Survival with Trastuzumab Emtansine in Residual HER2-Positive Breast Cancer.

Background: Patients with human epidermal growth factor receptor 2 (HER2)-positive early breast cancer with residual invasive disease after neoadjuvant systemic therapy have a high risk of recurrence and death. The primary analysis of KATHERINE, a phase 3, open-label trial, showed that the risk of invasive breast cancer or death was 50% lower with adjuvant trastuzumab emtansine (T-DM1) than with trastuzumab alone.

Methods: We randomly assigned patients with HER2-positive early breast cancer with residual invasive disease in the breast or axilla after neoadjuvant systemic treatment with taxane-based chemotherapy and trastuzumab to receive T-DM1 or trastuzumab for 14 cycles.

Circulating tumor cell plasticity determines breast cancer therapy resistance via neuregulin 1-HER3 signaling.

Circulating tumor cells (CTCs) drive metastasis, the leading cause of death in individuals with breast cancer. Due to their low abundance in the circulation, robust CTC expansion protocols are urgently needed to effectively study disease progression and therapy responses. Here we present the establishment of long-term CTC-derived organoids from female individuals with metastatic breast cancer.

Molecular adaptation to neoadjuvant immunotherapy in triple-negative breast cancer.

Therapy-induced molecular adaptation of triple-negative breast cancer is crucial for immunotherapy response and resistance. We analyze tumor biopsies from three different time points in the randomized neoadjuvant GeparNuevo trial (NCT02685059), evaluating the combination of durvalumab with chemotherapy, for longitudinal alterations of gene expression. Durvalumab induces an activation of immune and stromal gene expression as well as a reduction of proliferation-related gene expression.

The impact of physical activity on progression-free and overall survival in metastatic breast cancer based on molecular subtype.

Background: Although adequate physical activity has been shown to be beneficial in early breast cancer, evidence in metastatic breast cancer is sparse and contradictory, which could be related to distinct effects of physical activity on the different molecular cancer subtypes. Therefore, we here evaluated the effect of physical activity on progression-free and overall survival (PFS, OS) in metastatic breast cancer, specifically looking at molecular subtypes.

Methods: International Physical Activity Questionnaire (IPAQ) questionnaires, filled out by patients enrolled in the prospective PRAEGNANT registry (NCT02338167; n = 1,270) were used to calculate metabolic equivalent task (MET) minutes, which were subsequently categorized into low (n = 138), moderate (n = 995) or high IPAQ categories (n = 137).

On-treatment biopsies to predict response to neoadjuvant chemotherapy for breast cancer.

Background: Patients with pathologic complete response (pCR) to neoadjuvant chemotherapy for invasive breast cancer (BC) have better outcomes, potentially warranting less extensive surgical and systemic treatments. Early prediction of treatment response could aid in adapting therapies.

Methods: On-treatment biopsies from 297 patients with invasive BC in three randomized, prospective neoadjuvant trials were assessed (GeparQuattro, GeparQuinto, GeparSixto).

GAIN2 trial overall survival with intense versus tailored dose dense chemotherapy in early breast cancer.

GAIN-2 trial evaluated the optimal intense dose-dense (idd) strategy for high-risk early breast cancer. This study reports the secondary endpoints pathological complete response (pCR) and overall survival (OS). Patients (n = 2887) were randomized 1:1 between idd epirubicin, nab-paclitaxel, and cyclophosphamide (iddEnPC) versus leukocyte nadir-based tailored regimen of dose-dense EC and docetaxel (dtEC-dtD) as adjuvant therapy, with neoadjuvant therapy allowed after amendment.

Prognostic impact of selection criteria of current adjuvant endocrine therapy trials NATALEE and monarchE in postmenopausal HRpos/HER2neg breast cancer patients treated with upfront letrozole.

Background: The monarchE and NATALEE trials demonstrated the benefit of CDK4/6 inhibitor (CDK4/6i) therapy in adjuvant breast cancer (BC) treatment. Patient selection, based on clinical characteristics, delineated those at high (monarchE) and high/intermediate recurrence risk (NATALEE). This study employed a historical patient cohort to describe the proportion and prognosis of patients eligible for adjuvant CDK4/6i trials.

Susceptibility gene mutations in germline and tumors of patients with HER2-negative advanced breast cancer.

Germline mutations in BRCA1 and BRCA2 (gBRCA1/2) are required for a PARP inhibitor therapy in patients with HER2-negative (HER2-) advanced breast cancer (aBC). However, little is known about the prognostic impact of gBRCA1/2 mutations in aBC patients treated with chemotherapy. This study aimed to investigate the frequencies and prognosis of germline and somatic BRCA1/2 mutations in HER2- aBC patients receiving the first chemotherapy in the advanced setting.

Mutation analysis in individual circulating tumor cells depicts intratumor heterogeneity in melanoma.

Circulating tumor DNA (ctDNA) is the cornerstone of liquid biopsy diagnostics, revealing clinically relevant genomic aberrations from blood of cancer patients. Genomic analysis of single circulating tumor cells (CTCs) could provide additional insights into intra-patient heterogeneity, but it requires whole-genome amplification (WGA) of DNA, which might introduce bias. Here, we describe a novel approach based on mass spectrometry for mutation detection from individual CTCs not requiring WGA and complex bioinformatics pipelines.

Arbeitsgemeinschaft Gynäkologische Onkologie Recommendations for the Diagnosis and Treatment of Patients with Locally Advanced and Metastatic Breast Cancer: Update 2024.

The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) presents the 2024 update of the evidence-based recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer.

Arbeitsgemeinschaft Gynäkologische Onkologie Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2024.

Introduction: Each year the interdisciplinary AGO (Arbeitsgemeinschaft Gynäkologische Onkologie, German Gynecological Oncology Group) Breast Committee on Diagnosis and Treatment of Breast Cancer provides updated state-of-the-art recommendations for early and metastatic breast cancer.

Methods: The updated evidence-based treatment recommendations for early and metastatic breast cancer have been released in March 2024.

Results And Conclusion: This paper concisely captures the updated recommendations for early breast cancer chapter by chapter.

Impact of coadministration of proton-pump inhibitors and palbociclib in hormone receptor-positive/HER2-negative advanced breast cancer.

Background: The capsule formulation of CDK4/6 inhibitor palbociclib has reduced solubility at gastric pH > 4.5 and may have decreased activity when used with proton-pump inhibitors (PPI). Herein, we report the effect of PPI on palbociclib capsule activity and safety in the PARSIFAL study.

An Analysis of PIK3CA Hotspot Mutations and Response to Neoadjuvant Therapy in Patients with Breast Cancer from Four Prospective Clinical Trials.

Purpose: The PI3K signaling pathway is frequently dysregulated in breast cancer, and mutations in PIK3CA are relevant for therapy resistance in HER2-positive (HER2pos) breast cancer. Mutations in exons 9 or 20 may have different impacts on response to neoadjuvant chemotherapy-based treatment regimens.

Experimental Design: We investigated PIK3CA mutations in 1,691 patients with early breast cancer who were randomized into four neoadjuvant multicenter trials: GeparQuattro (NCT00288002), GeparQuinto (NCT00567554), GeparSixto (NCT01426880), and GeparSepto (NCT01583426).

CDK4/6 Inhibition - Therapy Sequences and the Quest to Find the Best Biomarkers - an Overview of Current Programs.

In recent years, new targeted therapies have been developed to treat patients with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) breast cancer. Some of these therapies have not just become the new therapy standard but also led to significantly longer overall survival rates. The cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i) have become the therapeutic standard for first-line therapy.

Attrition in the First Three Therapy Lines in Patients with Advanced Breast Cancer in the German Real-World PRAEGNANT Registry.

With more effective therapies for patients with advanced breast cancer (aBC), therapy sequences are becoming increasingly important. However, some patients might drop out of the treatment sequence due to deterioration of their life status. Since little is known about attrition in the real-world setting, this study assessed attrition in the first three therapy lines using a real-world registry.

Long-term outcomes of a randomized, open-label, phase II study comparing cabazitaxel versus paclitaxel as neoadjuvant treatment in patients with triple-negative or luminal B/HER2-negative breast cancer (GENEVIEVE).

Background: The GENEVIEVE study, comparing neoadjuvant cabazitaxel versus paclitaxel in triple-negative breast cancer (TNBC) and luminal B/human epidermal growth factor receptor 2 (HER2)-negative breast cancer (BC), previously reported significant differences in pathological complete response (pCR) rates. Effects on long-term outcome are unknown.

Patients And Methods: GENEVIEVE randomized patients with cT2-3, any cN or cT1, cN+/pN+, centrally confirmed TNBC or luminal B/HER2-negative BC (latter defined as estrogen/progesterone receptor-positive and >14% Ki-67-stained cells) to receive either cabazitaxel 25 mg/m q3w for four cycles or paclitaxel 80 mg/m weekly for 12 weeks.

Efficacy and safety of everolimus plus exemestane in patients with hormone receptor-positive, HER-2-negative advanced breast cancer: Results from the open-label, multicentre, non-interventional BRAWO study.

BRAWO, a real-world study, assessed the efficacy, quality of life (QoL) and safety of EVE + EXE in postmenopausal women with HR+/HER2- advanced breast cancer (ABC) in routine clinical practice. Postmenopausal women with HR+/HER2-ABC with recurrence or progression after a NSAI were included. Primary Observation parameters included the evaluation of the effectiveness of EVE + EXE.