Michael Gnant

• Professor
• Professor at Medical University of Vienna

526 Background: The PALLAS trial (NCT02513394) investigated the efficacy of the addition of palbociclib (palbo) to standard adjuvant endocrine therapy (ET) to reduce breast cancer recurrence. Previous analyses of this trial have not shown significant benefit of combination palbo+ET over ET alone. Given prior data showing that extent of neutropenia...

510 Background: Carboplatin-based regimen are effective in patients (pts) with eTNBC, and olaparib improves the outcome of pts with BRCA1/2 pathogenic variants (PV), but the safety / efficacy of OC co-treatment in HRD-positive TNBC is unknown. ABCSG 45 (EU CT 2024-512821-10) is a prospective multicenter phase II study investigating the efficacy and...

e13652 Background: Accurate assessment of Ki67 is critical for evaluating cellular proliferation and tumor aggressiveness in breast cancer diagnosis and prognosis. Traditionally, Ki67 immunohistochemistry (IHC) requires appropriate pre-analytical handling, standardized visual scoring, and experienced pathologists for correct interpretation. IHC is...

Purpose Although the relative proportion of triple-negative breast cancer (TNBC) decreases with age, its prevalence is rising with an ageing population. This study examines real-world treatment practices, whether age in older women with TNBC (owTNBC) affects therapy and outcomes, focusing on the potentially curable nature of early-stage TNBC. Meth...

Background This year, the St. Gallen Confernece was held from March 12th -15th, 2025, with the largest attendance since the pandemic, more than 3.000 participants from over 100 countries. Summary: The conference chairs professionally guided through the program on Early Breast Cancer, featuring abstracts submitted from all over the world. In additio...

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 1...

Purpose Using patient-reported outcomes (PROs) and more objective measures, we evaluated adherence to adjuvant palbociclib and ET in the PALLAS trial, and the impact of palbociclib on ET adherence. Methods The open-label, global, phase 3 PALLAS trial randomized patients with hormone receptor-positive (HR+), HER2-negative stage II–III breast cancer...

Background Insufficient patient accrual is a major challenge in clinical trials and can result in underpowered studies, as well as exposing study participants to toxicity and additional costs, with limited scientific benefit. Real-world data can provide external controls, but insufficient accrual affects all arms of a study, not just controls. Stud...

Plain Language Summary Why will we perform this study? People with early-stage breast cancer in which the cancer cells have receptors for the hormones estrogen and/or progesterone are typically treated with standard endocrine therapies, which are cancer treatments that remove or block hormones. After surgery, endocrine therapies such as tamoxifen,...

Background The Clinical Treatment Score post-5 years (CTS5) is a clinicopathological tool designed to estimate late distant recurrence (LDR) in hormone receptor-positive (HR+) breast cancer patients after 5 years of adjuvant endocrine therapy (ET). While intended as a prognostic algorithm, its predictive value for ET extension remains uncertain. M...

Background The PALLAS trial investigated the addition of palbociclib to standard adjuvant endocrine therapy to reduce breast cancer recurrence. This pre-specified analysis was conducted to determine whether adjuvant palbociclib benefited patients diagnosed with lower risk stage IIA disease compared to those with higher stage disease. Methods PALLA...

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have revolutionized the treatment of hormone-receptor positive (HR+), HER2 negative (HER2−) metastatic breast cancer, and are now also established agents in the treatment of high-risk and intermediate-risk HR+ early breast cancer. Several strategies regarding CDK4/6i combinations or continuation beyo...

The role of anthracyclines in the treatment of early breast cancer (EBC) is increasingly being challenged, especially in de-escalation strategies. However, owing to their immunogenic effects, anthracyclines are promising combination partners with immunotherapies. In the randomized phase 2 trial ABCSG-52 (EudraCT no. 2019-002364-27), we investigated...

Background Concomitant intake of proton pump inhibitors (PPIs) may create drug–drug interactions, potentially impacting efficacy of anticancer agents. In the phase III PALLAS trial, the addition of palbociclib capsules to standard adjuvant endocrine therapy in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negativ...

Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) have transformed the treatment of hormone-receptor-positive, human epidermal growth factor receptor 2‑negative (HR+/HER2−) breast cancer, becoming the standard in first-line endocrine therapy (ET). However, evidence supporting the optimal sequencing post-CDK4/6i progression remains scarce. Liquid bio...

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...

Background Monocytes comprise subsets of classical, intermediate and non-classical monocytes with distinct anti- or pro-tumor effects in breast cancer (BC). They are modulated by estrogen, and can contribute to BC control by endocrine therapy in preclinical models. Methods To elucidate whether changes in monocyte subsets are associated with treatm...

Background Bidirectional crosstalk between HER2 and estrogen receptor (ER) pathways may influence outcomes and the efficacy of endocrine therapy (ET). Low HER2 expression levels (HER2-low) have emerged as a predictive biomarker in patients with breast cancer (BC). Methods PALLAS is an open, international, phase 3 study evaluating the addition of p...

BACKGROUND Insufficient patient accrual is a major challenge in clinical trials and can result in underpowered studies, as well as exposing study participants to toxicity and additional costs, with limited scientific benefit. Real-world data can provide external controls, but insufficient accrual affects all arms of a study, not just controls. Stud...

Clinical trials frequently include multiple end points that mature at different times. The initial report, typically based on the primary end point, may be published when key planned co-primary or secondary analyses are not yet available. Clinical Trial Updates provide an opportunity to disseminate additional results from studies, published in JCO...

Background The PALLAS trial investigated the addition of palbociclib to standard adjuvant endocrine therapy reduces breast cancer recurrence. This pre-specified analysis was conducted to determine whether adjuvant palbociclib benefited patients diagnosed with lower risk stage IIA disease compared to those with higher stage disease. Methods PALLAS...

The advancements in the detection and characterization of circulating tumor DNA (ctDNA) have revolutionized precision medicine and are likely to transform standard clinical practice. The non‐invasive nature of this approach allows for molecular profiling of the entire tumor entity, while also enabling real‐time monitoring of the effectiveness of ca...

521 Background: Adjuvant dose dense chemotherapy for early breast cancer improves patient outcomes across all subgroups compared with standard interval treatment. However, the effect of dose dense treatment based on individual patient risk and over time, and the performance of the PREDICT model at this setting are not well-studied. Methods: This is...

538 Background: The phase 3 PALLAS trial compared 2 years of the CDK4/6 inhibitor palbociclib with endocrine therapy of provider choice, versus endocrine therapy alone, as adjuvant treatment for patients (pts) with Stage II-III hormone receptor-positive HER2-negative (HR+/HER2-) breast cancer. The SET2,3 index adjusts the measurement of SET ER/PR i...

TPS611 Background: Axillary lymph node dissection (ALND) is standard of care for most patients with clinically node-positive breast cancer (cN+BC), either in the adjuvant setting or in case of residual nodal disease after neoadjuvant chemotherapy (NACT). At least one quarter of patients with breast cancer experience long term morbidity after ALND....

Background The PENELOPE-B study demonstrated that the addition of 1-year post-neoadjuvant palbociclib to endocrine therapy (ET) in patients with high-risk early breast cancer (BC) did not improve invasive disease-free survival (iDFS) compared to placebo. Here, we report results for premenopausal women. Patients and methods Patients with hormone re...

587 Background: MUC1 glycoprotein is overexpressed in over 90% of breast cancers. It is involved in oncogenesis and confers resistance to anti-cancer therapies, thus representing a promising therapeutic target. Tecemotide (liposomal BLP25; Stimuvax) is a MUC1-based therapeutic cancer vaccine. The aim of the prospective, multicenter randomized two-a...

Purpose The aim of this retrospective analysis was to determine if the response to preoperative radio(chemo)therapy is predictive for survival among patients with locally advanced rectal cancer and may act as a potential surrogate endpoint for disease free survival and overall survival. Results Eight hundred seventy-eight patients from five center...

Introduction ABCSG-18 trial showed that 60mg denosumab subcutaneously every 6 months halves fracture risk in postmenopausal patients with early breast cancer, who are treated with adjuvant aromatase inhibitors. However, it has been reported that stopping denosumab may lead to overactivation of osteoclasts resulting in so called rebound vertebral fr...

Introduction: Analyses of multiple clinical trials have suggested racial and ethnic disparities in outcomes for early-stage, hormone receptor-positive and HER2-negative (HR+HER2-) breast cancer, however, none of these studies examined the use of adjuvant CDK4/6 inhibitors. The objective of this study was to explore racial and ethnic differences in...

Background: Data suggest that concomitant intake of proton pump inhibitors (PPI) may create drug-drug interactions, potentially impacting efficacy of agents including palbociclib, which is widely used in the treatment of metastatic hormone-receptor-positive/HER2-negative (HR+/HER2-) breast cancer. In the open label, randomized, phase 3 PALLAS trial...

Background: Camizestrant is a next-generation oral selective estrogen receptor (ER) degrader and pure ER antagonist being investigated in early and advanced breast cancer (BC). In postmenopausal women with advanced ER-positive/human epidermal growth factor receptor 2 (HER2)-negative BC and disease recurrence or progression on or after ≤1 endocrine...

Background: In the PENELOPEB trial, the addition of 1-year of cyclin-dependent kinase 4/6 (CDK4/6) inhibitor palbociclib to standard endocrine therapy (ET) for women with hormone receptor-positive (HR+)/human epidermal growth factor receptor 2-negative (HER2-) early breast cancer at high risk of recurrence after neoadjuvant chemotherapy (NACT) did...

Background. The phase 3 PALLAS trial (NCT02513394) compared two years of the CDK4/6 inhibitor palbociclib with endocrine therapy of provider choice, versus endocrine therapy alone, as adjuvant treatment for patients with Stage II-III hormone receptor-positive HER2-negative (HR+/HER2-) breast cancer. Genomic subtype (PAM50 intrinsic subtype) measure...

Background: Low levels of HER2 expression (HER2-low) have recently emerged as a therapeutic target in patients (pts) with breast cancer (BC). The aim of this study was to evaluate clinical and demographic variables associated with HER2 expression, as well as the value of HER2-low as a prognostic and predictive biomarker for palbociclib benefit in p...

Background: ABCSG-52/ATHENE investigated a neoadjuvant chemotherapy de-escalation/immunotherapy escalation approach with trastuzumab, pertuzumab, atezolizumab and epirubicin for early-stage HER2-positive breast cancer. The pathological complete response rate (pCR; ypT0/Tis, ypN0) - the primary endpoint of the trial - was 60.3% (95% CI 47.5% - 71.9%...

Clinical trials are subject to an ever-evolving landscape of treatment options, regulatory requirements, socioeconomic conditions, and paradigms of scientific research. In this opinion paper, we illustrate current methods and topics with a focus on clinical trial designs, conduct and modes of collaboration. The example of successful clinical breast...

Background Web-based learning activities are key components of continuing medical education (CME) for health care professionals (HCPs). However, the published outcomes of web-based educational interventions for early breast cancer (EBC) are limited. Objective This study aims to objectively assess knowledge, competence, and performance among HCPs f...

In this contribution, the Schemper–Henderson measure of explained variation for survival outcomes is extended to accommodate competing events (CEs) in addition to events of interest. The extension is achieved by moving from the unconditional and conditional survival functions of the original measure to unconditional and conditional cumulative incid...

Purpose The Clinical Treatment Score post-5 years (CTS5) is an easy-to-use tool estimating the late distant recurrence (LDR) risk in patients with hormone receptor-positive breast cancer after 5 years of endocrine therapy (ET). Apart from evaluating the prognostic value and calibration accuracy of CTS5, the aim of this study is to clarify if this s...

Background: Epirubicin/cyclophosphamide (EC) and docetaxel (D) are commonly used in a sequential regimen in the neoadjuvant treatment of early, high-risk or locally advanced breast cancer (BC). Novel approaches to increase the response rate combine this treatment with immunotherapies such as PD-1 inhibition. However, the expected stimulatory effect...

Background Tailored axillary surgery (TAS) is a novel surgical concept for clinical node-positive breast cancer. It consists of the removal of the sentinel lymph nodes (LNs), as well as palpably suspicious nodes. The TAS technique can be utilized in both the upfront and neoadjuvant chemotherapy (NACT) setting. This study assessed whether/how imagin...

Approximately 15% of newly diagnosed breast cancer patients have neither hormone receptors expression nor HER2 overexpression and/or HER2/neu gene amplification. This subtype of breast cancer is known as Triple Negative Breast Cancer (TNBC), and carries a significantly elevated risk of local and distant recurrence. In comparison with other breast c...

The 18th St. Gallen International Breast Cancer Conference held in March 2023, in Vienna, Austria, assessed significant new findings for local and systemic therapies for early breast cancer with a focus on the evaluation of multimodal treatment options. The emergence of more effective, innovative agents in both the preoperative (primary, or neoadju...

Purpose: BMI affects breast cancer risk and prognosis. In contrast to cytotoxic chemotherapy, CDK4/6 inhibitors are given at a fixed dose, irrespective of BMI or weight. This preplanned analysis of the global randomized PALLAS trial investigates the impact of BMI on the side-effect profile, treatment adherence, and efficacy of palbociclib. Method...

Background Twenty percent of colorectal cancer liver metastases (CLMs) are initially resectable with a 5-year survival rate of 25%–40%. Perioperative folinic acid, 5-fluorouracil, oxaliplatin (FOLFOX) increases progression-free survival (PFS). In advanced disease, the addition of targeting therapies results in an overall survival (OS) advantage. Th...

Treatment for early-stage breast cancer is complex, requiring multidisciplinary care with a multitude of treatment options available for each patient. Coupled with the rising importance of shared decision-making, patient-physician conversations are progressively more complicated. These conversations require frank disclosure of risks and benefits of...

BACKGROUND Web-based learning activities are key components of continuing medical education (CME) for health care professionals (HCPs). However, the published outcomes of web-based educational interventions for early breast cancer (EBC) are limited. OBJECTIVE This study aims to objectively assess knowledge, competence, and performance among HCPs f...

Importance: The role of axillary lymph node dissection (ALND) to determine nodal burden to inform systemic therapy recommendations in patients with clinically node (cN)-positive breast cancer (BC) is currently unknown. Objective: To address the association of ALND with systemic therapy in cN-positive BC in the upfront surgery setting and after n...

The cyclin-dependent kinase (CDK)4/6 inhibitors palbociclib, ribociclib, and abemaciclib are standard-of-care therapy for hormone receptor-positive advanced/metastatic breast cancer, based on randomized trials showing improved progression-free survival for all 3 drugs, and overall survival for ribociclib and abemaciclib. Results in early breast can...

Purpose The aim of this study was to evaluate clinical practice heterogeneity in use of neoadjuvant systemic therapy (NST) for patients with clinically node-positive breast cancer in Europe. Methods The study was preplanned in the international multicenter phase-III OPBC-03/TAXIS trial (ClinicalTrials.gov Identifier: NCT03513614) to include the fi...

The heterogeneous group of B3 lesions in the breast harbors lesions with different malignant potential and progression risk. As several studies about B3 lesions have been published since the last Consensus in 2018, the 3rd International Consensus Conference discussed the six most relevant B3 lesions (atypical ductal hyperplasia (ADH), flat epitheli...

600 Background: HER2-directed therapies are approved for the treatment of patients with HER2-positive invasive breast cancer as defined by HER2 protein overexpression, or HER2 gene amplification based on HER2/chromosome enumeration probe (CEP17) ratio ≥ 2.2. Above this accepted HER2 status determination, however, it is still unknown whether the eff...

We review key topics in the management of estrogen receptor (ER)-positive human epidermal growth factor receptor 2-negative breast cancer. The single biggest challenge in management of this disease is late relapse, and we review new methods for identifying which patients are at risk of late relapse and potential therapeutic approaches in clinical t...

The St. Gallen Consensus Conference on early breast cancer treatment 2023 was again a live event and took place in Vienna, Austria. After 4 years and one virtual event due to the pandemic, more than 2,800 participants from over 100 countries came together in Vienna, and the 2023 St. Gallen/Vienna conference was a great success. Over three days, the...

The aims of this Oncoplastic Breast Consortium and European Breast Cancer Research Association of Surgical Trialists initiative were to identify uncertainties and controversies in axillary management of early breast cancer and to recommend appropriate strategies to address them. By use of Delphi methods, 15 questions were prioritized by more than 2...

Inhibitors of the cyclin-dependent kinases 4/6 (CDK4/6i) have been practice-changing and are now considered the standard of care in combination with endocrine therapy for the first- or second-line treatment in advanced hormone-receptor-positive, human epidermal growth factor receptor 2‑negative breast cancer. Recently, CDK4/6i have also emerged as...

Background: Several Breast Cancer Multigene Signatures (BCMS) are available to profile early breast cancer (eBC) that according to current evidence, can provide reliable information on the risk of recurrence. However, knowledge regarding their perceived value and use in clinical practice is scarce. The first results regarding the panelists’ opinion...

Background: The PENELOPE-B (NCT01864746) and PALLAS (NCT02513394) trials are large prospective, randomized, phase III trials that evaluated adjuvant palbociclib (PAL) + endocrine treatment (ET) vs ET in patients with hormone receptor–positive/human epidermal growth factor receptor 2–negative (HER2–) early breast cancer (EBC). Both studies did not m...

Background: Breast cancer with low HER2 expression (HER2-low) is of high clinical relevance because of new therapeutic options with antibody-drug conjugates. We have recently shown in a large cohort from neoadjuvant clinical trials that HER2-low breast cancer has different molecular characteristics as well as different clinical outcomes compared to...

Purpose: Estrogen receptor (ER) expression predicts response to endocrine therapy and is a prognostic biomarker. However, no ER-associated biomarker is able to identify patients with particularly favorable outcome among ER+ tumors. We investigated the value of ESR1 amplification in predicting long-term outcome in tamoxifen-treated postmenopausal wo...

Background: The Penelope-B trial did not show improvement in invasive disease-free survival (iDFS) with the addition of palbociclib to endocrine therapy (ET) in patients with high-risk early breast cancer (BC) after neoadjuvant chemotherapy (NACT). Biomarkers may be able to identify subgroups of patients deriving benefit from Palbociclib and guide...

Background: The results of the Early Breast Cancer Trialist Group (EBCTCG) meta-analysis (Lancet 2015) led to the widespread adoption of bisphosphonates as adjuvant therapy for postmenopausal early-stage breast cancer (EBC). Despite evaluating multiple bisphosphonate agents and regimens, there was no signal of varying efficacy with different agents...

Background: Adjuvant ET has been the standard of care for patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor 2-negative (HER2-) EBC. A significant proportion of patients with increased risk still experience disease relapse despite available ET and more optimum ET is needed to prevent patients developing incurable...

Breast cancer multigene signatures (BCMS) have changed how patients with early-stage breast cancer (eBC) are managed, as they provide prognostic information and can be used to select patients who may avoid adjuvant chemotherapy. Clinical guidelines make recommendations on the use of BCMS; however, little is known on the current use of BCMS in clini...

Background: ExteNET showed that neratinib, an irreversible pan-HER tyrosine kinase inhibitor, given for 1 year after trastuzumab-based therapy significantly improved invasive disease-free survival in women with early-stage HER2-positive breast cancer. We report the final analysis of overall survival in ExteNET. Methods: In this international, ra...

Background: The widespread adoption of adjuvant bisphosphonate therapy for postmenopausal early breast cancer (EBC) patients was based on results of the Early Breast Cancer Trialist Group (EBCTCG) meta-analysis. Despite multiple regimens evaluated, there was no signal of varying efficacy with type, dose/dose intensity of bisphosphonate administrat...

Outcomes of Adjuvant Denosumab in Breast CancerIn this long-term report of a prospective, double-blind, placebo-controlled, phase 3 trial of adjuvant aromatase inhibitor in postmenopausal patients with early hormone receptor-positive breast cancer, adjuvant denosumab therapy improved disease-free survival by 3.5 percentage points, bone metastasis-f...

390216 Background: CDK4/6 inhibitors have become standard of care for advanced hormone receptor positive, HER2-negative (HR+/HER2-) breast cancer in combination with endocrine therapy (ET), with one approved for high-risk patients (pts) in the adjuvant setting. The PALLAS Trial investigated the addition of palbociclib to adjuvant ET in pts with sta...

Background: The randomized, double-blind OlympiA trial compared one year of the oral poly(adenosine diphosphate-ribose) polymerase) inhibitor, olaparib, to matching placebo as adjuvant therapy for patients with pathogenic or likely pathogenic variants in germline BRCA1 or BRCA2 (gBRCA1/2pv) and high-risk, human epidermal growth factor receptor 2 (...

Purpose of review: The standard of care in breast surgery has changed, from mastectomy to breast conserving surgery whenever possible, and from axillary dissection to sentinel node biopsy. Neoadjuvant systemic approaches have broadened the indications for organ-conserving and less mutilating surgery, but also raise important questions of balancing...

Background Patients with hormone receptor-positive, HER2-negative breast cancer who have residual invasive disease after neoadjuvant chemotherapy (NACT) are at a high risk of relapse. PENELOPE-B was a double-blind, placebo-controlled, phase III trial that investigated adding palbociclib (PAL) for thirteen 28-day cycles to adjuvant endocrine therapy...

In the past 12 months a plethora of relevant novel data for the treatment of metastatic HER2 positive breast cancer were published. To bring this new evidence into a clinical perspective, a group of Austrian breast cancer specialists updated their previously published treatment algorithm for those patients. For this consensus paper a total of eight...

Purpose Estrogen receptor (ER) expression is a prognostic parameter in breast cancer, and a prerequisite for the use of endocrine therapy. In ER⁺ early breast cancer, however, no receptor-associated biomarker exists that identifies patients with a particularly favorable outcome. We have investigated the value of ESR1 amplification in predicting the...

Introduction Oncoplastic techniques allow resection of larger tumors, permitting breast conservation in cases otherwise requiring mastectomy. We sought to prospectively compare quality of life (QoL) in patients undergoing oncoplastic surgery as compared to conventional breast conservation (CBC) or mastectomy is lacking. Methods Patients diagnosed...

518 Background: Body Mass Index (BMI) impacts breast cancer risk and prognosis. Conflicting results have been published regarding BMI as a predictive factor for endocrine therapy benefit. CDK4/6 inhibitors (CDK4/6i) in combination with endocrine treatment (ET) are standard-of-care treatments for metastatic hormone receptor-positive breast cancer. I...

TPS10616 Background: Women with BRCA1 mutations have a 50-70% lifetime risk of developing breast cancer. Currently, prophylactic mastectomy is the only strategy that significantly reduces breast cancer risk. Recent evidence suggests that the RANK/RANKL signaling pathway plays a pivotal role in the development of BRCA1-mutated tumors. Targeting the...

e13639 Background: Several Breast Cancer Multigene Signatures (BCMS) are available to profile early breast cancer (eBC) that according to current evidence, can provide reliable information on the risk of recurrence but the knowledge regarding their real use in clinical practice is scarce. The PROCURE Project aims to establish recommendations on the...

507 Background: State-of-the-art adjuvant endocrine therapy with aromatase inhibitors (AI) compromises bone health in postmenopausal patients with hormone receptor-positive (HR+) breast cancer, increasing fracture incidence. Adjuvant treatment with the anti-RANK ligand denosumab (Dmab) counteracts these side effects and may improve outcomes. We her...

Purpose To validate the prognostic role of urokinase-type plasminogen-activator (uPA) and plasminogen activator inhibitor type-1 (PAI-1) protein expression in FFPE archived tumor samples when assessed by immunohistochemistry. Patients and methods Fresh-frozen, paraffin-embedded (FFPE) samples from 303 postmenopausal women with hormone receptor-pos...