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Metastatic breast cancer (mBC) remains an incurable disease, and most patients will experience disease progression during their treatment course. Although endocrine therapy remains the mainstay of treatment for hormone receptor-positive/human epidermal growth factor receptor 2-negative mBC, significant progress has been and continues to be made in the treatment of this BC subtype. The discovery of molecular markers, mutations in key cellular pathways, and genomic signatures have led to the development of novel and targeted agents, such as antibody-drug conjugates, oral selective estrogen receptor downregulators, and inhibitors of the PI3K/AKT/mTOR pathway. This has resulted in significant improvements in the survival and quality of life of patients. With the increasing number of treatment options for patients, appropriate drug sequencing remains a challenge. Treatment discussions should involve patient-physician shared decision making, with consideration of genomic data, previous lines of therapy, side effect profiles, and clinical trial enrollment.

Background: Breast cancer (BC) in women aged ≤40 years carrying germline pathogenetic variants (PVs) in BRCA1/2 genes is infrequent but often associated with aggressive features. Human epidermal growth factor receptor 2 (HER2)-low-expressing BC has recently emerged as a novel therapeutic target but has not been characterized in this rare patient subset., Methods: Women aged ≤40 years with newly diagnosed early-stage HER2-negative BC (HER2-0 and HER2-low) and germline BRCA1/2 PVs from 78 health care centers worldwide were retrospectively included. Chi-square test and Student t-test were used to describe variable distribution between HER2-0 and HER2-low. Associations with HER2-low status were assessed with logistic regression. Kaplan-Meier method and Cox regression analysis were used to assess disease-free survival (DFS) and overall survival. Statistical significance was considered for p ≤ .05., Results: Of 3547 included patients, 32.3% had HER2-low BC, representing 46.3% of hormone receptor-positive and 21.3% of triple-negative (TN) tumors. HER2-low vs. HER2-0 BC were more often of grade 1/2 (p < .001), hormone receptor-positive (p < .001), and node-positive (p = .003). BRCA2 PVs were more often associated with HER2-low than BRCA1 PVs (p < .001). HER2-low versus HER2-0 showed better DFS (hazard ratio [HR], 0.86; 95% CI, 0.76-0.97) in the overall population and more favorable DFS (HR, 0.78; 95% CI, 0.64-0.95) and overall survival (HR, 0.65; 95% CI, 0.46-0.93) in the TN subgroup. Luminal A-like tumors in HER2-low (p = .014) and TN and luminal A-like in HER2-0 (p = .019) showed the worst DFS., Conclusions: In young patients with HER2-negative BC and germline BRCA1/2 PVs, HER2-low disease was less frequent than expected and more frequently linked to BRCA2 PVs and associated with luminal-like disease. HER2-low status was associated with a modestly improved prognosis., (© 2024 The Authors. Cancer published by Wiley Periodicals LLC on behalf of American Cancer Society.)

Background: Both immunotherapy (IO) and targeted therapy (TT) are used as adjuvant (adj) treatment for stage III melanoma, however, data describing real-world outcomes are limited. In addition, a significant proportion of patients relapse, for whom best management is unclear. The aim of our study was to assess the efficacy, and safety of adj anti-PD1 IO and TT in a real-world cohort of patients with resected stage III melanoma, and further delineate patterns of recurrence and treatment strategies., Methods: We retrospectively analyzed 130 patients who received adj therapy (100 anti-PD1 IO and 30 TT)., Results: At a median follow-up of 30 months, median relapse-free survival (RFS) was 24.6 (95% CI, 17-not reached [NR]) versus 64 (95% CI, 29.5-NR) months for the TT and IO groups, respectively (p = 0.26). Median overall survival (OS) was NR for either subgroup. At data cutoff, 77% and 82% of patients in TT and IO arms were alive. A higher number of grade ≥3 treatment-related adverse events (AEs) were noted in the IO group (11% vs. 3%), however, a higher proportion of patients permanently discontinued adj therapy in the TT group (43% vs. 11%) due to toxicity. Strategies at relapse and outcomes were variable based on location and timing of recurrence. A significant number of patients who relapsed after adj IO received a second round of IO. Among them, patients who were off adj IO at relapse had superior second median RFS (mRFS2), compared to those who relapsed while on adj IO; mRFS2 was NR versus 5.1 months (95% CI, 2.5-NR), respectively, p = 0.02., Conclusion: In summary, both TT and IO yielded prolonged RFS in a real-world setting, however, longer follow-up is needed to determine any potential OS benefit. Adj therapy, particularly TT, may not be as well tolerated as suggested in clinical trials, with lower completion rates (59% vs. 74%) in a real-life setting. Overall, patients who relapse during adj therapy have poor outcomes, while patients who relapse after discontinuation of adj IO therapy appear to benefit from IO re-treatment., (© 2024 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Metastatic or locally advanced cutaneous squamous cell carcinoma (cSCC) can be treated with immunotherapy (IO). Cranial nerve involvement (CNI) is uncommon in cSCC and is a poor prognostic factor. Our aim is to describe how patients with CNI respond to IO monotherapy and/or as an adjunct to RT., Methods: Under an IRB approved protocol, patients with histologically proven cSCC of the head and neck with CNI treated with IO were retrospectively reviewed., Results: Twelve patients were included and received cemiplimab or pembrolizumab. Eight patients had CNI at diagnosis, and 4 at time of recurrence after non-IO therapy. Best responses were complete response (1), partial response (7), stable disease (1), progressive disease (2), and pending response (1). Nine patients are alive, 6 of which remain on IO., Conclusions: In this cohort, IO showed clinical response in 83% of patients, indicating IO can be an effective monotherapy, reserving RT for instances of local failure after IO., (© 2023 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Purpose: Compared with people living without HIV (PWOH), people living with HIV (PWH) and cancer have traditionally been excluded from immune checkpoint inhibitor (ICI) trials. Furthermore, there is a paucity of real-world data on the use of ICIs in PWH and cancer., Methods: This retrospective study included PWH treated with anti-PD-1- or anti-PD-L1-based therapies for advanced cancers. Kaplan-Meier method was used to estimate overall survival (OS) and progression-free survival (PFS). Objective response rates (ORRs) were measured per RECIST 1.1 or other tumor-specific criteria, whenever feasible. Restricted mean survival time (RMST) was used to compare OS and PFS between matched PWH and PWOH with metastatic NSCLC (mNSCLC)., Results: Among 390 PWH, median age was 58 years, 85% (n = 331) were males, 36% (n = 138) were Black; 70% (n = 274) received anti-PD-1/anti-PD-L1 monotherapy. Most common cancers were NSCLC (28%, n = 111), hepatocellular carcinoma ([HCC]; 11%, n = 44), and head and neck squamous cell carcinoma (HNSCC; 10%, n = 39). Seventy percent (152/216) had CD4+ T cell counts ≥200 cells/µL, and 94% (179/190) had HIV viral load <400 copies/mL. Twenty percent (79/390) had any grade immune-related adverse events (irAEs) and 7.7% (30/390) had grade ≥3 irAEs. ORRs were 69% (nonmelanoma skin cancer), 31% (NSCLC), 16% (HCC), and 11% (HNSCC). In the matched mNSCLC cohort (61 PWH v 110 PWOH), 20% (12/61) PWH and 22% (24/110) PWOH had irAEs. Adjusted 42-month RMST difference was -0.06 months (95% CI, -5.49 to 5.37; P = .98) for PFS and 2.23 months (95% CI, -4.02 to 8.48; P = .48) for OS., Conclusion: Among PWH, ICIs demonstrated differential activity across cancer types with no excess toxicity. Safety and activity of ICIs were similar between matched cohorts of PWH and PWOH with mNSCLC.

Multiple myeloma is the second-most common hematologic malignancy in adults worldwide. Despite ongoing advancement in therapeutic modalities, it remains an incurable disease with a 5-year survival rate of approximately 50%. The recent development and introduction of anti-BCMA immunotherapies into clinical practice, including chimeric antigen receptor T-cell (CAR-T) therapies and bispecific antibodies, has radically shifted the treatment paradigm. However, despite the promising potential of these therapies for broader application, frequent and significant adverse effects have been reported, both in short- and in long-term settings, requiring increasing awareness and vigilance in the treating team, close monitoring, and prompt interventions with a multidisciplinary approach. In this review, we will discuss the toxicities associated with CAR-T cell and bispecific antibody therapies, focusing on results from major clinical studies and real-world observations. In addition, we will emphasize on effective strategies for prevention, monitoring and management, and provide expert recommendations.

Introduction: Triple negative breast cancer (TNBC) is a rare but aggressive biological subtype of breast cancer associated with higher locoregional and distant recurrence rates and lower overall survival despite advancements in diagnostic and treatment strategies., Areas Covered: This review explores the evolving landscape of locoregional recurrence (LRR) in TNBC with improved surgical and radiation therapy delivery techniques including salvage breast conserving surgery (SBCS), re-irradiation, and thermo-radiation. We review current retrospective and prospective, albeit limited, clinical data highlighting the optimal management of locoregionally recurrent TNBC. We also discuss tumor genomic profiling and transcriptome analysis and review potential investigational directions., Expert Opinion: Significant progress has been made in the prevention of LRR but rates remain suboptimal, particularly in the TNBC population, and outcomes following LRR are poor. Further prospective studies are needed to identify the most effective and safest systemic therapy regimens and to whom it should be offered. There has been growing interest in the role of molecular markers, genomic signatures, and tumor microenvironment in predicting outcomes and guiding LRR treatment. Transcriptome analyses and biomarker-driven investigations are currently being studied and represent a promising era of development in the management of LRR.

Introduction: 10-16% of non-small cell lung cancer (NSCLC) cases have the epidermal growth factor receptor (EGFR) amplified and/or mutated. Studies show that EGFR tyrosine kinase inhibitors (TKIs) significantly prolong progression-free survival (PFS) in patients with advanced NSCLC compared to those treated with platinum-based chemotherapy (CT) doublets. Our aim is to perform a real-world survival analysis of patients treated with TKI as first-line therapy at the Hospital of Leon (CAULE) in Spain. The impact on global survival rates and responses to clinical and histopathological factors were also analyzed., Material and Methods: We retrospectively reviewed patients diagnosed with EGFR-mutated NSCLC who received treatment with EGFR-TKI in the Department of Oncology at the University of Leon Health Center complex between March 2011 and June 2018. Data was analyzed with Kaplan-Meier and Cox regression models to show overall survival (OS), progression-free survival (PFS), and the associated variables., Results: 53 patients were included in the study, 50% (n = 27) were treated with gefitinib, 32% (n = 18) with erlotinib and 10% (n = 6) with afatinib. The median OS and PFS were 27.7 months (95% CI: 21-33.8 months) and 18 months (95% CI 14.25-21.89 months), respectively. The variables associated with OS and with PFS were exon19 deletion as a protective factor and presence of extrathoracic metastasis as a risk factor. The most frequent adverse effects were rash, diarrhea, asthenia, and conjunctivitis., Conclusions: Real-world analysis of this data confirms that treatment with TKI is beneficial for patients diagnosed with EGFR-mutated NSCLC. Our OS outcomes were similar to those reported in clinical trials.

Objectives: Evaluate outcomes of patients with recurrent or metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) treated with immunotherapy (IO)., Methods: Among patients with R/M HNSCC treated with IO in this retrospective single-institution cohort, Cox regression was used to compare overall survival (OS) for those with platinum-refractory disease and those treated in the first-line setting with OS from KEYNOTE-040/048, respectively. Multivariable Cox regression was used to identify predictors of OS., Results: There was no significant OS difference for those treated in the platinum-refractory setting when compared to patients on KEYNOTE-040 (HR = 1.22, p = 0.27), nor for the first-line setting compared to KEYNOTE-048 (HR = 1.23, p = 0.19). ECOG-PS 1 (HR = 2.00, p = 0.02) and ECOG-PS 2 (HR = 3.13, p < 0.01) were associated with worse OS. Higher absolute lymphocyte count (ALC) was associated with improved OS (HR = 0.93 per 100 cells/μL, p = 0.03)., Conclusions: Real-world outcomes of IO in R/M HNSCC are similar to outcomes in randomized control trials, with performance status and ALC correlating with OS., (© 2023 The Authors. Head & Neck published by Wiley Periodicals LLC.)

Art offers a visual document of ancestral suffering, as such mythological images in the arts can provide cathartic relief in our patients with existential anxiety. The image of Hercules fighting Hydra and Cancer may serve as an example on how art can help attaining that goal. One example of such an attempt is reflected in the story of Hercules who had to defeat Hydra and Cancer as part of his twelve labors to become immortal. The same way Hercules fought against Cancer to become immortal, humans fight against cancer to defeat death. Cancer is a constant threat to mankind; oftentimes feeling as if it belongs to an alternate reality; a different reality we cannot comprehend, but that will unavoidably reach and impact us all., (© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Cancer and atrial fibrillation (AF) are common co-morbid conditions in older adults. Both cancer and cancer treatment increase the risk of developing new AF which increases morbidity and mortality. Heart rate and rhythm control along with anticoagulation therapy remain the mainstay of treatment of AF in older adults with both cancer and AF. Adjustments to the treatment may be necessary because of drug interactions with concurrent chemotherapy. Cancer and old age increase the risk of both, thromboembolism and bleeding. The risk of these complications is further enhanced by concomitant cancer therapy, frailty, poor nutrition status and, coexisting geriatric syndromes. Therefore, careful attention needs to be given to the risks and benefits of using anticoagulant medications. This review focuses on the management of AF in older patients with cancer, including at the end-of-life care., (Copyright and License information: Journal of Geriatric Cardiology 2022.)

BACKGROUND The educational objective of this study was to describe 2 case reports in which patients were found to have an autoimmune disease concomitantly with a rare, benign histiocytic disorder known as Rosai-Dorfman disease (RDD). It is unclear if there is an underlying association between autoimmune disease and RDD. Lymphadenopathy, although most frequently seen bilaterally in the cervical region in RDD, may be present anywhere. A biopsy with histologic confirmation is required to not only evaluate for malignancy in these cases, but also necessary to diagnose RDD. CASE REPORT We describe 2 cases in which RDD was found incidentally in 2 patients who concomitantly had known autoimmune diseases. The first patient's history included Factor II deficiency, antiphospholipid syndrome, and autoimmune hemolytic anemia; whereas the second patient had a positive antinuclear antibody test, elevated rheumatoid factor, positive lupus anticoagulant, and positive beta-2 glycoprotein 1 antibodies, as well as positive anticardiolipin antibody panel, immune mediated thrombocytopenia, and pernicious anemia. Lymphadenopathy and an enlarged mass were seen in these cases respectively, which were histologically proven to be RDD. Steroid therapy was the mainstay of treatment. CONCLUSIONS Autoimmune diseases are relatively common in the general population and it appears that RDD coexists more often than suspected. When lymphadenopathy or a mass is seen, especially in those with other autoimmune diseases, RDD should remain within the differential diagnosis. Further research is required to determine characteristics and optimal management of RDD. We have observed in the cases presented, that if the autoimmune disease is well controlled, RDD can be an indolent disease.