Search Results (49)

Background/Objectives: Management of cancer treatment-induced bone loss (CTIBL) is essential for preserving quality of life among breast cancer (BC) patients receiving endocrine therapy. However, bone-modifying agents (BMAs) remain underused and delayed. In 2014, IRST launched the first bone health outpatient service in Romagna (the eastern area of the Emilia-Romagna region). A multi-centre, retrospective observational study with propensity score matching (PSM) was conducted to evaluate the impact of the IRST organisational model on bone health. Methods: The PSM matched the Emilia-Romagna patients who underwent BC surgery between 2014 and 2022 and were in follow-up in the Romagna area. Patients were grouped as follows: (1) IRST and (2) other Romagna hospitals (without bone health service, i.e., the control group). The matching was based on age, in situ/invasive cancer, and type of early-stage treatment (hormone treatment vs. chemotherapy). Logistic regression and Cox proportional-hazard models assessed factors associated with bone care treatment initiation and timings, respectively. Results: After PSM, we matched 3112 of the 8021 eligible patients into the two cohorts. IRST patients were 39% more likely to receive BMAs (OR: 1.393; 95% CI: 1.236–1.571) and initiated treatment approximately 12 months earlier. We observed that patients with invasive tumours were 77% more likely to initiate bone therapy than those with in situ tumours (OR: 1.766; 95% CI: 1.237–2.585). The early initiation of bone health therapy was influenced by age (p < 0.001) and neoadjuvant chemotherapy treatment (p < 0.001). Conclusions: The IRST model demonstrates responsiveness to bone health needs in BC patients and may be implemented elsewhere to support integrated CTIBL care. Full article

Background: Breast cancer is the most prevalent malignancy among women globally. In Romania, it is the most frequent form of cancer affecting women, with approximately 12,000 new cases diagnosed annually, and the second most common cause of cancer-related mortality, second only to lung cancer. Methods: This study looked at 79 breast cancer patients from Oltenia, concentrating on epidemiology, histology, diagnostic features, and treatments. Patients were chosen based on inclusion criteria such as histopathologically verified diagnosis, availability of clinical and treatment data, and follow-up information. The analyzed biological material consisted of tissue samples taken from the breast parenchyma and axillary lymph nodes. Even though not the primary subject of this paper, all patients underwent immunohistochemical (IHC) evaluation both preoperatively and postoperatively. Results: We found invasive ductal carcinoma to be the predominant type, while ductal carcinoma in situ (DCIS) and mixed types were rare. We performed cross-tabulations of metastasis versus nodal status and age versus therapy type; none reached significance (all p > 0.05), suggesting observed differences were likely due to chance. A chi-square test comparing surgical interventions (breast-conserving vs. mastectomy) in patients who did or did not receive chemotherapy showed, χ² = 3.17, p = 0.367, indicating that chemotherapy did not significantly influence surgical choice. Importantly, adjuvant chemotherapy and radiotherapy were used at similar rates across age groups, whereas neoadjuvant hormonal (endocrine) therapy was more common in older patients (but without statistical significance). Conclusions: Finally, we discussed the consequences of individualized care and early detection. Romania’s shockingly low screening rate, which contributes to delayed diagnosis, emphasizes the importance of improved population medical examination and tailored treatment options. Also, the country has one of the lowest rates of mammography uptake in Europe and no systematic population screening program. 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

Background: The role of neoadjuvant endocrine therapy (NET) in patients with luminal tumors is still not well defined in everyday clinical practice. To assess the efficacy of combination NET, we analyzed the outcomes of fulvestrant and aromatase inhibitors (AI) in combination in a real-world population. Methods: This was a single-arm, retrospective longitudinal study of the total population of patients diagnosed with locoregionally advanced, clinical stage II-III, HR+ HER2-, luminal-type eBC, who were treated with the neoadjuvant combination of fulvestrant and AI between 2019 and 2024 at the Clinical University Hospital of Split, Croatia. Results: We enrolled 44 patients in the intention-to-treat (ITT) population, while 34 completed NET and surgery (per-protocol population; PPP). The median duration of NET was 11 months (interquartile range [IQR] of 9–16 months). The best radiological objective response rate (partial or complete response) was achieved by 30 (68.2%) in ITT, and 26 (76.5%) in PPP, defined by radiological examination, breast ultrasound, or MR. In the PPP, the minimal or moderate pathological response according to residual cancer burden (I or II) was observed in 29 (85.3%) patients. The median of absolute changes in Ki-67 was −5 (95% CI: −9 to 0), and the median of relative Ki67 changes was −40% (95% CI: −72% to 0%). Post-surgical Ki-67 was significantly predicted by initial Ki-67, positive lymph nodes, and time from diagnosis to the initiation of NET. Treatment was well tolerated, with no therapy discontinuation or dose reductions needed due to toxicity. The most commonly reported side effects included musculoskeletal pain (45.5%), asthenia (34.1%), and hot flashes (29.5%). Conclusions: Dual hormonal therapy with fulvestrant and AI is an active, easily given, non-toxic, promising neoadjuvant treatment in real-world patients with locally advanced luminal-type eBC who are not candidates for chemotherapy. Full article

Breast cancer is a heterogeneous disease, and treatment resistance remains a critical challenge. Claudin-8 (CLDN8), a tight junction protein, has emerged as a potential indicator of therapeutic response and prognosis in breast cancer patients. In this study, we evaluated CLDN8 as a predictive biomarker and a potential therapeutic target. We analyzed CLDN8 gene expression in breast cancer patient cohorts to assess its association with clinical outcomes and response to therapy. We also established breast cancer cell models with altered CLDN8 expression to examine its effects on cell behavior and drug sensitivity. High CLDN8 expression was significantly associated with improved disease-free survival, particularly in estrogen receptor-negative patients (p = 0.007), suggesting a favorable prognostic role. Notably, tumors with elevated CLDN8 showed better outcomes in patients treated with surgery alone or endocrine therapy, whereas in those receiving chemotherapy (including neoadjuvant) or anti-HER2 therapy, high CLDN8 levels were paradoxically linked to poorer survival and therapy resistance. In vitro, CLDN8 knockdown reduced sensitivity to endocrine treatments, HER2-targeted agents, and chemotherapeutic drugs, mirroring clinical patterns. In conclusion, our findings identify CLDN8 as an important prognostic factor in breast cancer and as a novel predictor of treatment response. These results underscore the potential utility of CLDN8 status in guiding personalized therapy and highlight CLDN8 as a candidate target for overcoming treatment resistance in breast cancer. Full article

In triple-negative (TNBC) and human epidermal growth factor receptor 2-positive (HER2+) breast cancer patients, neoadjuvant systemic therapy is the standard recommendation for tumors larger than 2 cm. Monitoring the response to primary systemic therapy allows for the assessment of treatment effects, the need for breast-conserving surgery (BCS), and the achievement of pathological complete responses (pCRs). In estrogen receptor-positive/HER2-negative (ER+/HER2-) breast cancer, the benefit of neoadjuvant strategies is controversial, as they have shown lower tumor downstaging and pCR rates compared to other breast cancers. In recent decades, several gene expression assays have been developed to tailor adjuvant treatments in ER+/HER2- early breast cancer (EBC) to identify the patients that will benefit the most from adjuvant chemotherapy (CT) and those at low risk who could be spared from undergoing CT. It is still a challenge to identify patients who will benefit from neoadjuvant systemic treatment (CT or endocrine therapy (ET)). Here, we review the published data on the most common gene expression signatures (MammaPrint (MP), BluePrint (BP), Oncotype Dx, PAM50, the Breast Cancer Index (BCI), and EndoPredict (EP)) and their ability to predict the response to neoadjuvant treatment, as well as the possibility of using them on core needle biopsies. Additionally, we review the changes in the gene expression signatures after neoadjuvant treatment, and the ongoing clinical trials related to the utility of gene expression signatures in the neoadjuvant setting. Full article

Background: Did the COVID-19 pandemic lead to delays in breast cancer management, impacting treatment recommendations? The goal of this study was to assess the pandemic’s effect on breast cancer treatment and management practices. Methods: This study aimed to assess the pandemic’s effect on breast cancer treatment from March 2018 to February 2020 (pre-pandemic) and March 2020 to February 2022 (during the pandemic) in Canada. A retrospective cohort study at The Ottawa Hospital, Ontario, Canada, compared breast cancer patients diagnosed in the two years before and after the pandemic’s onset. The study examined patient demographics, cancer stages, treatment timelines, and procedures, including neoadjuvant chemotherapy, endocrine therapy, and surgical treatment. Descriptive statistics and frequencies identified changes. The study is limited to a single institution, which may restrict generalizability. Inclusion criteria focused on female patients over 18 years with newly diagnosed breast cancer, excluding recurrent cases. Stage IV patients were included, but further details on their management are needed. Results: Breast cancer diagnoses decreased from 2577 before the pandemic to 2290 after its onset. Surgeries decreased from 1226 to 1013 (p < 0.020), while neoadjuvant endocrine therapy increased from 148 to 169, and adjuvant radiotherapy rose from 586 to 722 (p < 0.001). The study revealed a decrease in breast cancer diagnoses and surgeries during the pandemic, with a rise in non-surgical treatments. Conclusions: These changes indicate significant shifts in breast cancer management due to the pandemic. The decrease in surgical treatments and increase in non-surgical options such as endocrine therapy and radiotherapy suggest adaptations in clinical practices to cope with the challenges posed by the pandemic. Understanding these shifts is crucial for developing strategies to mitigate the impact of future disruptions on breast cancer care and ensuring optimal patient outcomes. Full article

Background: Vitamin D (VD) supplementation has increased considerably in the last decade, whether for the prevention or treatment of numerous diseases, including bone, cardiovascular, endocrine, neurologic, psychological, respiratory, infectious, or oncological. The primary objective of this scoping review was to examine and synthesize the scientific evidence on the role of VD in all-type cancer patients undergoing adjuvant and neoadjuvant therapy with chemotherapy (CT) or radiotherapy (RT), namely in improving side effects. Methods: This review was conducted by selecting papers from the CINAHL, Scopus and PubMed databases based on the descriptor terms mesh and title/abstract, taking into consideration the defined inclusion and exclusion criteria, following the PRISMA-ScR (PRISMA extension for scoping reviews) statement. Results: A total of 758 papers were identified in different databases during this review. However, using the inclusion and exclusion criteria, only five publications made up the final sample of the study. The studies included heterogeneous study methodologies, objectives, cancer diagnosis, as well as methods to assess body composition, which makes it difficult to compare them. Based on the analyzed studies, associations were found between bone density and VD in patients who underwent preoperative chemoradiotherapy (CRT). In patients with non-small-cell lung cancer receiving CT, some of the side effects associated with the treatment were attenuated and reduced. In addition, another of the studies analyzed found that VD deficiency (VDD) has been associated with increased peripheral neuropathy (PN) induced by CT in the treatment of breast cancer. VD supplementation was found to be safe and effective. Conclusions: In this scoping review, VD is highlighted as a crucial factor in preventing the side effects of neoadjuvant RT or CT, as well as treating other treatment-related health conditions, such as osteoporosis, as well as ameliorating the side effects (nausea, vomiting, fatigue) associated with aggressive CT and RT. Full article

Introduction: Data are lacking on the optimal neoadjuvant systemic treatment (NST) for women with hormone receptor-positive (HR+) human epidermal growth factor receptor 2-positive (HER2+) breast cancer if they are unfit to receive the combination of chemotherapy and anti-HER2 therapy. The aim of this study was to determine whether the rates of ypT0 and ypN0 differ between patients treated with neoadjuvant endocrine therapy (NET) versus NET combined with anti-HER2 therapy (NET+aHER2). Materials and Methods: Data from the Netherlands Cancer Registry were analysed to identify women diagnosed with primary HR+/HER2+ breast cancer between 2008 and 2019, treated with either NET or NET+aHER2. The ypT0 and ypN0 rates were analysed (using uni- and multivariable logistic regression analyses, as applicable) in relation to the characteristics of the patient, the tumour, and the treatment. Results: Of the 190 patients identified (median age 77), 150 had been treated with NET and 40 with NET+aHER2. Patients with clinically node-positive disease (cN+) were significantly more likely to have been treated with NET+aHER2 (p = 0.029). The ypT0 rate was significantly higher after NET+aHER2, with 10.0% (4/40) versus 1.3% (2/150) following NET (p = 0.019). The ypN0 rate was significantly higher after NET+aHER2, with 25.0% (6/24) versus 5.5% (3/55) following NET in the cN+ patients (p = 0.020) and 81.3% (13/16) versus 55.8% (53/95) after NET in the cN- patients (p = 0.047). In the cN- patients, the ypN0 status was independently associated with age (p = 0.008) and the administration of NET+aHER2 (p = 0.016). Conclusions: The rates of ypT0 and ypN0 in women with HR+/HER2+ breast cancer treated with NST was significantly higher following NET+aHER2 than after NET. Full article

The role of combining neoadjuvant endocrine therapy with conventional chemotherapy remains unclear; therefore, we conducted an open-label, single-center, nonrandomized phase II trial to assess the effect of this combination. Patients with previously untreated stage II or III HR-positive, HER2-negative breast cancer received concurrent letrozole 2.5 mg with standard neoadjuvant chemotherapy. The primary endpoint was pathologic complete response (pCR) at the time of surgery. We used Simon’s minimax two-stage design; a pCR rate > 6% was necessary at the first stage to continue. Between November 2017 and November 2020, 53 women were enrolled in the first stage of the trial. Their median age was 49 years (range, 33–63), and 60% of them were premenopausal. Subsequently, 66% and 34% of patients with clinical stages II and III, respectively, were included; 93% had clinically node-positive disease. Two patients (4%) achieved pCR after neoadjuvant chemo–endocrine treatment, which did not satisfy the criteria for continuing to the second stage. The overall response rate was 83%. During the median follow-up of 53.7 months, the 3-year disease-free survival and overall survival rates were 87% and 98%, respectively. Neutropenia was the most common grade 3/4 adverse event (40%), but rarely led to febrile neutropenic episodes (4%). Myalgia (32%), nausea (19%), constipation (17%), heartburn (11%), oral mucositis (9%), and sensory neuropathy (9%) were frequently observed, but classified as grade 1 or 2. No deaths occurred during preoperative treatment. The addition of letrozole to standard neoadjuvant chemotherapy was safe and beneficial in terms of overall response rate, but did not provide a higher pCR rate in locally advanced HR-positive, HER2-negative breast cancer. Further research is needed to enhance neoadjuvant treatment strategies for this cancer subtype. Full article

Pancreatic cancer is a significant challenge in oncology due to its aggressive nature and complex management, leading to high mortality rates and a dismally low 5-year survival rate. Approximately 85% of cases manifest as adenocarcinoma, while endocrine tumors constitute less than 5%. Borderline resectable and locally advanced pancreatic cancers are particularly difficult to treat due to vascular involvement, which complicates complete resections and increases morbidity. Various therapeutic modalities aim to overcome these challenges and improve patient outcomes. Traditionally, upfront surgery was the standard for resectable tumors, with multimodal chemotherapy being central to treatment. Understanding surgical anatomy is pivotal in enhancing surgical outcomes and patient survival. Resectability challenges are several when seeking to achieve R0 resections, particularly for borderline resectable tumors. Various classification systems—the MD Anderson criteria, the NCCN criteria, the AHPA/SSAT/SSO consensus statement, and the Alliance definition—assess tumor involvement with major blood vessels, with the first of these systems being broadly accepted. Vascular staging integration is also important, with the Ishikawa staging system using preoperative imaging to assess venous involvement. Furthermore, neoadjuvant therapy enhances treatment effectiveness by addressing micro-metastatic disease early, increasing R0 resection chances, and downstaging tumors for optimal surgery. Insights from the Fox Chase Cancer Center’s neoadjuvant treatment approach highlight the importance of a multidisciplinary strategy when advancing therapy and improving patient prognosis. This commentary, inspired by Dr. Sanjay S. Reddy’s Keynote Conference during MedNews week, highlights current advancements and ongoing challenges in the treatment of pancreatic cancer, emphasizing the need for a comprehensive, multidisciplinary approach to improve outcomes. Full article

Oestrogen receptor (ER)-positive breast cancer (BC) is generally well responsive to endocrine therapy. Neoadjuvant endocrine therapy (NAET) is increasingly being used for downstaging ER-positive tumours. This study aims to analyse the effect of NAET on a well-characterised cohort of ER-positive BC with particular emphasis on receptor expression. This is a retrospective United Kingdom (UK) multicentre study of 391 patients who received NAET between October 2012 and October 2020. Detailed analyses of the paired pre- and post-NAET morphological changes and hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) expression were performed. The median duration of NAET was 86 days, with median survival and overall survival rates of 380 days and 93.4%, respectively. A total of 90.3% of cases achieved a pathological partial response, with a significantly higher rate of response in the HER2-low cancers. Following NAET, BC displayed some pathological changes involving the tumour stroma including central scarring and an increase in tumour infiltrating lymphocytes (TILs) and tumour cell morphology. Significant changes associated with the duration of NAET were observed in tumour grade (30.6% of cases), with downgrading identified in 19.3% of tumours (p < 0.001). The conversion of ER status from positive to low or negative was insignificant. The conversion of progesterone receptor (PR) and HER2 status to negative status was observed in 31.3% and 38.1% of cases, respectively (p < 0.001). HER2-low breast cancer decreased from 63% to 37% following NAET in the paired samples. Significant morphological and biomarker changes involving PR and HER2 expression occurred following NAET. The findings support biomarker testing on pre-treatment core biopsies and post-treatment residual carcinoma. Full article

Purpose. To assess the impact of the COVID-19 pandemic on adherence to oral endocrine therapy in patients diagnosed with breast cancer in the public healthcare system in Catalonia (Spain). Methods. Retrospective cohort study in patients starting endocrine therapy from 2017 to 2021. Adherence was measured during the first year of treatment, and the impact of the pandemic was calculated according to the calendar year and whether the first year of treatment included the peak period of the pandemic in our setting (March–September 2020). Analyses were performed using a chi-square test and multivariable logistic regression, with results stratified by year, age group, and drug type. Results. Mean overall adherence during the first year of treatment was 89.6% from 2017 to 2021. In contrast, the patients who started treatment in 2019 and 2020 and whose treatment included the peak pandemic period presented an adherence of 87.0% and 86.5%, respectively. Young age and tamoxifen or combination therapy were predictors of low adherence. An increase in neoadjuvant therapy was also observed in 2020. Conclusions. The COVID-19 pandemic had only a modest impact on adherence to endocrine therapy (≈3%), despite the enormous disruptions for patients, the healthcare system in general, and cancer care in particular that were occurring in that period. Full article

Background: Breast cancer (BC) remains a significant health care challenge, and treatment approaches continue to evolve. Among these, neoadjuvant endocrine therapy (NET) has gained prominence, particularly for postmenopausal, hormone-receptor positive, HER2-negative (HR+/HER2−) BC patients. Despite this, a significant gap exists in identifying patients who stand to benefit from NET. The objective of this study was to assess whether Magee equations (MEs) could serve as predictors of response to NET. Methods: This retrospective study included adult patients with invasive BC who underwent NET followed by curative surgery. Assessment of sociodemographic, clinical, and tumor-related variables was conducted. The ME1, ME2, ME3, and ME mean were analyzed to explore their predictive role for NET response. Receiver operating characteristic (ROC) curves were employed, along with the determination of optimal cutoff points. Logistic regression models were utilized to identify the most significant predictors of pathological response. Results: Among the 75 female participants, the mean age was 69.4 years, with the majority being postmenopausal (n = 72, 96%) and having an ECOG-PS of 0/1 (n = 63, 84%). Most patients were classified as luminal A (n = 41, 54.7%). ME3 emerged as a promising predictor, boasting an AUC of 0.734, with sensitivity of 90.62% and specificity of 57.50% when the threshold was ≤ 19.97. In univariate analysis, clinical staging (p = 0.002), molecular subtype (p = 0.001), and ME3 (continuous = 0.001, original 3-tier: p = 0.013, new 2-tier: <0.001) categories exhibited significant associations with pathological response. In the multivariate model, clinical staging and new 2-tier ME3 (<20 vs. ≥20) were included as significant variables. Conclusions: Patients with ME3 < 20 have a higher likelihood of presenting a pathological response, offering a cost-effective alternative tool to Oncotype DX. Larger future studies with a prospective design are awaited to confirm our findings. Full article

The expression of estrogen receptors (ERs) in breast cancer (BC) represents a strong prognostic and predictive biomarker and directs therapeutic decisions in early and advanced stages. ER-low-positive BC, defined by the immunohistochemical (IHC) expression of ERs from 1% to 9%, constitutes a distinct subset of total BC cases. Guidelines recommend that a low expression of ERs be reported in pathology reports since the benefit of endocrine therapy in patients with ER-low-positive BC is uncertain. Recently, several cohorts, mostly of a retrospective nature, have been published, reporting the clinicopathological characteristics and outcomes of ER-low-positive BC. However, the majority of the data focus on early-stage BC and the use of (neo)adjuvant therapy, and there is a significant lack of data regarding metastatic ER-low-positive BC. Further factors, including tumor heterogeneity as well as the potential loss of ER expression due to endocrine resistance, should be considered. Including patients with ER-low-positive BC in clinical trials for triple-negative breast cancer (TNBC) might improve the understanding of this entity and allow novel therapeutic approaches. The design and conduction of randomized clinical trials regarding this subgroup of patients are greatly anticipated. Full article