Prognostic impact of the choice of chemotherapy after first-line CDK4/6 inhibitor therapy in patients with metastatic hormone receptor-positive, HER2-negative breast cancer.

Introduction: Whereas CDK4/6 inhibitors (CDK4/6i) are the standard first-line therapy for patients with hormone receptor-positive (HRpos), HER2-negative (HER2neg) metastatic breast cancer, guidelines on treatment options after progression on CDK4/6i are more diverse. Chemotherapy is recommended if a patient develops endocrine resistance or experiences a visceral crisis. However, the impact of the choice of chemotherapy remains unknown.

Treatment of Patients with Early Breast Cancer: 19th St. Gallen International Breast Cancer Consensus Discussed against the Background of German Treatment Recommendations.

This year's 19th St. Gallen (SG) consensus conference on the treatment of patients with early breast cancer (SGBCC: St. Gallen Breast Cancer Conference) is based on numerous patient examples, each with different variables, to reflect the increasingly personalized treatment decision for early breast cancer.

Indirect Treatment Comparison between Ribociclib Combined with Non-Steroidal Aromatase Inhibitors and Ovarian Function Suppression vs. Tamoxifen in Premenopausal Women with Early Breast Cancer.

Background: This study provides an indirect treatment comparison of ribociclib combined with non-steroidal aromatase inhibitors and ovarian function suppression (ribociclib + NSAI + OFS) vs. a frequently used treatment option in German clinical routine (tamoxifen ± OFS) in premenopausal patients with HR-positive (HR+), HER2-negative (HER2-) early breast cancer (BC).

Material And Methods: Data on premenopausal women treated with ribociclib and tamoxifen were derived from the NATALEE clinical trial (NCT03701334) and the retrospective German data collection CLEAR-B, respectively.

Update Breast Cancer 2024 Part 3 - Patients with Advanced Stage Breast Cancer.

The use of CDK4/6 inhibitors, the new PI3K/AKT-kinase inhibitors, selective estrogen receptor-degraders (SERDs), antibody-drug conjugates, immune therapies and PARP inhibitors in recent years has resulted in a marked change in the therapy landscape for patients with advanced stage breast cancer. CDK4/6 inhibitors, trastuzumab deruxtecan, and sacituzumab govitecan have all been shown to provide significant overall survival benefits compared to conventional chemotherapy. Other substances are also showing promising results and hold out the hope that further analysis of the overall survival benefits will be available in the near future.

Update Breast Cancer 2024 Part 2 - Patients with Early Stage Breast Cancer.

This review summarizes the latest developments for the treatment of patients with early-stage breast cancer. Most of the clinically relevant changes were the result of using immune checkpoint inhibitors to treat patients with triple-negative breast cancer (TNBC) and CDK4/6 inhibitors to treat patients with hormone receptor-positive, HER2-negative (HRpos/HER2neg) tumors and a high risk of recurrence. Recent studies are presenting more and more data with long follow-up times and integrating translational analyses to evaluate new biomarkers such as circulating tumor DNA (ctDNA).

AGO Recommendations for the Diagnosis and Treatment of Patients with Locally Advanced and Metastatic Breast Cancer: Update 2025.

The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (AGO; German Gynecological Oncology Group) presents the 2025 update of the evidence-based recommendations for the diagnosis and treatment of patients with locally advanced and metastatic breast cancer (mBC).

AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2025.

The Breast Committee of the Arbeitsgemeinschaft Gynäkologische Onkologie (German Gynecological Oncology Group, AGO) presents the 2025 update of the evidence-based recommendations for the diagnosis and treatment of patients with early breast cancer.

and Other Predisposition Genes in High-Risk Hormone Receptor+/Human Epidermal Growth Factor Receptor 2- Breast Cancer Treated With Endocrine Therapy With or Without Palbociclib: A Secondary PENELOPE-B Study Analysis.

Purpose: The PENELOPE-B trial (ClinicalTrials.gov identifier: NCT01864746) recruited patients with hormone receptor+/human epidermal growth factor receptor 2- early breast cancer without a pathological complete response after taxane-containing neoadjuvant chemotherapy and at a high risk of relapse. Patients were randomly assigned (1:1) to receive 13 cycles of palbociclib once daily or placebo on days 1-21 in a 28-day cycle in addition to endocrine therapy (ET).

Systematic literature review and trial-level meta-analysis of aromatase inhibitors vs tamoxifen in patients with HR+/HER2- early breast cancer.

Background: Current standard of care for patients with HR+/HER2- early breast cancer (EBC) includes adjuvant endocrine therapy with an aromatase inhibitor (AI) or tamoxifen (TAM). We present a trial-level meta-analysis on efficacy of AI vs TAM in patients with HR+/HER2- EBC.

Methods: A systematic literature review was conducted using key medical literature databases (eg, PubMed; inception to October 2023) and data from conferences (to December 2023).

Health-Related Quality of Life in Patients with HR+/HER2- Early Breast Cancer Treated with Ribociclib Plus a Nonsteroidal Aromatase Inhibitor: Results from the NATALEE Trial.

Purpose: The phase III NATALEE trial reported a statistically significant invasive disease-free survival benefit with ribociclib plus nonsteroidal aromatase inhibitor (NSAI) versus an NSAI alone in stage II/III hormone receptor-positive, HER2-negative (HR+/HER2-) early breast cancer. In this study, we report health-related quality of life (HRQOL) data from NATALEE.

Patients And Methods: Patients were randomized to receive ribociclib plus NSAI or NSAI alone.

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.

Radar reflectors for marking of target lymph nodes in initially node-positive patients receiving neoadjuvant chemotherapy for breast cancer-a subgroup analysis of the prospective AXSANA (EUBREAST-03) trial.

Background: Surgical staging procedures of the axilla in initially clinically node-positive (cN +) breast cancer patients receiving neoadjuvant chemotherapy (NACT) vary across countries. Different procedures such as axillary lymph node dissection, sentinel lymph node biopsy, target lymph node biopsy and targeted axillary dissection are currently in use. To date, data on radar reflectors as a non-wire and non-radioactive technique for marking target lymph nodes are limited.

Characteristics and prognosis of patients with primary metastatic disease vs. recurrent HER2-negative, hormone receptor-positive advanced breast cancer.

Background: Patients with first-line metastatic breast cancer (MBC) comprise patients with de novo metastases (dnMBC) or recurrent disease after primary breast cancer (rMBC). This analysis aimed to explore the prognostic value of dnMBC versus rMBC overall and particularly in subgroups according to age and metastasis site, in addition to other prognostic clinicopathological parameters in a first-line, hormone receptor (HR)-positive, HER2-negative (HRpos/HER2neg) population.

Methods: Within the prospective PRAEGNANT MBC registry (NCT02338167), 508 HRpos/HER2neg patients, receiving first-line treatment for advanced disease, were identified.

Dynamics of molecular heterogeneity in high-risk luminal breast cancer-From intrinsic to adaptive subtyping.

We evaluate therapy-induced molecular heterogeneity in longitudinal samples from high-risk, hormone-receptor positive/HER2-negative breast cancer patients with residual tumor after neoadjuvant chemotherapy from the Penelope-B trial (NCT01864746; EudraCT 2013-001040-62). Intrinsic subtypes are prognostic in pre-therapeutic (Tx) samples (n = 629, p < 0.0001) and post-Tx residual tumors (n = 782, p < 0.

Surrogate End Points for Overall Survival in Neoadjuvant Randomized Clinical Trials for Early Breast Cancer.

Purpose: To assess trial-level surrogacy value for overall survival (OS) of the pathologic complete response (pCR) and invasive disease-free survival (iDFS) in randomized clinical trials (RCTs) for early breast cancer (BC).

Methods: Individual patient data of neoadjuvant RCTs with available data on pCR, iDFS, and OS were included in the analysis. We used the coefficient of determination from weighted linear regression models to quantify the association between treatment effects on OS and on the surrogate end points.

Prediction of pathological complete response after neoadjuvant chemotherapy for HER2-negative breast cancer patients with routine immunohistochemical markers.

Background: Pathological complete response (pCR) is an established surrogate marker for prognosis in patients with breast cancer (BC) after neoadjuvant chemotherapy. Individualized pCR prediction based on clinical information available at biopsy, particularly immunohistochemical (IHC) markers, may help identify patients who could benefit from preoperative chemotherapy.

Methods: Data from patients with HER2-negative BC who underwent neoadjuvant chemotherapy from 2002 to 2020 (n = 1166) were used to develop multivariable prediction models to estimate the probability of pCR (pCR-prob).

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.

Benefit from dose-dense adjuvant chemotherapy for breast cancer: subgroup analyses from the randomised phase 3 PANTHER trial.

Background: It is unclear whether some patients with high-risk breast cancer do not warrant adjuvant dose-dense chemotherapy due to small expected absolute benefit.

Methods: The phase 3 PANTHER trial (NCT00798070) compared adjuvant sequential epirubicin/cyclophosphamide (EC) and docetaxel (D) administered in either tailored dose-dense (tDD EC/D) or standard interval schedule (FEC/D) to patients with high-risk resected early breast cancer (n = 2003). We compared outcomes across key subgroups of interest, evaluated the performance of the online prognostication and treatment benefit estimation tool PREDICT and conducted a subpopulation treatment effect pattern plot (STEPP) analysis.

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.

Palbociclib in Combination with either Aromatase Inhibitors or Fulvestrant for Patients with Advanced HR+/HER2- Breast Cancer in Germany: Final Results of the Phase 2 Multicohort INGE-B Trial.

Introduction: The INGE-B trial (NCT02894398) aimed to confirm the efficacy and safety data from the PALOMA trials for patients treated first line (1L) with palbociclib (PAL) and letrozole or 1L and later line with PAL and fulvestrant. In addition, so far lacking evidence for efficacy and safety on the combination of PAL with anastrozole, exemestane (1L), or letrozole (later line) was investigated.

Methods: The prospective, multicenter, multicohort phase 2 trial INGE-B enrolled adult patients with locally advanced, inoperable, or metastatic HR+/HER2- breast cancer in Germany.

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).

Overall Survival with Pembrolizumab in Early-Stage Triple-Negative Breast Cancer.

Background: In patients with early-stage triple-negative breast cancer, the phase 3 KEYNOTE-522 trial showed significant improvements in pathological complete response and event-free survival with the addition of pembrolizumab to platinum-containing chemotherapy. Here we report the final results for overall survival.

Methods: We randomly assigned, in a 2:1 ratio, patients with previously untreated stage II or III triple-negative breast cancer to receive neoadjuvant therapy with four cycles of pembrolizumab (at a dose of 200 mg) or placebo every 3 weeks plus paclitaxel and carboplatin, followed by four cycles of pembrolizumab or placebo plus doxorubicin-cyclophosphamide or epirubicin-cyclophosphamide.

Palbociclib: Randomized Studies and Real-world Evidence as the Basis for Therapeutic Planning in Metastatic Breast Cancer.

Endocrine-based combination therapy with an inhibitor of the cyclin-dependent kinases 4 and 6 (CDK4/6 inhibitors) is currently the first-line therapy of choice for patients with hormone receptor-positive (HR+) and human epidermal growth factor receptor 2-negative (HER2-), locally advanced or metastatic breast cancer (mBC). The efficacy and safety of the treatment with palbociclib, the first CDK4/6 inhibitor approved for this indication, have been confirmed in large randomized controlled clinical trials (RCTs) with strictly defined patient cohorts. Since then, many relevant questions about CDK4/6 inhibition with palbociclib for mBC have been investigated in RCTs and real-world studies.