DE LAURENTIIS , Michelino

: A novel class of drugs, antibody-drug conjugates (ADCs), are now rapidly emerging as highly effective treatments for solid tumours. ADCs conjugate conventional chemotherapeutics with highly selective targeted monoclonal antibodies. Anti-HER2 therapies selectively target cancer cells expressing human epidermal growth factor receptor 2 (HER2),...

Background: Several trials evaluated the role of ovarian function suppression for the adjuvant treatment of premenopausal patients with hormone receptor-positive early breast cancer. Based on the results of the SOFT and TEXT trials, international guidelines recommend the addition of ovarian function suppression to standard adjuvant endocrine...

: Endocrine therapy is one of the standard adjuvant treatments to reduce the risk of recurrence and mortality in patients with hormone receptor positive early breast cancer. Despite its proven efficacy, ET side effects, which persist over time even if low grade, may deteriorate quality of life. During follow-up visits, emphasis is generally...

Introduction: Advancements in monoclonal antibodies, tyrosine kinase inhibitors, and antibody drug conjugates (ADCs) have notably enhanced outcomes for metastatic HER2-positive breast cancer patients. Despite the expanding treatment options and clinical complexities, determining the optimal sequence of HER2-targeted therapies remains partly...

Cyclin-dependent kinases (CDK) 4/6 inhibitors, namely abemaciclib, palbociclib, and ribociclib, interfere with cell cycle progression, induce cell senescence and might promote cancer cell disruption by a cytotoxic T cells-mediated effect. Phase III randomized clinical trials have proven that CDK4/6 inhibitors (CDK4/6i) in combination with...

: Antibody-drug conjugates (ADCs) represent a novel class of molecules composed of a recombinant monoclonal antibody targeted to a specific cell surface antigen, conjugated to a cytotoxic agent through a cleavable or non-cleavable synthetic linker. The rationale behind the development of ADCs is to overcome the limitations of conventional...

Background: Treatment for HER2-positive (+) metastatic breast cancer has improved in the last decade. We analyzed treatment changes over time and their impact on patients outcomes in a real-world dataset. Methods: Data from 637 HER2+ patients with metastatic breast cancer enrolled in the multicenter Italian GIM14/BIOMETA study were retrieved....

: Estrogen receptor (ER) signaling represents the main driver of tumor growth and survival in hormone receptor positive (HR+) breast cancer (BC). Thus, endocrine therapy (ET) alone or in combination with targeted agents constitutes the mainstay of the treatment for this BC subtype. Despite its efficacy, intrinsic or acquired resistance to ET...

The treatment of HR+/HER2- metastatic breast cancer with cyclin-dependent kinases 4 and 6 inhibitors combined with endocrine therapy has recently emerged as the most relevant therapeutic strategy. However, in routine clinical practice, the best therapeutic approach in patients with comorbidities at early relapsing or ab initio metastatic...

Neoadjuvant chemotherapy (NACT) for breast cancer (BC) increases surgical and conservative surgery chances. However, a significant proportion of patients will not be eligible for conservative surgery following NACT because of large tumor size and/or low chemosensitivity, especially for hormone receptor (HR)-positive/ human epidermal growth...

Background: Although international guidelines support the administration of hormone therapies with or without targeted therapies in postmenopausal women with hormone-receptor-positive, HER2-negative metastatic breast cancer, upfront use of chemotherapy remains common even in the absence of visceral crisis. Because first-line or second-line...

Background: The last years have seen unprecedented improvement in breast cancer (BC) survival rates. However, this entirely apply to female BC patients, since gender minorities (male, transgender/gender-diverse) are neglected in BC phase III registration clinical trials. Methods: We conducted a scoping review of phase III clinical trials of...

The GIM2 phase III trial demonstrated the benefit of dose-dense chemotherapy in node-positive early breast cancer (eBC). To better define the dose-dense effect in the hormone receptor-positive subgroup, we evaluated its benefit through a composite measure of recurrence risk. We conducted an ancillary analysis of the GIM2 trial evaluating the...

: Approximately 20% of breast cancers (BCs) overexpress human epidermal growth factor receptor 2 (HER2), a transmembrane glycoprotein with tyrosine kinase activity, encoded by ERBB2 gene. Historically, HER2 overexpression has been linked with increased disease recurrence and a worse prognosis. However, the increasing availability of different...

Ribociclib plus letrozole demonstrated manageable safety and efficacy profiles in hormone receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer (ABC) in the Phase 3b CompLEEment-1 trial.

Background: Intermediate clinical endpoints (ICEs) are frequently used as primary endpoint in randomised trials (RCTs). We aim to assess whether changes in different ICEs can be used to predict changes in overall survival (OS) in adjuvant breast cancer trials. Methods: Individual patient level data from adjuvant phase III RCTs conducted by the...

Background: Previous analyses of the GIM (Gruppo Italiano Mammella) 2 study showed that addition of fluorouracil to epirubicin, cyclophosphamide, and paclitaxel in patients with node-positive early breast cancer does not improve outcome, whereas dose-dense chemotherapy induces a significant improvement in both disease-free survival and overall...

The introduction of PARP inhibitors has revolutionized the management and treatment of patients with pathogenic germline variants of BRCA1/2 who have developed breast cancer. The implementation of PARP inhibitors in clinical settings can be challenging due to their overlapping indications with other drugs, including both recently approved...

Background: Prior exposure to adjuvant endocrine therapy (ET) and timing to recurrence are crucial factors for first-line treatment choices in patients with hormone receptor-positive/HER2-negative (HR+/HER2-) breast cancer (BC) and in clinical trial eligibility, classifying metastatic HR+/HER2- BC as endocrine sensitive (ES) or primary...

Simple Summary Breast cancer is one of the most common oncological diseases among women in Western Countries and Italy as well. GIM 13-AMBRA is a patient journey study regarding how the prognosis of metastatic breast cancer patients has changed in the last decades as a result of the introduction of new drugs in clinical practice. This study...