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Background: Cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors show promising results in metastatic breast cancer. However, an increased incidence of adverse events is remarkable. Among others, gastrointestinal (GI) involvement is of momentous impact on patients and their quality of life. Methods: Our search included PubMed, ASCO, ESMO and SABCS databases. Randomized phase II/III trials in metastatic breast cancer receiving CDK4/6 inhibitors were identified and considered relevant based on providing a sufficient safety profile on the incidence of adverse GI effects. Results: Of the 999 records initially screened for relevance, 33 articles were found relevant and 4 studies were finally eligible for meta-analysis with a total of 2007 patients. The relative risk (RR) for all-grade nausea was 1.48 [95% confidence interval (CI): 1.12-1.93, p = 0.005], vomiting was 1.74 (95% CI: 1.09-2.76, p = 0.02), decreased appetite was 1.42 (95% CI: 1.07-1.88, p = 0.02), and for diarrhea it was 1.44 (95% CI: 1.19-1.74, p = 0.0002). Meanwhile, the RR for high-grade nausea was 1.10 (95% CI: 0.29-4.13, p = 0.89), vomiting was 1.38 (95% CI: 0.25-7.75, p = 0.72), decreased appetite was 4.00 (95% CI: 0.87-18.37, p = 0.07), and highgrade diarrhea was 1.19 (95% CI: 0.44-3.21, p = 0.73). Conclusion: Selective CDK4/6 inhibitors were not associated with higher-grade GI toxicities reflecting a well-tolerated safety profile. Regarding the increase in all-grade GI toxicities, it needs further caution with addition of cytotoxic chemotherapy.

Our analysis provides evidence that the use of CDK 4/6 inhibitors is associated with an increased risk of all-grade and high-grade hematological adverse events, which seems to be a class-effect, but not of febrile neutropenia compared with hormonal therapy alone.

CDK4/6 inhibitors were associated with an increased risk of fatigue, alopecia and stomatitis. Further studies with self-reported questionnaires may elucidate the impact of the increased risk of these selected adverse effects on the patients' quality of life.

Background Contrast-enhanced mammography (CEM) has been discovered to be more sensitive and specific than two-dimensional full-field digital mammography (FFDM) in both screening and diagnostic settings. The aim of the study was to assess the additive role of CEM in the detection and characterization of breast lesions in women with increased risk of developing breast cancer. This prospective study included 283 female patients with increased risk of developing breast cancer (i.e., positive family history of breast cancer, personal history of breast cancer, and heterogeneously dense mammary parenchyma) coming for either screening (n = 127/283 (49.1%)) or diagnostic (n = 156/283 (55.1%)) purpose. All patients had FFDM and CEM done, and the findings were evaluated independently; final Breast Imaging Reporting And Data System (BIRADS) classification was given for each modality. Results were then compared with histopathology or ultrasound findings with routine follow-up for normal and typically benign findings. Results In this study, 283 women with mean age of 48 were enrolled. Among the studied cases regardless to a specific risk factor, 15/283 (5.3%) were diagnosed as normal, 13/283 (4.6%) as inflammatory lesions, 72/283(25.4%) as benign lesions, 6/283 (2.1%) as benign precancerous lesions, and 177/283 (62.5%) as malignant. The overall sensitivity and specificity of the CEM were 92.7 and 71.43 %, respectively, while FFDM were 80.90 and 59.05%, respectively. Conclusion Contrast-enhanced mammography is a valuable screening and diagnostic imaging modality in patients with increased risk of developing breast cancer with diagnostic indices higher than mammography resulting in a significantly higher cancer detection rate.

Background With the expansion of the use of the neoadjuvant chemotherapy(NAC) in locally advanced breast cancer (LABC), both dynamic contrast enhanced magnetic resonance imaging (DCE-MRI) and 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET CT) are promising methods for assessment of the tumor response during chemotherapy. We aimed to evaluate the diagnostic accuracy of DCE-MRI of breast &18 F-FDG PETCT regarding the assessment of early response to neoadjuvant chemotherapy (NAC) in locally advanced breast cancer patients (LABC) and pathologic complete response (pCR) prediction. Results A total of forty LABC patients who had NAC were included in the study. Before and during NAC, PET/CT and DCE-MRI were used. Various morphological and functional criteria were compared and linked with post-operative pathology for both. The MRI sensitivity and specificity in assessing NAC response in conjunction with pathological data were 100% (p = 0.001) and 12.5% (p = 0.18) respectively. The equivalent readings for PET/CT were 94.1% (p = 0.001) and 25% (p = 0.18), respectively, although the estimated total accuracy for both MRI and PETCT was the same measuring 94.1% (p = 0.001) and 25% (p = 0.18) (72%). PETCT had a higher overall accuracy than MRI in assessing the response of axillary lymph nodes (ALN) to NAC (64% and 56%, respectively). Longest diameter of lesion, ADC value, and maximal enhancement in baseline MRI, SUVmax and SUV mean in baseline PETCT were all significant predictors of rCR. Conclusion During NAC in the primary breast mass and ALN, DCE-MRI demonstrated a better sensitivity in predicting pCR in LABC patients. Although both MRI and PETCT were equally accurate in detecting pCR of LABC patients to NAC, PETCT was more accurate in detecting pathological response of ALN to NAC.

Background: Breast cancer is a heterogenous group of diseases classified into the biological subtypes luminal A, luminal B, HER2-enriched and triple negative. These subtypes have different treatment response patterns and survival rates. Ki-67 is the most commonly used proliferative marker in breast cancer and is used for the distinction between luminal A and B subtypes. Methods: A retrospective study that included patients with early breast cancer diagnosed between 2010 and 2016 and treated in a single cancer center. Results: The medical records of 498 patients were retrospectively reviewed. The median age of patients was 51 years (range: 21-81) and the median value of Ki-67 level among them was 20% (interquartile range: 10-30%). Ki-67 was significantly higher in younger (<35 years) and premenopausal patients (p=0.0002 and 0.0055, respectively). Higher Ki-67 level associated significantly with higher T stage, estrogen and progesterone receptors-negativity, HER2-positivity and higher grade (p=0.0256, <0.0001, <0.0001, =0.0001 and =0.0031; respectively). Univariate Cox regression analysis showed that the ≥14% and ≥20% cutoff values of Ki-67 level are associated with poorer diseasefree survival (DFS) (HR=1.989 [95%CI: 1.163-3.402, p=0.0121] and HR=1.616 [95%CI: 1.001-2.61, p=0.0496], respectively). On stratifying patients according to the Ki-67 proliferation index into three strata, <14%, ≥14%-<20% and ≥20%; DFS differed significantly between them (p=0.0394). The 5-year DFS rate for the three strata was 82.2%, 64.7% and 64.8%; respectively. Conclusion: Early breast cancer patients with lower Ki-67 levels have significantly better DFS. A Ki-67 cutoff value of ≥14% appears to correlate better with DFS than the newer cutoff value of ≥20%.

PurposeTo investigate the modalities of tumour bed (TB) localisation of target volume delineation [clinically computed tomography (CT), ultrasound (US) compared with surgical clips-guided] and the impact of their differences in delineated TB volumes.Material and methodsIn total, 27 patients who underwent oncoplastic breast conservative surgery with surgical clips insertion (at least three) were included. CT and US imaging for TB localisation were done 3–4 weeks post-operatively in the same treatment position. TB was delineated four times, guided by surgical clips, clinical data, CT (seroma) and US. A plan was done for each TB delineated. The four delineated volumes were compared regarding the volumetric differences, the geographical miss index (GMI) and the overlap index.ResultsComparing the four modalities, median TB volume was for clinical (60.7), CT (60.8) and US (49.3) cm3, in comparison with 59.7 cm3 for clips, p=0.05. Median of GMI (represented the tissue at risk of recurrence and not had been treated) was for clinical (61.8), CT (45) and US (62.4)%, with significant difference of p=0.02. Median of normal tissue index (normal tissue has been included unnecessarily) was for clinical (59.5), CT (49.6) and US (62.3)%, p=0.17. Overlap index with clips-guided was for clinical (0.36), CT (0.42) and US (0.35) with significance of p=0.04. Median superior/inferior direction was 0.72, −0.03 and −0.2 cm for clinical, CT and US, respectively, with significant value of p=0.02, whereas the anterior–posterior was −0.07, −0.15 and −0.09 cm, p-value=0.45 and the medio–lateral was 0.4, −0.13 and 0.09 cm, p=0.60.ConclusionSignificant differences in shifts and indices were detected between each of modalities compared with surgical clips. Thus, in the setting of oncoplastic breast surgery, surgical clips should be routinely used for TB localisation. In view of the larger volumes of breast tissue excised and the extensive remodelling that are inherent to oncoplastic procedures, the concept of TB boost irradiation should be re-challenged.