Comparison of an Affibody-based Molecular Probe and 18F-FDG for Detecting HER2-Positive Breast Cancer at PET/CT.

Background Human epidermal growth factor receptor 2 (HER2) affibody-based tracers could be an alternative to nonspecific radiotracers for noninvasive detection of HER2 expression in breast cancer lesions at PET/CT. Purpose To compare an affibody-based tracer, Al18F-NOTA-HER2-BCH, and fluorine 18 (18F) fluorodeoxyglucose (FDG) for detecting HER2-positive breast cancer lesions on PET/CT images. Materials and Methods In this prospective study conducted from June 2020 to July 2023, participants with HER2-positive breast cancer underwent both Al18F-NOTA-HER2-BCH and 18F-FDG PET/CT. HER2 positivity was confirmed with pathologic assessment (immunohistochemistry test results of 3+, or 2+ followed by fluorescence in situ hybridization, indicated HER2 amplification). Two independent readers visually assessed the uptake of tracers on images. Lesion uptake was quantified using the maximum standardized uptake value (SUVmax) and target to background ratio (TBR) and compared using a general linear mixed model. Results A total of 42 participants (mean age, 56.3 years ± 10.1 [SD]; 41 female) with HER2-positive breast cancer were included; 42 (100%) had tumors that were detected with Al18F-NOTA-HER2-BCH PET/CT and 40 (95.2%) had tumors detected with 18F-FDG PET/CT. Primary tumors in two of 21 participants, lymph node metastases in four of 21 participants, bone metastases in four of 15 participants, and liver metastases in three of nine participants were visualized only with Al18F-NOTA-HER2-BCH. Lung metastasis in one of nine participants was visualized only with 18F-FDG. Al18F-NOTA-HER2-BCH enabled depiction of more suspected HER2-positive primary tumors (26 vs 21) and lymph node (170 vs 130), bone (92 vs 66), and liver (55 vs 27) metastases than 18F-FDG. The SUVmax and TBR values of primary tumors and lymph node, bone, and liver metastases were all higher on Al18F-NOTA-HER2-BCH images than on 18F-FDG images (median SUVmax range, 10.4-13.5 vs 3.4-6.2; P value range, <.001 to .02; median TBR range, 2.7-17.6 vs 1.2-7.8; P value range, <.001 to .001). No evidence of differences in the SUVmax and TBR for chest wall or lung metastases was observed between Al18F-NOTA-HER2-BCH and 18F-FDG (P value range, .06 to .53). Conclusion PET/CT with the affibody-based tracer Al18F-NOTA-HER2-BCH enabled detection of more primary lesions and lymph node, bone, and liver metastases than PET/CT using 18F-FDG. ClinicalTrials.gov Identifier: NCT04547309 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Ulaner in this issue.

Abemaciclib plus endocrine therapy versus chemotherapy after progression on prior palbociclib in HR+/HER2- metastatic breast cancer: A single center real-world study in China.

BACKGROUND: Cyclin-dependent kinase (CDK) 4/6 inhibitor plus endocrine therapy (ET) become standard-of-care for patients with hormone receptor-positive, human epidermal growth factor receptor-2 negative (HR+/HER2-) metastatic breast cancer (MBC). However, the optimal therapeutic paradigm after progression on CDK4/6 inhibitor remains unclear. This study aimed to evaluate the efficacy and safety of abemaciclib with switching ET versus chemotherapy after progression on prior palbociclib-based ET in Chinese patients with HR+/HER2- MBC. METHODS: From 414 consecutive patients with HR+/HER2- MBC who had been treated with palbociclib plus ET from September 2018 to May 2022 in Peking University Cancer Hospital, we identified 80 patients who received abemaciclib plus switching ET or chemotherapy after progression on palbociclib, matched for age, original stage at diagnosis, disease-free interval, and tumor burden at 1:1 ratio. The primary endpoint was progression-free survival (PFS) compared using the Kaplan-Meier method. A Cox proportional hazard model was performed to identify clinical factors associated with PFS in the abemaciclib group. RESULTS: The median PFS was 6.0 months (95% confidence interval [CI]: 3.94-8.06) in abemaciclib group and 4.0 months (95% CI, 2.52-5.49) in chemotherapy group (p = 0.667). And, there was no difference in median PFS between the sequential and nonsequential arm (6.0 vs. 6.0 months) in the abemaciclib group though fewer lines of prior systemic therapy and longer PFS from prior palbociclib in the sequential arm. However, patients with prior palbociclib as the first-line therapy had a significantly longer median PFS versus prior palbociclib as ≥2nd-line therapy (11.0 vs. 5.0 months, p = 0.043). Based on multivariable analysis, ER+/PR+ was an independent factor associated with longer PFS. There was no significant difference in overall survival between the abemaciclib and chemotherapy groups (p = 0.069). CONCLUSION: Our findings indicate that abemaciclib plus switching ET might be one of feasible treatment options for Chinese patients with HR+/HER2- MBC after progression on prior palbociclib-based therapy in addition to chemotherapy.

Effectiveness of gonadotropin-releasing hormone agonists for ovarian function suppression in premenopausal patients with hormone receptor-positive breast cancer: a retrospective single-center real-world study.

PURPOSE: This study evaluated the effectiveness of ovarian function suppression (OFS) of various gonadotropin-releasing hormone agonists (GnRHa) combined with aromatase inhibitors (AI) in premenopausal patients with hormone receptor-positive (HR-positive) breast cancer. Potential risk factors associated with insufficient OFS were analyzed. PATIENTS AND METHODS: Premenopausal HR-positive breast cancer patients who had received AI with GnRHa were studied retrospectively. Patients were divided into different groups according to monthly or trimonthly GnRHa schedules they received, and the effectiveness of OFS was compared between groups. Insufficient OFS was defined as at least one instance of estradiol ≥ 30 pg/ml. Patient data was gathered from medical records for this comparison. RESULTS: Of the 264 patients enrolled in this study, 117 were administered 3.6 mg of goserelin monthly (goserelin 1 M group), 63 received 3.75 mg of leuprorelin monthly (leuprorelin 1 M group) and 84 were given 11.25 mg of leuprorelin every three months (leuprorelin 3 M group). Overall, 7.20% experienced insufficient OFS. The incidence rates in the three GnRHa depot groups were 7.69%, 6.35%, and 7.14%, respectively, without a significant statistical difference (P = 0.900). Notably, younger patients exhibited a higher likelihood of insufficient OFS [OR = 0.900, 95%CI (0.824-0.982), P = 0.018]. CONCLUSION: Insufficient OFS remains a concern during GnRHa and AI treatment. The effectiveness of the three GnRHa depots commonly used in China seems comparable. Younger patients face a heightened risk of insufficient OFS.

Real-world study of palbociclib combined with endocrine therapy for patients with metastatic breast cancer: A comparison of subsequent treatment patterns and HER2 expression analysis.

BACKGROUND: Cyclin-dependent kinase 4/6 inhibitors combined with endocrine therapy (ET) comprise the standard treatment for patients with hormone receptor-positive and human epidermal growth factor 2 (HER2)-negative metastatic breast cancer. The optimal systematic treatment after progression on palbociclib and the role of HER2 expression among these patients remain unclear. METHODS: The authors retrospectively identified 361 patients who received palbociclib combined with ET. Progression-free survival (PFS) and overall survival (OS) were analyzed based on subsequent treatments and HER2 status (PFSsub and OSsub, respectively). PFS1 and OS1 were calculated from palbociclib administration to disease progression/death and death from any cause, respectively. PFSsub and OSsub were calculated from subsequent treatment initiation. RESULTS: The median PFS1 and OS1 were 10.2 and 39.9 months, respectively. The median PFSsub and OSsub of 111 patients (54.7%) who received chemotherapy were 4.9 months and 20.0 months, respectively, whereas those of 89 patients (43.8%) who received endocrine backbone therapy were 5.9 months and 29.3 months, respectively. Among them, 31 patients (15.3%) who received abemaciclib combined with new ET showed better PFSsub and OSsub (12.2 months and not reached, respectively). The median PFS1 was significantly shorter in the HER2-low subgroup than in the HER2-zero subgroup among patients who received second-line or later palbociclib (6.1 vs. 7.8 months; p = .040) but did not differ among patients who received first-line palbociclib. CONCLUSIONS: Various regimens after palbociclib use were received. An improvement was noted in PFS among patients who received endocrine backbone therapy relative to chemotherapy, which may have been secondary to the receipt of chemotherapy by patients with more aggressive disease. HER2 status was not related to the effect of first-line palbociclib, but it may play a role in later lines.

Long-term Outcome Analysis of Pyrotinib in Patients With HER2-Positive Metastatic Breast Cancer and Brain Metastasis: A Real-World Study.

BACKGROUND: Pyrotinib is currently approved for the treatment of HER2-positive advanced breast cancer in China. Data on the overall survival (OS) and efficacy in patients with brain metastasis (BM) remain scarce. This study evaluated the effectiveness of pyrotinib in a real-world setting, especially in patients with BM. METHODS: We reviewed patients with metastatic breast cancer treated with pyrotinib-based therapy between June 2018 and June 2022. Progression-free survival (PFS), OS, objective response rate, and safety were analyzed following the administration of pyrotinib. RESULTS: A total of 239 patients were included. The median PFS in patients who received pyrotinib-based therapy as first-line (15/239), second-line (115/239), or third-or-higher-line (109/239) treatment was 14.00, 9.33, and 8.20 months, respectively, and the median OS was not reached, 29.07 and 22.23 months, respectively. The median PFS in patients who pretreated with trastuzumab (214/239), trastuzumab plus pertuzumab (22/239), lapatinib (68/239), or trastuzumab emtansine (14/239) was 9.33, 6.87, 7.20, and 7.20 months, respectively. In 61 patients with BM, the median PFS was 7.50 months, the median central nervous system (CNS)-PFS was 11.17 months, and the median OS was 21.27 months. Furthermore, 19 patients with concomitant brain radiotherapy tended to achieve a longer OS than 42 patients without radiation (34.17 vs. 20.70 months, P = .112). CONCLUSIONS: Long-term outcomes of pyrotinib-based therapy are promising for patients with HER2-positive metastatic breast cancer in real world and in patients with BM, regardless of the treatment lines and prior anti-HER2 therapies.

Trastuzumab Biosimilar (HLX02), Pertuzumab Plus Chemotherapy in Patients with HER2-Positive Metastatic Breast Cancer after Progression of Trastuzumab: A Prospective, Phase II Study.

Purpose: This study aims to evaluate the efficacy and safety of trastuzumab biosimilar (HLX02) in combination with pertuzumab and chemotherapy in patients with HER2-positive metastatic breast cancer (MBC) after progression of trastuzumab. Materials and Methods: In this prospective, single-arm, phase II study, patients with HER2-positive MBC after progression of tratuzumab received pertuzuamb, HLX02 and chemotherapy (PTC) in Beijing Cancer Hospital from March 2020 to December 2022. The primary endpoint was progression free survival (PFS), and secondary endpoints included objective response rate (ORR), disease control rate (DCR), overall survival (OS), and safety. The study was registered with ClinicalTrials.gov (NCT05188495). Results: A total of 45 patients were included in this study. 12(26.7%) patients were treated in second line and 33(73.3%) patients were in third-line and later setting. 80% and 15.5% patients had previously received pyrotinib/lapatinib and T-DM1, respectively. With a median follow-up of 24.4 months (range: 1.2-43.9), the median PFS was 7.6 months (95% confidence interval [CI],4.3- 10.9m), OS was not reached, the ORR was 31.1%, and DCR was 91.1%. The treatment was well tolerated. Conclusion: The combination of trastuzumab biosimilar HLX02, pertuzumab, and chemotherapy exhibited promising efficacy and a favorable safety profile as second- and beyond line treatment in HER2-positive metastatic breast cancer.

Three-Week Versus 4-Week Schedule of nab-Paclitaxel in Patients With Metastatic Breast Cancer: A Randomized Phase II Study.

BACKGROUND: This head-to-head study compared a 3-week versus 4-week schedule of nab-paclitaxel in patients with metastatic breast cancer (mBC). METHODS: Patients with HER2-negative mBC were enrolled and randomly assigned (1:1) to receive nab-paclitaxel for a 3-week schedule (125 mg/m2 on days 1 and 8) or a 4-week schedule (same dose on days 1, 8, and 15) until disease progression or treatment intolerance. Patients with intolerable toxicities were allowed to receive a maintenance regimen after benefiting from nab-paclitaxel. The primary endpoint was progression-free survival (PFS). RESULTS: Ninety-four patients were included in the analysis (n = 47 in each arm). A longer median PFS (mPFS) was observed in the 3-week versus the 4-week schedule in the overall population (not reached vs. 6.8 months; hazard ratio [HR] = 0.44; P = .029). Patients in the 2 arms had a similar overall survival (28.0 vs. 25.8 months), objective response rate (51.1% vs. 48.9%), and disease control rate (93.6% vs. 80.9%). The 3-week schedule was associated with a lower rate of toxicity-related treatment discontinuation (8.5% vs. 29.8%) and dose delays (6.4% vs. 23.4%). CONCLUSION: This study demonstrated the better antitumor activity and safety profile of a 3-week over 4-week nab-paclitaxel schedule in HER2-negative mBC, suggesting that a 3-week schedule may be a better treatment regimen in clinical practice (ClinicalTrials.gov Identifier: NCT04192331).

CHRM3 is a novel prognostic factor of poor prognosis and promotes glioblastoma progression via activation of oncogenic invasive growth factors.

Glioblastoma (GBM) is the most aggressive cancer of the brain and has a high mortality rate due to the lack of effective treatment strategy. Clarification of molecular mechanisms of GBM's characteristic invasive growth is urgently needed to improve the poor prognosis. Single-nuclear sequencing of primary and recurrent GBM samples revealed that levels of M3 muscarinic acetylcholine receptor (CHRM3) were significantly higher in the recurrent samples than in the primary samples. Moreover, immunohistochemical staining of an array of GBM samples showed that high levels of CHRM3 correlated with poor prognosis, consistent with The Cancer Genome Atlas database. Knockdown of CHRM3 inhibited GBM cell growth and invasion. An assay of orthotopic GBM animal model in vivo indicated that inhibition of CHRM3 significantly suppressed GBM progression with prolonged survival time. Transcriptome analysis revealed that CHRM3 knockdown significantly reduced an array of classic factors involved in cancer invasive growth, including MMP1/MMP3/MMP10/MMP12 and CXCL1/CXCL5/CXCL8. Taken together, CHRM3 is a novel and vital factor of GBM progression via regulation of multiple oncogenic genes and may serve as a new biomarker for prognosis and therapy of GBM patients.

Efficacy of apatinib 250 mg combined with chemotherapy in patients with pretreated advanced breast cancer in a real-world setting.

Objectives: This study evaluated the efficacy and safety of apatinib (an oral small-molecule tyrosine kinase inhibitor targeting VEGFR-2) 250 mg combined with chemotherapy in patients with pretreated metastatic breast cancer in a real-world setting. Patients and methods: A database of patients with advanced breast cancer who received apatinib between December 2016 and December 2019 in our institution was reviewed, and patients who received apatinib combined with chemotherapy were included. Progression-free survival (PFS), overall survival (OS), the objective response rate (ORR), the disease control rate (DCR), and treatment-related toxicity were analyzed. Results: In total, 52 evaluated patients with metastatic breast cancer previously exposed to anthracyclines or taxanes who received apatinib 250 mg combined with chemotherapy were enrolled in this study. Median PFS and OS were 4.8 (95% confidence interval [CI] = 3.2-6.4) and 15.4 months (95% CI = 9.2-21.6), respectively. The ORR and DCR were 25% and 86.5%, respectively. Median PFS for the previous line of treatment was 2.1 months (95% CI = 0.65-3.6), which was significantly shorter than that for the apatinib-chemotherapy combination (p < 0.001). No significant difference was identified in the ORR and PFS among the subgroups(subtypes, target lesion, combined regimens and treatment lines). The common toxicities related to apatinib were hypertension, hand-foot syndrome, proteinuria, and fatigue events. Conclusion: Apatinib 250 mg combined with chemotherapy provided favorable efficacy in patients with pretreated metastatic breast cancer regardless of molecular types and treatment lines. The toxicities of the regimen were well tolerated and manageable. This regimen could be a potential treatment option in patients with refractory pretreated metastatic breast cancers.

Comparison of renal clearance of [18F]AlF-RESCA-HER2-BCH and [18F]AlF-NOTA-HER2-BCH in mice and breast cancer patients.

PURPOSE: A novel HER2 affibody-based molecular probe, [18F]AlF-RESCA-HER2-BCH, was developed for reducing renal uptake, evaluated, and compared with [18F]AlF-NOTA-HER2-BCH. METHODS: In preclinical studies, micro-PET/CT was performed using HER2-positive gastric cancer patient-derived xenografts (PDX) model at 0.5-1 (dynamic), 2, 4, and 6 h post-injection. For blocking experiment, 0.5 mg cold affibody was co-injected with probes. Biodistribution were performed on HER2-positive PDX models at 2 h post-injection. For clinical study, PET/CT images were acquired at 2 h and 4 h after injection of 231.29 ± 17.77 MBq [18F]AlF-NOTA-HER2-BCH or [18F]AlF-RESCA-HER2-BCH in five breast cancer patients (4 HER2-positive and 1 HER2-low). Standardized uptake values (SUVs) were measured in tumors and source-organs for semi-quantitative analysis. The OLINDA/EXM software (version 1.2) was used to calculate the radiation doses. RESULTS: [18F]AlF-NOTA-HER2-BCH and [18F]AlF-RESCA-HER2-BCH were stably labeled with [18F]F, with high binding specificity and affinity to HER2. Micro-PET/CT of both tracers could clearly visualize HER2-positive PDX tumors with high uptake of 16.24 ± 1.74% ID/g and 14.39 ± 2.45% ID/g at 2 h post-injection. The renal accumulation of [18F]AlF-RESCA-HER2-BCH was significantly lower than that of [18F]AlF-NOTA-HER2-BCH (5.16 ± 0.22% ID/g vs. 158.73 ± 5.44% ID/g at 2 h, p < 0.0001). In the clinical study, both [18F]AlF-NOTA-HER2-BCH and [18F]AlF-RESCA-HER2-BCH demonstrated favorable tumor targeting and image contrast. [18F]AlF-RESCA-HER2-BCH showed a higher SUVmax in both primary tumor and metastases, and a significantly higher target-to-nontarget ratio in metastases than [18F]AlF-NOTA-HER2-BCH. Moreover, [18F]AlF-RESCA-HER2-BCH had lower renal accumulation (43.56 ± 7.88 vs. 79.81 ± 3.81 at 2 h, p < 0.0001; 33.23 ± 6.89 vs. 78.63 ± 4.00 at 4 h, p < 0.0001) as well as a significantly lower renal absorbed dose than [18F]AlF-NOTA-HER2-BCH (0.4450 ± 0.1117 mGy/MBq vs. 0.8030 ± 0.1604 mGy/MBq, p < 0.01). CONCLUSIONS: [18F]AlF-RESCA-HER2-BCH tended to provide better image contrast than [18F]AlF-NOTA-HER2-BCH with a higher target-to-nontarget ratio in detection of metastases. Notably, [18F]AlF-RESCA-HER2-BCH had lower renal accumulation than [18F]AlF-NOTA-HER2-BCH.

The most likely but largely ignored triggering factor for breast (or all) cancer invasion.

Breast cancer development and progression are believed to be a sequential process, from normal to hyperplastic, to in situ, and to invasive and metastatic stages. Given that over 90% of cancer deaths are caused by invasive and metastatic lesions, countless factors and multiple theories have been proposed as the triggering factor for the cascade of actions of cancer invasion. However, those factors and theories are largely based on the studies of cell lines or animal models. In addition, corresponding interventions based on these factors and theories have failed to reduce the incidence rate of invasive and metastatic lesions, suggesting that previous efforts may have failed to arm at the right target. Considering these facts and observations, we are proposing "A focal aberrant degeneration in the myoepithelial cell layer (MECL) as the most likely triggering factor for breast cancer invasion". Our hypothesis is based on our recent studies of breast and multiple other cancers. Our commentary provides the rationale, morphologic, immunohistochemical, and molecular data to support our hypotheses. As all epithelium-derived cancers share a very similar architecture, our hypothesis is likely to be applicable to invasion of all cancer types. We believe that human tissue-derived data may provide a more realistic roadmap to guide the clinic practice.

Pegylated liposomal doxorubicin (Duomeisu®) monotherapy in patients with HER2-negative metastatic breast cancer heavily pretreated with anthracycline and taxanes: a single-arm, phase II study.

PURPOSE: To evaluate the efficacy and safety of pegylated liposomal doxorubicin (PLD) in patients with human epidermal growth factor receptor 2 (HER2)-negative metastatic breast cancer (MBC) heavily pretreated with anthracycline and taxanes. METHODS: In this single-arm, phase II study, patients with HER2-negative MBC previously treated with anthracycline and taxanes as second- to fifth chemotherapy received PLD (Duomeisu®, generic doxorubicin hydrochloride liposome) 40 mg/m2 every 4 weeks until disease progression, unacceptable toxicity, or completion of six cycles. Primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR), and safety. RESULTS: Of 44 enrolled patients (median age, 53.5 years; range, 34-69), 41 and 36 were evaluable for safety and efficacy, respectively. In total, 59.1% (26/44) of patients had ≥ 3 metastatic sites, 86.4% (38/44) had visceral disease, and 63.6% (28/44) had liver metastases. Median PFS was 3.7 months (95% confidence interval [CI] 3.3-4.1) and median OS was 15.0 months (95% CI 12.1-17.9). ORR, DCR, and CBR were 16.7%, 63.9%, and 36.1%, respectively. The most common adverse events (AEs) were leukopenia (53.7%), fatigue (46.3%), and neutropenia (41.5%), with no grade 4/5 AEs. The most common grade 3 AEs were neutropenia (7.3%) and fatigue (4.9%). Patients experienced palmar-plantar-erythrodysesthesia (24.4%, 2.4% grade 3), stomatitis (19.5%, 7.3% grade 2), and alopecia (7.3%). One patient displayed a left ventricular ejection fraction decline of 11.4% from baseline after five cycles of PLD therapy. CONCLUSION: PLD (Duomeisu®) 40 mg/m2 every 4 weeks was effective and well-tolerated in patients with HER2-negative MBC heavily pretreated with anthracycline and taxanes, revealing a potentially viable treatment option for this population. Trial registration Chinese Clinical Trial Registry: ChiCTR1900022568.

The prognostic value of neutrophil-to-lymphocyte ratio in de novo stage IV breast cancer: a retrospective cohort study.

Background: The presence of a high neutrophil-to-lymphocyte ratio (NLR) has been associated with increased mortality in several malignancies. And the majority of studies on breast cancer (BC) analyzed patients with early-stage. Fewer studies focused on metastatic BC (MBC). De novo stage IV BC with no prior treatment is more suitable for analyzing prognostic factors. Herein, we examined the prognostic value of baseline NLR in de novo stage IV BC patients. Methods: We retrospectively screened the medical records of female patients who were diagnosed with de novo stage IV BC at Peking University Cancer Hospital between January 2011 and December 2020. All patients were followed up by telephone every 6 months. Receiver operating characteristic (ROC) curve analysis was used to determine the optimal cutoff value of NLR for progression-free survival (PFS). Peripheral blood lymphocyte subsets and tumor infiltrating lymphocytes (TILs) were analyzed by flow cytometry and immunohistochemistry, respectively. Correlations of PFS and overall survival (OS) with NLR and other clinicopathological factors were evaluated using Kaplan-Meier method and Cox regression analyses. Results: A total of 128 patients between January 2011 and December 2020 were enrolled. 70 (54.7%) cases were hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (HER2)-negative, 79 (61.7%) patients had visceral metastasis and 67 (52.3%) patients had more than 2 metastatic sites. The cutoff values of NLR were 2.9, optimized by ROC curve analysis. Totals of 77 and 51 patients were assigned to the NLR-low (≤2.9) and NLR-high (>2.9) groups, respectively. Compared with NLR-high patients, the NLR-low patients had significantly longer median PFS (14.8 vs. 7.2 months; hazard ratio =1.791; P=0.003). The OS showed no significant difference (64.1 vs. 56.0 months, P=0.980). The patients with NLR-low had a higher level of peripheral CD3+ T cells (P=0.028) and a lower level of peripheral CD4+CD25+ regulatory T (Treg) cells (P=0.041). Patient samples with NLR-low also demonstrated higher levels of TILs than those with NLR-high (P=0.025). Conclusions: The baseline NLR-high is associated with adverse PFS in patients with de novo stage IV BC. The NLR-high status may indicate immune suppression status, which can help identify patients with unfavorable prognosis and assist with physicians' treatment decision.

Successful resuscitation and multidisciplinary management of penetrating brain injury caused by tire explosion: A case report.

RATIONALE: Penetrating brain injury (PBI) is a rare trauma that presents as a difficult and serious surgical emergency for neurosurgeons in clinical practice. Our patient was admitted with a PBI caused by a tire explosion, which is an extremely rare cause of injury. PATIENT CONCERNS: We report a case of a 28-year-old male patient who suffered a PBI when a tire exploded while it was being inflated with a high-pressure air pump. DIAGNOSES: The patient was diagnosed with PBI presenting with multiple comminuted skull fractures, massive bone fragments with foreign bodies penetrating the underlying brain tissue of the top right frontal bone, multiple cerebral contusions, and intracranial hematoma. INTERVENTIONS: Emergency combined multidisciplinary surgery was performed for the removal of the fragmented bone pieces, hematoma, and foreign bodies; decompression of the debridement flap; reconstruction of the anterior skull base; and repair of the dura mater. OUTCOMES: The patient was successfully resuscitated and discharged 1 month later and is now recovering well. LESSONS: Patients with PBI are critically ill. Therefore, timely, targeted examinations and appropriate multidisciplinary interventions through a green channel play a key role in assessing the condition, developing protocols, and preventing complications.

Association of Taxane Type With Patient-Reported Chemotherapy-Induced Peripheral Neuropathy Among Patients With Breast Cancer.

Importance: Understanding the detailed symptom spectrum of chemotherapy-induced peripheral neuropathy (CIPN) could facilitate shared decision-making and promote early intervention. Objective: To compare the symptom spectrum of patient-reported CIPN associated with nab-paclitaxel, paclitaxel, and docetaxel treatments among patients with breast cancer. Design, Setting, and Participants: This prospective cohort study was conducted at 9 medical centers across China from 2019 to 2021. Participants included hospitalized women diagnosed with invasive breast cancer, assessed with overlap propensity score weighting. Data were analyzed from from December 2021 to May 2022. Exposures: Treatment with nab-paclitaxel-, paclitaxel-, or docetaxel-based regimens. Main Outcomes and Measures: Patient-reported CIPN on the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire: CIPN 20-item instruments, consisting of sensory, motor, and autonomic scales. Multiple regression models were adjusted for baseline patient, tumor, and treatment characteristics. Results: Of 1234 participants, the mean (SD) age was 50.9 (10.4) years, and 295 patients (23.9%) received nab-paclitaxel, 514 patients (41.7%) received paclitaxel, and 425 patients (34.4%) received docetaxel. The nab-paclitaxel group mostly reported numbness in hands or feet related to sensory symptoms (83 patients [81.4%]), while the paclitaxel and docetaxel groups reported mainly motor (eg, weakness in legs: 60 patients [47.2%] in the paclitaxel group; 52 patients [44.4%] in the docetaxel group) and autonomic (eg, blurred vision: 58 patients [45.7%] in the paclitaxel group; 51 patients [43.6%] in the docetaxel group) symptoms. Patients reported motor symptoms earlier than sensory abnormalities, with a median of 0.4 (95% CI, 0.4-2.3) weeks in the nab-paclitaxel group, 2.7 (95% CI, 1.7-3.4) weeks in the paclitaxel group, and 5.6 (95% CI, 3.1-6.1) weeks in the docetaxel group. After overlap propensity score weighting and compared with the nab-paclitaxel group, the risks of patient-reported CIPN were lower in the paclitaxel (hazard ratio [HR], 0.59 [95% CI, 0.41-0.87]; P = .008) and the docetaxel (HR, 0.65 [95% CI, 0.45-0.94]; P = .02) groups. Similarly, patients who received paclitaxel (HR, 0.44 [95% CI, 0.30-0.64]; P < .001) or docetaxel (HR, 0.52 [95% CI, 0.36-0.75]; P < .001) reported less sensory discomfort compared with those who received nab-paclitaxel. However, the risk of patients in the paclitaxel or docetaxel groups reporting motor (paclitaxel: HR, 0.76 [95% CI, 0.52-1.11]; P = .15; docetaxel: HR, 0.69 [95% CI, 0.47-1.01]; P = .05) and/or autonomic (paclitaxel: HR, 1.00 [95% CI, 0.68-1.49]; P = .98; docetaxel: HR, 0.88 [95% CI, 0.59-1.30]; P = .52) symptoms was not lower than that in the nab-paclitaxel group. Conclusions and Relevance: In this cohort study of women with invasive breast cancer, nab-paclitaxel was associated with more severe CIPN than either paclitaxel or docetaxel. In addition to sensory symptoms, the risk of motor and autonomic abnormalities was not low among these 3 taxanes, and patients-reported motor symptoms even earlier than sensory symptoms. These findings may facilitate early detection and intervention for CIPN in taxane treatments for breast cancer.

Proxalutamide in patients with AR-positive metastatic breast cancer: Results from an open-label multicentre phase Ib study and biomarker analysis.

AIM: Proxalutamide is a novel second-generation non-steroidal androgen receptor (AR) antagonist. This study aimed to evaluate the preliminary efficacy and safety of proxalutamide in patients with AR-positive metastatic breast cancer (AR+ mBC). METHODS: In this open-label, dose-expansion, multicentre phase Ib trial, patients with AR+ mBC (immunohistochemistry [IHC] ≥1%) received proxalutamide orally once daily. Two proxalutamide dose cohorts (cohort A: 200 mg; cohort B: 300 mg) were sequentially investigated. Primary endpoints were disease control rate (DCR) at 8 and 16 weeks and recommended phase II dose (RP2D). RESULTS: Forty-five patients with three median lines (range, 1-13) prior systemic therapy were enrolled (cohort A, n = 30; cohort B, n = 15). Among 39 evaluable patients, DCR at 8 and 16 weeks was 25.6% (95% confidence interval [CI], 11.9-39.4%), with 26.9% in cohort A and 23.1% in cohort B. No patient achieved partial response or complete response. Proxalutamide 200 mg/day was determined as RP2D. The 6-month progression-free survival (PFS) rate was 19.6% (95% CI, 10.2-37.5%). In the triple-negative subgroup, DCR at 8 weeks was 38.5%, with median PFS of 9.1 months (95% CI, 7.8-NA) in those who achieved response at 8 weeks (n = 5). Most common grade 3/4 adverse events were aspartate aminotransferase increase (8.9%) and γ-glutamyltransferase increase (8.9%). By biomarker analysis, patients with moderate AR expression of IHC (26%-75%), PIK3CA pathogenic mutations, or <60 ng/ml cell-free DNA yield showed longer PFS. CONCLUSION: Proxalutamide showed promising anti-tumour activity with good tolerability in patients with heavily pretreated AR+ mBC, supporting further investigation. TRIAL REGISTRATION: This clinical study was prospectively registered at chinadrugtrials.org.cn (Identifier: CTR20170757) and clinical trials.gov (Identifier: NCT04103853).

The prognostic value of chemotherapy or endocrine therapy choice according to circulating tumor cell count in HR+HER2- metastatic breast cancer: a retrospective study.

Background: Circulating tumor cell (CTC) count have prognostic role for metastatic breast cancer (MBC). No clear biomarkers can guide selection of chemotherapy (CT) or endocrine therapy (ET) in 1st-line setting of hormone-receptor positive and human epidermal growth factor receptor 2 negative (HR+HER2-) MBC. The present study investigated the prognostic role CT or ET according to the CTC count in HR+HER2- MBC. Methods: We consecutively collected the data of 53 HR+HER2- MBC patients who received 1st-line CT or ET, who had CTC count detected by our peptide-based nanomagnetic CTC isolation system (Pep@MNPs) from January 2014 to December 2015. The clinicopathological characteristics according the CTC count and 1st-line ET vs. CT were compared. Follow-up was conducted every 6 months. The primary endpoint was progression-free survival (PFS) and overall survival (OS). A Cox regression analysis was conducted to determine the prognostic roles of CTC and 1st-line therapy of ET vs. CT for PFS and OS. Results: The median CTC count of the 53 patients was 2 (range, 0-18). The clinicopathological characteristics of the patients in the CTC count <2 group and the CTC count ≥2 group were similar. The patients with a CTC count <2 had a significantly longer PFS than those with a CTC count ≥2 (P=0.005, hazard ratio =4.138, 12.1 vs. 7.1 months). The patients who received CT had a significantly longer PFS than those who received ET (P=0.041, hazard ratio =2.721, 9.9 vs. 7.2 months). In the CTC count ≥2 group, the patients who received CT had a significantly longer PFS than those who received ET (P=0.048, hazard ratio =2.475, 8.7 vs. 6.3 months). In the CTC count <2 group, there was no significant difference in PFS between the CT and ET groups (P=0.071). Additionally, the CTC count had no significant effect on OS (P=0.116, hazard ratio =2.391, 54.2 vs. 34.2 months). Conclusions: The present study showed that CTC count determined by the Pep@MNP system confirmed the prognostic value in the HR+HER2- MBC patients. And it might be helpful in choosing a 1st-line treatment of CT or ET for HR+HER2- MBC patients.

Prognostic Value of Pretreatment Neutrophil-to-Lymphocyte Ratio in HER2-Positive Metastatic Breast Cancer.

This study aimed to examine the prognostic value of the neutrophil-to-lymphocyte ratio (NLR) and other clinicopathological features in HER2+ MBC patients who received first-line anti-HER2 therapy. A total of 129 patients were assigned to NLR-low and NLR-high groups based on a cutoff value of 3.0 at baseline. Peripheral blood lymphocyte subsets and gene mutations in circulating tumor DNA were analyzed by flow cytometry and Next-generation sequencing, respectively. Survival was evaluated by the Kaplan−Meier method and Cox regression analysis. Of the 129 patients, 77 and 52 were assigned to the NLR-low (≤3) and NLR-high (>3) groups, respectively. Compared with NLR-high patients, the NLR-low patients had significantly longer median progression-free survival (PFS) (11.7 vs. 7.7 months) (p = 0.001, HR = 2.703 95% CI 1.543−4.736 and overall survival (OS) (37.4 vs. 28.7 months) (p = 0.044, HR = 2.254 95% CI 1.024−4.924). Furthermore, this association was independent of metastatic sites or estrogen receptor status. Peripheral blood CD3+ (p = 0.034) and CD4+ (p = 0.010) T cell numbers were significantly higher in the NLR-low group than the NLR-high group. The mutational profile of MBC was generally similar between the two groups. Baseline NLR was a prognostic factor of PFS and OS for patients with HER2+ MBC in the first-line setting. These results may facilitate the selection of patients who will benefit most from anti-HER2 treatment.

Safety, tolerability, and pharmacokinetics/pharmacodynamics of JMT103 in patients with bone metastases from solid tumors.

Bone metastases are common complications of solid tumors. The outcome is poor despite major progress in cancer therapies. We describe a multicenter, open-label, phase 1, dose escalation and expansion trial of JMT103, a novel fully humanized receptor activator of nuclear factor kappa-B ligand (RANKL)-targeting monoclonal antibody, in adults with bone metastases from solid tumors. The study assessed the safety, tolerability, and pharmacokinetics/pharmacodynamics of JMT103. Patients received JMT103 at doses of 0.5, 1.0, 2.0, and 3.0 mg/kg every 4 weeks for 3 cycles. Among 59 patients enrolled, 20 and 39 patients participated in the dose-escalation and dose-expansion phases, respectively. One dose-limiting toxicity was observed at 2.0 mg/kg. The maximum tolerated dose was not determined. Treatment-related adverse events were reported in 29 (49.2%) patients, most commonly hypophosphatemia (30.5%), hypocalcemia (23.7%), and hypermagnesemia (10.2%). No treatment-related serious adverse events were reported. Two patients died due to disease progression, which were attributed to gastric cancer and lung neoplasm malignant respectively. Dose proportionality occurred between exposure levels and administered dose was within a dose range of 0.5 to 3.0 mg/kg. The suppression of urinary N-telopeptide corrected for creatinine was rapid, significant, and sustained across all doses of JMT103, with the median change from baseline ranging from -61.4% to -92.2% at day 141. JMT103 was well tolerated in patients with bone metastases from solid tumors, with a manageable safety profile. Bone antiresorptive activity shows the potential of JMT103 for treatment of bone metastases from solid tumors. Registration No.: NCT03550508; URL: https://www.clinicaltrials.gov/.

Surgical reduction in chest wall disease to prolong survival in breast cancer patients: a retrospective study.

Background: Patients with breast cancer (BC) may develop locoregional recurrence alone or with distant metastases. Results of previous studies discussing the benefit of local surgery among patients with chest wall disease were controversial. Whether surgical reduction for chest wall disease could influence survival outcome is still a question. The objective of this study was to compare overall survival (OS) in patients with recurrence involving the chest wall who did or did not undergo surgical reduction after previous treatment of the primary BC to explore the role of surgical reduction. Methods: We retrospectively reviewed BC patients with chest wall as the first recurrent/metastatic site selected between January 2012 and December 2018 to explore whether surgical reduction for chest wall disease could influence OS. Clinicopathological data, including age at initial diagnosis, TNM stage, the pathological parameters, and treatment were recorded and analyzed. OS was primarily described using the Kaplan-Meier estimator for each group, with the statistical significance between groups being tested by the log-rank test. Results: A total of 198 patients with a median age of 48 years (range, 22-73 years) were analyzed. Chest wall as the only site of recurrence occurred in 139 patients (70.2%), and the other 59 (29.8%) patients had other metastatic sites. There were 88 patients who underwent surgical reduction for chest wall recurrence. The median OS was significantly longer for the patients who had chest wall disease reduction than for those who did not {194.2 months [95% confidence interval (CI): 140.4-247.9 months] vs. 102.7 months (95% CI: 79.7-125.7 months), respectively, P=0.001}. From multivariate analysis, surgical reduction was an independent factor significantly influenced OS (HR =0.52, 95% CI: 0.33-0.81, P=0.004). Subgroup analyses showed that OS was statistically longer in the chest wall disease surgical reduction group than in the no reduction group with respect to hormone receptor (HR) negative (-), human epidermal growth factor receptor 2 (HER2) negative (-), triple-negative breast cancer (TNBC), disease-free survival (DFS) >24 months, and chest wall disease only. Conclusions: BC patients with chest wall recurrence could benefit from surgical reduction with a prolonged OS. In a certain selected group, surgical reduction may be warranted.