BACKGROUND: Breast cancer incidence has been on the rise significantly in the Asian population, occurring at an earlier age and a later stage. The potential predictive value of molecular subtypes, biomarkers, and genetic variations has not been deeply explored in the Asian population. This study evaluated the effect of molecular subtype classification and the presence or absence of biomarkers and genetic variations on pathological complete response (pCR) after neoadjuvant treatment in Asian breast cancer patients.
METHODS: A systematic search was conducted in MEDLINE (PubMed), Science Direct, Scopus, and Cochrane Library databases. Studies were selected if they included Asian breast cancer patients treated with neoadjuvant chemotherapy and contained data for qualitative or quantitative analyses. The quality of the included studies was assessed using the Newcastle Ottawa Scale. Following the random effects model, pooled odds ratios or hazard ratios with 95% confidence intervals for pCR were analysed using Review Manager Software. Heterogeneity between studies was assessed using Cochran\'s Q-test and I2 test statistics.
RESULTS: In total, 19,708 Asian breast cancer patients were pooled from 101 studies. In the neoadjuvant setting, taxane-anthracycline (TA) chemotherapy showed better pCR outcomes in triple-negative breast cancer (TNBC) (p<0.0001) and human epidermal growth factor receptor 2 enriched (HER2E) (p<0.0001) than luminal breast cancer patients. Similarly, taxane-platinum (TP) chemotherapy also showed better pCR outcomes in TNBC (p<0.0001) and HER2E (p<0.0001). Oestrogen receptor (ER)-negative, progesterone receptor (PR)-negative, HER2-positive and high Ki-67 were significantly associated with better pCR outcomes when treated with either TA or TP. Asian breast cancer patients harbouring wildtype PIK3CA were significantly associated with better pCR outcomes when treated with TA in the neoadjuvant setting (p=0.001).
CONCLUSIONS: In the neoadjuvant setting, molecular subtypes (HER2E and TNBC), biomarkers (ER, PR, HER2, HR, Ki-67, nm23-H1, CK5/6, and Tau), and gene (PIK3CA) are associated with increased pCR rates in Asian breast cancer patients. Hence, they could be further explored for their possible role in first-line treatment response, which can be utilised to treat breast cancer more efficiently in the Asian population. However, it needs to be further validated with additional powered studies.
BACKGROUND: PROSPERO CRD42021246295.

Pancreatic adenocarcinoma (PDAC) is disease with a 5-year survival of only 12%. Many patients with PDAC present with late-stage disease and even early-stage disease can often be characterized by an aggressive tumor biology. Standard therapy for metastatic PDAC consists mainly of chemotherapy regimens like FOLFIRINOX, FOLFOX, or gemcitabine and nab-paclitaxel. Research has focused on sequencing PDAC tumors to understand better the mutational landscape and transcriptomics of PDAC with the goal to develop targeted therapies. Targeted therapies may potentially minimize the toxic risks of chemotherapy and provide a long-term survival benefit. We herein review the underlying molecular pathogenesis of PDAC, as well as the classification schema created from current sequencing data, and recent updates related to targeted therapy for PDAC.

Diabetes mellitus (DM) has been proposed to be positively associated with breast cancer (BCa) risk due to shared risk factors, metabolic dysfunction, and the use of antidiabetic medications. We conducted a systematic review and meta-analysis to evaluate the association between DM and BCa risk. We searched PubMed, Embase, and Web of Science for cohort and case-control studies assessing the association between DM and BCa published before 10 December 2021. Two reviewers independently screened the studies for inclusion, abstracted article data, and rated study quality. Random effects models were used to estimate summary risk ratios (RRs) and 95% confidence intervals (CIs). From 8396 articles identified in the initial search, 70 independent studies were included in the meta-analysis. DM was associated with an overall increased risk of BCa (RR = 1.20, 95% CI: 1.11-1.29). The 24 case-control studies demonstrated a stronger association (RR = 1.26, 95% CI: 1.13-1.40) than the 46 cohort studies (RR = 1.15, 95% CI: 1.05-1.27). Studies reporting risk by menopausal status found that postmenopausal women had an elevated risk of developing BCa (RR = 1.12, 95% CI: 1.07-1.17). No association between DM and BCa risk was observed among premenopausal women (RR = 0.95, 95% CI: 0.85-1.05). In addition, DM was associated with significantly increased risks of oestrogen receptor (ER)+ (RR = 1.09, 95% CI: 1.00-1.20), ER- (RR = 1.16, 95% CI: 1.04-1.30), and triple negative BCa (RR = 1.41, 95% CI: 1.01-1.96). The association estimate for human epidermal growth factor 2-positive BCa was also positive (RR = 1.21, 95% CI: 0.52-2.82), but the CI was wide and crossed the null. Our meta-analysis confirms a modest positive association between DM and BCa risk. In addition, our results suggest that the association between DM and BCa may be modified by menopausal status, and that DM may be differentially associated with BCa subtypes defined by receptor status. Additional studies are warranted to investigate the mechanisms underlying these associations and any influence of DM on BCa receptor expression.

BACKGROUND: Associations between reproductive factors and breast cancer (BC) risk vary by molecular subtype (i.e., luminal A, luminal B, HER2, and triple negative/basal-like [TNBC]). In this systematic review and meta-analysis, we summarized the associations between reproductive factors and BC subtypes.
METHODS: Studies from 2000 to 2021 were included if BC subtype was examined in relation to one of 11 reproductive risk factors: age at menarche, age at menopause, age at first birth, menopausal status, parity, breastfeeding, oral contraceptive (OC) use, hormone replacement therapy (HRT), pregnancy, years since last birth and abortion. For each reproductive risk factor, BC subtype, and study design (case-control/cohort or case-case), random-effects models were used to estimate pooled relative risks and 95% confidence intervals.
RESULTS: A total of 75 studies met the inclusion criteria for systematic review. Among the case-control/cohort studies, later age at menarche and breastfeeding were consistently associated with decreased risk of BC across all subtypes, while later age at menopause, later age of first childbirth, and nulliparity/low parity were associated with increased risk of luminal A, luminal B, and HER2 subtypes. In the case-only analysis, compared to luminal A, postmenopausal status increased the risk of HER2 and TNBC. Associations were less consistent across subtypes for OC and HRT use.
CONCLUSIONS: Identifying common risk factors across BC subtypes can enhance the tailoring of prevention strategies, and risk stratification models can benefit from subtype specificity. Adding breastfeeding status to current BC risk prediction models can enhance predictive ability, given the consistency of the associations across subtypes.

Breast cancer is a destructive lump type that affects women globally. Despite the availability of multi-directional therapeutic strategies, advanced stages of breast cancer are difficult to treat and impose major healthcare burdens. This situation reinforces the need to identify new potential therapeutic compounds with better clinical features. In this context, different treatment methods were included such as Endocrine therapy, chemotherapy, Radiation therapy, antimicrobial peptide-dependent growth inhibitor, liposome-based drug delivery, antibiotics used as a co-medication, photothermal, immunotherapy, and nano drug delivery systems such as Bombyx mori natural protein sericin and its mediated nanoparticles are promising biomedical agents. They have been tested as an anticancer agent against various malignancies in pre-clinical settings. The biocompatible and restricted breakdown properties of silk sericin and sericin-conjugated nanoparticles made them perfect contenders for a nanoscale drug-delivery system.

Metaplastic breast carcinoma (MpBC) is a heterogeneous group of tumors that clinically could be divided into low risk and high risk. It is important to recognize the different types of MpBC, as the high-risk subtypes have worse clinical outcomes than triple-negative breast cancer. It is important for the pathologist to be aware of the MpBC entities and use the proposed algorithms (morphology and immunohistochemistry) to assist in rendering the final diagnosis. Few pitfalls are discussed, including misinterpretation of immunohistochemistry and certain histomorphologies, particularly spindle lesions associated with complex sclerosing lesions.

Breast cancer patients who have pathological complete response (pCR) to neoadjuvant chemotherapy (NAC) are more likely to have better clinical outcomes. The ability to predict which patient will respond to NAC early in the treatment course is important because it could help to minimize unnecessary toxic NAC and to modify regimens mid-treatment to achieve better efficacy. Machine learning (ML) is increasingly being used in radiology and medicine because it can identify relationships amongst complex data elements to inform outcomes without the need to specify such relationships a priori. One of the most popular deep learning methods that applies to medical images is the Convolutional Neural Networks (CNN). In contrast to supervised ML, deep learning CNN can operate on the whole images without requiring radiologists to manually contour the tumor on images. Although there have been many review papers on supervised ML prediction of pCR, review papers on deep learning prediction of pCR are sparse. Deep learning CNN could also incorporate multiple image types, clinical data such as demographics and molecular subtypes, as well as data from multiple treatment time points to predict pCR. The goal of this study is to perform a systematic review of deep learning methods that use whole-breast MRI images without annotation or tumor segmentation to predict pCR in breast cancer.

There are no established biomarkers to guide patient selection for neoadjuvant chemotherapy prior to radical cystectomy for muscle-invasive bladder cancer. Recent studies suggest that molecular subtype classification holds promise for predicting chemotherapy response and/or survival benefit in this setting. Here, we summarize and discuss the scientific literature examining transcriptomic or panel-based molecular subtyping applied to neoadjuvant chemotherapy-treated patient cohorts. We find that there is not sufficient evidence to conclude that the basal subtype of muscle-invasive bladder cancer responds well to chemotherapy, since only a minority of studies support this conclusion. More evidence indicates that luminal-like subtypes may have the most improved outcomes after neoadjuvant chemotherapy. There are also conflicting data concerning the association between biopsy stromal content and response. Subtypes indicative of high stromal infiltration responded well in some studies and poorly in others. Uncertainties when interpreting the current literature include a lack of reporting both response and survival outcomes and the inherent risk of bias in retrospective study designs. Taken together, available studies suggest a role for molecular subtyping in stratifying patients for receiving neoadjuvant chemotherapy. The precise classification system that best captures such a predictive effect, and the exact subtypes for which other treatment options are more beneficial remains to be established, preferably in prospective studies.

Metaplastic breast carcinoma (MpBC) is a heterogeneous group of tumors that clinically could be divided into low risk and high risk. It is important to recognize the different types of MpBC, as the high-risk subtypes have worse clinical outcomes than triple-negative breast cancer. It is important for the pathologist to be aware of the MpBC entities and use the proposed algorithms (morphology and immunohistochemistry) to assist in rendering the final diagnosis. Few pitfalls are discussed, including misinterpretation of immunohistochemistry and certain histomorphologies, particularly spindle lesions associated with complex sclerosing lesions.

BACKGROUND: Breast cancer has four distinct molecular subtypes which are discriminated using gene expression profiling following biopsy. Radiogenomics is an emerging field which utilises diagnostic imaging to reveal genomic properties of disease. We aimed to perform a systematic review of the current literature to evaluate the value radiomics in differentiating breast cancers into their molecular subtypes using diagnostic imaging.
METHODS: A systematic review was performed as per PRISMA guidelines. Studies assessing radiomictumour analysis in differentiatingbreast cancer molecular subtypeswere included. Quality was assessed using the radiomics quality score (RQS). Diagnostic sensitivity and specificity of radiomic analyses were included for meta-analysis; Study specific sensitivity and specificity were retrieved and summary ROC analysis were performed to compile pooled sensitivities and specificities.
RESULTS: Forty-one studies were included. Overall, there were 10,090 female patients (mean age of 47.6 ± 11.7 years, range: 21-93) and molecular subtypewas reported in 7,693 of cases, with Luminal A (LABC), Luminal B (LBBC), Human Epidermal Growth Factor Receptor-2 overexpressing (HER2+), and Triple Negative (TNBC) breast cancers representing 51.3%, 19.9%, 12.3% and 16.3% of tumour respectively. Seven studies provided radiomic analysis to determine molecular subtypes using mammography to differentiateTNBCvs.others (sensitivity: 0.82,specificity:0.79). Thirty-five studies reported on radiomic analysis of magnetic resonance imaging (MRI); LABC versus others(sensitivity:0.78,specificity:0.83),HER2+versusothers(sensitivity:0.87,specificity:0.88), andLBBCversusTNBC (sensitivity: 0.79,specificity:0.88) respectively.
CONCLUSIONS: Radiomic tumour assessment of contemporary breast imaging provide a novel option in determining breast cancer molecular subtypes. However, amelioration of such techniques are required and genetic expression assessment will remain the gold standard.