The presence of circulating tumor cell (CTC) clusters is associated with disease progression and reduced survival in a variety of cancer types. In breast cancer, preclinical studies showed that inhibitors of the Na+/K+ ATPase suppress CTC clusters and block metastasis. Here we conducted a prospective, open-label, proof-of-concept study in women with metastatic breast cancer, where the primary objective was to determine whether treatment with the Na+/K+ ATPase inhibitor digoxin could reduce mean CTC cluster size. An analysis of nine patients treated daily with a maintenance digoxin dose (0.7–1.4 ng ml−1 serum level) revealed a mean cluster size reduction of −2.2 cells per cluster upon treatment (P = 0.003), meeting the primary endpoint of the study. Mechanistically, transcriptome profiling of CTCs highlighted downregulation of cell–cell adhesion and cell-cycle-related genes upon treatment with digoxin, in line with its cluster-dissolution activity. No treatment-related adverse events occurred. Thus, our data provide a first-in-human proof of principle that digoxin treatment leads to a partial CTC cluster dissolution, encouraging larger follow-up studies with refined Na+/K+ ATPase inhibitors and that include clinical outcome endpoints. ClinicalTrials.gov identifier: NCT03928210 . This proof-of-concept phase 1 trial shows that the size of circulating tumor cell clusters (which can promote metastatic spread) can be reduced by treatment with the Na+/K+ ATPase inhibitor digoxin in patients with metastatic breast cancer.

Circulating tumor cell (CTC) clusters are highly efficient metastatic seeds in various cancers. Yet, their genetic heterogeneity and clonal architecture is poorly characterized. Using whole-exome sequencing coupled with phylogenetic inference from CTC clusters of patients with breast and prostate cancer, as well as mouse cancer models alongside barcode-mediated clonal tracking in vivo, we demonstrate oligoclonal composition of individual CTC clusters. These results improve our understanding of metastasis-relevant clonal dynamics.

Background: Patients with endocrine-resistant metastatic breast cancer (MBC) require cytostatic therapy. Single-agent taxanes and anthracyclines, including pegylated liposomal doxorubicin (PLD), are standard treatment options. There are no prospective data regarding optimal treatment sequences, and real-world data regarding both treatment options are limited. Methods: We analyzed electronic records of all patients with Her2-negative MBC treated with either first-line PLD or first-line taxane and subsequent crossover at the University Hospital Basel between 2003 and 2021. The primary endpoint was time to next chemotherapy or death (TTNC). Secondary endpoints were overall survival (OS), progression-free survival (PFS), and objective response rate (ORR). We used the Kaplan–Meyer method and logrank test to compare time-to-event endpoints and the Fisher exact test to compare discrete variables. Results: We retrospectively identified 42 patients with Her2-negative MBC who have received either single-agent PLD or single-agent taxane as first-line chemotherapy with subsequent crossover, including 23 patients who received first-line PLD and 19 patients who received first-line taxane. Baseline characteristics were similar between treatment groups. Treatment sequence PLD–taxane was significantly inferior to taxane–PLD regarding all endpoints: median TTNC 4.9 vs. 9.9 months (p = 0.006), median OS 17.8 vs. 24.6 months (p = 0.05), median PFS 4.4 vs. 9.0 months (p = 0.005), and ORR 13% vs. 53% (p = 0.01). Conclusions: Here, we report a first retrospective head-to-head comparison of the treatment sequence PLD–taxane versus taxane–PLD in patients with MBC, showing a substantial advantage of using taxanes first, followed by PLD. An inherent treatment bias in favor of first-line taxanes cannot be excluded, thus calling for prospective validation.

PDF file - 762K, (A) Immunoliposomes bind specifically to their targets in vitro. Specific binding capacity was evaluated in MDA-MB468, a human breast cancer cell line, with endogenous overexpession of EGFR. Cells were incubated with DiIC18(3)- DS-labeled immunoliposomes containing DC101-Fab'(anti-mVEGFR2), C225-Fab' (anti-hEGFR) or with control liposomes, where the Fab' regions of the antibodies were omitted. A shift of two log was detected in anti-hEGFR-ILs, while the anti-mVEGFR2-ILs were comparable with the DiIC18(3)- DS-labeled liposomes. This confirmed target specificity. (1) filled black histogram: untreated MDA-MB468 cells; (2) dark grey open histogram: control non-targeted DiIC18(3)- DS-labeled liposomes; (3) light grey open histogram: anti-VEGFR2-ILs; (4) filled light grey histogram: anti-EGFR-ILs. (B) Anti-VEGFR2-ILs specifically bind to VEGFR2 positive cells in vivo (immunofluorescence). Vessel in the endocrine pancreas of a Rip1Tag2 mouse treated with anti-VEGFR2 ILs-dox or PLD. The Fab` fragment of DC101, a rat antibody, was coupled to the liposomal surface. VEGFR2 was detected with a goat-derived antibody. Detection with anti-rat-Fab`-FITC labeled antibody showed specific binding of VEGFR2 in the tumor tissue in anti-VEGFR2-ILs treated mice, but not in PLD treated mice. Red = staining for anti-VEGFR2, green = staining for anti-rat-Fab', blue = DAPI. (C) Anti-VEGFR2-ILs specifically bind to CD31-positive tumor-associated vascular cells in vivo (FACS). For uptake studies in vivo, liposomes were labeled with 0.1-0.3 mol% DiIC18(3)-DS (DiI-Ls). 12 weeks old Rip1Tag2 mice were injected i.v. with DiI-ILs or anti-VEGFR2 liposomes labeled with DiI (anti-VEGFR2-DiI-ILs). 36h after injection mice were sacrificed and a single cell suspension of pancreatic tumors was prepared by Dispase digestion. For subsequent FACS analysis cells were stained with PerCp-CD45 and APC-CD31 Ab. The CD31 positive cells were gated and the incorporated DiI was measured. Mice injected with anti-VEGFR2-DiI-ILs showed an increase in DiI uptake compared to control mice (70.1% and 24.8%, respectively). The mean fluorescence augmented from 30.4 to 61.1 in anti-VEGFR2-DiI-ILs treated mice.

IntroductionCancer-related impairments often co-occur with bodily disturbances. Body psychotherapy (BPT) can improve bodily wellbeing, yet evidence in cancer survivors is scarce. Hence, we aimed to evaluate whether blended group BPT alleviates bodily disturbances in post-treatment cancer patients.MethodsWe conducted a bi-center study (registered in ClinicalTrials.gov, under No. NCT03707548), applying a pre-post convergent parallel design of weekly group BPT interspersed with smartphone-based ambulatory interventions using a waiting-period comparator. We included patients with completed curatively intended treatment for malignant neoplasms, suffering from bodily disturbances. The primary outcome was body image disturbances. Secondary outcomes were experiencing and appreciating body awareness, mental wellbeing, and health-related quality of life.ResultsForty patients (mean age 51.7 years) attended group BPT. Mixed-effect linear regression models contrasting intervention with the waiting period did not show statistically significant differences regarding the primary outcome [Pre-post difference contrasts: 1.44, 95% confidence interval (CI): −1.51 to 4.93, p = 0.339]. However, patients showed greater improvements in appreciating body awareness, measured by the “Body Mindfulness Questionnaire” (BMQ), from pre- to post-intervention as compared to the waiting period (pre-post difference contrasts: 7.31 95% CI: 4.15–10.47, Bonferroni-Holm corrected q = 0.0002).DiscussionWe found no evidence that blended group BPT was effective in improving body image disturbances in post-treatment cancer patients, but found indications for an increase in body awareness appreciation.Clinical trial registrationClinicalTrials.gov, identifier NCT03707548.

Introduction: Standard-dose eribulin mesylate (1.4 mg/m2 d1 + 8) achieves clinical benefit rates of 26%-52% in patients with metastatic breast cancer (mBC). <10% of patients in the registration trial were >= 70 years old; dose reductions were common in these older patients. Materials and Methods: This single-arm phase II trial explored the efficacy of reduced starting dosing of first-line eribulin at 1 mg/m2 d1 + 8 q3 weeks in patients with mBC aged >= 70 years. The primary endpoint was a disease control rate (DCR) >= 55%. The secondary endpoints were objective response (OR), progression-free survival (PFS), overall survival (OS), and patient-reported neurotoxicity. Results: Overall, 77 patients were accrued; their median age was 76 years and Eastern Cooperative Oncology Group performance status was 0-1 in 90%. The DCR was 40% (90% confidence interval [CI]: 31-50); therefore, the primary endpoint was not reached. The overall response rate was 22% (95%CI: 13-33), median PFS 5.4 months (95%CI: 4.5-7.7), and median OS 16.1 months (95%CI: 13.5-26.9). Dose modifications were necessary in 35% of patients. In nine patients, more than fifteen cycles were given; 48 patients (62%) experienced at least one grade 3 toxicity. Median patient-reported neurotoxicity scores remained stable for at least fifteen cycles. The main reason for treatment discontinuation was disease progression (57%).Discussion: We report the first prospective data on first-line eribulin in older patients. The reduced starting dose of 1.1 mg/m2 was safe, with prolonged treatment and DC achieved in a considerable proportion of patients (but less than the 55% assumed), without cumulative neurotoxicity. The reduced dose was apparently within the range of the minimal effective dose, as shown by the efficacy lack in patients requiring further dose reductions. Thus, our results do not support the approach of a reduced starting dose for older patients.

Background Cancer is related to not only physical but also mental suffering. Notably, body image disturbances are highly relevant to cancer-related changes often persisting beyond recovery from cancer. Scalable and low-barrier interventions that can be blended with face-to-face psychotherapy for cancer survivors are highly warranted. Objective The aim of the study is to investigate whether smartphone-based bodily interventions are more effective to improve the mood of patients with cancer than smartphone-based fairy tale interventions (control intervention). Methods We recruited patients with cancer in 2 Swiss hospitals and conducted daily, fully automated smartphone-based interventions 6 times a week for 5 consecutive weeks, blended with weekly face-to-face group body psychotherapy. We applied 2 types of smartphone-based interventions using a within-subject design, randomly assigning patients daily to either bodily interventions or fairy tales. Each intervention type was presented 3 times a week. For this secondary analysis, 3-level mixed models were estimated with mood assessed by the 3 Multidimensional Mood Questionnaire subscales for good-bad mood, wakefulness, and calmness as key indicators. In addition, the effects on experience of presence, vitality, and burden assessed with visual analog scales were investigated. Results Based on the data from s=732 interventions performed by 36 participants, good-bad mood improved (β=.27; 95% CI 0.062-0.483), and participants became calmer (β=.98; 95% CI 0.740-1.211) following smartphone-based interventions. Wakefulness did not significantly change from pre- to postsmartphone–based intervention (β=.17; 95% CI –0.081 to 0.412). This was true for both intervention types. There was no interaction effect of intervention type with change in good-bad mood (β=–.01; 95% CI –0.439 to 0.417), calmness (β=.22; 95% CI –0.228 to 0.728), or wakefulness (β=.14; 95% CI –0.354 to 0.644). Experience of presence (β=.34; 95% CI 0.271-0.417) and vitality (β=.35; 95% CI 0.268-0.426) increased from pre- to postsmartphone–based intervention, while experience of burden decreased (β=–0.40; 95% CI –0.481 to 0.311). Again, these effects were present for both intervention types. There were no significant interaction effects of intervention type with pre- to postintervention changes in experience of presence (β=.14; 95% CI –0.104 to 0.384), experience of vitality (β=.06; 95% CI –0.152 to 0.265), and experience of burden (β=–.16; 95% CI –0.358 to 0.017). Conclusions Our results suggest that both smartphone-based audio-guided bodily interventions and fairy tales have the potential to improve the mood of cancer survivors. Trial Registration ClinicalTrials.gov NCT03707548; https://clinicaltrials.gov/study/NCT03707548 International Registered Report Identifier (IRRID) RR2-10.1186/s40359-019-0357-1

PDF file - 208K, (A) VEGFR2 is selectively expressed in tumor blood endothelial cells (BECs). Single cell suspension of pancreatic tumors of 12 weeks old Rip1Tag2 mice were prepared by Dispase digestion. For subsequent isolation of GLP-1R+ -tumor cells (TC) and tumor-derived CD31+ blood vessel endothelial cells (BEC) by fluorescence-activated cell sorting (FACS), cells were stained with FITC-labeled glucagon-like peptide 1 receptor (GLP-1R) peptide ligand exendin-4 and with APC-CD31. Quantitative RT-PCR analysis verified VEGFR2 expression in CD31-positive BECs but not in TC. Cultured MS-1 cells express low levels of VEGFR2. (B) VEGFR2 is expressed in tumor-associated microvessels. Immunofluorescence staining of vessels in the pancreas of a Rip1Tag2 mouse treated with PLD. VEGFR2 is expressed in microvessels, but not in larger vessels or mature vessels. Vessels in the exocrine pancreas express lower levels of VEGFR2. Bar, 100 m. The tumor tissue is delineated with a white line. Green = staining with anti-CD31, red = staining with anti-VEGFR2, blue = DAPI. Merge= overlay of single stainings.

Supplementary Table from An In Vivo CRISPR Screen Identifies Stepwise Genetic Dependencies of Metastatic Progression

PDF file - 85K, Biodistribution of anti-VEGFR2 Immunliposomes Analysis of tissue samples showed a non-significant trend to a higher concentration of ILs in parenchymal organs (lung, liver and spleen) but not in the tumor (A and B). Rip1Tag2 mice were treated with liposomes (black columns) and anti-VEGFR2 ILs (dotted columns), which were labelled with 3H-cholesteryl hexadecylether, injected via tail vein at a dose of 31.25 mol phospholipid/kg mouse (cohorts of 4-6 mice x time point and treatment). At 24 (A) or 48 (B) hours mice and 3H-cholesteryl hexadecyl concentration were determined. The final distribution was expressed as % of injected dose (ID)/g tissue and % ID/concentration in blood circulation. Columns: mean; bars: SD (non-significant by Dunn's multiple comparison test).

Advanced triple negative breast cancer (TNBC) is an aggressive, but initially chemo-sensitive disease. The prognosis is poor and more than three quarters of patients experience progression 12 months after the initiation of conventional first-line chemotherapy. Approximately two thirds of TNBC express epidermal growth factor receptor 1 (EGFR). We have developed an anti-EGFR targeted nanocontainer drug by inserting anti-EGFR antibody fragments into the membrane of pegylated liposomes (anti-EGFR-ILs-dox). The payload consists of doxorubicin, a standard drug for TNBC. In a first-in-human phase I trial in 26 patients with various advanced solid malignancies, anti-EGFR-ILs-dox has shown little toxicity and encouraging efficacy. In this single-arm phase II trial, we assessed the efficacy of anti-EGFR-ILs-dox as first-line therapy in patients with advanced, EGFR + TNBC. The primary endpoint was progression-free survival at 12 months (PFS12m). Secondary endpoints included overall response rate (ORR), duration of response (DOR), time to progression (TTP), overall survival (OS) and adverse events (AEs). 48 patients received anti-EGFR-ILs-dox 50 mg/m 2 iv, on day one of a 28 days-cycle until progression. The Kaplan–Meier estimate for PFS12m was 13% (one-sided 90% CI 7%, 95% CI [5%, 25%]), median PFS was 3.5 months (95% CI 1.9, 5.4). The trial has not reached its primary endpoint. There were no new toxicity signals. Based on these results, anti-EGFR-ILs-dox should not be further developed for TNBC. It remains an open question whether anti-EGFR-ILs-dox would offer more opportunities in other EGFR-expressing malignancies, where targeting this receptor has already shown anticancer effects. Trial registration: This trial was registered at clinicaltrials.gov: NCT02833766. Registered 14/07/2016.

PDF file - 222K, Histopathological analysis of tumor sections by staining with hematoxylin and eosin (H&E). Hemorrhagic lacunae are visible in the center of tumors treated with anti-VEGFR2 ILs-dox in the Rip1Tag2 and the MMTV-PyMT tumor mouse model (top and middle rows). No hemorrhagic necroses are seen in the HT-29 xenograft tumor sections (bottom row). Scale bar = 200 m.

INTRODUCTION:As fertility may be impaired due to gonadotoxic cancer treatment, fertility preservation should be offered to young cancer patients. Despite affirmative guidelines, sperm cryopreservation rates are still unsatisfying.OBJECTIVE:To examine how male cancer patients experience the current practice of counseling regarding fertility preservation and the needs they have for additional online support tools.METHODS:A cross-sectional mixed methods study of men above 18 years old with a cancer diagnosis within the last 10 years. The quantitative part was a retrospective questionnaire-based online survey; the qualitative part used focus-group methodology. The mean age of participants (n=72) was 32.94 years (SD 8.38) and the predominant cancer types were testicular cancer (55.6%), lymphomas (16.7%), and leukemias (13.9%).RESULTS:Participants rated the significance of the counseling as high (M=4.2, SD=1.05) and experienced professionals as supportive (M=4.37, SD=0.66). A majority of participants (70.8%) stated that they would use an additional support tool designed for male cancer patients. The tool should contain not only information about fertility preservation, but also about sexuality, virility, consequences for partners, and experience reports from other patients.CONCLUSIONS:Cancer patients undergoing gonadotoxic therapies should be counseled about fertility preservation. Professional, individualized information and a well-organized fertility preservation process improve the subjective experience of cancer patients. An online support tool that provides information about fertility preservation and general reproductive health was considered as a helpful, low-threshold offer that would be appreciated.

The metastatic spread of cancer is achieved by the haematogenous dissemination of circulating tumour cells (CTCs). Generally, however, the temporal dynamics that dictate the generation of metastasis-competent CTCs are largely uncharacterized, and it is often assumed that CTCs are constantly shed from growing tumours or are shed as a consequence of mechanical insults1. Here we observe a striking and unexpected pattern of CTC generation dynamics in both patients with breast cancer and mouse models, highlighting that most spontaneous CTC intravasation events occur during sleep. Further, we demonstrate that rest-phase CTCs are highly prone to metastasize, whereas CTCs generated during the active phase are devoid of metastatic ability. Mechanistically, single-cell RNA sequencing analysis of CTCs reveals a marked upregulation of mitotic genes exclusively during the rest phase in both patients and mouse models, enabling metastasis proficiency. Systemically, we find that key circadian rhythm hormones such as melatonin, testosterone and glucocorticoids dictate CTC generation dynamics, and as a consequence, that insulin directly promotes tumour cell proliferation in vivo, yet in a time-dependent manner. Thus, the spontaneous generation of CTCs with a high proclivity to metastasize does not occur continuously, but it is concentrated within the rest phase of the affected individual, providing a new rationale for time-controlled interrogation and treatment of metastasis-prone cancers.

Purpose: Real-world data about pegylated liposomal doxorubicin (PLD) in patients with metastatic breast cancer (MBC) are limited. We have aimed to highlight the role of PLD in daily practice focusing on older patients and patients with comorbidities with MBC.Methods: We analyzed electronic records of all patients with advanced/metastatic breast cancer treated with single-agent PLD at the University Hospital Basel between 2003 and 2021. Primary endpoint was time to next chemotherapy or death (TTNC). Secondary endpoints were overall survival (OS), progression-free survival (PFS), and overall response rate (ORR). We performed univariate and multivariate analysis for clinical variables.Results: 112 patients with MBC having received single-agent PLD in any treatment line were analyzed, including 34 patient who were older than 70 years and 61 patients with relevant comorbidities. Median TTNC, OS, and PFS for treatment with PLD were 4.6, 11.9, and 4.4 months, respectively. ORR was 13.6%. Age >70 years predicted shorter OS (median 11.2 months) in multivariate analysis (hazard ratio [HR] 1.83, 95% CI 1.07-3.11, p = 0.026). Age and comorbidities did not significantly affect other endpoints. Unexpectedly, hypertension predicted longer TTNC (8.3 months, p = 0.04) in univariate analysis, maintained in multivariate analysis as a trend for both TTNC (HR 0.62, p = 0.07) and OS (HR 0.63, p = 0.1).Conclusion: Age predicted shorter OS significantly but median OS was not relevantly shorter in older patients. PLD remains a treatment option in patients with comorbidities and older patients with MBC. However, our real-world results of PLD appear underwhelming compared to relevant phase II trials through all age groups, pointing to an efficacy-effectiveness gap, possibly due to sampling bias.

Abstract Blood-borne metastasis of breast cancer involves a series of tightly regulated sequential steps, including the growth of a primary tumor lesion, intravasation of circulating tumor cells (CTC), and adaptation in various distant metastatic sites. The genes orchestrating each of these steps are poorly understood in physiologically relevant contexts, owing to the rarity of experimental models that faithfully recapitulate the biology, growth kinetics, and tropism of human breast cancer. Here, we conducted an in vivo loss-of-function CRISPR screen in newly derived CTC xenografts, unique in their ability to spontaneously mirror the human disease, and identified specific genetic dependencies for each step of the metastatic process. Validation experiments revealed sensitivities to inhibitors that are already available, such as PLK1 inhibitors, to prevent CTC intravasation. Together, these findings present a new tool to reclassify driver genes involved in the spread of human cancer, providing insights into the biology of metastasis and paving the way to test targeted treatment approaches. Significance: A loss-of-function CRISPR screen in human CTC-derived xenografts identifies genes critical for individual steps of the metastatic cascade, suggesting novel drivers and treatment opportunities for metastatic breast cancers.

Background: We assessed the capacity of epidermal growth factor receptor (EGFR)-targeted immunoliposomes to deliver cargo to brain tumor tissue in patients with relapsed glioblastoma harboring an EGFR amplification. We aimed to assess the tolerability and effectiveness of anti-EGFR immunoliposomes loaded with doxorubicin (antiEGFR ILs-dox) in glioblastoma multiforme patients. Patients and methods: Patients with EGFR-amplified, relapsed glioblastoma were included in this phase I pharmacokinetic trial. Patients received up to four cycles of anti-EGFR ILs-dox. Twenty-four hours later, plasma and cerebrospinal fluid (CSF) samples were obtained. In addition, we also treated three patients with anti-EGFR ILs-dox before resection of their relapsed glioblastoma. Doxorubicin concentrations were measured in plasma, CSF, and tumor tissue. Safety and efficacy parameters were also obtained. Results: There were no or negligible levels of doxorubicin found in the CSF demonstrating that anti-EGFR ILs-dox are not able to cross the bloodebrain barrier (BBB). However, significant levels were detected in glioblastoma tissue 24 h after the application, indicating that the disruption of BBB integrity present in high-grade gliomas might enable liposome delivery into tumor tissue. No new safety issues were observed. The median progression-free survival was 1.5 months and the median overall survival was 8 months. One patient undergoing surgery had a very long remission suggesting that neoadjuvant administration may have a positive effect on outcome. Conclusions: We clearly demonstrate that anti-EGFR-immunoliposomes can be targeted to EGFR-amplified glioblastoma and cargodin this case doxorubicindcan be delivered, although these immunoliposomes do not cross the intact BBB.

Introduction The decision, whether to undergo fertility preservation or not is highly demanding for cancer patients. Decision aids may act as an additional source of support. So far, only a limited number of decision aids regarding fertility preservation for female cancer patients exist and have been evaluated systematically. This paper presents the results of secondary analyses of the first randomized controlled trial evaluating an online decision aid for female cancer patients affected by different types of cancer. It focuses on fertility-related knowledge, attitude toward fertility preservation, and long-term effectiveness regarding decisional regret. Material and methods Young female cancer patients between 18 and 40 years of age were recruited after fertility counseling with a reproductive specialist. They were assigned to either the control group (counseling only) or the intervention group (counseling followed by the additional use of the decision aid). Both groups had to complete a questionnaire after counseling as well as 1 and 12 months later, covering topics such as fertility-related knowledge, attitude towards fertility preservation, decisional conflict and regret. Recruitment was ongoing during 18 months in eight fertility centers located in Switzerland and Germany. Results Mean age of participating women was 29.31 years (SD 4.57). Of the entire sample (n = 51) 53% were affected with breast cancer, 27.4% with lymphoma, and 19.6% with various other types of cancer. Knowledge regarding the most common fertility preservation methods was high and comparable in both groups. Positive attitude significantly exceeded negative attitude among all participants (p = 0.001). Although the altogether low scores for decisional regret were on a higher level in the control group (T2: mean = 19.00, SD = 13.24; T3: mean = 22.0, SD = 20.67) than in the intervention group (T2: mean = 14.12, SD = 11.07; T3: mean = 12.94, SD = 13.24), there were no statistically significant differences between and within both groups. There was a positive association between decisional conflict and decisional regret at T3 (p = 0.001, r = 0.510). Conclusions This decision aid was suitable as an additional source of knowledge and may positively impact decisional regret in the long term. Results suggest that the provision of an online decision aid as a complement to fertility counseling may facilitate decision-making.

Advanced triple-negative breast cancer (TNBC) is an aggressive, but initially chemo-sensitive disease. The prognosis is poor and more than three quarters of patients experience a progression 12 months after the initiation of conventional first-line chemotherapy. Approximately 2/3 of TNBC express epidermal growth factor receptor 1 (EGFR) on malignant cells. We have developed an anti-EGFR targeted nanocontainer drug by inserting anti-EGFR antibody fragments into the membrane of pegylated liposomes (anti-EGFR-ILs-dox).