Invasive disease-free and overall survival after (neo)adjuvant chemotherapy in postmenopausal patients with hormone receptor-positive, HER2-negative early breast cancer treated with upfront letrozole: Experiences from the phase IV PreFace trial.

Patients with hormone receptor-positive (HRpos), HER2-negative (HER2neg) breast cancer (BC) benefit less from neoadjuvant chemotherapy (NACT) than patients with triple-negative and HER2-positive BC. In this retrospective analysis of the phase IV PreFace clinical trial (NCT01908556), where postmenopausal HRpos BC patients (n = 3297) were treated with 5-year upfront adjuvant letrozole therapy, we evaluated the prognosis of patients treated with adjuvant versus neoadjuvant chemotherapy in HRpos/HER2neg early-stage BC. HRpos/HER2neg patients with information on (neo)adjuvant chemotherapy (n = 2895) were retrospectively selected from all patients enrolled in the PreFace trial.

Effects of pregnancy on breast cancer immunology: immune biomarker and TIL quantification.

Breast cancer diagnosed during pregnancy (PrBC) is a rare occurrence but may become more prevalent as women nowadays tend to postpone childbearing until later in life. Further understanding of how pregnancy affects the tumor microenvironment (TME) is essential. We constructed Tissue Microarrays (TMA) of tumor specimens from 126 pregnant breast cancer (BC) patients and examined standard BC markers such as ER, PR, Ki67, HER2, tumor infiltrating lymphocytes (TILs), and immunomarkers HLA class I, HLA-G, PD-L1, TIGIT and Nectin-4.

Real-world utilization of aromatase inhibitors, tamoxifen, and ovarian function suppression in premenopausal patients with early hormone receptor-positive, HER2-negative breast cancer with increased recurrence risk.

Background: The optimal adjuvant endocrine treatment in premenopausal patients with hormone receptor-positive, HER2-negative (HRpos/HER2neg) early breast cancer (eBC) remains debated, particularly the choice between aromatase inhibitors plus ovarian function suppression (AI + OFS) or tamoxifen (TAM) with or without additional OFS. This study assessed the use of adjuvant endocrine therapies for premenopausal patients with intermediate/high-risk HRpos/HER2neg eBC.

Methods: CLEAR-B (AGO-B-059; NCT05870813) was a retrospective study analyzing data, collected from January 2016 to June 2019 and from January 2022 to December 2023 during the certification process of breast centers in Germany.

Targeting PI3K inhibitor resistance in breast cancer with metabolic drugs.

Activating PIK3CA mutations, present in up to 40% of hormone receptor-positive (HR), human epidermal growth factor receptor 2-negative (Her2) breast cancer (BC) patients, can be effectively targeted with the alpha isoform-specific PI3K inhibitor Alpelisib. This treatment significantly improves outcomes for HR, Her2, and PIK3CA-mutated metastatic BC patients. However, acquired resistance, often due to aberrant activation of the mTOR complex 1 (mTORC1) pathway, remains a significant clinical challenge.

Neoadjuvant Paclitaxel/Olaparib in Comparison to Paclitaxel/Carboplatin in Patients with HER2-Negative Breast Cancer and HRD-Long-term Survival of the GeparOLA Study.

Purpose: The GeparOLA study evaluated paclitaxel plus olaparib (PO) in neoadjuvant chemotherapy for patients with HER2-negative early breast cancer with homologous recombination deficiency (HRD). HRD was defined by high HRD score or germline (g)/tumor (t) BRCA1/2 mutations (g/tBRCA1/2mut). In this study, we report long-term outcome data.

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.

Tailored Dose-Dense Versus Standard Adjuvant Chemotherapy for High-Risk Early Breast Cancer: End-of-Study Results of the Randomized PANTHER Trial.

JCO .Although dose-dense adjuvant chemotherapy administered once every 2 weeks leads to superior outcomes compared with standard regimens once every 3 weeks, the observed improvement is largely limited to studies using the suboptimal paclitaxel schedule once every 3 weeks as control. PANTHER is an international phase III trial which compared sequential epirubicin/cyclophosphamide and docetaxel administered either once every 2 or once every 3 weeks, with tailored dosing at the dose-dense schedule according to hematologic toxicity.

Long-term Follow-up and Safety of Patients after an Upfront Therapy with Letrozole for Early Breast Cancer in Routine Clinical Care - The PreFace Study.

Introduction: Adjuvant treatment of patients with early-stage breast cancer (BC) should include an aromatase inhibitor (AI). Especially patients with a high recurrence risk might benefit from an upfront therapy with an AI for a minimum of five years. Nevertheless, not much is known about the patient selection for this population in clinical practice.

Caveolin Gene Expression Predicts Clinical Outcomes for Early-Stage HER2-Negative Breast Cancer Treated with Paclitaxel-Based Chemotherapy in the GeparSepto Trial.

Purpose: Caveolin-1 and -2 (CAV1/2) dysregulation are implicated in driving cancer progression and may predict response to nab-paclitaxel. We explored the prognostic and predictive potential of CAV1/2 expression for patients with early-stage HER2-negative breast cancer receiving neoadjuvant paclitaxel-based chemotherapy regimens, followed by epirubicin and cyclophosphamide.

Experimental Design: We correlated tumor CAV1/2 RNA expression with pathologic complete response (pCR), disease-free survival (DFS), and overall survival (OS) in the GeparSepto trial, which randomized patients to neoadjuvant paclitaxel- versus nab-paclitaxel-based chemotherapy.

Inferred Immune-Cell Activity Is an Independent Predictor of HER2-Negative Breast Cancer Prognosis and Response to Paclitaxel-Based Therapy in the GeparSepto Trial.

Purpose: Tumor microenvironment (TME) immune markers have been correlated with both response to neoadjuvant therapy and prognosis in patients with breast cancer. Here, immune-cell activity of breast cancer tumors was inferred by expression-based analysis to determine if it is prognostic and/or predictive of response to neoadjuvant paclitaxel-based therapy in the GeparSepto (G7) trial (NCT01583426).

Experimental Design: Pre-study biopsies from 279 patients with HER2-negative breast cancer in the G7 trial underwent RNA-seq-based profiling of 104 immune-cell-specific genes to assess inferred Immune Cell Activity (iICA) of 23 immune-cell types.

Subcutaneous injection of trastuzumab into the thigh versus abdominal wall in patients with HER2-positive early breast cancer: Pharmacokinetic, safety and patients' preference - Substudy of the randomised phase III GAIN-2 study.

Background: Trastuzumab given intravenously in combination with chemotherapy is standard of care for patients with early HER2-positive breast cancer (BC). Different randomised studies have shown equivalent efficacy of a subcutaneous injection into the thigh compared to the intravenous formulation. Other body regions for injection have not been investigated but might be more convenient for patients.

Outcome of breast cancer patients treated with chemotherapy during pregnancy compared with non-pregnant controls.

Background: A diagnosis of breast cancer during pregnancy (PrBC) does not impact prognosis if standard treatment is offered. However, caution is warranted as gestational changes in pharmacokinetics may lead to reduced chemotherapy concentration.

Methods: Survival of PrBC patients treated with chemotherapy during pregnancy was compared to non-pregnant breast cancer patients treated with chemotherapy, diagnosed after 2000, excluding patients older than 45 years or with a postpartum diagnosis.

Phase III randomised trial comparing intense dose-dense chemotherapy to tailored dose-dense chemotherapy in high-risk early breast cancer (GAIN-2).

Background: The GAIN-2 trial was designed to identify a superior intense dose-dense (idd) strategy for high-risk patients with early breast cancer. Here, we report an interim analysis, at which the predefined futility boundary was crossed.

Patients And Methods: GAIN-2 was an open-label, randomised, multicentre phase III trial.

TGFB-induced factor homeobox 1 (TGIF) expression in breast cancer.

Background: Breast cancer (BC) is the most frequent female cancer and preferentially metastasizes to bone. The transcription factor TGFB-induced factor homeobox 1 (TGIF) is involved in bone metabolism. However, it is not yet known whether TGIF is associated with BC bone metastasis or patient outcome and thus of potential interest.

Clinical and molecular characteristics of HER2-low-positive breast cancer: pooled analysis of individual patient data from four prospective, neoadjuvant clinical trials.

Background: The development of anti-HER2 antibody-drug conjugates opens new therapeutic options for patients with breast cancer, including patients with low expression of HER2. To characterise this new breast cancer subtype, we have compared the clinical and molecular characteristics of HER2-low-positive and HER2-zero breast cancer, including response to neoadjuvant chemotherapy and prognosis.

Methods: In this pooled analysis of individual patient data, we evaluated a cohort of 2310 patients with HER2-non-amplified primary breast cancer that were treated with neoadjuvant combination chemotherapy in four prospective neoadjuvant clinical trials (GeparSepto, NCT01583426; GeparOcto, NCT02125344; GeparX, NCT02682693; Gain-2 neoadjuvant, NCT01690702) between July 30, 2012, and March 20, 2019.

Chemotherapy-induced ovarian failure in young women with early breast cancer: Prospective analysis of four randomised neoadjuvant/adjuvant breast cancer trials.

Background: Young women receiving chemotherapy for early breast cancer (EBC) have a high probability for ovarian failure, defined by chemotherapy-induced amenorrhea (CIA) as a surrogate. CIA is insufficiently reliable and reproducible. We analysed chemotherapy-induced ovarian failure (CIOF) by assessing hormone parameters, CIA, and antral follicle count (AFC).

Efficacy of Endocrine Therapy for the Treatment of Breast Cancer in Men: Results from the MALE Phase 2 Randomized Clinical Trial.

Importance: The extent of changes in estradiol levels in male patients with hormone receptor-positive breast cancer receiving standard endocrine therapies is unknown. The sexual function and quality of life related to those changes have not been adequately evaluated.

Objective: To assess the changes in estradiol levels in male patients with breast cancer after 3 months of therapy.

Neo-adjuvant and/or Adjuvant Subcutaneous Trastuzumab (Herceptin) in Patients With Early HER2-positive Breast Cancer: Real World Data from a German Observational Study - (NIS HerSCin).

Background/aim: Subcutaneous Herceptin (HER SC) has been shown to be equally effective and safe compared to intravenous Herceptin (HER i.v.) application in early HER2-positive breast cancer (HER2+ BC).

Correction: Residual Axillary Burden After Neoadjuvant Chemotherapy (NACT) in Early Breast Cancer in Patients with a priori Clinically Occult Nodal Metastases - a transSENTINA Analysis.

[This corrects the article DOI: 10.1055/a-1298-3453.].

NAB-Paclitaxel Improves Disease-Free Survival in Early Breast Cancer: GBG 69-GeparSepto.

Purpose: The GeparSepto trial demonstrated that weekly nanoparticle albumin-bound (NAB)-paclitaxel significantly improves the pathologic complete remission rate compared with weekly solvent-based (sb) paclitaxel followed by epirubicin plus cyclophosphamide as neoadjuvant treatment in patients with primary breast cancer (BC). Here, we report data on long-term outcomes.

Methods: Patients with histologically confirmed primary BC were randomly assigned in a 1:1 ratio to 12 times weekly NAB-paclitaxel 150 mg/m (after study amendment, 125 mg/m) or weekly sb-paclitaxel 80 mg/m followed in both arms by four times epirubicin 90 mg/m plus cyclophosphamide 600 mg/m every 3 weeks.