Search Results (177)

Guidelines in early breast cancer place adjuvant chemotherapy before radiotherapy, permit radiotherapy concurrently with endocrine and anti-HER2 agents, but discourage it before or during cytotoxic chemotherapy. This narrative review asks whether that convention remains defensible. Its historical basis, a single randomised trial whose distant-metastasis signal did not survive long-term follow-up, is weaker than is commonly assumed. Its contemporary basis is stronger and is stated here explicitly: an asymmetry of absolute benefit, in which a two-point gain in locoregional control yields roughly half a percentage point of mortality benefit once the EBCTCG four-to-one relationship is applied, whereas degradation of systemic therapy reaches mortality undiscounted. We specify three conditions under which a sequencing change could be justified and note that the absolute loss from a short chemotherapy delay cannot presently be quantified from randomised data. Meanwhile, chemotherapy has lengthened while radiotherapy has contracted to a one- to three-week whole-breast schedule, potentially extended when a sequential tumour-bed boost is required. The retrospective evidence is limited: one cohort offers a hypothesis-generating locoregional signal qualified by an unexpectedly high control-arm event rate and an unplanned subgroup analysis, while another supports only short-term feasibility and tolerability; neither demonstrates benefit in distant control or survival. We further argue that the population in which the question remains clinically live is narrow and probably contracting, since genomic de-escalation withdraws from chemotherapy the phenotypes with the most favourable arithmetic. Adjuvant sequencing is best regarded as an open, testable question within a defined population rather than a general case for change. Full article

Ketogenic metabolic therapy (KMT), typically implemented as a ketogenic diet (KD), has re-emerged as a potential adjuvant strategy in oncology. Its rationale is grounded in the metabolic reprogramming of cancer cells, including their reliance on glucose and lipid substrates and the signaling functions of ketone bodies. Despite extensive preclinical evidence of anti-proliferative and immunomodulatory effects, clinical translation in cancer therapy has been slow and inconsistent. This review critically examines the mechanistic basis, experimental and clinical evidence, and translational challenges of KMT across epithelial cancers. We emphasize that “ketogenic interventions” comprise mechanistically distinct modalities, including classical KD, fasting, fasting-mimicking diets, and exogenous ketone supplementation, which are frequently conflated yet differ substantially in their endocrine and metabolic contexts. Across clinical studies, KMT is generally feasible and associated with improvements in quality of life and metabolic parameters; however, robust evidence for the survival benefit of KMT remains limited and heterogeneous. Mechanistically, ketone bodies exert both metabolic and signaling functions, including inhibition of histone deacetylases, lysine β-hydroxybutyrylation, and receptor-mediated effects. Tumor responses are highly context-dependent: ketolytic capacity, governed by enzymes such as OXCT1, can render ketones either a metabolic vulnerability or an alternative fuel for cancer cells. KMT can modify the complex tumor microenvironment, exerting potentially opposing effects on cancer cells, immune cell populations, fibroblasts, and adipocytes. We argue that the central limitation of the field is not a lack of biological activity, but of insufficient integration of tumor-intrinsic metabolism, host physiology, and microenvironmental context. KD/KMT should therefore be regarded not as a universal anticancer therapy, but as a stratified metabolic intervention, whose progress will depend on biomarker-guided patient selection, improved experimental models, and rational combination strategies within a “press-pulse” therapeutic framework. Full article

Background/Objectives: Treatment with adjuvant abemaciclib plus endocrine therapy (ET) has been demonstrated to improve outcomes in patients with HR+/HER2- early breast cancer at high risk of recurrence. However, real-world data regarding abemaciclib tolerability and treatment maintenance remain limited. In this study we describe the occurrence of adverse events (AEs) and their management through dose adjustments—dose reductions and temporary treatment interruptions—reflecting strategies that maximize compliance. Methods: We conducted a retrospective cohort study at the Oncology Department of ULS São João, in Porto, Portugal. Inclusion criteria comprised patients with HR+/HER2- early breast cancer treated, for at least three months, with abemaciclib, between January 2022 and January 2026. Clinical data were collected from electronic medical records and were analyzed using descriptive statistics, with continuous variables reported as median (IQR) and categorical variables as frequencies and percentages. Results: Fifty-six patients were included in this cohort. With the median follow-up of 14.5 months, 98.2% of patients experienced at least one AE. Most common AEs were gastrointestinal and hematological and occurred within the first 3 months of treatment. Dose reductions occurred in 46.4% of patients and temporary treatment interruptions in 25% of patients. However, no permanent treatment discontinuations were reported. Conclusions: In this cohort, AEs associated with adjuvant abemaciclib were common but generally low-grade and manageable. Early recognition of AEs allows appropriate dose adjustments and supportive measures, which support treatment maintenance. These findings highlight the importance of close clinical monitoring and patient counseling to enhance treatment compliance. Full article

Breast cancer (BC) can be treated by combinations of surgery, radiotherapy, chemotherapy, endocrine therapy and targeted therapies. High-risk patients, including all patients with axillary involved lymph nodes with triple-negative BC (TNBC) and Her2-positive BC, are treated by neoadjuvant chemotherapy (NAC). For high-risk patients, immunotherapy for TNBC, trastuzumab and pertuzumab then trastuzumab deruxtecan for Her2-positive BC have improved survival. In this narrative review, we will discuss therapy for small triple-negative and HER2-positive early BC without involved or suspicious axillary lymph nodes. Upfront surgery is recommended for cT1a-b cN0 usN0 TNBC and Her2-positive BC with adjuvant therapy for pT1b pN0 BC, discussed case by case for pT1a pN0 Her2-positive BC. No adjuvant chemotherapy is considered for pT1a TNBC. However, lymph vascular invasion can also be contributive on pathologic results. For pT1c pN0 TNBC and Her2-positive BC, adjuvant therapy is recommended. For cT2 or cN+ TNBC and Her2-positive BC, NAC is the treatment recommended with adjuvant therapy after surgery according to pathologic results. For cT1c cN0 usN0 TNBC and Her2-positive BC, upfront surgery is the usual treatment proposed but NAC can be strongly considered according to clinic pathologic characteristics, tumor size 10–15 mm or 16–20 mm, grade, young age (≤35-years) and co-morbidities, particularly for elderly patients. Recent tools such as TIL level determined on core needle biopsy may help when considering NAC or upfront surgery and systemic therapy regimens. Other prognostic tools can contribute to the determined therapeutic strategy and systemic therapy regimens with escalation or de-escalation, such as TNBCDX or HER2DX, possibly in combination with TIL level. Full article

Cyclin-dependent kinase 4/6 inhibitors have fundamentally changed the management of hormone receptor-positive, human epidermal growth factor receptor 2-negative breast cancer. However, these drugs are not interchangeable and the field is moving away from the notion of a uniform “class effect.” In early breast cancer, adjuvant abemaciclib and ribociclib improve invasive disease-free survival in patients at a high risk of recurrence, whereas palbociclib does not. This difference likely stems from agent-specific pharmacological profiles, differences in trial design, and patient selection, rather than simply dosing nuances. In metastatic breast cancer, all three agents prolong progression-free survival when combined with endocrine therapy, but only ribociclib and potentially abemaciclib have shown an overall survival advantage. In addition, resistance remains a major obstacle in clinical practice. We propose that resistance mechanisms can be meaningfully grouped into two categories: target-driven (e.g., RB1 loss, CDK6 amplification) and bypass-driven (e.g., ESR1 mutations, PI3K/AKT pathway activation, APOBEC3-mediated mutagenesis). Distinguishing between these classes helps in the design of rational sequencing algorithms and combinatorial regimens. Emerging strategies, such as next-generation protein degraders, oral selective estrogen receptor degraders, antibody–drug conjugates, and inhibition of autophagy, are promising methods for overcoming resistance. Moving forward, the greatest need in breast cancer treatment will be not simply developing additional agents but using current therapies more intelligently by refining biomarker-guided patient selection, tailoring treatment duration, and ensuring broad global access. Full article

Hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2–) metastatic breast cancer (MBC) is the most prevalent subtype of advanced breast cancer and is predominantly driven by estrogen receptor (ER) signaling. Endocrine therapy (ET) has become the backbone of first-line treatment; however, both intrinsic and acquired resistance limit long-term disease control. The introduction of cyclin-dependent kinase 4/6 (CDK4/6) inhibitors has fundamentally reshaped the therapeutic landscape even in subsets of patients with aggressive or symptomatic visceral metastatic disease. Advances in molecular profiling have also enabled more precise, adaptive therapy. Circulating tumor DNA (ctDNA)-based liquid biopsy now allows real-time detection of emerging resistance mutations, particularly in ESR1. Additionally, patients with PIK3CA-mutated tumors who had progressed on or within 12 months of completing adjuvant ET and had no prior systemic therapy for metastatic disease had better treatment outcomes when treated with the PI3K inhibitor inavolisib in combination with palbociclib and fulvestrant. Together, these developments mark a shift from fixed treatment sequencing toward a more dynamic, biomarker-driven approach in first-line HR+/HER2– MBC. Integration of CDK4/6 inhibitors with next-generation endocrine agents and liquid biopsy-guided therapy offers the potential to delay resistance, improve survival outcomes, and individualize treatment. Full article

Background: Triple-negative breast cancer (TNBC), devoid of actionable targets for endocrine or HER2-directed therapy, is highly aggressive with elevated risks of recurrence and metastasis; surgical resection remains the mainstay of treatment, and postoperative chemotherapy serves as a key adjuvant modality for controlling residual disease. Doxorubicin (DOX), although widely used, shows limited tumor selectivity, considerable systemic toxicity, and poor control over drug release at the tumor site. To address these issues, we developed near-infrared (NIR)-responsive gold-decorated phase-change nanodroplets (AuNPs-DOX-NDs) that combine photothermal conversion, liquid-to-gas phase transition, and controlled DOX release in a single platform. Methods: The nanodroplets consisted of a perfluorohexane (PFH) core, a DOX-loaded lipid shell, and polyethyleneimine-modified gold nanoparticles (PEI-AuNPs) conjugated to the surface as the NIR photothermal component. Physicochemical characterization was performed to evaluate morphology, colloidal dispersity, and storage stability. Under 808 nm laser irradiation, the photothermal behavior, PFH vaporization, and DOX release properties of AuNPs-DOX-NDs were investigated. In vitro studies using 4T1 TNBC cells were conducted to assess intracellular DOX accumulation, cell proliferation, migration, and apoptosis. Results: Physicochemical characterization showed that the nanodroplets had a uniform nanoscale morphology, good colloidal dispersity, and acceptable storage stability. Under 808 nm laser irradiation, AuNPs-DOX-NDs exhibited concentration-dependent photothermal heating, which induced PFH vaporization and accelerated DOX release, indicating a clear stimulus-responsive release behavior. In vitro studies using 4T1 TNBC cells showed enhanced intracellular DOX accumulation after treatment with AuNPs-DOX-NDs. Upon laser irradiation, the nanodroplets further inhibited cell proliferation and migration and promoted apoptosis, suggesting an enhanced combined photothermal–chemotherapeutic effect in 4T1 TNBC cells. Conclusions: These results indicate that AuNPs-DOX-NDs may serve as a useful NIR-responsive platform for externally controlled drug release and enhanced combined photothermal-chemotherapy, and deserve further evaluation in vivo. Full article

Purpose: Vasomotor, sexual, and musculoskeletal symptoms are common adverse effects of adjuvant endocrine therapy in breast cancer survivors. Social media use has not been investigated with altered symptom perception in patients receiving adjuvant endocrine therapy. This study aimed to investigate whether social media use or addiction independently predicts endocrine therapy-related symptom burden in breast cancer survivors. Methods: A cross-sectional survey study was conducted among 153 breast cancer survivors receiving adjuvant endocrine therapy. The Social Media Use Scale (SMUS) and Bergen Social Media Addiction Scale (BSMAS) were assessed using validated Turkish versions of each scale. Endocrine therapy-related toxicities (specifically hot flashes, vaginal dryness, loss of libido, and musculoskeletal pain severity) were evaluated using specific self-reported 5-point Likert scale items. Results: All of the patients were female and menopausal, either neutral or induced with ovarian function suppression. In the univariate analysis, the BSMAS score showed a weak positive correlation with vasomotor/sexual symptoms (r = 0.194; p = 0.017), but this association disappeared after adjustment for clinical variables. Younger age was associated with greater vasomotor/sexual symptoms in univariate testing. Neither the SMUS nor BSMAS independently predicted musculoskeletal symptom severity in univariate and multivariate models, while higher educational attainment remained the only independent predictor of musculoskeletal pain severity (OR = 1.96; 95% CI: 1.06–3.57; p = 0.031). Conclusions: This study is unique in investigating unstructured social media use and endocrine therapy-related physical symptoms. In this cohort, unstructured social media use was not associated with the endocrine therapy-related physical symptom burden. While these cross-sectional findings do not support social media behavior as a significant predictor, clinical assessments should continue to prioritize established determinants such as age and educational background. Full article

Improving accrual to clinical trials is critical in oncology, particularly in studies evaluating treatment de-escalation or modification strategies, such as endocrine therapy (ET) switch trials in breast cancer. In disease-free patients who have completed an initial period of standard adjuvant ET, decision-making is shaped by individual, clinical, and contextual factors that may act as barriers and facilitators to trial participation. The lack of validated instruments complicates the comprehensive evaluation of these determinants. Therefore, our study aimed to develop and validate a scale for measuring barriers and facilitators to clinical trial participation in adjuvant endocrine therapy switch trials (CAMBRIA-1 and EMBER-4) among breast cancer patients. Therefore, a multiphase study was undertaken: phase one focused on item generation through literature review and expert consensus; phase two assessed preliminary validity through content and face validation (S-CVI and CVR) and pre-testing (Cronbach’s alpha). The final scale encompassed 17 items and exhibited strong evidence of face and content validity (S-CVI = 0.78 and CVR > 0.725 for all items) and internal consistency (Cronbach’s alpha = 0.874). Since preliminary internal consistency has been established, this tool may support future psychometric refinement and large-scale investigations. An understanding of these determinants may inform trial enrolment and drug development in breast cancer management, as well as tailor patient engagement strategies. Full article

The introduction of adjuvant immunotherapy with immune checkpoint inhibitors (ICIs) has significantly changed the management of high-risk urological cancers, particularly clear cell renal cell carcinoma and muscle-invasive urothelial carcinoma. This review provides a comprehensive narrative overview of immune-related adverse events (irAEs) associated with adjuvant ICIs, integrating evidence from pivotal registrational trials and real-world clinical experience. Clinical studies and reports were reviewed to characterize the incidence, type, severity, and management of irAEs. Across registrational trials, endocrine, cutaneous, and gastrointestinal toxicities were the most frequently reported irAEs and were predominantly mild to moderate in severity. Severe events were less common and required early recognition and structured management, often including corticosteroids and targeted immunomodulatory therapies. In our real-world cohort, irAEs occurred in 5 of 13 patients (38.5%) receiving adjuvant anti-PD-1 therapy, mainly involving endocrine and cutaneous systems, with a frequency and severity profile consistent with that reported in the KEYNOTE-564 and CheckMate-274 trials. Most irAEs were grades 1–2 according to CTCAE criteria and were manageable with standard treatments; permanent discontinuation of immunotherapy was required in a single case. Overall, the integration of clinical trial data and real-world evidence supports a favourable and manageable safety profile of adjuvant ICIs in high-risk urological cancers. Multidisciplinary management remains essential to optimise patient outcomes. Full article

Background/Objectives: The clinical management of ductal carcinoma in situ (DCIS) remains controversial due to its heterogeneous biological behavior and uncertain risk of progression. Standard treatment often includes surgery and radiotherapy, although the actual recurrence risk varies considerably among patients. This study aimed to evaluate recurrence patterns and associated clinicopathological factors in a large single-center cohort of patients with pure DCIS. Methods: We retrospectively analyzed 403 patients with histologically confirmed pure DCIS treated with breast-conserving surgery or mastectomy between 2016 and 2023. Clinical, imaging, pathological, and treatment-related variables were assessed. Descriptive and exploratory comparative analyses were performed between patients with and without ipsilateral recurrence. Results: A total of 417 lesions were analyzed, with 21 ipsilateral recurrences (5%) observed during follow-up. Among recurrent cases, 57% were non-invasive recurrent DCIS and 38% were invasive carcinomas. Most recurrences occurred in patients treated with breast-conserving surgery, and 52% of recurrent patients had not received adjuvant radiotherapy. All recurrent cases were estrogen receptor–positive at initial diagnosis, whereas none had received endocrine therapy. No clear association between recurrence patterns and tumor grade or tumor size emerged in this exploratory analysis. No distant metastases or disease-related deaths were observed during follow-up. Conclusions: Recurrence after treatment for pure DCIS was relatively uncommon and frequently non-invasive. Traditional clinicopathological variables alone appeared insufficient to consistently identify recurrence patterns in this cohort. These findings support the need for more individualized risk stratification approaches integrating clinical, imaging, and molecular factors in order to reduce potential overtreatment in selected patients with DCIS. Full article

Background/Objectives: Oncologic surgery to the pelvis and post-surgery adjuvant therapy are dangerous to the reproductive potential of childbearing-aged women. Clinical practices in fertility preservation (FP) have become an essential aspect of multidisciplinary cancer care; however, uniform practices remain inconsistent among the different varieties of cancer and/or areas. To systematically compare the fertility preservation procedures employed in women who have undergone pelvic oncologic surgery and to measure their reproductive and oncologic stages. This review focuses primarily on gynecologic pelvic malignancies and addresses fertility preservation strategies within the context of multimodal oncologic care, including surgery, chemotherapy, radiotherapy, and multidisciplinary decision-making. Methods: A systematic review was performed using PRISMA 2020 to investigate publications from to 2013–2025 in PubMed, Embase, Scopus, Cochrane Library, and Web of Science. The inclusion criteria were women of childbearing age with pelvic malignancies who underwent either fertility-sparing or cryopreservation procedures. PICO-based data mining was performed, and AMSTAR 2, NOS, and AGREE II methodological quality evaluation instruments were used. Mixed inductive–deductive thematic analysis was used to synthesize the findings of the study. Results: A range of articles, including systematic reviews, cohort studies, and clinical guidelines, were included. Fertility-sparing surgery and cryopreservation were found to be as safe and oncologically effective as traditional therapy, with a five-year survival rate of more than 90. Cryopreservation maintained the functioning of the ovary in over 60 percent of the patients and recorded live delivery rates of up to 40 percent. Thematic analysis revealed five main spheres: oncologic safety, creation of FP approaches, psychosocial benefits, limiting access, and the necessity of standardized procedures. Conclusions: Fertility preservation can securely supplement oncologic treatment courses, favoring tumor traits and individual preferences. Unified reporting, extended follow-up, and equitable access are pertinent in maximizing results and reproductive self-corrective action among female cancer endocrine survivors. Fertility preservation should be considered as an integral component of multidisciplinary oncologic management in women with gynecologic pelvic cancers, extending beyond surgical approaches to include coordinated medical, reproductive, and supportive care. Full article

Breast cancer is the second most common malignancy worldwide, and over 70% of new diagnosis are of the hormone receptor-positive (HR+) and HER2-negative (HER2−) subtype. The cornerstone in management of early stage HR+ breast cancer has historically consisted of chemotherapy and endocrine therapies. Genomic assays in early stage HR+HER2− breast cancer has provided a prognostic tool for recurrence and a predictive tool to select patients for adjuvant chemotherapy. The introduction of bone-modifying agents and adjuvant CDK 4/6 inhibitors into early stage disease represents new therapeutic modalities aimed at reducing risk in high-risk HR+HER2− cancers. This manuscript aims to provide a comprehensive overview of the evidence behind endocrine therapy and recommended duration of treatment, genomic assays to guide chemotherapy delivery, data guiding use of bisphosphonate therapy to reduce bone recurrence, and indications for incorporating CDK 4/6 inhibitors. In addition, novel endocrine agents and targeted therapies under investigation are highlighted. Full article

Background: Patients with estrogen receptor (ER)-positive ductal carcinoma in situ (DCIS) derive a greater benefit from endocrine therapy than patients with ER-negative disease. The relevance of ER status and progesterone receptor (PR) status in DCIS to radiation therapy has not been well explored. Methods: Patients undergoing breast-conserving surgery with or without radiation were grouped by ER and PR status and matched using rank-based Mahalanobis optimal matching with respect to lesion size and grade and patient age and race. Cumulative incidences were estimated and competing risk regressions with subdistribution hazard ratios (sHRs) were calculated. Results: Among patients who underwent breast-conserving surgery only, 369 patients with ER-PR- disease were matched to 738 patients with ER+PR+ disease (1:2 matching). In multivariate models, patients with ER-PR- disease were at increased risk of any invasive events (sHR = 2.47, p = 0.007) and early ipsilateral invasive events (sHR = 2.64, p = 0.02 in the 0-to-4-year period) relative to patients with ER+PR+ disease. Among patients who underwent breast-conserving surgery with adjuvant radiation, 1498 patients with ER+PR+ disease were matched to 1498 patients with ER-PR- disease. No significant differences were noted with respect to cumulative incidence of any invasive event (5.6% vs. 5.6%) or ipsilateral invasive events (1.9% vs. 2.9%). In multivariate models, no significant differences were noted. Patients with ER-PR+ lesions had similar cumulative incidences of ipsilateral invasive events to patients with ER-PR- disease in the absence of radiation (5.9% vs. 5.9%) and similar cumulative incidences of contralateral invasive events to patients with ER+PR+ disease when radiation was administered (3.2% vs. 4.2%). Conclusion: The statuses of ER and PR carry independent prognostic and therapeutic implications beyond those of traditional clinicopathologic risk factors. Given that ER and PR statuses are routinely collected for patients with DCIS, incorporation of these variables into clinicopathologic risk classification systems is warranted. Full article

Menopause represents a key transitional phase in women’s health, characterized by declining estrogen levels and increased risk for cardiometabolic, musculoskeletal, and urogenital disorders. Beyond its endocrine roots, emerging evidence highlights the gut microbiome as a critical modulator of systemic hormonal balance. This review synthesizes current understanding of the bidirectional relationship between estrogen and the gut microbiome and its implications for women’s health during menopause. Evidence from current studies reveals distinct findings across populations, reflecting the complexity of estrogen regulation in part by the gut microbiome (i.e., estrobolome). While no ideal gut microbial composition has been identified for women across stages of perimenopause, likely due to geographically unique gut microbiome profiles among healthy women, greater microbial diversity has been positively associated with improved estrogen regulation. Conversely, reduced diversity and altered Firmicutes/Bacteroidetes ratios have been linked to biomarkers of inflammation during perimenopause, which is a key driver across many perimenopausal symptoms. Although hormone replacement therapy remains the primary clinical intervention during perimenopause, we highlight emerging evidence on the adjuvant potential of diet, synbiotics, phytoestrogens, and strain-specific probiotics in modulating the estrogen–gut microbiome axis for improved health span trajectories and better symptom management. Future longitudinal studies integrating diet, gut microbiome profiles and symptom trajectories are essential to clarify these mechanisms across ethnicity and geography. Ultimately, understanding localized diet–microbiome interactions will enable the development of accessible, personalized, and non-hormonal strategies to complement and increase agency in proactive management during the perimenopausal transition. Full article