Photothermal therapy (PTT), which converts light energy to heat energy, has become a new research hotspot in cancer treatment. Although researchers have investigated various ways to improve the ...efficiency of tumor heat ablation to treat cancer, PTT may cause severe damage to normal tissue due to the systemic distribution of photothermal agents (PTAs) in the body and inaccurate laser exposure during treatment. To further improve the survival rate of cancer patients and reduce possible side effects on other parts of the body, it is still necessary to explore PTAs with high selectivity and precise treatment. In this review, we summarized strategies to improve the treatment selectivity of PTT, such as increasing the accumulation of PTAs at tumor sites and endowing PTAs with a self-regulating photothermal conversion function. The views and challenges of selective PTT were discussed, especially the prospects and challenges of their clinical applications.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose
Breast cancer is the most common cancer in females and the leading cause of death worldwide. The effects of statins on breast cancer prognosis have long been controversial; thus, it is ...important to investigate the relationship between statin type, exposure time, and breast cancer prognosis. This study sought to explore the effect of statins, as well as the different effects of statin solubility and variable follow-up times, on breast cancer prognosis.
Methods
We searched the MEDLINE (via PubMed), EMBASE (via OvidSP), Cochrane Library, and ISI Web of Knowledge databases using combinations of the terms “breast neoplasmsMeSH,” “statins” or “lipid-lowering drug,” “prognosis” or “survival,” or “mortality” or “outcome” with no limit on the publication date. We searched the databases between inception and October 15, 2016. Reference lists of the included studies and relevant reviews were also manually screened. The initial search identified 71 publications, and 7 of these studies, which included a total of 197,048 women, met the selection criteria. Two authors independently screened each study for inclusion and extracted the data. The data were analyzed using Stata/SE 11.0.
Results
Overall statin use was associated with lower cancer-specific mortality and all-cause mortality, although the benefit appeared to be constrained by statin type and follow-up time. Lipophilic statins were associated with decreased breast cancer-specific and all-cause mortality; however, hydrophilic statins were weakly protective against only all-cause mortality and not breast cancer-specific mortality. Of note, one group with more than 4 years of follow-up did not show a significant correlation between statin use and cancer-specific mortality or all-cause mortality, whereas groups with less than 4 years of follow-up still showed the protective effect of statins against cancer-specific mortality and all-cause mortality.
Conclusions
Although statins can reduce breast cancer patient mortality, the benefit appears to be constrained by statin type and follow-up time. Lipophilic statins showed a strong protective function in breast cancer patients, whereas hydrophilic statins only slightly improved all-cause mortality. Finally, the protective effect of statins could only be observed in groups with less than 4 years of follow-up. These findings are meaningful in clinical practice, although some conclusions contradict conventional wisdom and will thus require further exploration.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Antibody-drug conjugates (ADCs) combine the high specificity of monoclonal antibodies with the high anti-tumor activity of small molecular cytotoxic payloads. The anti-tumor activity of ADCs is ...mainly achieved by the direct blocking of the receptor by monoclonal antibodies, direct action and bystander effect of cytotoxic drugs, and antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity. ADCs have been used in adjuvant therapy and rescue treatment of human epidermal receptor 2 (HER2)-positive breast cancer, greatly improving the prognosis of breast cancer patients. Several ongoing clinical trials of ADC for breast cancer and other solid tumors proved the potential of ADCs will provide more promising treatment options for patients with malignant tumors. This review introduces the mechanism and latest clinical progress of ADC drugs approved for HER2-positive breast cancer to guide clinical practice and conduct research.
To characterize the clinical and pathological features and survival of patients with human epidermal growth factor receptor 2 (HER2)-low breast cancer in China.
The China National Cancer Center ...database was used to identify 1,433 metastatic breast cancer patients with HER2-negative disease diagnosed between 2005 and 2015. Clinicopathological features, survival, and prognosis information were extracted. Overall survival (OS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Prognostic factors associated with OS were analyzed using Cox regression model with 95% confidence interval (95% CI).
There were 618 (43.1%) and 815 (56.9%) HER2-low and HER2-zero tumors out of 1,433 tumors, respectively. The proportion of hormone receptor (HR)-positive tumors was significantly higher in HER2-low tumors than in those with HER2-zero tumors (77.8% vs. 69.2%,
< 0.001). Patients with HER2-low tumors survived significantly longer than those with HER2-zero tumors in the overall population (48.5 months vs. 43.0 months,
= 0.004) and HR-positive subgroup (54.9 months vs. 48.1 months,
= 0.011), but not in the HR-negative subgroup (29.5 months vs. 29.9 months,
= 0.718). Multivariate regression analysis revealed that HER2-low tumors were independently associated with increased OS in HER2-negative population (HR: 0.85, 95% CI: 0.73-0.98,
= 0.026).
Our findings demonstrate that HER2-low tumors could be identified as a more distinct clinical entity from HER2-zero tumors, especially for the HR-positive subgroup. A more complex molecular landscape of HER2-low breast cancer might exist, and more precise diagnostic algorithms for HER2 testing could be investigated, thus offering new therapeutic targets for breast cancer treatment.
In this study, we characterized the biological parameters extracted from a subset of enrolled patients with human epithelial growth factor receptor-2 (HER2) negative metastatic breast cancer (MBC) in ...the CAMELLIA study (ClinicalTrials.gov: NCT01917279). ...the prediction model may require further external prospective intervention studies to validate. ...our pretreatment multi-omics fusion models with machine learning effectively predicted the survival of HER2− MBC patients with good discrimination power and outperformed conventional clinicopathological models. Wang J, Liu Y, Zhang R, Liu Z, Yi Z, Guan X, Zhao X, Jiang J, Tian J, Ma F. Multi-omics fusion analysis models with machine learning predict survival of HER2-negative metastatic breast cancer: a multicenter prospective observational study.
We investigated the clinicopathological characteristics and survival of breast cancer lung metastases (BCLM) patients at initial diagnosis of metastatic breast cancer (MBC) in the Han population.
We ...attained clinical data of 3155 MBC patients initially diagnosed between April 2000 and September 2019 from the China National Cancer Center and finally included 2263 MBC patients in this study, among which 809 patients presented with lung metastases at first MBC diagnosis. The risk factors for BCLM were determined using multivariate logistic regression analysis and the prognostic factors of BCLM patients were assessed by univariate and multivariate Cox regression analyses.
Patients with triple-negative subtype (42.3%) harbored the highest incidence proportions of lung metastases. Age ≥ 50 years, Eastern Cooperative Oncology Group (ECOG) 2, M1, hormone receptor-negative (HR-)/human epidermal growth factor receptor 2-positive (HER2) + subtype, triple-negative subtype and disease-free survival (DFS) > 2 years were remarkably associated with higher incidence of lung metastases, while invasive lobular carcinoma (ILC) and bone metastases were significantly correlated with lower odds of lung metastases at diagnosis. The median survival of BCLM patients was 41.7 months, with triple-negative subtype experiencing the worst prognosis of 26.8 months. ECOG 2, triple-negative subtype, liver metastases, multi-metastatic sites and DFS ≤ 2 years were significantly correlated with poor survival of BCLM patients.
Our study provides essential information on clinicopathological features and survival outcomes of BCLM patients at initial diagnosis of MBC in China.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Everolimus, an inhibitor of mammalian target of rapamycin (mTOR), has been shown to increase the efficacy of endocrine therapies in hormone receptor (HR)-positive metastatic breast cancer. However, ...because breast cancer is a highly heterogeneous disease, the responses of different patients to everolimus may vary. Therefore, we performed this study to better select patients who will benefit most from or be resistant to everolimus.
Patients with HR-positive breast cancer who were treated with everolimus at the Cancer Hospital, Chinese Academy of Medical Sciences from February 2014 to March 2017 were enrolled in the present study. Mutations in ctDNA were assayed in 1021 tumor-related genes via gene panel target capture-based next-generation sequencing.
In total, 120 patients with metastatic breast cancer who were treated with everolimus were enrolled in the present study. The median progression-free survival (PFS) of all patients was 5.1 months (95% confidence interval CI 3.9-6.3 months). No difference in survival was observed between patients who received endocrine drugs used in previous treatment regimens and patients who did not receive these drugs (median PFS 5.2 and 5.1 months, respectively, p > 0.05). Additionally, we did not find any difference in outcomes between patients who had primary resistance to previously used endocrine drugs and patients who had nonprimary resistance to previous treatments (p > 0.05). Multivariate analysis showed that < 3 metastatic sites, < 2 lines of previous endocrine therapy, < 2 lines of previous chemotherapy, and treatment with everolimus combined with fulvestrant were associated with improved survival (p < 0.05). Sixteen patients underwent ctDNA analysis before everolimus treatment. The frequency of PIK3CA gene mutations was 62.5%, and H1047R was the most frequently detected mutation. Patients with the PIK3CA/H1047R mutation had longer PFS than patients with wild-type or other mutant forms of PIK3CA, and the median PFS in these two groups of patients was 8.8 and 4.1 months, respectively (p < 0.05).
Our data suggest that patients who receive more lines of chemotherapy or endocrine therapy are less likely to benefit from everolimus. For everolimus combination therapy, we can even select endocrine drugs that gave rise to primary resistance in previous treatments. Additionally, the PIK3CA/H1047R mutation may be a potential biomarker of sensitivity to everolimus.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Circulating tumor DNA (ctDNA) is a potential biomarker of prognosis and therapeutic response. We conducted this study to explore the role of the molecular tumor burden index (mTBI) in ctDNA as a ...therapeutic response and prognostic biomarker in a larger cohort prospective phase III randomized multicenter study. We collected 291 plasma samples from 125 metastatic breast cancer patients from the CAMELLIA study (NCT01917279). Target-capture deep sequencing of 1021 genes was performed to detect somatic variants in ctDNA from the plasma samples. The pretreatment mTBI value was correlated with tumor burden (P = 0.025). Patients with high-level pretreatment mTBI had shorter overall survival than patients with low-level pretreatment mTBI, and the median overall survival was 40.9 months and 68.4 months, respectively (P = 0.011). Patients with mTBI decrease to less than 0.02% at the first tumor evaluation had longer progression-free survival and overall survival (P < 0.001 and P = 0.007, respectively). The mTBI has good sensitivity to identify complete response/partial response and progressive disease based on computed tomography scans (88.5% and 87.5%, respectively). The patients classified as molecular responders had longer progression-free survival and overall survival than the nonmolecular responders in the overall cohort (P < 0.001 and P = 0.036, respectively), as well as in the cohort in which computed tomography scans were defined as representing stable disease (P = 0.027 and P = 0.015, respectively). The mTBI in ctDNA detected in liquid biopsies is a potential biomarker of therapeutic response and prognosis in patients with metastatic breast cancer.
This pooled analysis explored the possibility and potential of pyrotinib plus capecitabine as a first‐line regimen in relapsed or metastatic HER2‐positive breast cancer patients who received prior ...adjuvant or neoadjuvant chemotherapy with trastuzumab and discussed the potential treatment options for these patients, especially for the patients relapsed during or within 6 months after adjuvant trastuzumab.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Purpose:
Low-dose metronomic chemotherapy can achieve disease control with reduced toxicity compared to conventional chemotherapy in maximum tolerated dose. Characterizing the gut microbiota of ...cancer patients under different dosage regimens may describe a new role of gut microbiota associated with drug efficacy. Therefore, we evaluated the composition and the function of gut microbiome associated with metronomic capecitabine compared to conventional dosage.
Methods:
The fecal samples of HER2-negative metastatic breast cancer patients treated with capecitabine as maintenance chemotherapy were collected and analyzed by 16S ribosome RNA gene sequencing.
Results:
A total of 15 patients treated with metronomic capecitabine were compared to 16 patients under a conventional dose. The unweighted-unifrac index of the metronomic group was statistically significantly lower than that of the routine group (
P
= 0.025). Besides that, the Bray–Curtis distance-based redundancy analysis illustrated that the microbial genera between the two groups can be separated partly. Nine Kyoto Encyclopedia of Genes and Genomes (KEGG) modules were enriched in the metronomic group, while no KEGG modules were significantly enriched in the routine group. Moreover, univariate and multivariate analyses suggested that the median progression-free survival (PFS) was significantly shorter in patients with the gut microbial composition of
Slackia
(9.2 vs. 32.7 months,
P
= 0.004), while the patients with
Blautia obeum
had a significantly prolonged PFS than those without (32.7 vs. 12.9 months,
P
= 0.013).
Conclusions:
The proof-of-principle study suggested that the gut microbiota of patients receiving metronomic chemotherapy was different in terms of diversity, composition, and function from those under conventional chemotherapy, and the presence of specific bacterial species may act as microbial markers associated with drug resistance monitoring and prognostic evaluation.
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