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Objectives: to evaluate the incidence of advanced-stage breast cancer (BC) - an early surrogate indicator of effectiveness of mammography screening - among women who attended the Friuli Venezia Giulia (FVG) Region (Northern Italy) screening programme compared to women who did not attend. Design: retrospective cohort study. Women invited to the first screening round (2006-2007) were identified from the database of the programme. The cohort was record-linked to the archive of women invited to the second round (2008-2009). The definition of attendance to screening was based on attendance to at least one of the two rounds. The incidence of BC was assessed through record linkage with the FVG cancer registry using an anonymous univocal identifier (end of follow-up: 31st December 2013). Three distinct definitions of advanced stage were used: pT2 or greater (pT2+), positive lymph nodes (pN+), and TNM stage II or greater (stage II+). Setting and participants: organized mammography screening programme for women aged 50-69 years in the five regional healthcare districts. Main outcome measures: incidence rate ratio (IRR) between attenders and non-attenders, adjusted for age and deprivation index, with 95% confidence interval (95%CI). Results: the cohort included 104,488 attenders and 49,839 non-attenders. During follow-up (median duration 84 months), 2,717 invasive BCs were diagnosed among attenders and 1,149 among non-attenders. Total incidence rate was 13% higher among attenders (IRR 1.13; 95%CI 1.05-1.21). These, conversely, had a 36% lower rate of pT2+ BC (IRR 0.64; 95%CI 0.56-0.72), a 13% lower rate of pN+ BC (IRR 0.87; 95%CI 0.78-0.98), a 22% lower rate of stage II+ BC (IRR 0.78; 95%CI 0.70-0.87), and a 32% lower rate of mastectomy (IRR 0.68; 95%CI 0.60-0.78). Conclusions: attenders had lower incidence rates of advanced-stage BC. This early effect is suggestive of a future impact of the screening programme on BC mortality.

Fine needle aspiration (FNA) has traditionally been regarded as the simplest, less invasive and less expensive diagnostic procedure for the definition of breast lesions. In expert hands, it allows obtaining an accurate diagnosis in most breast lesions. The introduction of widespread mammographic screeningprogrammes and the consequent detection of a large number of small, non-palpable lesions have increasingly brought to the routine use of other minimally invasive biopsy methods using heavier gauge cutting needles – the so-called core biopsies (CB) and other automatic, imaging-guideddevices, such as vacuum assisted biopsies (VAB) – partially obscuring the central role of FNA. Recently, new recommendations propose to definitively abandon FNA, restricting all morphological investigations to CB.Has FNA completely lost its role as to let us to remove it from the routine diagnostic practice? In our personal experience from the breast unit of Trieste, where there systematic use of FNA is available, it is proved that this method may bring to a definitive diagnosis 2/3 of the lesions investigated. The unjustified abandonment of the technique by breast healthcare centres must be avoided, since it could only have negative repercussions on the whole preoperative diagnostics.it is necessary for the pathologists to guarantee the maintenance of their professional expertise in this field, and to transmit it to the young.

The role of breastfeeding as protective factor for breast cancer incidence is controversial among scientific literature. The Interdisciplinary Senology Unit of Trieste has analyzed the relation between breast cancer incidence and lactation habits among a total of 4307 Trieste’s women. In this study, the statistical analysis revealed that over having children, the breastfeeding is a further protective factor for breast cancer. In particular, the decrease of breast cancer risk by breastfeeding resulted to be significant for lactation more than 12 months. It is worth noting that breastfeeding resulted protective only for women in childbearing age and it didn’t result to decrease breast cancer risk among post-menopausal women.

Friuli Venezia Giulia holds the higest row incidence rate for breast carcinoma in Italy (218%00) and Trieste, where live 125.000 women (105.000 women of age below 75) has the highest incidence rate among the other provinces of the region (220%00). The risk of developing breast carcinoma seems to be correlated with many different factors. The goal of this study is to focus on same specific breast carcinoma risk factors in the Trieste population.

Differences in fixation and IHC and subjective interpretation can substantially affect the accuracy and reproducibility of estrogen receptor (ER), progesterone receptor (PR) and HER2 expression. The commercially available TargetPrint test measures the mRNA expression level of ER, PR and HER2 and is 98% concordant with centrally assessed ER as presented by Viale et al, SABCS 2011. This study compares results from the microarray-based TargetPrint with IHC and FISH (for HER2 IHC2+) generated by local standard procedures

Breast cancer is thecmost frequency malignancy in women in the world and also in Italy.In Trieste most of breast lesions are investigated by fine needle aspiration cytology under ultrasound guidance (FNAC). Tru-cut is used when FNAC is inadequate, for discrepancy with radiology or to have a biomolecular profiling,expecially in neoadjuvant chemotherapy. Vacuum Aspiration Biopsy (VAB) is used in case of microcalcifications or mammographic abnormalitues without evidence of nodules.FNAC's goal is to define breast lesions avoiding more invasive procedures,, it provides several benefits for women, for pathologists and for the public health

International audience; Recent studies have reported the potential clinical utility for metastatic breast cancer (MBC) patients of continuing trastuzumab beyond progression. Based on those results, here the authors have examined the benefits of trastuzumab-continuation by specifically evaluating RECIST responses upon first line trastuzumab-treatment as a potential predictive marker for therapeutic effect of trastuzumab-continuation beyond metastatic disease progression. The authors carried out a retrospective analysis of 272 HER2 positive MBC patients under trastuzumab treatment at 22 different oncology Italian centers during the years of 2000 and 2001 who progressed under first line trastuzumab-treatment. The primary end point of the study was the survival from the date of first documented progression upon first line trastuzumab treatment of disease. Data analysis involved the use of matching on propensity score to balance variables between treated and untreated subjects and to reduce bias. Of the 272 HER2-positive MBC patients, 154 (56.6%) continued treatment. 79 (51.3%) of those 154 patients showed responses based on RECIST criteria during first-line trastuzumab-treatment. Of the 118 patients that suspended trastuzumab, RECIST responses had been observed in 44 (37.3%). Cox proportional hazards analysis of progressed patients, matched using propensity score, showed that discontinuation of trastuzumab at metastatic disease progression was a risk factor for significantly reduced overall survival in both responder (HR = 2.23; 95% CI = 1.03-4.82) and non-responder groups (HR = 3.53, 95% CI = 1.73-7.21), with no significant differences in the two estimated HRs (-value of the likelihood-ratio test = 0.690). Continued trastuzumab treatment after disease progression has clinically and statistically significant effects in both RECIST responder and non-responder MBC patients.

Target Print (TP) is a microarray-based gene expression test which offers a quantitative assessment of the patient'slevel of estrogen receptor (ER), progesterone receptor (PR) and HER2/neu overexpression within her breast cancer. As compared to Immunohistochemistry (IHC), TP delivers an added benefit to the diagnostic process. IHC provide a semi-quantitative positive or negative result, whereas the gene expression result provided by TP allows to integrate the absolute level of ER, PR and HER2 gene expression into treatment planning. It is known that differences in tissue fixation, choice of antibody and interpretation can severely affect IHC accuracy and reproducibility.

The 70-gene profile MammaPrint was established as a powerful predictor of disease outcome in breast cancer. The St Gallen 2009 recommendations include gene-expression signatures as an indicator for adjuvant therapy. Here we determined in an international cohort how MammaPrint could assist in patient management. Fresh tumor samples (n = 877) from breast cancer patients (T1–4N0–1M0) were collected from 23 hospitals in Europe, 2 in New Zealand and 1 in Japan between 2007 and 2010 by core needle biopsy or from a surgical specimen (study protocol MP090). We assessed agreement between the treatment advice as recommended by the 2009 St Gallen Highlights and classification according to MammaPrint.For the majority (93%) of these 877 breast cancer patients from international hospitals the St Gallen 2009 either recommends or suggests considering treatment with cytotoxic adjuvant therapy for whom MammaPrint indicates a low risk of recurrence in 38% of cases.

Sentinel node biopsy (SNB) is accepted as gold standard in axillary management of early breat cancer patients. The choice of SN identification procedure is still controversial. The blue dyed method has been increasingly used, but it needs a validation in terms of concordance with the radioguided method, commonly considered ad gold standar procedure in SNB. We evaluated the "same patient" concordance between the two techniques, in aim to understand if the two methods leads to the same SN, as a result to define the accuracy of the blue dye method

Background: The 70-gene tumor expression profile ‘‘MammaPrint’’ was established as a powerful predictor of disease outcome in breast cancer. The St Gallen 2009 recommendations include gene-expression signatures as an indicator for adjuvant therapy. Here we determined in an Italian cohort how the 70-gene profile could assist in patient management. Methods: Fresh tumor samples (n=584) from breast cancer patients (clinical T1-4N0- 3M0) aged 26 to 98 years (median age 63 years), were collected in 12 Italian hospitals IN 2008 and 2009 by core needle biopsy or from a surgical specimen (study protocol MP 090). We assessed agreement between the treatment advice as recommended by the 2009 St Gallen Highlights and classification according to the 70-gene MammaPrint profile. Results: According to the St Gallen 2009 treatment recommendations, 4 patients could forego any adjuvant treatment (50%) and 198 would be recommended adjuvant chemotherapy being either Grade III, or 34LN, or >5cm, or ER

Background: The 70-gene tumor expression profile ‘‘MammaPrint’’ was established as a powerful predictor of disease outcome in breast cancer. The St Gallen 2009 recommendations include gene-expression signatures as an indicator for adjuvant therapy. Here we determined in an Italian cohort how the 70-gene profile could assist in patient management. Methods: Fresh tumor samples (n=584) from breast cancer patients (clinical T1-4N0- 3M0) aged 26 to 98 years (median age 63 years), were collected in 12 Italian hospitals IN 2008 and 2009 by core needle biopsy or from a surgical specimen (study protocol MP 090). We assessed agreement between the treatment advice as recommended by the 2009 St Gallen Highlights and classification according to the 70-gene MammaPrint profile. Results: According to the St Gallen 2009 treatment recommendations, 4 patients could forego any adjuvant treatment (50%) and 198 would be recommended adjuvant chemotherapy being either Grade III, or 34LN, or >5cm, or ER

Trieste is one of the italian areas with the highest incidence of breast carcinoma. Mammographical screening has been active since 2006 inolving womenn 50-69 years old. Breast screening introduction has been led to an increase both of Tis lesions and of invasive carcinoma. The oserved growth is due to increase of subclinical lesions (T1a and T1b), while lesions larger than 2 cm maintained steady.

Accordin to the guidelines ofBreast Unit of Trieste's Province (Italy) all the mammographic abnormalities and lesions with clinical symptoms must be submitted to echography and in presenc of a doubtful finiding they must be investigated with fine needle Aspiration (FNA)under ultrasound guidance. Core or aspiation biopsy is reserved instead for those cases with inconclusive (C3-C4)

Background The standardization of the HER2 score and recent changes in therapeutic modalities points to the need for a reevaluation of the role of HER2 in recently diagnosed breast carcinoma. Patients and methods A multicenter, retrospective study of 1794 primary breast carcinomas diagnosed in Italy in 2000/2001 and scored in HER2 four categories according to immunohistochemistry was conducted. Results Ductal histotype, vascular invasion, grade, MIB1 positivity, estrogen and progesterone receptor expression differed significantly in HER2 3+ tumors compared with the other categories. HER2 2+ tumors almost showed values intermediate between those of the negative and the 3+ subgroups. The characteristics of HER2 1+ tumors were found to be in between those of HER2 0 and 2+ tumors. With a median follow-up of 54 months, HER2 3+ status was associated with higher relapse rates in node-positive and node-negative subgroups, while HER2 2+ only in node positive. Analysis of relapses according to type of therapy provided evidence of responsiveness of HER2-positive tumors to chemotherapy, especially taxanes. Conclusions The present prognostic significance of HER2 is correlated to receptor expression level and points to the need to consider HER2 2+ and HER2 3+ tumors as distinct diseases with different outcomes and specific features.

A feasibility study of breast CT with synchrotron radiation is currently being carried on at Elettra, the Trieste synchrotron radiation facility. Breast CT cannot be implemented easily with conventional radiographic tubes, due to the high dose that would be delivered to the breast by a polychromatic X-ray spectrum. The possibility of tuning the beam energy, available at a synchrotron radiation beamline, allows a significant reduction in the delivered dose, and at the same time the use of monochromatic beams avoids beam hardening artifacts on the reconstructed image. Images of in vitro breast tissue samples have been acquired by means of a high efficiency linear array detector coupled to a VLSI single photon counting readout electronics. The pixel width, determining the pixel size of the reconstructed image, is 200 micrometers , while the pixel height, determining the CT slice thickness, is 300 micrometers . Tomograms have been reconstructed by means of standard filtered backprojection algorithms. Images of normal and pathologic breast tissue samples show a good visibility of glandular structure. The delivered dose was in all cases comparable to the one delivered in clinical planar mammography. Due to the promising results we obtained, in vivo studies are under evaluation

Background: In Western countries, breast cancer (BC) is the most common cancer in women. Early detection has a positive impact on survival, quality of life, and public health costs. Mammography screening programs have increased early detection rates, but new approaches to more personalized surveillance could further improve diagnosis. Circulating cell-free DNA (cfDNA) in blood could provide a potential tool for early diagnosis by analyzing cfDNA quantity, circulating tumor DNA mutations, or cfDNA integrity (cfDI). Methods: Plasma was obtained from the blood of 106 breast cancer patients (cases) and 103 healthy women (controls). Digital droplet PCR was used for the determination of ALU 260/111 bp and LINE-1 266/97 bp copy number ratio and cfDI. cfDNA abundance was calculated using copies of the EEF1A2 gene. The accuracy of biomarker discrimination was analyzed with receiver operating characteristic curve (ROC). Sensitivity analyses were performed to account for age as a potential confounder. Results: Cases had significantly lower ALU 260/111 or LINE-1 266/97 copy number ratios (median; ALU 260/111 = 0.08, LINE-1 266/97 = 0.20), compared with control (median; ALU 260/111 = 0.10, LINE-1 266/97 = 0.28) (p < 0.001). ROC analysis showed that copy number ratio discriminated cases from controls (area under the curve, AUC = 0.69, 95% CI: 0.62–0.76 for ALU and 0.80, 95% CI: 0.73–0.86 for LINE-1). ROC from cfDI confirmed the better diagnostic performance of LINE-1 compared with ALU. Conclusions: Analysis of LINE-1 266/97 copy number ratio or cfDI by ddPCR appears to be a useful noninvasive test that could aid in early BC detection. Further studies in a large cohort are needed to validate the biomarker.

Purpose: Prediction algorithms estimating survival rates for breast cancer (BC) based upon risk factors and treatment could give a help to the clinicians during multidisciplinary meetings. The aim of this study was to evaluate accuracy and clinical utility of three different scores: the Clinical Treatment Score Post-5 Years (CTS5), the PREDICT Score, and the Nottingham Prognostic Index (NPI). Methods: This is a retrospective cohort analysis conducted on prospectively recorded databases of two EUSOMA certified centers (Breast Unit of Trieste Academic Hospital and of Cremona Hospital, Italy). We included patients with Luminal BC undergone to breast surgery between 2010 and 2015, and subsequent endocrine therapy for 5 years for curative intent. Results: A total of 473 patients were enrolled in this study. ROC analysis showed fair accuracy for NPI, good accuracy for PREDICT, and optimal accuracy for CTS5 (AUC 0.7, 0.76, and 0.83, respectively). The three scores seemed strongly correlated in Spearman's rank correlation coefficient analysis. PREDICT partially overestimated OS in patients undergone to mastectomy, and in pT3-4, G3 tumors. Considering DRFS as a surrogate of OS, CTS5 showed women in intermediate and high risk class had shorter OS too (respectively p = 0.001 and p < 0.001). Combining scores does not improve prognostication power. Conclusion: Mathematical models may help clinicians in decision making (adjuvant therapies, CDK4/6i, genomic test's gray zones). CTS5 has the higher prognostic accuracy in predicting recurrence, while score predicting OS did not show substantial advances, proving that pN, G, and pT are still the most important variables in predicting OS.

Histopathological analysis is the current gold standard in breast cancer diagnosis and management, however, as imaging technology improves, the amount of potential diagnostic information that may be demonstrable radiologically should also increase. We aimed to evaluate the potential clinical usefulness of 3-D phase-contrast micro-computed tomography (micro-CT) imaging at high spatial resolutions as an adjunct to conventional histological microscopy. Ten breast tissue specimens, 2 mm in diameter, were scanned at the SYRMEP beamline of the Elettra Synchrotron using the propagation-based phase-contrast micro-tomography method. We obtained $1.2~\mu \text{m}$ pixel size images, which were analyzed and compared with corresponding histological sections examined under light microscopy. To evaluate the effect of spatial resolution on breast cancer diagnosis, scans with four different pixel sizes were also performed. Our comparative analysis revealed that high-resolution images can enable, at a near-histological level, detailed architectural assessment of tissue that may permit increased breast cancer diagnostic sensitivity and specificity when compared with current imaging practices. The potential clinical applications of this method are also discussed.

Breast cancer (BC) is the second most common cause of cancer-related deaths in women worldwide. The availability of reliable biomarkers of response/resistance to cancer treatments would benefit patients and clinicians allowing for a better selection of BC patients most likely to respond to a specific treatment. Phosphatidylinositol 3-kinase (PI3K) enzymes are involved in numerous cellular- functions and processes. The gene encoding for PI3K catalytic subunit p110α is mutated in 20-40% of BC. We performed a meta-analysis of the current literature on randomized clinical trials, investigating the role of PIK3CA mutational status as prognostic factor and predictor of response to anti-cancer treatments. Overall 1929 cases were included. The pooled analysis confirmed that the presence of a PIK3CA mutation represents an independent negative prognostic factor (HR = 1.67, 95% CI: 1.15-2.43; p = 0.007) in BC, as previously reported. Since PI3K signalling is also a result of other pathways’ hyperactivation, further investigation of potential biomarkers able to predict likelihood of response to anti-PI3K/mTOR, anti-HER2 and other TKRs is warranted in future randomized clinical trials. This article is protected by copyright. All rights reserved

In the medical literature, the role of breastfeeding and reproductive factors in the risk of breast carcinoma is still an open debate in premenopausal women. We highlight the role of breastfeeding and reproductive factors in luminal A and luminal B, the most frequent breast cancers. This case-control study analyzes a White premenopausal population of 286 breast cancer patients, divided into molecular subtypes, and 578 controls matched by age. Multivariate logistic regression models were used to assess the relationships of breastfeeding and other reproductive factors (age at menarche, parity, age at first pregnancy, number of children) with the risk of breast cancers. Among the variables examined, reproductive factors did not alter the risk of cancer, whereas breastfeeding up to 12 months was a significant protective factor against luminal B breast cancer (multivariate odds ratio: 0.22, 95% confidence interval: 0.09-0.59, P=0.002). In contrast, luminal A cases did not significantly correlate with breastfeeding or other reproductive factors. Breastfeeding up to 12 months is strongly protective against the more aggressive luminal B, but not against the less aggressive luminal A breast cancer in premenopausal White women.

The aim of this study was to optimise the experimental protocol and data analysis for in-vivo breast cancer x-ray imaging. Results are presented of the experiment at the SYRMEP beamline of Elettra Synchrotron using the propagation-based phase-contrast mammographic tomography method, which incorporates not only absorption, but also x-ray phase information. In this study the images of breast tissue samples, of a size corresponding to a full human breast, with radiologically acceptable x-ray doses were obtained, and the degree of improvement of the image quality (from the diagnostic point of view) achievable using propagation-based phase-contrast image acquisition protocols with proper incorporation of x-ray phase retrieval into the reconstruction pipeline was investigated. Parameters such as the x-ray energy, sample-to-detector distance and data processing methods were tested, evaluated and optimized with respect to the estimated diagnostic value using a mastectomy sample with a malignant lesion. The results of quantitative evaluation of images were obtained by means of radiological assessment carried out by 13 experienced specialists. A comparative analysis was performed between the x-ray and the histological images of the specimen. The results of the analysis indicate that, within the investigated range of parameters, both the objective image quality characteristics and the subjective radiological scores of propagation-based phase-contrast images of breast tissues monotonically increase with the strength of phase contrast which in turn is directly proportional to the product of the radiation wavelength and the sample-to-detector distance. The outcomes of this study serve to define the practical imaging conditions and the CT reconstruction procedures appropriate for low-dose phase-contrast mammographic imaging of live patients at specially designed synchrotron beamlines.

Aim Her2 protein is the key marker determining the choice of Herceptin therapy after a diagnosis of breast cancer. Its evaluation is made in most laboratories by immunohistochemistry, and interpreted by a pathologist using an optical microscope, a process subject to inter-observer variability, particularly for samples scored as equivocal (2+). Software analysis products have been introduced, seeking to reduce this variability. In this study, we compared the results of both traditional evaluation and a specific software package (VISIA Imaging) to those from fluorescent in situ hybridization (FISH). Materials and methods We selected 176 cases of invasive breast cancer sampled during 2012–2014 that were classified as equivocal after evaluation of Her2 immunohistochemistry, and that were also evaluated by FISH. Each tissue slide was scanned with a digital D-Sight Fluo 2.0 microscope and analysed with VISIA Imaging S.r.l. software. The final results were categorised as follows: negative (0–1+), equivocal (2+), or positive (3+). Then each result was compared to that obtained by FISH. Result The digital method confirmed 85 samples (48.3%) as equivocal (2+), while 23 (15.1%) were reclassified as negative (1+) and 44 (28.9%) as positive (3+). Of the 176 cases, 24 (13.6%) were not suitable for digital analysis (inadequate). Of 67 reclassified cases (1+ or 3+), 62 were in agreement with FISH results (concordance rate 92.5%). The sensitivity and specificity of the digital method were 100% and 82%, respectively. Conclusion The application of this analysis software led to an improvement in the interpretation of cases classified as equivocal, decreasing the need for FISH and increasing diagnostic certainty.

Breast cancer (BC) is the most common malignancy and second only to lung cancer in terms of mortality in women. Despite the incredible progress made in this field, metastatic breast cancer has a poor prognosis. In an era of personalized medicine, there is an urgent need for better knowledge of the biology leading to the disease, which can lead to the design of increasingly accurate drugs against patients’ specific molecular aberrations. Among one of the actionable targets is the fibroblast growth factor receptor (FGFR) pathway, triggered by specific ligands. The Fibroblast Growth Factor Receptors/Fibroblast Growth Factors (FGFRs/FGFs) axis offers interesting molecular targets to be pursued in clinical development. This mini-review will focus on the current knowledge of FGFR mutations, which lead to tumor formation and summarizes the state-of-the-art therapeutic strategies for targeted treatments against the FGFRs/FGFs axis in the context of BC.

Rationale and Objectives This study employs clinical/radiological evaluation in establishing the optimum imaging conditions for breast cancer imaging using the X-ray propagation-based phase-contrast tomography. Materials and Methods Two series of experiments were conducted and in total 161 synchrotron-based computed tomography (CT) reconstructions of one breast mastectomy specimen were produced at different imaging conditions. Imaging factors include sample-to-detector distance, X-ray energy, CT reconstruction method, phase retrieval algorithm applied to the CT projection images and maximum intensity projection. Observers including breast radiologists and medical imaging experts compared the quality of the reconstructed images with reference images approximating the conventional (absorption) CT. Various radiological image quality attributes in a visual grading analysis design were used for the radiological assessments. Results The results show that the application of the longest achievable sample-to-detector distance (9.31 m), the lowest employed X-ray energy (32 keV), the full phase retrieval, and the maximum intensity projection can significantly improve the radiological quality of the image. Several combinations of imaging variables resulted in images with very high-quality scores. Conclusion The results of the present study will support future experimental and clinical attempts to further optimize this innovative approach to breast cancer imaging.

Breast cancer (BC) is the most common cancer in women and second only to lung cancer in terms of mortality. Among the three different BC subtypes, the oestrogen receptor positive represents nearly 70% of all cases and it is usually treated with anti-oestrogen drugs. However, the majority of hormone receptor positive metastatic BC patients develop resistance to anti-oestrogen treatments. The need for more down-stream therapies brought to the development of therapeutic strategies inhibiting the phosphatidylinositol 3-kinase-mammalian target of rapamycin (mTOR) pathway. Inhibitors of the mTOR have been tested in different clinical trials; everolimus has been Food and Drug Administration approved for the treatment of oestrogen receptor positive /human epidermal growth factor receptor2 negative BC patients in combination with exemestane in patients who have progressed to anastrozole or letrozole after the encouraging results coming from BOLERO-2 trial. Similar results were obtained by the TAMRAD investigatory study testing tamoxifen in combination with everolimus in advanced BC. This editorial focuses on the results from BOLERO-2, BOLERO 4 and BOLERO-6, which tested the clinical importance of mTOR inhibition. We comment also on the role of phosphatidylinositol 3-kinase-mTOR inhibition as reported in the BELLE-2 and BELLE-3 trials and the future directions for the inhibition of this tumour metabolic axis.

Breast cancer (BC) is the most common cancer in women worldwide. One in eight women will develop the disease in her lifetime. Notwithstanding the incredible progress made in this field, BC still represents the second most common cause of cancer-related death in women. Targeted drugs have revolutionised breast cancer treatment and improved the prognosis as well as the life expectancy of millions of women. However, the phenomenon of primary and secondary pharmacological resistance is becoming increasingly evident, limiting the efficacy of these agents and calling for a better in-depth knowledge and understanding of the biology as well as the biochemical crosstalk underlying the disease. The advent of laboratory technologies in the clinical setting such as the routine use of next generation sequencing has allowed identification of new genetic alterations as well as providing a precise picture of the molecular landscapes of each tumour. Consequently, new specific therapeutic approaches are becoming available to minimise or delay the occurrence of resistance. In this review, we analyse the latest research and news from the clinical development side for each BC subtype.