary pathological complete response (ypN0) and increase the accuracy of SNB.

A Unique Morphological Phenotype in Chemoresistant Triple-Negative Breast Cancer Reveals Metabolic Reprogramming and PLIN4 Expression as a Molecular Vulnerability.

The major obstacle in successfully treating triple-negative breast cancer (TNBC) is resistance to cytotoxic chemotherapy, the mainstay of treatment in this disease. Previous preclinical models of chemoresistance in TNBC have suffered from a lack of clinical relevance. Using a single high dose chemotherapy treatment, we developed a novel MDA-MB-436 cell-based model of chemoresistance characterized by a unique and complex morphologic phenotype, which consists of polyploid giant cancer cells giving rise to neuron-like mononuclear daughter cells filled with smaller but functional mitochondria and numerous lipid droplets.

Pathologic complete response and outcomes by intrinsic subtypes in NSABP B-41, a randomized neoadjuvant trial of chemotherapy with trastuzumab, lapatinib, or the combination.

Purpose: NSABP B-41, a phase three randomized trial, evaluated neoadjuvant lapatinib, trastuzumab, or the combination with chemotherapy in patients with HER2-positive operable breast cancer. Though no significant difference in pathologic complete response (pCR) was found among the three arms, pCR was associated with prolonged survival. We analyzed tumor intrinsic subtypes with Prediction Analysis of Microarray 50 in a subset of B-41 patients to determine their value in predicting HER2-targeting benefit.

Randomized Phase II Study Evaluating Palbociclib in Addition to Letrozole as Neoadjuvant Therapy in Estrogen Receptor-Positive Early Breast Cancer: PALLET Trial.

Purpose: CDK4/6 inhibitors are used to treat estrogen receptor (ER)-positive metastatic breast cancer (BC) in combination with endocrine therapy. PALLET is a phase II randomized trial that evaluated the effects of combination palbociclib plus letrozole as neoadjuvant therapy.

Patients And Methods: Postmenopausal women with ER-positive primary BC and tumors greater than or equal to 2.

Efficacy of Chemotherapy for ER-Negative and ER-Positive Isolated Locoregional Recurrence of Breast Cancer: Final Analysis of the CALOR Trial.

Purpose Isolated locoregional recurrence (ILRR) predicts a high risk of developing breast cancer distant metastases and death. The Chemotherapy as Adjuvant for LOcally Recurrent breast cancer (CALOR) trial investigated the effectiveness of chemotherapy (CT) after local therapy for ILRR. A report at 5 years of median follow-up showed significant benefit of CT for estrogen receptor (ER)-negative ILRR, but additional follow-up was required in ER-positive ILRR.

Comparative Evaluation of Iodine-125 Radioactive Seed Localization and Wire Localization for Resection of Breast Lesions.

Purpose: Radioactive seed localization (RSL) uses a titanium seed labeled with iodine-125 energy for surgery of nonpalpable breast lesions. RSL facilitates radiology-surgery scheduling and allows for improved oncoplasty compared with wire localization (WL). The purpose of this work was to compare the 2 techniques.

The identification of challenges in tissue collection for biomarker studies: the Q-CROC-03 neoadjuvant breast cancer translational trial experience.

One of the major challenges in biomarker development is the collection of tumor tissue of adequate quality for analysis. A prospective clinical trial was initiated to collect tissues from triple negative breast cancers prior to and after neoadjuvant chemotherapy in order to study the mechanisms of chemoresistance. Sixty patients had pre-chemotherapy biopsies performed by either a surgeon or a radiologist, while those with residual tumor after chemotherapy had research-only biopsies and/or surgical samples collected in liquid nitrogen, RNA-later and formalin.

Limitations of Personalized Medicine and Gene Assays for Breast Cancer.

Adjuvant systemic treatments reduce the risk of breast cancer recurrence following the local treatment of primary stage I-III breast cancers. For patients with hormone-positive breast cancers receiving hormonal therapy, the risk of distant recurrence is under 20% and therefore, many patients may potentially be spared of chemotherapy. Consequently, several molecular signatures based on gene expression were developed to better determine which breast cancer patients would benefit from chemotherapy.

Using the 21-gene assay from core needle biopsies to choose neoadjuvant therapy for breast cancer: A multicenter trial.

Objective: We hypothesized that the Oncotype Dx 21-gene Recurrence Score (RS) could guide neoadjuvant systemic therapy (NST) to facilitate breast conserving surgery (BCS) for hormone receptor positive (HR+) breast cancers.

Methods: This study enrolled patients with HR+, HER2-negative, invasive breast cancers not suitable for BCS (size ≥ 2 cm). Core needle biopsy blocks were tested.

The Effect on Surgical Complications of Bevacizumab Added to Neoadjuvant Chemotherapy for Breast Cancer: NRG Oncology/NSABP Protocol B-40.

Background: NRG Oncology/NSABP trial B-40 tested the impact of adding bevacizumab (bev) to neoadjuvant chemotherapy for operable breast cancer. Secondary endpoints included rates of surgical complications after surgery in patients who did or did not receive bev.

Methods: A total of 1206 women with HER2-negative operable breast cancer were randomly assigned to receive one of three different docetaxel-plus-anthracycline-based regimens, without or with bev (15 mg/kg every 3 weeks) for the first 6 of 8 cycles and for 10 doses postoperatively.

Epirubicin With Cyclophosphamide Followed by Docetaxel With Trastuzumab and Bevacizumab as Neoadjuvant Therapy for HER2-Positive Locally Advanced Breast Cancer or as Adjuvant Therapy for HER2-Positive Pathologic Stage III Breast Cancer: A Phase II Trial of the NSABP Foundation Research Group, FB-5.

Background: The purpose of this study was to determine the cardiac safety and clinical activity of trastuzumab and bevacizumab with docetaxel after epirubicin with cyclophosphamide (EC) in patients with HER2-positive locally advanced breast cancer (LABC) or pathologic stage 3 breast cancer (PS3BC).

Patients And Methods: Patients received every 3 week treatment with 4 cycles of EC (90/600 mg/m) followed by 4 cycles of docetaxel (100 mg/m). Targeted therapy with standard-dose trastuzumab with bevacizumab 15 mg/kg was given for a total of 1 year.

Poor Prognosis After Second Locoregional Recurrences in the CALOR Trial.

Background: Isolated locoregional recurrences (ILRRs) of breast cancer confer a significant risk for the development of distant metastasis. Management practices and second ILRR events in the Chemotherapy as Adjuvant for LOcally Recurrent breast cancer (CALOR) trial were investigated.

Methods: In this study, 162 patients with ILRR were randomly assigned to receive postoperative chemotherapy or no chemotherapy.