Search Results (366)

Cyclin-dependent kinase (CDK)4/6 inhibitors have become a key component of adjuvant treatment for patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) early breast cancer who are at high risk of recurrence. The addition of abemaciclib and ribociclib to standard endocrine therapy has demonstrated clinically meaningful improvements in invasive disease-free survival, supported by the monarchE and NATALEE trials, respectively. With expansion of patient eligibility for CDK4/6 inhibitors, multidisciplinary coordination among medical oncologists, surgeons, nurses, pharmacists, and other health care providers is critical to optimizing patient identification, monitoring, and management of adverse events. This expert guidance document provides practical recommendations for implementing adjuvant CDK4/6 inhibitor therapy in routine clinical practice, incorporating insights from multiple specialties and with patient advocacy representation. Key considerations include patient selection based on clinical trial data, treatment duration, dosing schedules, adverse event profiles, monitoring requirements, drug–drug interactions, and patient-specific factors such as tolerability, cost, and quality of life. This guidance aims to support Canadian clinicians in effectively integrating CDK4/6 inhibitors into clinical practice, ensuring optimal patient outcomes through a multidisciplinary and patient-centric approach. Full article

Background/Objectives: Breast cancer was the leading cause of malignant tumors among women in 2022. About two-thirds of breast cancer cases are hormone-receptor-positive. In these patients, aromatase inhibitors are a mainstay of treatment, but associated musculoskeletal symptoms can negatively affect patient compliance. Aromatase-inhibitor-induced carpal tunnel syndrome represents one of the main causes of aromatase inhibitor discontinuation, with a non-compliance rate of up to 67%, potentially leading to increased cancer mortality. This study investigates estrogen receptor expression in aromatase-inhibitor-induced carpal tunnel syndrome tissues, in order to better define its etiopathogenesis and derive preventive or therapeutic measures that can improve aromatase inhibitor patient compliance. To our knowledge, there is no study on this subject in the literature. Methods: Between 2023 and 2024, we recruited 14 patients at the Jewish Hospital of Rome, including seven patients with aromatase-inhibitor-induced carpal tunnel syndrome (study group) and seven with postmenopausal idiopathic carpal tunnel syndrome (control group). Each patient was evaluated based on a clinical visit, a questionnaire, instrumental exams, and serum hormone dosages and were treated with open carpal tunnel release surgery, during which transverse carpal ligament and flexor tenosynovium samples were collected. For immunohistochemical experiments, sections were treated with anti-estrogen receptor α and anti-estrogen receptor β antibodies. Results: The immunohistochemical features in the study and control groups were similar, demonstrating that tissues affected by aromatase-inhibitor-induced carpal tunnel syndrome are targets of direct estrogen action and that estrogen deprivation is correlated with disease etiogenesis. Surgery was effective in patient treatment. Conclusions: Aromatase-inhibitor-induced carpal tunnel syndrome represents a newly defined form of the disease. This syndrome represents one of the main causes of aromatase inhibitor discontinuation, due to its negative impact on the patient’s quality of life. The identification by clinicians of aromatase inhibitor use as a possible risk factor for carpal tunnel syndrome development is of essential importance, as early diagnosis and prompt management can improve patient compliance and overall breast cancer treatment outcomes. Full article

Background/Objectives: This study aimed to assess real-world toxicity and efficacy data of patients with early and advanced breast cancer (BC) who received treatment with abemaciclib. Methods: This was a prospective/retrospective multi-institutional collection of clinicopathological, toxicity, and outcome data from patients with early or metastatic hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative BC who received treatment with abemaciclib in combination with endocrine therapy in departments of oncology in Greece. Treatment combinations of abemaciclib with any endocrine therapy were accepted. The primary end point was toxicity rate in all patients of the study. Results: From June/2021 to May/2024, 245 women received abemaciclib/endocrine combination therapy; the median age was 57 years. Of these, 169 (69%) received abemaciclib as adjuvant therapy for early-stage disease, while 76 (31%) were treated for advanced BC. At the time of the data cutoff, 133 (84.7%) patients remained in the 2-year treatment period. The most common adverse event (AE) was diarrhea (51%), primarily Grade ≤ 2. Dose modifications due to AEs were required in 19.2% of cases, while treatment discontinuation occurred in 5.1%. There was no difference in dose modification/discontinuation rates between older patients (>65 years) and the remaining patients. For early-stage BC patients, the 2-year DFS and OS rates were 90.8% and 100%, respectively. In patients with advanced cancer (70, 30.8%), 1-year PFS and OS rates were 78% and 96.3%, respectively. Conclusions: This study confirms the safety and effectiveness of abemaciclib in alignment with registrational trials offering valuable insights into toxicity management and clinical outcomes in routine practice without identifying new safety concerns. Clinical Trial Registration: ClinicalTrials.gov NCT04985058. Full article

Breast cancer (BC) is the most common malignancy and the second-leading cause of cancer-related mortalities in women. Epidemiological studies suggested the reduced BC incidence in Mediterranean populations due to the daily consumption of diets rich in extra-virgin olive oil (EVOO). EVOO secoiridoid phenolics are widely known for their positive outcomes on multiple cancers, including BC. The current study investigates the suppressive effects of individual and combined EVOO phenolics for BC progression and motility. Screening of a small library of EVOO phenolics at a single dose of 10 µM against the viability of the BC cell lines ZR-75-1 (luminal A) and MDA-MB-231 (triple negative BC, TNBC) identified oleocanthal (OC) and ligstroside aglycone (LA) as the most active hits. Screening of EVOO phenolics for BC cells migration inhibition identified OC, LA, and the EVOO lignans acetoxypinoresinol and pinoresinol as the most active hits. Combination studies of different olive phenolics showed that OC combined with LA had the best synergistic inhibitory effects against the TNBC MDA-MB-231 cells migration. A combination of 5 µM of each of OC and LA potently suppressed the migration and invasion of the MDA-MB-231 cells versus LA and OC individual therapies and vehicle control (VC). Animal studies using the ZR-75-1 BC cells orthotopic xenografting model in female nude mice showed significant tumor progression suppression by the combined OC-LA, 5 mg/kg each, ip, 3X/week treatments compared to individual LA and OC treatments and VC. The BC suppressive effects of the OC-LA combination were associated with the modulation of SMYD2–EZH2–STAT3 signaling pathway. A metastasis–clonogenicity animal study model using female nude mice subjected to tail vein injection of MDA-MB-231-Luc TNBC cells also revealed the effective synergy of the combined OC-LA, 5 mg/kg each, compared to their individual therapies and VC. Thus, EVOO cultivars rich in OC with optimal LA content can be useful nutraceuticals for invasive hormone-dependent BC and TNBC progression and metastasis. Full article

Background: Pathological complete response (pCR) serves as a prognostic surrogate endpoint for long-term clinical outcomes in breast cancer patients receiving neoadjuvant systemic therapy (NAST). This study aims to develop and evaluate machine learning-based biomarkers for predicting pCR and recurrence-free survival (RFS). Methods: This retrospective monocentric study included 235 women (mean age 46 ± 11 years) with non-metastatic breast cancer treated with NAST. We developed various machine learning models using clinical features (age, genetic mutations, TNM stage, hormonal receptor expression, HER2 status, and histological grade), along with morphological features (size, T2 signal, and surrounding edema) and radiomics data extracted from pre-treatment MRI. Patients were divided into training and test groups with different MRI models. A customized machine learning pipeline was implemented to handle these diverse data types, consisting of feature selection and classification components. Results: The models demonstrated superior prediction ability using radiomics features, with the best model achieving an AUC of 0.72. Subgroup analysis revealed optimal performance in triple-negative breast cancer (AUC of 0.80) and HER2-positive subgroups (AUC of 0.65). Conclusion: Machine learning models incorporating clinical, qualitative, and radiomics data from pre-treatment MRI can effectively predict pCR in breast cancer patients receiving NAST, particularly among triple-negative and HER2-positive breast cancer subgroups. Full article

Background and Objectives: The objective of this review is to evaluate the current evidence regarding hormone treatments for both premenopausal and postmenopausal women with early-stage hormone receptor (HR) positive breast cancer. Materials and Methods: An in-depth exploration of the existing literature was conducted, with landmark clinical trials such as TEXT, SOFT, ATLAS, and aTTom serving as primary references. Results: Through an extensive review of the literature, our findings indicate that for premenopausal women with HR-positive, HER2-negative BC with a low risk of recurrence, standard 5-year monotherapy with tamoxifen represents the optimal therapeutic management, given its favorable clinical outcomes and lower associated toxicity. In contrast, for premenopausal women with an intermediate to high risk of recurrence with the same tumor characteristics, the most effective approach stated in the literature is a combination of ovarian suppression therapy (chemical/surgical) and an aromatase inhibitor/selective estrogen receptor modulator (tamoxifen), with a possible extension of the standard therapeutic period. In postmenopausal patients with HR-positive, HER2-negative breast cancer with a low recurrence risk, the first line of treatment is usually a standard 5-year period of treatment with aromatase inhibitors (AIs)(letrozole, anastrozole, or exemestane). On the other hand, in postmenopausal women with an intermediate to high risk, combination therapy might be needed, as well as an extension of the standard therapeutic time. Conclusions: Treatment consensus depends on pre- vs. postmenopausal status and recurrence risk. Full article

Emerging evidence suggests a bidirectional relationship between gut microbiota, melatonin synthesis, and breast cancer (BC) development in hormone receptor-positive patients (HR+HER2+ and HR+HER2-). This study investigated alterations in gut microbiota composition, the serum serotonin–N-acetylserotonin (NAS)–melatonin axis, fecal short-chain fatty acids (SCFAs) and beta-glucuronidase (βGD) activity, and serum zonulin in HR+ BC patients compared to healthy controls. Blood and fecal samples were analyzed using mass spectrometry for serotonin, NAS, melatonin, and SCFAs; ELISA for AANAT, ASMT, 14-3-3 protein, and zonulin; fluorometric assay for βGD activity; and 16S rRNA sequencing for gut microbiota composition. HR+ BC patients exhibited gut dysbiosis with reduced Bifidobacterium longum and increased Bacteroides eggerthii, alongside elevated fecal βGD activity, SCFA levels (e.g., isovaleric acid), and serum zonulin, indicating increased intestinal permeability. Serum serotonin and N-acetylserotonin (NAS) levels were elevated, while melatonin levels were reduced, with a higher NAS/melatonin ratio in BC patients. AANAT levels were increased, and ASMT levels were decreased, suggesting disrupted melatonin synthesis. Bifidobacterium longum positively correlated with melatonin and negatively with βGD activity, while Bacteroides eggerthii showed a positive correlation with βGD activity. These findings suggested that gut microbiota alterations, disrupted melatonin synthesis, microbial metabolism, and intestinal permeability may contribute to BC pathophysiology. The NAS/melatonin ratio could represent a potential biomarker, necessitating further mechanistic studies to confirm causality and explore therapeutic interventions. Full article

The adjuvant treatment landscape for hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) early breast cancer (EBC) is rapidly evolving, with a diverse range of therapeutic options—including endocrine therapies, bisphosphonates, ovarian function suppression, olaparib, CDK4/6 inhibitors, and emerging agents such as immunotherapy. While these advances have markedly improved patient outcomes, they also introduce challenges related to implementation, monitoring, and resource allocation. Notably, therapies like CDK4/6 inhibitors require particularly close monitoring, creating logistical and capacity challenges for medical oncologists, whose workloads are already stretched due to rising cancer incidence and treatment complexities. These challenges underscore the need for innovative care delivery solutions to ensure patients with EBC continue to receive optimal care. This paper offers a comprehensive guide—a playbook—of multidisciplinary-team-based care models designed to optimize adjuvant treatment delivery in EBC. Drawing on real-world evidence and successful applications across Canadian centers, we explore models led by nurses, nurse practitioners (NPs), general practitioners in oncology (GPO), and pharmacists. Each model leverages the unique expertise of its team to manage treatment toxicities, facilitate adherence, and enhance patient education, thereby promoting effective and sustainable care delivery. Importantly, these models are not intended to compete with one another, but rather to serve as a flexible recipe book from which breast cancer care teams can draw strategies tailored to their local resources and patient needs. By detailing implementation strategies, benefits, and challenges—in many instances supported by quantitative metrics and economic evaluations—this work aims to inspire care teams nationwide to optimize the adjuvant management of patients with HR+, HER2– EBC. Full article

Purpose: Neoadjuvant endocrine therapy (NET) represents a valuable treatment option for hormone receptor-positive (HR+)/HER2-negative breast cancer, particularly in postmenopausal women. This study aimed to evaluate the clinical and histopathological efficacy of NET and to explore early and late changes in Ki-67 and progesterone receptor (PgR) expression as indicators of endocrine response. Methods: A prospective cohort of 127 postmenopausal patients with stage cT1–4N0–3M0 HR+/HER2− breast cancer was enrolled between 2019 and 2021. Patients received NET (mostly letrozole) for a mean of 7.7 months. In 80 cases, a second core biopsy was performed after four weeks. Tumor size, histological grade, and biomarkers (Ki-67, PgR) were assessed pre- and post-treatment. Results: NET led to a significant reduction in tumor size, with median shrinkage of 47.0% (from 32.0 mm to 17.0 mm, p < 0.0001). Breast-conserving surgery (BCS) was performed in 52.2% of patients and lymph node negativity (pN0) was observed in 50.4%. Median Ki-67 decreased from 20.0% at baseline to 5.0% after four weeks (p < 0.0001) and remained low in surgical specimens (median 5.0%, p < 0.0001). In 33.3% of patients, Ki-67 dropped below 2.7%, and 67.0% showed a concordant decrease in both Ki-67 and PgR. PgR expression declined significantly during treatment (p < 0.0001). HER2 status conversion was noted in 6.4% of patients during treatment. Pathological complete response (pCR) occurred in 3.5%, while minimal or moderate residual disease (RCB I–II) was identified in 71.3% of cases. Conclusions: NET effectively reduced tumor burden and histological aggressiveness, enabling higher rates of BCS. Early reduction in Ki-67 and PgR may serve as surrogate markers of endocrine responsiveness, supporting their use for treatment stratification and monitoring during NET in HR+/HER2− breast cancer. Full article

Pathological complete response (pCR) following neoadjuvant therapy for IBC has shown a strong correlation with event-free survival and overall survival. Over the past three decades, the five-year net survival rate for breast cancer has generally increased; however, several Eastern European countries exhibit lower survival rates. Data from Romania, specifically regarding Her2-positive breast cancer response to therapy, are notably limited. Background/Objectives: The aim of our study was to evaluate the response to NAT using chemotherapy and Her2-targeted therapy in a cohort of 167 patients diagnosed with invasive breast cancer in our institution. Methods: We retrospectively analyzed 167 consecutive cases diagnosed with IBC in our institution between January 2020 and September 2024 with Stages II and III Her2-positive IBC. The overall pCR rates and several factors cited in the literature as predictors of pCR were analyzed. Results: Overall, the pCR rate was 50.29%, with higher values in 3+ cases (62.28%) compared to 2+ cases/ISH amplified (24.53%). Higher pCR rates were observed in hormone-negative cases, Stage II cases, estrogen receptor-negative cases, and high Ki-67 values. Patient age, ISH group, Her2 copy number, Her2:CEP17 ratio, and clinical lymph node involvement did not seem to influence pCR rates in our study. Conclusions: The data presented in our study represent, to the best of our knowledge, the largest cohort of patients diagnosed with Her2-positive IBC from Romania. The presented results and the pCR predictive factors were comparable to those cited in other studies on Her2-positive IBC cases. Full article

Background: Approximately 15–20% of early-stage breast cancers overexpress HER2, which is associated with an increased risk of recurrence. Although adjuvant anti-HER2 therapies have significantly improved patient outcomes, the optimal treatment strategy remains uncertain, particularly for patients with small, lymph node-negative tumors, where concerns about potential overtreatment and toxicity persist. The objective of this study was to evaluate overall survival (OS), recurrence-free survival (RFS), and treatment-related neuropathy in patients with early-stage HER2-positive breast cancer treated with adjuvant trastuzumab and paclitaxel. Methods: A total of 129 patients, aged 18 to 75 years, diagnosed with early-stage HER2-positive breast cancer, were retrospectively analyzed in this multicenter study. All patients had received adjuvant treatment with trastuzumab and paclitaxel (TH regimen) between November 2016 and July 2023. The study involved the collection of demographic information, pathological features, and treatment-related details. Overall survival (OS) was defined as the primary study endpoint, while recurrence-free survival (RFS), disease control rate (DCR), and treatment-related neuropathy were evaluated as secondary outcomes. Results: The median follow-up time was 70.9 months. The 2-year and 5-year OS rates were 95.3%, and the 5-year RFS rate was 96.8%. No statistically significant differences in OS or RFS were observed in relation to tumor size (T1 vs. T2), hormone receptor status, Ki-67 index, tumor grade, or the use of adjuvant endocrine or radiotherapy (all p > 0.05). Neuropathy developed in 53.5% of patients, mostly grade 1. Conclusions: Adjuvant TH therapy shows favorable long-term outcomes in early-stage HER2-positive breast cancer. Full article

Mammary tumors are the most common neoplasms diagnosed in female dogs and have been considered excellent models for studying human breast cancer. Establishing cell lines from primary cultures of canine mammary tumors provides an in vitro model to better understand the disease and develop new treatments. This study aimed to establish and characterize canine mammary tumor cell lines. Ten cell cultures were generated from tumor tissue obtained from affected dogs, including seven from primary mammary tumors and three from metastatic sites. Characterization included molecular marker expression (ER, PR, HER2, cytokeratin 5/6 (CK5/6), vimentin, and the marker of cell proliferation Ki67) and in vitro tumorigenic capacity assessment. Additionally, the susceptibility of five cell lines to DOX, 5-FU, paclitaxel, colchicine, and carboplatin was evaluated using the MTT assay. ICC analysis revealed negative expression of hormonal receptors (ER and PR) in five cell lines, while only one cell line was positive for both. Six cell lines were HER2-negative and positive for vimentin. Five cell lines exhibited in vitro tumorigenic capacity, forming colonies in soft agar. DOX showed the highest growth-inhibitory effect (DOX > Paclitaxel > Colchicine > 5-FU > Carboplatin). Two cell lines had a minimal concentration for 50% inhibition in vitro (IC₅₀) < 0.63 µM and 4.37 ± 0.40 µM for DOX, while one was sensitive to colchicine and paclitaxel (IC₅₀ 0.19 µM and 0.04 µM, respectively). All tested cell lines were resistant to carboplatin and 5-FU. These cell lines provide a valuable model for studying breast cancer in humans and dogs and evaluating new potential therapeutic strategies. Full article

Background and Objectives: The clinical value of HER2-low breast cancer (BC), defined by immunohistochemistry (IHC) scores of 1+ or 2+/ISH-negative without HER2 amplification, remains unclear in the neoadjuvant setting. This study aimed to determine whether HER2-low and HER2-zero tumors differ in pathological complete response (pCR) rates and disease-free survival (DFS) among early-stage breast cancer patients undergoing neoadjuvant chemotherapy (NAC). Materials and Methods: We retrospectively analyzed 134 early BC patients treated with NAC between 2017 and 2023. Patients were categorized as HER2-zero (IHC 0) or HER2-low (IHC 1+ or 2+/ISH–). The primary endpoint was total pCR (tpCR); secondary endpoints included breast (bpCR), nodal (npCR), and radiologic complete response (rCR), alongside DFS analysis stratified by hormone receptor (HR) status. Results: Of the cohort, 91 patients (67.9%) were HER2-zero and 43 (32.1%) were HER2-low. There was no statistically significant difference in tpCR (26.4% vs. 27.9%, p = 0.852), bpCR (28.6% vs. 30.2%, p = 0.843), npCR (37.4% vs. 32.6%, p = 0.588), and rCR (23.1% vs. 30.2%, p = 0.374) between HER2-zero and HER2-low groups. DFS did not significantly differ between HER2-zero and HER2-low groups overall (p = 0.714), nor within HR-positive (p = 0.540) or TNBC (p = 0.523) subgroups. Conclusions: HER2-low tumors demonstrated similar pathological responses and survival outcomes compared to HER2-zero tumors. While a HER2-low status does not appear to define a distinct biological subtype in early BC, it remains a relevant classification for emerging HER2-targeted therapies, needing further investigation in prospective studies. Full article

Background: Hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer frequently involves liver metastases, which are linked to poor outcomes. The optimal first-line treatment strategy in this subgroup remains unclear. Methods: This multicenter, retrospective study evaluated 121 patients with HR-positive, HER2-negative breast cancer and liver metastasis who had not received prior systemic chemotherapy or cyclin-dependent kinase (CDK) 4/6 inhibitors (e.g., palbociclib, ribociclib). Patients were classified based on their initial treatment during the liver metastatic phase (CDK4/6 inhibitors or chemotherapy). Clinical characteristics, treatment patterns, and survival outcomes were assessed. Cox regression analysis identified independent prognostic factors. Results: The median age was 53 years; 62% were postmenopausal. Chemotherapy was administered to 36.4%, and CDK4/6 inhibitors to 63.6% of patients. Most cases (59.5%) were recurrent disease. Baseline characteristics were comparable, except for the use of local liver-directed therapies. Progression-free survival favored CDK4/6 inhibitors (10.9 vs. 4.8 months; p < 0.01), while overall survival favored chemotherapy (42.2 vs. 25.9 months; p = 0.042). In multivariate analysis, initial treatment modality, local liver-directed therapy, hormonal status, and the size of the largest liver lesion were independent predictors of survival. Conclusions: In patients with HR-positive, HER2-negative breast cancer and liver metastasis, first-line chemotherapy was associated with improved overall survival compared to CDK4/6 inhibitors. Local liver-directed therapies contributed to longer survival, while larger liver lesions and endocrine-resistant disease correlated with worse outcomes. These findings support considering chemotherapy as first-line treatment in selected patients with aggressive liver metastatic disease. Full article

Immunotherapy has a defined role in the treatment of both early- and late-stage triple-negative breast cancer (TNBC) and is under active exploration in human epidermal receptor 2-positive as well as high-risk hormone-receptor-positive subtypes. It is critical to balance the efficacy and toxicity of immunotherapy while keeping the cost and duration of treatment in check. In addition to the immunohistochemistry testing of PD-L1 expression, which only predicts the efficacy of immunotherapy in metastatic TNBC, there is a lack of biomarkers that are better standardized to predict efficacy and treatment response, detect early relapse, and guide prognosis in breast cancer patients treated with immunotherapy. Circulating tumor DNA (ctDNA) is a minimally invasive, dynamic, real-time, blood-based biomarker that has shown promising value in the management of solid tumors, including breast cancer. This review discusses the emerging evidence for the potential application of ctDNA to further refine patient-centered care and personalize treatment based on a molecularly defined risk assessment for breast cancer patients treated with immunotherapy-based approaches. We further discuss the challenges and barriers to widespread adoption of this promising tool in the management of breast cancer patients requiring immunotherapy. Full article