Background The identification of the most appropriate targeted therapies for advanced cancers is challenging. We performed a molecular profiling of metastatic solid tumors utilizing a comprehensive next-generation sequencing (NGS) assay to determine mutations’ type, frequency and actionability and potential correlations with PD-L1 expression. Methods 304 adult patients with heavily-pretreated metastatic cancers treated between 01/2019-03/2021 were recruited. The CLIA-/UKAS-accredit Oncofocus® assay targeting 505 genes was used on newly-obtained or archived biopsies. Chi-square, Kruskal-Wallis and Wilcoxon rank-sum test were used where appropriate. Results were significant for p < 0.05. Results A total of 237 tumors (78%) harbored actionable mutations. Tumors were positive for PD-L1 in 68.9% cases. The median number of mutant genes/tumor was of 2.0 (IQR: 1.0–3.0). Only 34.5% were actionable ESCAT Tier I-II with different prevalence according to cancer type. The DNA damage repair (14%), the PI3K/AKT/mTOR (14%) and the RAS/RAF/MAPK (12%) pathways were the most frequently altered. No association was found between PD-L1, ESCAT, age, sex and tumor mutational status. Sixty-two patients underwent targeted treatment, with 37.1% obtaining objective responses. Conclusions We highlight the clinical value of molecular profiling in metastatic solid tumors using comprehensive NGS-based panels to improve treatment algorithms in situations of uncertainty and facilitate clinical trial recruitment.

Research on cancer therapies has benefited from predictive tools capable of simulating treatment response and other disease characteristics in a personalized manner, in particular three-dimensional cell culture models. Such models include tumor-derived spheroids, multicellular spheroids including organotypic multicellular spheroids, and tumor-derived organoids. Additionally, organoids can be grown from various cancer cell types, such as pluripotent stem cells and induced pluripotent stem cells, progenitor cells, and adult stem cells. Although patient-derived xenografts and genetically engineered mouse models replicate human disease in vivo, organoids are less expensive, less labor intensive, and less time-consuming, all-important aspects in high-throughput settings. Like in vivo models, organoids mimic the three-dimensional structure, cellular heterogeneity, and functions of primary tissues, with the advantage of representing the normal oxygen conditions of patient organs. In this review, we summarize the use of organoids in disease modeling, drug discovery, toxicity testing, and precision oncology. We also summarize the current clinical trials using organoids.

1014 Background: The Cyclin Dependent Kinase 4/6 inhibitors (CDK4/6i) Palbociclib, Ribociclib and Abemaciclib in combination with Endocrine Therapy (ET) represent the standard-of-care, 1st line treatment for patients with Hormone Receptor-positive, Human Epidermal growth factor Receptor 2-negative, advanced Breast Cancer (HR+/HER2- aBC). So far, no large real-world studies have compared the efficacy of the three CDK4/6i in this clinical setting. Methods: The multicenter, population-based study PALMARES-2 evaluated the antitumor efficacy of 1st line Palbociclib, Ribociclib or Abemaciclib in combination with ET in consecutive HR+/HER2- aBC patients treated in 18 Italian cancer centers between 1st January 2016 and 1st September 2023. The primary study endpoint was real-world Progression-Free Survival (rwPFS), as defined as the time interval between ET plus CDK4/6i initiation and disease progression. Multivariate Cox regression model was used to adjust the association between individual CDK4/6i and rwPFS for clinically relevant variables. Results: With a data cut-off date of January 1st, 2024, we enrolled 1850 patients, 750 (40.6%), 676 (36.5%) and 424 (22.9%) of whom received Palbociclib, Ribociclib and Abemaciclib, respectively. Among 1226 (66.3%) patients with endocrine-sensitive disease, 1087 (89%) received concomitant Aromatase Inhibitors, whereas 441 (70.7%) out of 624 (33.7%) patients with endocrine-resistant disease received concomitant Fulvestrant. Patients treated with Abemaciclib were more likely to have endocrine-resistant disease, liver metastases, lobular tumor histology and lower PgR tumor expression, and less likely to have de novometastatic disease (p<0.001). Median rwPFS in the whole study cohort was 34.9 months (95% CI 32.0-37.4). Abemaciclib and Ribociclib were independently associated with better rwPFS when compared to Palbociclib (Table), whereas Abemaciclib and Ribociclib showed no significantly different efficacy (aHR 0.91, 95% CI 0.70-1.19; p=0.505). Other covariates independently associated with rwPFS are shown (Table). Conclusions: The real-world study PALMARES-2 revealed different antitumor efficacy of individual CDK4/6i in HR+/HER2- aBC patients. Longer follow-up is required to study if Palbociclib, Ribociclib and Abemaciclib are associated with different overall survival. [Table: see text]

Transgender and gender-diverse (TGD) individuals face an elevated risk of cancer in comparison with the general population. This increased risk is primarily attributed to an imbalanced exposure to modifiable risk factors and a limited adherence to cancer screening programmes, stemming from historical social and economic marginalisation. Consequently, these factors contribute to poorer clinical outcomes in terms of cancer diagnosis and mortality. A focal point of interest is the potential carcinogenic effect of gender-affirming hormone therapy (GAHT). It is crucial to recognise that GAHT serves as an essential, life-saving treatment for TGD individuals. Therefore, if a demonstrated direct correlation between GAHT and elevated cancer risk emerges, essential shared decision-making discussions should occur between oncology practitioners and patients. This narrative review aims to collect and discuss evidence regarding potential correlations between GAHT and the most prevalent tumours known to be influenced by sex hormones. The objective is to comprehend how these potential carcinogenic effects impact health and inform health interventions for TGD individuals. Unfortunately, the scarcity of epidemiological data on cancer incidence in the TGD population persists due to the absence of sexual orientation and gender identity data collection in cancer centres. Consequently, in most cases, establishing a positive or negative correlation between GAHT and cancer risk remains speculative. There is an urgent need for concerted efforts from researchers and clinicians worldwide to overcome barriers and enhance cancer prevention and care in this specific population.

Metastatic breast cancer (MBC) is still an incurable disease, which eventually develops resistance mechanisms against systemic therapies. While most patients experience widespread disease progression during systemic treatment (ST), in some cases, progression may occur at a limited number of metastatic sites. Evidence from other malignancies suggests that local treatment with stereotactic ablative radiotherapy (SABR) of oligoprogressive disease (OPD) may allow effective disease control without the need to modify ST. Available evidence regarding local treatment of oligoprogressive breast cancer is limited, mostly consisting of retrospective studies. The only randomized data come from the randomized CURB trial, which enrolled patients with oligoprogressive disease, including both small cell lung cancer and breast cancer patients, and did not show a survival benefit from local treatment in the latter group. However, local treatment of oligoprogressive MBC is still considered in clinical practice, especially to delay the switch to more toxic STs. This review aims to identify patients who may benefit from this approach based on the current available knowledge, focusing also on the potential risks associated with the combination of radiotherapy (RT) and ST, as well as on possible future scenarios.

Since 2019, the world has been experiencing an outbreak of a novel beta-coronavirus, severe acute respiratory syndrome coronavirus (SARS-CoV)-2. The worldwide spread of this virus has been a severe challenge for public health, and the World Health Organization declared the outbreak a public health emergency of international concern. As of June 8, 2023, the virus' rapid spread had caused over 767 million infections and more than 6.94 million deaths worldwide. Unlike previous SARS-CoV-1 and Middle East respiratory syndrome coronavirus outbreaks, the COVID-19 outbreak has led to a high death rate in infected patients; this has been caused by multiorgan failure, which might be due to the widespread presence of angiotensin-converting enzyme 2 (ACE2) receptors—functional receptors of SARS-CoV-2—in multiple organs. Patients with cancer may be particularly susceptible to COVID-19 because cancer treatments (e.g., chemotherapy, immunotherapy) suppress the immune system. Thus, patients with cancer and COVID-19 may have a poor prognosis. Knowing how to manage the treatment of patients with cancer who may be infected with SARS-CoV-2 is essential. Treatment decisions must be made on a case-by-case basis, and patient stratification is necessary during COVID-19 outbreaks. Here, we review the management of COVID-19 in patients with cancer and focus on the measures that should be adopted for these patients on the basis of the organs or tissues affected by cancer and by the tumor stage.

Approximately 6% of metastatic breast cancers arise de novo . While systemic therapy (ST) remains the treatment backbone as for patients with metachronous metastases, locoregional treatment (LRT) of the primary tumor remains a controversial method. The removal of the primary has an established role for palliative purposes, but it is unclear if it could also determine a survival benefit. Retrospective evidence and pre-clinical studies seem to support the removal of the primary as an effective approach to improve survival. On the other hand, most randomized evidence suggests avoiding LRT. Both retrospective and prospective studies suffer several limitations, ranging from selection bias and outdated ST to a small sample of patients. In this review we discuss available data and try to identify subgroups of patients which could benefit the most from LRT of the primary, to facilitate clinical practice decisions, and to hypothesize future studies design on this topic.

The phosphoinositide 3 kinase (PI3K)-protein kinase B (PKB/AKT)-mammalian target of the rapamycin (mTOR) axis is a key signal transduction system that links oncogenes and multiple receptor classes which are involved in many essential cellular functions. Aberrant PI3K signalling is one of the most commonly mutated pathways in cancer. Consequently, more than 40 compounds targeting key components of this signalling network have been tested in clinical trials among various types of cancer. As the oncogenic activation of the PI3K/AKT/mTOR pathway often occurs alongside mutations in other signalling networks, combination therapy should be considered. In this review, we highlight recent advances in the knowledge of the PI3K pathway and discuss the current state and future challenges of targeting this pathway in clinical practice.

The research on non-invasive circulating biomarkers to guide clinical decision is in wide expansion, including the earliest disease settings. Several new intensification/de-intensification strategies are approaching clinical practice, personalizing the treatment for each patient. Moreover, liquid biopsy is revealing its potential with multiple techniques and studies available on circulating biomarkers in the preoperative phase. Inflammatory circulating cells, circulating tumor cells (CTCs), cell-free DNA (cfDNA), circulating tumor DNA (ctDNA), and other biological biomarkers are improving the armamentarium for treatment selection. Defining the escalation and de-escalation of treatments is a mainstay of personalized medicine in early breast cancer. In this review, we delineate the studies investigating the possible application of these non-invasive tools to give a more enlightened approach to escalating/de-escalating strategies in early breast cancer.

Introduction: Cyclin-dependent kinase 4/6 inhibitors (CDK4/6i) in combination with endocrine therapy (ET) are the standard first-line treatment for patients with hormone receptor-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (HR+/HER2- aBC). HER2-low BC, which is defined by an IHC score for HER2 of 1+ or 2+ with negative ISH assay, accounts for more than half of all HR+/HER2- aBC cases, and it is associated with remarkable clinical benefit from the novel anti-HER2 antibody drug conjugate (ADC) trastuzumab-deruxtecan. Evidence on the prognostic impact of HER2-low status is controversial in both limited-stage and advanced BC. Here, we sought to investigate the possible prognostic relevance of HER2-low status in a population of aBC patients treated with CDK4/6i plus ET. Methods: We conducted a retrospective-prospective study in six Italian Cancer Centers to investigate the impact of HER2 status (low vs. 0) on the progression-free survival (PFS) and overall survival (OS) of consecutive HR+/HER2- aBC patients treated with CDK4/6i plus ET (aromatase inhibitors or fulvestrant) as a first-line therapy. In the main study analysis, we considered HER2 status in the last tumor assessment (i.e., primary tumor, or, when available, a metastatic lesion). We also performed a subgroup analysis including only patients with HER2 status evaluation in a metastatic lesion collected before CDK4/6i plus ET therapy initiation. The association between HER2 status (low vs. 0) and PFS or OS was evaluated using log-rank test and Cox regression modeling. Results: We evaluated 767 consecutive HR+/HER2- aBC patients treated with CDK4/6i plus ET between January 2017 and January 2022. Of these, 436 patients (56.8%) received CDK4/6i plus ET as a first-line therapy, and they were included in this analysis. Median age was 63 years (range 27-87), and 362 patients (83.0%) were postmenopausal. The majority of patients were treated with palbociclib (68.3%), while 91 (20.9%) and 47 (10.8%) patients received ribociclib and abemaciclib, respectively. Regarding HER2 status, 269 (62.9%) patients had HER2-low tumors, while 159 (37.1%) patients had HER2-0 neoplasms. HER2-low status was associated with significantly lower PFS when compared to HER2-0 status [median PFS (mPFS) 23.6 vs. 32.3 months, respectively; p=0.014]. HER2-low status was also associated with significantly worse OS (mOS 48.7 vs 58.3 months, respectively; p=0.025). These results were confirmed in multivariable models adjusting the impact of HER2 status for clinically-relevant covariates, namely estrogen receptor status, Ki-67, age, number of metastatic sites, presence of liver metastases, disease free interval, ECOG Performance Status. In this analysis, HER2-low status, compared with HER2-0 status, was independently associated with worse PFS [adjusted Hazard Ratio (aHR): 1.62; 95% confidence interval (CI): 1.17-2.24; p< 0.01] and OS (aHR: 1.74; 95% CI: 1.09-2.76; p=0.019). Subgroup analysis conducted in the subset of 256 patients with available metastatic tumor samples collected before CDK4/6i plus ET initiation confirmed that HER2-low status (n=157), when compared to HER2-0 status (n=99), was independently associated with worse PFS (mPFS 24.5 vs 35.2 months, p=0.01; aHR 2.07; 95% CI: 1.28-3.34, p< 0.01) and worse OS (mPFS 48.7 vs 72.3 months, p=0.027; aHR 3.12; 95% CI 1.44-6.77, p< 0.01). Conclusions: This multicenter Italian study revealed that HER2-low status has independent, negative prognostic value in patients with HR+/HER2- aBC treated with CDK4/6i plus ET in the first-line setting. Our results suggest that HER2-low status might be associated with different clinical benefit from standard anticancer therapies in specific clinical settings. The definition of treatment algorithms also taking into account HER2 status is a clinical priority in patients with HR+/HER2- aBC. Citation Format: Emma Zattarin, Caterina Sposetti, Rita Leporati, Luigi Mariani, Alice Menichetti, Chiara Corti, Chiara Benvenuti, Giovanni Fucà, Riccardo Lobefaro, Francesca Ligorio, Daniele Presti, Leonardo Provenzano, Andrea Vingiani, Gaia Griguolo, Marianna Sirico, Ottavia Bernocchi, Antonio Marra, Paola Zagami, Elisa Agostinetto, Flavia Jacobs, Pierluigi Di Mauro, Andrea Esposito, Carlo Alberto Giorgi, Luca Lalli, Laura Boldrini, Pier Paolo Maria Berton Giachetti, Ambra Carnevale Schianca, Valentina Guarneri, Rebecca Pedersini, Agnese Losurdo, Alberto Zambelli, Daniele Giulio Generali, Giuseppe Curigliano, Giancarlo Pruneri, Filippo de Braud, Maria Vittoria Dieci, Claudio Vernieri. HER2-02 HER2-Low Status is Associated with Worse Clinical Outcomes in Hormone Receptor-Positive, HER2-Negative Advanced Breast Cancer Patients Treated With First-Line Cyclin-Dependent Kinase 4/6 Inhibitors Plus Endocrine Therapy [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr HER2-02.

Background: Routine imaging can be inaccurate, especially in metastatic breast cancer (MBC) with bone-only disease or mainly bone disease. This analysis investigates how the use of whole-body magnetic resonance imaging (WB-MRI), in addition to routine computed tomography (CT) and bone scintigraphy (BS), can influence treatment decisions in patients with known MBC. Methods: In a prospective observational study, in our Institute, we performed WB-MRI as baseline and follow-up examination in addition to routine imaging (CT, BS) in luminal/HER2-negative BC patients with prevalence of bone disease potentially candidate to CDK 4/6 inhibitors. All examinations were interpreted by two experienced radiology specialists. Using the results of the examination, a multidisciplinary oncology committee (MOC) reported on the treatment strategy. A positive impact on clinical management was considered if the examination determined a modification in the treatment strategy compared to the MOC decision before WB-MRI. Results: Thirty consecutive luminal breast cancer patients in a metastatic setting at standard imaging were recruited. All these patients underwent CT and BS followed by WB-MRI study. At standard imaging, fourteen patients (46.7%) presented with bone-only disease, while eight patients (26.6%) did not show bone lesions. In 18 of 30 cases (60%) WB-MRI led to a modification of the therapeutic approach. Due to the detection of new metastatic lesions or progression of known metastatic sites, reported on WB-MRI alone, the therapeutic decision changed in 6 (20%) and 3 (10%) patients, respectively. In one patient (3%) the therapeutic decision changed because of both findings. Nine patients (30%) started a new therapeutic line due to evidence of progressive disease on WB-MRI, while 4 patients (13.3%) underwent radiotherapy and 1 patient received orthopaedic counselling for high risk WB-MRI-assessed bone lesions. In 8 patients (26.6%) the disease was re-classified as early breast cancer based on WB-MRI assessment. Conclusions: WB-MRI could play a role in the clinical assessment of luminal MBC. Further studies are needed to better address the potential use of WB-MRI in the assessment and monitoring of bone only/bone predominant luminal MBC and/or in equivocal cases. Citation Format: Filippo Merloni, Michela Palleschi, Alice Rossi, Andrea Prochowski Iamurri, Caterina Gianni, Samanta Sarti, Francesca Mannozzi, Federica Fiori, Giandomenico Di Menna, Lorenzo Cecconetto, Marianna Sirico, Chiara Casadei, Sara Bleve, Lorenzo Gasperoni, Roberto Casadei, Luca Tontini, Antonino Romeo, Domenico Barone, Ugo De Giorgi. Clinical impact of whole-body magnetic resonance imaging on subsequent management in luminal/HER2-negative breast cancer patients [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P1-05-13.

Background:Cyclin-Dependent Kinase 4/6 inhibitors (CDK4/6i) combined with Endocrine Therapy (ET) are the standard treatment for patients with Hormone Receptor-positive/HER2-negative advanced breast cancer (HR+/HER2- aBC).Objectives:While CDK4/6i are known to reduce several peripheral blood cells, such as neutrophils, lymphocytes and platelets, the impact of these modulations on clinical outcomes is unknown.Design:A multicenter, retrospective-prospective Italian study.Methods:We investigated the association between baseline peripheral blood cells, or their early modifications (i.e. 2 weeks after treatment initiation), and the progression-free survival (PFS) of HR+/HER2- aBC patients treated with ETs plus CDK4/6i. Random Forest models were used to select covariates associated with patient PFS among a large list of patient- and tumor-related variables.Results:We evaluated 638 HR+/HER2- aBC patients treated with ET plus CDK4/6i at six Italian Institutions between January 2017 and May 2021. High baseline lymphocyte counts were independently associated with longer PFS [median PFS (mPFS) 20.1 versus 13.2 months in high versus low lymphocyte patients, respectively; adjusted Hazard Ratio (aHR): 0.78; 95% confidence interval (CI): 0.66-0.92; p = 0.0144]. Moreover, patients experiencing a lower early reduction of lymphocyte counts had significantly longer PFS when compared to patients undergoing higher lymphocyte decrease (mPFS 18.1 versus 14.5 months; aHR: 0.82; 95% CI: 0.73-0.93; p = 0.0037). Patients with high baseline lymphocytes and undergoing a lower reduction, or even an increase, of lymphocyte counts during CDK4/6i therapy experienced the longest PFS, while patients with lower baseline lymphocytes and undergoing a higher decrease of lymphocytes had the lowest PFS (mPFS 21.4 versus 11 months, respectively).Conclusion:Baseline and on-treatment modifications of peripheral blood lymphocytes have independent prognostic value in HR+/HER2- aBC patients. This study supports the implementation of clinical strategies to boost antitumor immunity in patients with HR+/HER2- aBC treated with ETs plus CDK4/6i.

Metastatic breast cancer (BC) is considered an incurable disease and is usually treated with palliative intent. However, about 50% of metastatic BCs present with only a few metastatic lesions and are characterized by longer overall survival. These patients, defined as oligometastatic, could benefit from a multimodal approach, which combines systemic therapy with metastasis-directed treatment (stereotactic ablative therapy or surgery). The current definition of oligometastatic seems incomplete since it is based only on imaging findings and does not include biological features, and the majority of relevant data supporting this strategy comes from retrospective or non-randomized studies. However, the chance of reaching long-term complete remission or even a cure has led to the development of randomized trials investigating the impact of combined treatment in oligometastatic BC (OMBC). The SABR-COMET trial, the first randomized study to include BC patients, showed promising results from a combination of stereotactic ablative radiotherapy and systemic therapy. Considering the randomized trial's results, multidisciplinary teams should be set up to select OMBC patients who could achieve long-term survival with aggressive multimodal treatment.

We extensively characterized a metastatic UPS with a 71-month lasting complete response to immunotherapy.

Background: One year of adjuvant trastuzumab with 12 cycles of weekly paclitaxel represents the standard of care for patients with pathological tumor size ≤2cm, node-negative, HER2-positive early breast cancer. Data supporting this indication derive from a single-arm, phase II trial that enrolled 410 patients in the United States only, where the 3 years invasive disease-free survival (DFS) rate was 98.7% (95% CI 97.6-99.8). Therefore, real-world data regarding the clinical outcomes of these patients are needed to confirm the efficacy and safety of this adjuvant anthracycline-free regimen in this population. Methods: We conducted a retrospective, observational, multicentric study to investigate survival outcomes of patients with stage I HER2-positive early breast cancer treated with adjuvant paclitaxel and trastuzumab in seven selected sites in two countries (Belgium and Italy). Eligible patients were men and women with early breast cancer of pathological tumor size between 5 and 20 mm, node-negative (N0 or N1mic), and treated with weekly adjuvant paclitaxel for 12 weeks and trastuzumab (6 mg/kg every 3 weeks administration for 1 year). Patients with a history of previous cancers were not included. The primary endpoint was disease-free survival (DFS) at 3 years from diagnosis. Thus, an optimal follow-up of 3 years from surgery was required. Baseline clinico-pathological characteristics, treatment data, disease recurrences and survival status were extracted from medical records. Survival analysis was performed using log-rank regression test. Results: Overall, 240 patients who received their adjuvant treatment between January 2014 and December 2018 were included in the analysis. The median age was 59.5 years (IQR 50.0-66.9), and 69.6% of patients were post-menopausal at the time of diagnosis. Seventy (31.8%) patients had hypertension and 20 (8.3%) had other cardiac comorbidities. Ductal carcinoma was the most represented histological type (86.3%). The median tumor size was 12mm (IQR 9-15), only seven (2.9%) patients had N1miC, and the majority of tumors (85.0%) were ER-positive. Breast-conserving surgery was performed in 80.8% of patients and 78.2% of patients had adjuvant radiotherapy. The median number of administrated cycles of weekly paclitaxel was 12 (range 1-12) and for trastuzumab 18 (range 1-19). Only one patient stopped trastuzumab prematurely because of safety reason. Aromatase inhibitors were the most frequently administered endocrine therapy (75.7% of patients with ER-positive disease). With a median follow-up of 4.7 (IQR 3.6-5.6) years, we observed a 3-year DFS rate of 98.8% (95% CI 96.2-99.6), with only three disease recurrences (one local and two distant) and four deaths (none of which was breast cancer related) during the duration of the follow-up. Conclusions: In this real-world clinical outcome of patients with stage I HER2-positive breast cancer treated with adjuvant trastuzumab and paclitaxel appeared excellent, with a 1.2% rate of recurrence at 3 years. Our data support the efficacy of an anthracycline-free regimen in this population. A longer follow-up will provide more mature data on overall survival and late relapses, especially in the ER-positive subgroup of patients. Citation Format: Veronique Debien, Elisa Agostinetto, Marianna Sirico, Flavia Jacobs, Chiara Molinelli, Michel Moreau, Marianne Paesmans, Ugo De Giorgi, Armando Santoro, Donatienne Taylor, François P. Duhoux, Andrea Botticelli, Giacomo Barchiesi, Matteo Lambertini, Evandro de Azambuja, Martine Piccart. Real-world clinical outcomes of patients with stage I HER2-positive breast cancer treated with adjuvant paclitaxel and trastuzumab [abstract]. In: Proceedings of the 2022 San Antonio Breast Cancer Symposium; 2022 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2023;83(5 Suppl):Abstract nr P2-01-04.

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. In our retrospective study of 240 patients, the median tumor size was 12.0 mm (IQR 9 -15), and 204 (85%) had estrogen receptor-positive disease. After a median follow-up of 4.6 years, 3-year real-world disease-free survival, distant DFS, and overall survival were 98.8% (95% confidence interval (CI), 96.2-99.6), 99.2% (95% CI, 96.7-99.8), and 98.3% (95% CI, 96.2-99.6), respectively. In a real-world setting, an adjuvant paclitaxel/trastuzumab regimen was associated with low recurrence rates among women with stage I, HER2-positive breast cancer. Additionally, we reviewed other treatment optimization strategies attempted or ongoing in HER2-positive breast cancer.

Whether Human Epidermal growth factor Receptor 2 (HER2)-low status has prognostic significance in HR + /HER2- advanced Breast Cancer (aBC) patients treated with first-line Endocrine Therapy plus CDK 4/6 inhibitors remains unclear. In 428 patients evaluated, HER2-low status was independently associated with significantly worse PFS and OS when compared with HER2-0 status. Based on our findings, HER2-low status could become a new prognostic biomarker in this clinical setting.