Pembrolizumab and chemotherapy in high-risk, early-stage, ER/HER2 breast cancer: a randomized phase 3 trial.

Addition of pembrolizumab to neoadjuvant chemotherapy followed by adjuvant pembrolizumab improved outcomes in patients with high-risk, early-stage, triple-negative breast cancer. However, whether the addition of neoadjuvant pembrolizumab to chemotherapy would improve outcomes in high-risk, early-stage, estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER/HER2) breast cancer remains unclear. We conducted a double-blind, placebo-controlled phase 3 study (KEYNOTE-756) in which patients with previously untreated ER/HER2 grade 3 high-risk invasive breast cancer (T1c-2 (≥2 cm), cN1-2 or T3-4, cN0-2) were randomly assigned (1:1) to neoadjuvant pembrolizumab 200 mg or placebo Q3W given with paclitaxel QW for 12 weeks, followed by four cycles of doxorubicin or epirubicin plus cyclophosphamide Q2W or Q3W.

Drug-drug interactions between palbociclib and proton pump inhibitors in early breast cancer: an exploratory analysis of PALLAS (ABCSG-42/AFT-05/BIG-14-13/PrE0109).

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-negative early breast cancer did not improve invasive disease-free survival (iDFS). We explored whether concomitant use of PPIs affected survival outcomes in patients treated with palbociclib in PALLAS.

[Advances in immunotherapy of colorectal cancer].

Treatment of locally advanced rectal cancer involves neoadjuvant chemoradiotherapy (CRT), including induction or consolidation chemotherapy. Introduction of immunotherapy has brought success in several solid tumors and hematological diseases. In colorectal tumors, it was only introduced later.

Glucocorticoid Receptor Isoforms in Breast Cancer Raise Implications for Personalised Supportive Therapies.

Glucocorticoid receptor (GR) activation may promote metastasis in oestrogen receptor-negative and triple-negative breast cancer (TNBC). However, the role of the GRβ isoform, which has opposing effects to the main isoform, has not been studied in clinical samples. We aimed to analyse the intracellular localisation of total GR and GRβ in vitro using plasmid constructs and fluorescent immunocytochemistry.

[Retrospective analysis of metaplastic breast cancer cases].

Metaplastic breast tumour is a rare, aggressive, mostly triple- negative, dedifferentiated malignancy, which poorly responds to chemotherapy compared to other invasive breast tumours. Since 2000, the WHO has considered it as a separate entity among breast tumours. Given the extremely poor prognosis of the tumour, more studies are needed to establish the most effective treatment strategy supported by data to increase overall survival.

How to Tackle Discordance in Adjuvant Chemotherapy Recommendations by Using Oncotype DX Results, in Early-Stage Breast Cancer.

Background: The use of the Oncotype DX test reduces the rate of adjuvant chemotherapy recommendations. Few in-depth analyses have been performed on this decision-making process.

Methods: We retrospectively analyzed patient data based on available Oncotype DX test results (RS) irrespective of nodal status at a single center.

The role of everolimus in metastatic breast cancer and possibilities of moving forward-a narrative review.

Background And Objective: In hormone-receptor-positive (HR) and human epidermal growth factor receptor 2-negative (HER2) metastatic breast cancer endocrine-based therapies are preferred over chemotherapy. One of the treatment options is the combination of everolimus with exemestane or other endocrine drug in later lines mainly based on progression-free survival (PFS) results of the phase 3 BOLERO-2 trial. Altogether, clinical trials did not prove an overall survival (OS) benefit and considerable side effects hampered its application in the day-by-day practice.

[Fertility preservation in female cancer patients.].

In Hungary, an average of 2066 women under the age of 40 are diagnosed with cancer each year according to data from the National Cancer Registry. Approximately two-thirds of these patients require gonadotoxic treatment for their disease, which could potentially reduce their chances of future conception and childbirth. Currently, there are no professional guidelines on fertility preservation in Hungary, however, it is important to inform patients about their options.

TROPION-Breast01: Datopotamab deruxtecan vs chemotherapy in pre-treated inoperable or metastatic HR+/HER2- breast cancer.

Improving the prognosis for patients with metastatic HR+/HER2- breast cancer remains an unmet need. Patients with tumors that have progressed on endocrine therapy and/or are not eligible for endocrine therapy had limited treatment options beyond chemotherapy. Antibody-drug conjugates are a novel and promising treatment class in this setting.

Corrigendum: Systemic treatment of breast cancer. 1st Central-Eastern European professional Consensus Statement on breast cancer.

[This corrects the article DOI: 10.3389/pore.2022.

Avelumab Plus Talazoparib in Patients With Advanced Solid Tumors: The JAVELIN PARP Medley Nonrandomized Controlled Trial.

Importance: Preclinical data suggest that poly(ADP-ribose) polymerase (PARP) inhibitors have synergistic activity when combined with immune checkpoint inhibitors (ICIs); however, it is unknown which tumor types or molecular subtypes may benefit from this combination.

Objective: To investigate responses associated with the combination of avelumab and talazoparib in different tumor types and/or molecular subtypes.

Design, Setting, And Participants: In this phase 1b and 2 basket nonrandomized controlled trial, patients with advanced solid tumors were enrolled in the following cohorts: non-small cell lung cancer (NSCLC); DNA damage response (DDR)-positive NSCLC; triple-negative breast cancer (TNBC); hormone receptor-positive, human epidermal growth factor receptor 2 (ERBB2)-negative, DDR-positive breast cancer; recurrent, platinum-sensitive ovarian cancer (OC); recurrent, platinum-sensitive, BRCA1/2-altered OC; urothelial cancer; metastatic castration-resistant prostate cancer (mCRPC); DDR-positive mCRPC; and BRCA1/2- or ATM-altered solid tumors.

Systemic Treatment of Breast Cancer. 1st Central-Eastern European Professional Consensus Statement on Breast Cancer.

This text is based on the recommendations accepted by the 4th Hungarian Consensus Conference on Breast Cancer, modified based on the international consultation and conference within the frames of the Central-Eastern European Academy of Oncology. The professional guideline primarily reflects the resolutions and recommendations of the current ESMO, NCCN and ABC5, as well as that of the St. Gallen Consensus Conference statements.

Ribociclib plus letrozole in patients with hormone receptor-positive, HER2-negative advanced breast cancer with no prior endocrine therapy: subgroup safety analysis from the phase 3b CompLEEment-1 trial.

Background: The CDK4/6 inhibitor, ribociclib in combination with endocrine therapy significantly improved progression-free survival in the first line setting in post-menopausal patients with HR+/HER2- advanced breast cancer (ABC) in a pivotal phase 3, placebo-controlled trial (MONALEESA-2) and demonstrated superior overall survival in premenopausal patients with HR+/HER2- ABC (MONALEESA-7). The multinational, phase 3b, CompLEEment-1 trial, which assessed the safety and efficacy of ribociclib plus letrozole in a broader population of patients who have not received prior endocrine therapy for advanced disease, is the largest phase 3 clinical trial to date to evaluate the safety and efficacy of a CDK4/6 inhibitor. We report a subanalysis of data from patients (N = 339) enrolled in the central and south European countries of the SERCE (Southern Europe, RUC, Central Europe) cluster of CompLEEment-1.

Management Strategies for Hyperglycemia Associated with the α-Selective PI3K Inhibitor Alpelisib for the Treatment of Breast Cancer.

Alpelisib is an α-selective phosphatidylinositol 3-kinase inhibitor used for treating hormone receptor-positive (HR+), human epidermal growth receptor 2-negative (HER2-), -mutated locally advanced or metastatic breast cancer following disease progression on or after endocrine therapy. Hyperglycemia is an on-target effect of alpelisib affecting approximately 60% of treated patients, and sometimes necessitating dose reductions, treatment interruptions, or discontinuation of alpelisib. Early detection of hyperglycemia and timely intervention have a key role in achieving optimal glycemic control and maintaining alpelisib dose intensity to optimize the benefit of this drug.

Trifluridine/tipiracil in combination with oxaliplatin and either bevacizumab or nivolumab in metastatic colorectal cancer: a dose-expansion, phase I study.

Background: In preclinical studies trifluridine/tipiracil (FTD/TPI) plus oxaliplatin (Industriestrasse, Holzkirchen, Germany) sensitised microsatellite stable (MSS) metastatic colorectal cancer (mCRC) to anti-programmed cell death protein-1; the addition of oxaliplatin or bevacizumab (F Hoffmann- la ROCHE AG, Kaiseraugst, Switzerland) enhanced the antitumour effects of FTD/TPI. This study aimed to investigate the safety and efficacy of FTD/TPI plus oxaliplatin and either bevacizumab or nivolumab (Uxbridge business Park, Uxbridge, United Kingdom) in patients with mCRC who had progressed after at least one prior line of treatment.

Patients And Methods: In 14-day cycles, patients received FTD/TPI 35 mg/m (twice daily, days 1-5) plus oxaliplatin 85 mg/m (day 1), and, on day 1, either bevacizumab 5 mg/kg (cohort A) or nivolumab 3 mg/kg (cohort B).

Pathologic Complete Response Rates After Neoadjuvant Pertuzumab and Trastuzumab with Chemotherapy in Early Stage HER2-Positive Breast Cancer - Increasing Rates of Breast Conserving Surgery: A Real-World Experience.

The neoadjuvant use of pertuzumab and trastuzumab with chemotherapy improves the pathologic complete response (pCR) in early HER2+ breast cancer. The aim of this study was to determine the pCR rate obtained with dual HER2 blockade in routine clinical practice. The secondary and tertiary objective was to investigate the impact of neoadjuvant systemic therapy (NST) on performing breast-conserving surgery and survival data.

Demographic Characteristics and Treatment Patterns Among Patients Receiving Palbociclib for HR+/HER2- Advanced Breast Cancer: A Nationwide Real-World Experience.

Background: This nationwide retrospective study reports data on the real-world use of the selective cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor palbociclib in a large population of advanced breast cancer (ABC) patients during a 2-year period in Hungary.

Methods: All patients with ABC who received palbociclib between May 1, 2017 and June 30, 2019 were included in the analysis. Patient demographic and clinical characteristics, disease-related factors and treatment patterns were examined during the early access program and in the regular reimbursement period.

Palbociclib with adjuvant endocrine therapy in early breast cancer (PALLAS): interim analysis of a multicentre, open-label, randomised, phase 3 study.

Background: Palbociclib added to endocrine therapy improves progression-free survival in hormone-receptor-positive, HER2-negative, metastatic breast cancer. The PALLAS trial aimed to investigate whether the addition of 2 years of palbociclib to adjuvant endocrine therapy improves invasive disease-free survival over endocrine therapy alone in patients with hormone-receptor-positive, HER2-negative, early-stage breast cancer.

Methods: PALLAS is an ongoing multicentre, open-label, randomised, phase 3 study that enrolled patients at 406 cancer centres in 21 countries worldwide with stage II-III histologically confirmed hormone-receptor-positive, HER2-negative breast cancer, within 12 months of initial diagnosis.

Long-Term Dynamic Changes in Cosmetic Outcomes and Patient Satisfaction after Implant-Based Postmastectomy Breast Reconstruction and Contralateral Mastopexy with or without an Ultrapro Mesh Sling Used for the Inner Bra Technique. A Retrospective Correlational Study.

Immediate implant-based postmastectomy breast reconstruction (IPMBR) with contralateral symmetrization has mostly short-term limited evidence of cosmetic outcomes. Because 84% of early-stage breast cancer patients have overall survival of more than 10 years, reconstructed breast symmetry should provide long-lasting results and acceptable patient satisfaction. Ageing, changes in body weight, and biomechanical changes after IPMBR and symmetrization may contribute to symmetry worsening.

[Systemic treatment of breast cancer: professional guideline].

Since the III. Breast Cancer Consensus Conference, a number of new evidence based on clinical trial results have been published which justified updating the 2016 recommendation. In addition to classical prognostic factors, some multigenic tests, which we have incorporated into the recommendation, will play an important role in therapeutic decision-making.

Alpelisib plus fulvestrant for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer: final overall survival results from SOLAR-1.

Background: Activation of the phosphatidylinositol-3-kinase (PI3K) pathway via PIK3CA mutations occurs in 28%-46% of hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancers (ABCs) and is associated with poor prognosis. The SOLAR-1 trial showed that the addition of alpelisib to fulvestrant treatment provided statistically significant and clinically meaningful progression-free survival (PFS) benefit in PIK3CA-mutated, HR+, HER2- ABC.

Patients And Methods: Men and postmenopausal women with HR+, HER2- ABC whose disease progressed on or after aromatase inhibitor (AI) were randomized 1 : 1 to receive alpelisib (300 mg/day) plus fulvestrant (500 mg every 28 days and once on day 15) or placebo plus fulvestrant.

[Immunotherapy possibilities and results in breast cancer].

In recent years, a number of tumor types have shown significant therapeutic benefit with immunotherapy. Breast cancer has not been regarded traditionally as a typical immunogenic tumor, however, based on results so far, immunotherapy may play a role in the therapy. The most important change in attitude is that the target of therapy is not the disease but the host.

Influence of mutagenic versus non-mutagenic pre-operative chemotherapy on the immune infiltration of residual breast cancer.

Chemotherapeutic agents are often mutagenic. Induction of mutation associated neo-epitopes is one of the mechanisms by which chemotherapy is thought to increase the number of tumor-infiltrating lymphocytes. It is not known, however, whether treatment with various chemotherapeutic agents with different mutagenic capacity induce a significantly different number of stromal tumor-infiltrating lymphocytes (StrTIL) in residual cancer.

A long-term retrospective comparative study of the oncological outcomes of 598 very young (≤35 years) and young (36-45 years) breast cancer patients.

Background: Breast cancer diagnosed in very young women (VYWBC; ≤35 years) and young women (YWBC; 36-45 years) tends to be heterogeneous. The current study aimed to compare the clinicopathological characteristics and long-term clinical outcomes between YWBC and VYWBC subgroups.

Patients And Methods: The institutional prospectively led database was retrospectively analysed from 2000 to 2014 at the National Institute of Oncology, Hungary.