Laura Biganzoli

• MD
• Director at Azienda USL Toscana centro

Cell-free DNA (cfDNA) extracted from peripheral blood has emerged as a crucial biomarker source in oncology research. To enhance the detection of somatic copy number alterations (SCNAs) and circulating tumor DNA (ctDNA), we developed eSENSES, a 2 Mb breast cancer-targeted NGS panel. It includes 15,000 genome-wide SNPs, 500 focal SNPs in breast canc...

PURPOSE Human epidermal growth factor receptor 2 (HER2)–targeted therapy is standard of care for HER2-positive (HER2+) breast cancer, but most patients develop progressive disease with persistent HER2 expression. No definitive treatment guidance currently exists beyond second line. Trastuzumab duocarmazine (T-Duo) is a third-generation, HER2-target...

Article highlights Breast cancer treatment overview in older patients In patients with advanced hormone receptor- (HR-) positive/HER2-negative breast cancer, the combination of endocrine therapy with CDK4/6 inhibitors is the standard of care as initial treatment approach. Older cancer patients are underrepresented in clinical trials, including piv...

Background: Outcomes in patients with hormone receptor-positive metastatic breast cancer worsen after one or more lines of endocrine-based therapy. Trastuzumab deruxtecan has shown efficacy in patients with metastatic breast cancer with low expression of human epidermal growth factor receptor 2 (HER2) after previous chemotherapy. Methods: We con...

With the aging population, older adults constitute a growing proportion of the new cancer cases. Given the heterogeneous health status among older adults and their susceptibility to aging-related vulnerabilities, understanding their diversity and its implications becomes increasingly crucial for prognostication and guiding diagnostics, treatment de...

Background Most premenopausal patients with early breast cancer (eBC) are diagnosed with hormone receptor-positive disease and therefore candidate for adjuvant endocrine therapy (ET). Patients and methods The Gruppo Italiano Mammella (GIM) 23-POSTER (GIM23) is a multicenter, prospective, observational study conducted in 26 Italian institutions, ai...

Background and purpose: While the prevalence of older breast cancer patients is rapidly increasing, these patients are greatly underrepresented in clinical trials. We discuss barriers to recruitment of older patients to clinical trials and propose solutions on how to mitigate these challenges and design optimal clinical trials through the paradigm...

The analysis of circulating tumor DNA (ctDNA) is increasingly used for monitoring disease in patients with metastatic cancer. Here, we introduce a robust and reproducible strategy combining low-pass whole methylome sequencing of plasma DNA with METER, a novel computational tool. Engaging prediction models trained on independent available datasets,...

LBA1000 Background: T-DXd is approved for HER2-low (IHC 1+ or 2+/ISH-negative) mBC after ≥1 line of chemotherapy (CT). DB-06 (NCT04494425) evaluated T-DXd in pts with HER2-low or -ultralow (IHC 0 with membrane staining), HR+ mBC after disease progression (PD) on endocrine-based therapy and no prior CT for mBC. Methods: Pts with HER2-low or -ultralo...

TPS1132 Background: Current evidence from both randomized trials and real-world evidence studies suggests that older patients with advanced hormone receptor-positive/human epidermal growth factor receptor 2-negative (HR+/HER2-) breast cancer derive clinical benefit from the addition of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors to endocrin...

Background The presence and amount of blood circulating tumor DNA (Tumor Content, TC) is emerging as a clinically relevant factor in many cancers, including BC. In the metastatic setting, a commonly used tumor tissue agnostic approach involves analyzing Copy Number Alterations (CNA) from low-pass whole-genome sequencing (lpWGS) by ichorCNA. However...

This manuscript describes the Advanced Breast Cancer (ABC) international consensus guidelines updated at the last two ABC international consensus conferences (ABC 6 in 2021, virtual, and ABC 7 in 2023, in Lisbon, Portugal), organized by the ABC Global Alliance. It provides the main recommendations on how to best manage patients with advanced breast...

PURPOSE To identify prognostic circulating biomarkers to cyclin-dependent kinase 4 and 6 inhibitors (CDK4/6i), we performed a mutational analysis on circulating tumor DNA (ctDNA) samples from patients included in the TREnd trial, which randomly assigned patients to receive the CDK4/6i palbociclib alone or with the endocrine treatment (ET) to which...

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 also pr...

Purpose The interim analysis of the phase IIIb LUCY trial demonstrated the clinical effectiveness of olaparib in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (mBC), with median progression-free survival (PFS) of 8.11 months, which was similar to that in the olaparib...

Background: In the era of targeted therapies, chemotherapy (CT) is still a valuable treatment option for patients (pts) with HER2 negative metastatic breast cancer (MBC). The identification of predictive and prognostic markers might improve treatment response and survival. Here we investigated the role of tumor subtypes, circulating tumor cells (CT...

Background: We have previously identified two potentially predictive signatures of palbociclib resistance: the RBsig, composed of E2F1/E2F2 dependent genes, which is correlated with genetic loss of RB1, and the ratio between the gene expression levels of CCNE1 to RB1 (CCNE1/RB1). Both signatures have been previously tested in vitro and in neoadjuva...

Background: Thymidine kinase-1 is a cell proliferation marker downstream of the CDK4/6 pathway, whose activity can be measured in serum to reflect tumor proliferation. The CDK4/6 inhibitor palbociclib (P) is approved for the treatment of patients (pts) with hormone receptor positive metastatic breast cancer (MBC) in first or second line endocrine-b...

Aims: Improvement in the care of patients with metastatic breast cancer (MBC) can only occur if the adequate quality of care is implemented and verified, including access to multidisciplinary, specialised care given in accordance with high-quality guidelines. To this purpose, European Society of Breast Cancer Specialists and the Advanced Breast Ca...

DNA-methylation alterations are common in cancer and display unique characteristics that make them ideal markers for tumor quantification and classification. Here we present MIMESIS, a computational framework exploiting minimal DNA-methylation signatures composed by a few dozen informative DNA-methylation sites to quantify and classify tumor signal...

Background We previously showed that metabolomics predicts relapse in early breast cancer (eBC) patients, unselected by age. This study aims to identify a “metabolic signature” that differentiates eBC from advanced breast cancer (aBC) patients, and to investigate its potential prognostic role in an elderly population. Methods Serum samples from el...

Aims We analyzed the impact of the SARS-CoV-2 pandemic (COVID-19) on the quality of breast cancer care in certified EUSOMA breast centers. Materials and methods The results of the EUSOMA quality indicators (QIs) were compared, based on pseudonymized individual records, for the periods 1 March 2020 till 30 June 2020 (first COVID19 peak in most coun...

Background Approximately 5–10% of unselected breast cancer (BC) patients retain a hereditary predisposition related to a germline mutation in BRCA1/2 genes. The poly-ADP ribose polymerase (PARP)-inhibitors olaparib and talazoparib have been granted marketing authorization by both FDA and EMA for adults with BRCA1/2 germline mutations and HER2-negat...

Background The benefit of chemotherapy for older patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative early breast cancer (EBC) is a key area of debate. Gene expression profiling (GEP) may identify patients deriving benefit, but their predictive role has not been established for older adults. We sum...

Aim of the studyThe study aims to evaluate the performance of selected, high-volume, highly specialized, Italian Breast Centers at the time of COVID-19 pandemic (year 2020), compared to pre-pandemic time (year 2019), highlighting differences in terms of clinical presentation of breast cancer (BC) and therapeutic strategies.Methods Patients’ data we...

Simple Summary Breast cancer is one of the major causes of cancer-related morbidity and mortality in women worldwide. Despite recent improvements in adjuvant treatment of hormone receptor-positive/HER2−negative breast cancer, estimating the risk of relapse of breast cancer on an individual basis is still challenging. The IRIDE (high risk definition...

In the past decade, nine antibody-drug conjugates (ADCs) have been approved for the treatment of various tumors, four of which specifically for solid malignancies. ADCs deliver the cytotoxic payload to the cancer site, thereby improving chemotherapy efficacy while reducing systemic drug exposure and toxicity. With their high selectivity, ADCs are a...

Introduction: Breast cancer (BC) is a heterogeneous disease characterized by different molecular "intrinsic" subtypes (PAM50) with distinct prognostic and therapeutic implications. DNA methylation (DNAm) is one of the most studied epigenetic mechanisms involved in BC tumorigenesis and progression. Recently, many studies have demonstrated the capabi...

INTRODUCTION: Somatic mutations of the PIK3CA gene, encoding for the class IA PI3K p110α subunit, are the most common activating mutations in breast cancer (BC), occurring in 30-50% of early and in 28% of metastatic ER+/HER2- disease. We have previously demonstrated that PIK3CA mutations co-occurring with copy number (CN) gain (PIK3CA-mut/gain) are...

We aim to elucidate the prognostic value of PIK3CA mutations and copy number (CN) gain (PIK3CA-mut/gain) in hormone receptor-positive and HER2-negative (HR + /HER2−) breast cancer (BC). We analyzed primary HR + /HER2− BC from three publicly available datasets comprising over 2000 samples and assessed the associations with tumoral and clinical chara...

Background: Colorectal cancer (CRC) is the fourth most commonly diagnosed and third most deadly cancer worldwide. Surgery is the main treatment option for early disease; however, a relevant proportion of CRC patients relapse. Here, variations among preoperative and postoperative serum metabolomic fingerprint of CRC patients were studied, and possib...

Purpose CXCR1, one of the receptors for CXCL8, has been identified as a druggable target on breast cancer cancer stem cells (CSC). Reparixin (R), an investigational oral inhibitor of CXCR1, was safely administered to metastatic breast cancer patients in combination with paclitaxel (P) and appeared to reduce CSC in a window-of-opportunity trial in o...

Background In the phase III OlympiAD trial, olaparib significantly increased progression-free survival (PFS) compared with chemotherapy of physician's choice in patients with germline BRCA-mutated (gBRCAm), human epidermal growth factor 2 (HER2)-negative metastatic breast cancer (mBC). The phase IIIb LUCY trial assessed the clinical effectiveness o...

Purpose of review: In this review, we describe the evidence on the efficacy and the safety of systemic treatments for the management of early breast cancer (EBC) in older individuals. Recent findings: Chemotherapy has a temporary impact on quality of life (QoL) for older EBC patients and improves survival outcomes for those with oestrogen receptor...

Adjuvant treatment for patients with early stage colorectal cancer (eCRC) is currently based on suboptimal risk stratification, especially for elderly patients. Metabolomics may improve the identification of patients with residual micrometastases after surgery. In this retrospective study, we hypothesized that metabolomic fingerprinting could impro...

Simple Summary Biomarkers found in the blood of patients with hormone receptor positive and HER2 negative metastatic breast cancer are being investigated to understand how patients respond to treatments. Circulating biomarkers have the potential advantage of giving important information with a simple withdrawal of peripheral blood. Here, we review...

Breast cancer is increasingly prevalent in older adults and is a substantial part of routine oncology practice. However, management of breast cancer in this population is challenging because the disease is highly heterogeneous and there is insufficient evidence specific to older adults. Decision making should not be driven by age alone but should i...

Precision oncology is an emerging approach in cancer care. It aims at selecting the optimal therapy for the right patient by considering each patient’s unique disease and individual health status. In the last years, it has become evident that breast cancer is an extremely heterogeneous disease, and therefore, patients need to be appropriately strat...

Breast cancer is the most common tumour in women and the first cause of death for cancer in the female population. Preserving the quality of life has therefore become an important objective in the management of the disease. The benefits of adjuvant chemotherapy in patients with HR+ HER2- early breast cancer should always be balanced against its pot...

Background Circulating tumor cells (CTCs) are prognostic in patients with advanced breast cancer (ABC). However, no data exist about their use in patients treated with palbociclib. We analyzed the prognostic role of CTC counts in patients enrolled in the cTREnd study, a pre-planned translational sub-study of TREnd (NCT02549430), that randomized pat...

Background: HER2 blockade in combination with chemotherapy (CT) remains the treatment of choice for patients with HER2+ early breast cancer (BC), irrespective of estrogen receptor (ER) status. Patients with ER+/HER2+ early BC may benefit from HER2 blockade in combination with endocrine therapy (ET) and potentially also new targeted agents. Recent d...

Liquid biopsy based on cell-free DNA (cfDNA) enables non-invasive dynamic assessment of disease status in patients with cancer, both in the early and advanced settings. The analysis of DNA-methylation (DNAm) from cfDNA samples holds great promise due to the intrinsic characteristics of DNAm being more prevalent, pervasive, and cell- and tumor-type...

CDK4/6 inhibitors (CDK4/6i) in combination with endocrine therapy are the mainstay of treatment for patients with hormone receptor-positive, HER2 negative (HR+/HER2neg) metastatic breast cancer. However, resistance - either de novo or acquired - invariably occurs, leading to treatment failure and cancer progression. Genomic alterations, gene expres...

Background Metronomic chemotherapy can induce disease control in patients with metastatic breast cancer (MBC) and has better safety profiles than conventional chemotherapy. Evidence suggests that cytotoxics can be antiangiogenic in pre-clinical models and may have synergistic effects when combined with anti-vascular endothelial growth factor therap...

Purpose: Determine if the androgen receptor (AR) inhibitor enzalutamide improves effectiveness of endrocrine therapy (ET) in hormone receptor-positive (HR+) breast cancer. Methods: In this phase 2 trial, patients with HR+/HER2-normal advanced/metastatic breast cancer were randomized 1:1 to exemestane 25 mg with placebo or exemestane 50 mg with e...

Background: Limited data are available regarding the use of nab-paclitaxel in older patients with breast cancer. A weekly schedule is recommended, but there is a paucity of evidence regarding the optimal dose. We evaluated the efficacy of two different doses of weekly nab-paclitaxel, with a specific focus on their corresponding impact on patient f...

Age is the most relevant risk factor for breast cancer, and almost half of breast cancer cases in the US are diagnosed in women older than 70 years.¹ However, elderly adults are a heterogeneous population characterized by considerable differences in biological age, function, burden of comorbidities, cognition, nutritional status, psychosocial probl...

There is a growing understanding as science evolves that different cancer types require different approaches to treatment evaluation, especially in the metastatic stages. The introduction of new metastatic breast cancer (MBC) treatments may be hindered by several elements including the availability of relevant evidence related to disease-specific o...

Purpose: The activating mutation AKT1E17K occurs in ~7% of ER+ metastatic breast cancer (MBC). We report, from a multipart, first-in-human, Phase I study (NCT01226316), tolerability and activity of capivasertib, an oral AKT inhibitor, as monotherapy or combined with fulvestrant in expansion cohorts of AKT1E17K-mutant ER+ MBC patients. Patients an...

Background CLEOPATRA was a phase 3 study comparing the efficacy and safety of pertuzumab, trastuzumab, and docetaxel with placebo, trastuzumab, and docetaxel in patients with HER2-positive metastatic breast cancer. In the primary analysis and subsequent reports, progression-free and overall survival were significantly improved in the pertuzumab gro...

Background Limited data are available on nab-paclitaxel in older breast cancer patients, with this population being under-represented in clinical trial. A weekly schedule is recommended, but there is a paucity of evidence regarding the optimal dose. We evaluated the efficacy of two different doses of weekly nab-paclitaxel, with a specific focus on...

Background: Limited data are available regarding the use of nab-paclitaxel in older patients with breast cancer. A weekly schedule is recommended, but there is a paucity of evidence regarding the optimal dose. We evaluated the efficacy of two different doses of weekly nab-paclitaxel, with a specific focus on their corresponding impact on patient fu...

BACKGROUND Pts with ABC have a diverse clinical course and OS rates vary significantly among pts. New strategies had potentially changed the natural history of these pts, however data from clinical studies are still lacking and Real-World Studies (RWS) are crucial in clinical outcome evaluation. PATIENTS AND METHODS AMBRA is a longitudinal cohort s...

Introduction: Thymidine kinase is an established marker of cancer cell proliferation and its activity can be measured in blood. We and others have recently shown that baseline and dynamic evaluation of circulating thymidine kinase activity (TKa) during treatment gives prognostic and predictive information in patients with HR+, HER2-negative metasta...

Background: TNBC shows a very bad prognosis: median time to relapse is 18 months and median overall survival (OS) is less than 24 months. Methods: AMBRA is a longitudinal cohort study, describing the choice of 1st- and subsequent treatments in HER2-ve MBC pts in the years 2012-2015. The present analysis is focused on TNBC pts (127 out of 879 evalua...

This article is an update of the requirements of a specialist breast centre, produced by EUSOMA and endorsed by ECCO as part of Essential Requirements for Quality Cancer Care (ERQCC) programme, and ESMO.To meet aspirations for comprehensive cancer control, healthcare organisations must consider the requirements in this article, paying particular at...

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Purpose: Thymidine kinase 1 (TK1) is downstream to the CDK4/6 pathway, and TK activity (TKa) measured in blood is a dynamic marker of outcome in patients with advanced breast cancer (ABC). This study explores TK1 as a biomarker of palbociclib response, both in vitro and in patients with ABC. Experimental design: Modulation of TK1 levels and acti...

Targeted agents have significantly prolonged survival and improved response rates in first- and second-line settings of hormone receptor-positive/HER2-negative metastatic breast cancer. Optimal sequencing of the available options may prolong endocrine sensitivity, slow disease progression and delay the need for chemotherapy. However, the optimal tr...

Background Chemotherapy added to anti-HER2 agents (H) is the treatment of choice in patients with HER2+ early breast cancer. However, HER2+ tumours are clinically and biologically heterogeneous, and treatment response varies significantly by hormone receptor (HR) status and molecular subtype. Predictive biomarkers are needed in this context. This s...

Cancer is a disease of older adults, with approximately 50% of cancer cases and 70% of cancer-related deaths occurring in individuals older than 65 years.¹ Older adults are also the fastest-growing portion of the general population worldwide,² which suggests that the incidence of cancer in this age group will continue to increase. Managing cancer i...

Background: EUSOMA undertook the commitment of defining the requirements for a specialist breast centre, which has become the reference document for the implementation of breast centres. Summary: The EUSOMA requirements for a specialist breast centre give clear indications regarding the requisite caseload, dedicated team composition (core and no...

Background Tumor phenotype may change during breast cancer (BC) progression and discordance between primary and metastases ranges between 16% and 21% for Hormone Receptor (HR) expression in some series. The impact of this change on patient (pts) management and outcome is not yet clear, even though preliminary data indicate that the molecular charac...

Background Adjuvant treatment decisions for pts with eCRC are currently based on suboptimal risk stratification factors, especially for elderly pts. Metabolomics measures multiple cancer-related metabolites with potential to identify new biomarkers in this setting. We have shown that serum metabolomics can discriminate pts with eCRC from pts with m...

Background HER2 blockade in combination with chemotherapy (CT) remains the treatment of choice for patients with early HER2+ BC, irrespective of ER status. Patients with HER2+ early BC co-expressing ER may benefit from HER2 blockade in combination with endocrine therapy (ET) and new targeted agents. Elderly patients benefit from HER2 blockade as mu...

In the absence of identified therapeutic targets, chemotherapy is the main systemic treatment option for triple-negative breast cancer (TNBC). The achievement of a pathological complete response (pCR) after neoadjuvant chemotherapy leads to good outcome, whereas patients not achieving a pCR are at high risk of relapse. Various trials have evaluated...

Despite recent refinements to the 21-gene g score, allowing a better identification of patients who may derive no benefit from the addition of adjuvant chemotherapy to that of endocrine therapy, patients with early breast cancer still stand to be over-treated in the setting of clinical and/or genomic uncertainty or discordance. Here we describe and...

Background: The CDK4/6 inhibitor palbociclib (P) is approved for the treatment of luminal metastatic breast cancer (MBC) in combination with endocrine therapy (ET). It leads to reduced phosphorylation of the Rb protein resulting in a decrease in E2F activity and eventual cell cycle arrest. Thymidine kinase 1 is a well-known cancer proliferation mar...

Overall survival (OS), disease‐free survival (DFS), and distant recurrence‐free interval (DRFI) were evaluated from 169 patients diagnosed with early triple negative breast cancer. Overall, 5 and 10 years OS, DFS, and DRFI were 77% and 65%; 60% and 46%; and 74% and 73%, respectively. Forty‐seven patients did not receive chemotherapy. A separate ana...

Background: The CDK4/6 inhibitor palbociclib (P) is approved for the treatment of luminal metastatic breast cancer (MBC) in combination with endocrine therapy (ET). It leads to reduced phosphorylation of the Rb protein resulting in a decrease in E2F activity and eventual cell cycle arrest. Thymidine kinase 1 is a well-known cancer proliferation mar...

BACKGROUND: Thymidine kinase 1 (TK1) plays a critical role in DNA synthesis and cell proliferation. Recent studies have shown potential for serum TK1 activity (sTKa) as a prognostic marker and indicator of early response to endocrine therapy in advanced breast cancer. The aim of this study is to assess the correlation between sTKa and patient outco...

HER2-positive (HER2+) breast cancer (BC) affects older women nearly as frequently as younger ones. Many older patients have cardiovascular comorbidity and risk greater toxicity from therapy. Treatment therefore requires careful consideration, especially since trials include few patients over 65 and so provide limited guidance. A multidisciplinary t...