Resistance to neoadjuvant chemotherapy in breast cancers: a metabolic perspective.

Neoadjuvant chemotherapy (NAC) is a cornerstone in the treatment of early-stage high-risk breast cancers (BC), particularly in triple-negative, HER2-positive, and selected hormone receptor-positive subtypes. However, its effectiveness is frequently hindered by intrinsic or acquired resistance, resulting in a significant residual cancer burden (RCB) in more than half of patients. Despite extensive genomic profiling, reliable predictive biomarkers for treatment response remain limited, impeding the development of personalized therapeutic strategies.

Adjuvant chemotherapy and hormonotherapy versus adjuvant hormonotherapy alone for women aged 70 years and older with high-risk breast cancer based on the genomic grade index (ASTER 70s): a randomised phase 3 trial.

Background: For women aged 70 years or older with oestrogen receptor-positive HER2-negative invasive breast cancer, hormonotherapy is a standard adjuvant treatment, while the role of chemotherapy is debated. We aimed to assess the effect of adjuvant chemotherapy on overall survival in these older patients with high-risk tumours according to a prognostic genomic signature.

Methods: This phase 3, randomised, superiority study was conducted at 84 clinical sites in France and Belgium in women aged 70 years and older with oestrogen receptor-positive and HER2-negative primary breast cancer or isolated local recurrence before any systemic treatment and after complete surgery.

Breastfeeding after breast cancer in young BRCA carriers.

Background: We investigated safety of breastfeeding after breast cancer in patients carrying germline BRCA pathogenic or likely pathogenic variants.

Methods: This was an international, multicentre, hospital-based, retrospective cohort study including BRCA carriers diagnosed with stage I-III invasive breast cancer at age 40 years or younger between January 2000 and December 2020 (NCT03673306). Locoregional recurrences and/or contralateral breast cancers, disease-free survival (DFS) and overall survival (OS) were compared between patients who breastfed after delivery and those who did not.

Real-World 5-Year Outcomes of Patients Treated With the Adjuvant Paclitaxel Trastuzumab (APT) Regimen for Stage I HER2-Positive Early Breast Cancer: A Retrospective International Study.

Background: An anthracycline-free regimen of adjuvant paclitaxel and trastuzumab is the standard-of-care for patients with HER2-positive (HER2+) early breast cancer (eBC) with tumors ≤20 mm, node-negative tumors, based on the results of a single-arm phase II trial. We investigated the outcomes of this regimen in a real-world (RW) setting.

Methods: This retrospective, international RW study included patients with stage I HER2+ eBC treated with the APT regimen (tumors of 5-20 mm, node-negative (N0 or Nmi) and no previous history of BC).

Assisted reproductive technology in young BRCA carriers with a pregnancy after breast cancer: An international cohort study.

Introduction: Very limited data exist on assisted reproductive technology (ART) use in BRCA1/2 carriers conceiving after breast cancer. This study aimed to investigate the safety of ART to achieve a pregnancy after breast cancer in BRCA1/2 carriers.

Methods: This is an international, hospital-based, retrospective cohort study including BRCA1/2 carriers with a pregnancy after prior breast cancer diagnosis at ≤ 40 years of age between 2000 and 2020.

Reproducibility of Equivocal HER2 In Situ Hybridization Groups 3 and 4, and Comparison With HER2 mRNA Expression: The Thin Line Between Amplified and Nonamplified Breast Cancers.

Context.—: Breast carcinomas (BCs) with equivocal HER2 (human epidermal growth factor receptor 2) immunohistochemistry are subjected to in situ hybridization (ISH) to assess HER2 copy numbers. Infrequently, dual-probe ISH also provides equivocal results, designated as ISH groups 2, 3, or 4.

The Challenge of Calculating EUSOMA Quality Indicators with Administrative Data: A Pilot Study in Belgium.

Introduction: The study aimed to assess the feasibility of calculating the European Society of Breast Cancer Specialists (EUSOMA) quality indicators (QIs) using Belgian Cancer Registry data coupled to administrative health data and to provide national results.

Methods: Women diagnosed with ductal carcinoma in situ (DCIS) or invasive breast cancer (IBC) in 2014-2018 were selected from the cancer registry. Fourteen EUSOMA QIs were chosen to assess the quality of care.

Clinical Behavior of Breast Cancer in Young Carriers and Prediagnostic Awareness of Germline Status.

Purpose: To investigate the clinical behavior of breast cancer in young carriers according to the specific gene () and the association of the timing of genetic testing (before at diagnosis) with prognosis.

Methods: This was an international, multicenter, hospital-based, retrospective cohort study that included 4,752 patients harboring germline pathogenic/likely pathogenic variants (PVs) in or , who were diagnosed with stage I-III invasive breast cancer at 40 years or younger between January 2000 and December 2020 in 78 centers worldwide (ClinicalTrials.gov identifier: NCT03673306).

Response to neoadjuvant chemotherapy in early breast cancers is associated with epithelial-mesenchymal transition and tumor-infiltrating lymphocytes.

Epithelial-mesenchymal transition (EMT) and tumor-infiltrating lymphocytes (TILs) play a central role in early-stage breast cancer (BC) and are associated with chemoresistance, stemness, and invasion. The objective of this study was two fold: (a) by investigating the predictive value of EMT and TILs, we aimed to estimate the chance of achieving a response after neoadjuvant chemotherapy (NAC) and (b) to evaluate the potential changes of EMT and TILs in BC upon NAC. Using bulk RNA sequencing and immunofluorescence (IF) for EMT (E-cadherin and vimentin) and lymphocyte markers (CD3, CD8, FOXP3), we analyzed pre- and post-NAC tumor samples from 100 early-BC patients treated with NAC.

Hypnosis Sedation Used in Breast Oncologic Surgery Significantly Decreases Perioperative Inflammatory Reaction.

Background: Hypnosis sedation has recently been used for anesthesia in breast oncologic surgery.

Methods: Between January 2017 and October 2019, 284 patients from our Breast Clinic (Cliniques Universitaires Saint-Luc, Université Catholique de Louvain) and from the Jolimont Hospital were prospectively included in an interventional non-randomized study approved by our two local ethics committees and registered on clinicaltrials.gov (NCT03330117).

Expert recommendations on treatment sequencing and challenging clinical scenarios in human epidermal growth factor receptor 2-positive (HER2-positive) metastatic breast cancer.

Human epidermal growth factor receptor 2 (HER2) overexpression and/or ERBB2 gene amplification occurs in approximately 15-20% of breast cancers and is associated with poor prognosis. While the introduction of HER2-targeted therapies has significantly improved survival in patients with HER2-positive metastatic breast cancer, the incidence of brain metastases has increased due to patients living longer. Current recommendations sequence treatments by line of therapy, as well as by the status of brain metastases in patients with HER2-positive breast cancer.

Higher relative survival in breast cancer patients treated in certified and high-volume breast cancer centres - A population-based study in Belgium.

Objectives: The study was undertaken to assess the association between certification and volume of breast centres on the one hand and survival on the other in patients with invasive breast cancer (IBC).

Methods: The study comprises a cohort of 46,035 patients diagnosed with IBC between 2014 and 2018, selected from the nation-wide Belgian Cancer Registry (BCR) database, which was linked with health insurance, hospital discharge and vital status data. Overall and relative survival probabilities were obtained with Kaplan-Meier method and an actuarial approach based on Ederer II, respectively.

Trastuzumab deruxtecan versus treatment of physician's choice in patients with HER2-positive metastatic breast cancer (DESTINY-Breast02): patient-reported outcomes from a randomised, open-label, multicentre, phase 3 trial.

Background: In DESTINY-Breast02, patients with HER2-positive unresectable or metastatic breast cancer who received trastuzumab deruxtecan demonstrated superior progression-free and overall survival compared with those receiving treatment of physician's choice. We present the patient-reported outcomes (PROs) and hospitalisation data.

Methods: In this randomised, open-label, phase 3 trial conducted at 227 clinical sites globally, enrolled patients had to be aged 18 years or older with HER2-positive unresectable or metastatic breast cancer that had progressed on trastuzumab emtansine and had an Eastern Cooperative Oncology Group performance status of 0 or 1.

Metabolic adaptation towards glycolysis supports resistance to neoadjuvant chemotherapy in early triple negative breast cancers.

Background: Neoadjuvant chemotherapy (NAC) is the standard of care for patients with early-stage triple negative breast cancers (TNBC). However, more than half of TNBC patients do not achieve a pathological complete response (pCR) after NAC, and residual cancer burden (RCB) is associated with dismal long-term prognosis. Understanding the mechanisms underlying differential treatment outcomes is therefore critical to limit RCB and improve NAC efficiency.

Late onset toxicities associated with the use of CDK 4/6 inhibitors in hormone receptor positive (HR+), human epidermal growth factor receptor-2 negative (HER2-) metastatic breast cancer patients: a multidisciplinary, pan-EU position paper regarding their optimal management. The GIOCONDA project.

The personalization of therapies in breast cancer has favoured the introduction of new molecular-targeted therapies into clinical practice. Among them, cyclin-dependent kinases 4 and 6 (CDK4/6) inhibitors have acquired increasing importance, with the approval in recent years of palbociclib, ribociclib, and abemaciclib in combination with endocrine therapy. Currently, no guidelines are available to monitor and manage potential long-term toxicities associated with the use of these drugs.

Paclitaxel plus Eftilagimod Alpha, a Soluble LAG-3 Protein, in Metastatic, HR+ Breast Cancer: Results from AIPAC, a Randomized, Placebo Controlled Phase IIb Trial.

Purpose: Eftilagimod alpha (efti), a soluble lymphocyte activation gene (LAG-3) protein and MHC class II agonist, enhances innate and adaptive immunity. Active Immunotherapy PAClitaxel (AIPAC) evaluated safety and efficacy of efti plus paclitaxel in patients with predominantly endocrine-resistant, hormone receptor-positive, HER2-negative metastatic breast cancer (ET-resistant HR+ HER2- MBC).

Patients And Methods: Women with HR+ HER2- MBC were randomized 1:1 to weekly intravenous paclitaxel (80 mg/m2) and subcutaneous efti (30 mg) or placebo every 2 weeks for six 4-week cycles, then monthly subcutaneous efti (30 mg) or placebo maintenance.

Paclitaxel plus carboplatin and durvalumab with or without oleclumab for women with previously untreated locally advanced or metastatic triple-negative breast cancer: the randomized SYNERGY phase I/II trial.

Chemo-immunotherapy is the first-line standard of care for patients with PD-L1 positive metastatic triple-negative breast cancer (mTNBC). SYNERGY (NCT03616886) is a dose-finding phase I and a randomized phase II, open-label trial evaluating if targeting the immunosuppressive adenosine pathway can enhance the antitumor activity of chemo-immunotherapy. The phase I part included 6 patients with untreated locally-advanced or mTNBC to determine the safety and recommended phase II dose of the anti-CD73 antibody oleclumab in combination with the anti-PD-L1 durvalumab and 12 cycles of weekly carboplatin and paclitaxel.

Surgery of the primary tumor in patients with de novo metastatic breast cancer: a nationwide population-based retrospective cohort study in Belgium.

Purpose: We aimed to assess the impact of surgery of primary tumor in overall survival (OS) of women with de novo metastatic breast cancer.

Methods: Nationwide, population-based retrospective cohort study of women diagnosed with de novo metastatic breast cancer in Belgium, between Jan/2010-Dec/2014. Data was obtained from the Belgian Cancer Registry and administrative databases.

Real-world clinical outcomes of patients with stage I HER2-positive breast cancer treated with adjuvant paclitaxel and trastuzumab.

Up to 20% of breast cancer overexpress HER2 protein, making it a reliable target for antibody-based treatments. In early HER2-positive breast cancer avoiding anthracycline-based chemotherapy is a challenge. Based on the single-arm phase II APT trial results, adjuvant paclitaxel/trastuzumab is an accepted regimen for patients with stage I HER2-positive disease.

Predictive markers for pathological complete response (pCR) after neo-adjuvant chemotherapy in HER2-positive breast carcinoma.

Objectives: Patients with HER2-positive invasive breast cancer that is node-positive and/or larger than 3 cm are generally treated with neoadjuvant chemotherapy (NAC). We aimed to identify predictive markers for pathological complete response (pCR) after NAC in HER2-positive breast carcinoma.

Methods: Hematoxylin/eosin-stained slides of 43 HER2-positive breast carcinoma biopsies were histopathologically reviewed.