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Surgery for breast cancer has changed in the last few decades in favor of more conservative approaches, without compromising loco‐regional control and survival. Common immediate complications fol ‐lowing breast surgery are hematoma, seroma, and wound infection.1Traditionally, surgeons have implemented the use of closed‐suction drains in this setting with the aim of preventing these complications, which can cause discomfort, morbidity, increased follow‐up visits,and possible delay in the beginning of adjuvant therapies.2 On the other hand, potential benefits of performing breast procedures without using a drain have been increasingly considered.3 There is lack of modern and official guidelines on use of drains in breast sur ‐gery, with no consensus regarding their management and the appro‐priate use of antibiotics in this setting. Almost all reports agree withthe use of drains after breast procedures, especially if they are asso‐ciated with reconstruction or axillar lymph node dissection (ALND), but an extreme variability is reported regarding practice patterns.4A national survey regarding the management of drains afterbreast cancer surgery was sent by email on January 2018 to all Breast Centers (BC) registered with Senonetwork Italia. Data col ‐lected by the administrative office of Senonetwork were de‐iden‐tified and exported for statistical analysis. A Steering Committeecomposed of general surgeons and plastic surgeons was appointedto coordinate the survey, which consisted of 22 multiple choicequestions, designed to inquire about surgeons' demographics, use of drains after breast procedures with and without reconstructionand/or ALND, antibiotic use and to characterize drain managementin their clinical practice.

Small (pT1a-b), node-negative (pN0) breast cancer generally has a good prognosis. However, HER2-positive status is associated with an increased risk of relapse and decreased survival even in these tumors. Although there are only few data from prospective randomized trials, results of retrospective studies suggest adjuvant chemotherapy plus trastuzumab may improve outcomes of patients with pT1a-b pN0 HER2-positive breast cancer. On the other hand, trastuzumab is potentially associated with increased cardiac toxicity, especially when combined with anthracycline-based chemotherapy. A valid strategy for improving cardiac safety is the addition of trastuzumab to non-anthracycline chemotherapy, whereas a shorter duration of trastuzumab should be not routinely considered although might represent an option for selected patients at low risk of relapse and very high risk of cardiac events. Therefore, the choice of adjuvant treatment for patients with pT1a-b pN0 HER2-positive breast cancer should be done on individual basis, carefully weighing benefits and risks.

To evaluate the differences between conventional fractionated intensity-modulated radiotherapy (IMRT) and hypofractionated (HypoRT) volumetric modulated arc therapy (VMAT) in elderly women affected by early-stage breast cancer (BC) in terms of RT-related acute/late side effect. Between October 2011 and July 2015, 80 consecutive elderly BC patients were treated with IMRT for 5 weeks (40 patients) or HypoRT-VMAT for 3 weeks (40 patients). Inclusion criteria were: age ≥ 70 years, early BC (pT1-2 pN0-1), no prior neoadjuvant chemotherapy and non-metastatic disease. For patients receiving IMRT or HypoRT-VMAT, a total dose of 50 Gy (25 fractions) or 40.5 Gy (15 fractions) was prescribed to the whole ipsilateral breast, respectively. All patients received a simultaneously integrated boost up to a total dose of 60 Gy for IMRT and 48 Gy for HypoRT-VMAT. Acute and late side effects were evaluated using the RTOG/EORTC radiation morbidity scoring system. With a median follow-up of 45 months, acute skin toxicity was overall very low, with grade 1 in 25 cases (62.5%) of the IMRT group and 21 cases (52.5%) of the HypoRT-VMAT group, while grade 2 toxicity was reported in 10 IMRT patients (25%) and 1 HypoRT-VMAT patient (2.5%) (p = 0.001). Regarding late adverse events, only grade 1 skin toxicity was recorded. The present study showed that whole breast IMRT and HypoRT-VMAT are feasible and well tolerated in early-stage BC elderly patients and that HypoRT-VMAT is affected by lower risk of acute and late RT-related side effects.

To evaluate the impact of comorbidity assessment on compliance to intensity modulated radiotherapy with simultaneous integrated boost (SIB-IMRT) in elderly patients affected by early stage breast cancer (BC). 40 consecutive patients were treated with SIB-IMRT (50 Gy in 25 fractions to the whole breast, and simultaneously 60 Gy to the surgical bed) for invasive BC after conserving surgery. Inclusion criteria were: age ≥ 70 years, pT1-2 disease, pN0-1, no neoadjuvant chemotherapy, non-metastatic disease. Charlson comorbidity index was used for comorbidity evaluation. Median follow-up was 44 months. At the time of the analysis, OS and LC rates were 100%. All patients completed the SIB-IMRT without interruptions. Acute skin toxicity was recorded as follows: grade 0 in 5 patients (12.5%), grade 1 in 25 cases (62.5%), and grade 2 in 10 patients (25%). Regarding late adverse events, skin toxicity was registered as follows: grade 0 in 27 patients (67.5%) and grade 1 in 13 cases (32.5%). No toxicity ≥grade 2 was registered. At statistical analysis, the presence of comorbidities and the breast volume >700 cc were related to skin grade 2 acute toxicity (p = 0.01, p = 0.04). In terms of cosmetic results, 98 and 2% of patients considered the result as good/excellent and as fair after RT, respectively. No patients had a poor cosmetic outcome. The present study showed the feasibility of SIB-IMRT in early stage BC elderly patients and that the absence of comorbidity reduced the risk of acute radiation toxicity.

AIMS Primary neuroendocrine (NE) breast carcinoma (BC) is an entity with a wide range of prevalence and poorly defined clinical behaviour. We evaluated the prevalence, clinicopathological features and clinical outcome of NEBC. METHODS AND RESULTS Immunohistochemical staining for synaptophysin and chromogranin A was performed on whole sections from 1232 consecutive cases of invasive BC. We divided NEBC into focal (10-49% positive cells) and diffuse (≥50% positive cells) and compared the outcome of patients with NEBC with strictly matched non-NEBC. A total of 128 BC showed NE differentiation (10.4%): 84 diffuse (6.8%) and 44 focal (3.6%). NE differentiation showed a significant association with T4 stage (P = 0.001), solid-papillary and mucinous histotype (P < 0.0001), G2 grading (P = 0.002), positive oestrogen receptor (ER) (P = 0.003) and progesterone receptor (PR) (P = 0.002). Almost 90% of NEBC were ER(+) /HER2(-) and more than half ER(+) /HER2(-) /Ki67≥14%. Kaplan-Meier analysis revealed that patients with NEBC showed worse disease-free survival (DFS) (P = 0.04) compared to matched non-NEBC. We did not find significant differences regarding clinicopathological features, DFS and CSS between diffuse and focal neuroendocrine BC. CONCLUSIONS This study demonstrates that NEBC represents 7-10% of invasive BC and that NE differentiation does not affect the prognosis of BC in terms of CSS.

To investigate the feasibility and tolerance in the use of adjuvant intensity modulated radiation therapy (IMRT) and simultaneous integrated boost in patients with a diagnosis of breast cancer after breast-conserving surgery.Between September 2011 to February 2013, 112 women with a diagnosis of early breast cancer (T1-2, N0-1, M0) were treated with IMRT and simultaneous integrated boost after breast-conserving surgery in our institution. A dose of 50Gy in 25 fractions was prescribed to the whole breast and an additional dose of radiation was prescribed on the tumour bed. A dose prescription of 60Gy in 25 fractions to the tumour bed was used in patients with negative margins after surgery, whereas if the margins were close (1mm) or positive (without a new surgical resection) a dose of 64Gy was prescribed. All patients were followed with periodic clinical evaluation. Acute and late toxicity were scored using the EORTC/RTOG radiation morbidity score system. Both patient and physician recorded cosmetic outcome evaluation with a subjective judgment scale at the time of scheduled follow-up.The median follow-up was 28 months (range 24-40 months). The acute skin grade toxicity during the treatment was grade 0 in 8 patients (7%), grade 1 in 80 (72%), grade 2 in 24 cases (21%). No grade 3 or higher acute skin toxicity was observed. At 12 months, skin toxicity was grade 0 in 78 patients (70%), grade 1 in 34 patients (30%). No toxicity grade 2 or higher was registered. At 24 months, skin toxicity was grade 0 in 79 patients (71%), grade 1 in 33 patients (29%). No case of grade 2 toxicity or higher was registered. The pretreatment variables correlated with skin grade 2 acute toxicity were adjuvant chemotherapy (P=0.01) and breast volume ≥700cm(3) (P=0.001). Patients with an acute skin toxicity grade 2 had a higher probability to develop late skin toxicity (P0.0001). In the 98% of cases, patients were judged to have a good or excellent cosmetic outcome. The 2-year-overall survival and 2-year-local control were 100%.These data support the feasibility and safety of IMRT with simultaneous integrated boost in patients with a diagnosis of early breast cancer following breast-conserving surgery with acceptable acute and late treatment-related toxicity. A longer follow-up is needed to define the efficacy on outcomes.

UNLABELLED : Neuroendocrine carcinoma of the breast is considered a rare entity, and for this reason there are no data from prospective clinical trials on its optimal management. Early stage tumors are usually treated with the same strategy used for the other types of invasive breast cancer. Anthracycline- and taxane-based regimens represent the most frequently administered chemotherapy in neoadjuvant and adjuvant setting, as well as for metastatic disease, although combinations of platinum compounds and etoposide have been widely used, in particular for small-cell histology and tumors with a high proliferation index. For metastatic disease, a multimodality therapeutic strategy can be considered on an individual basis, with chemotherapy, endocrine therapy, peptide receptor radionuclide therapy, radiation therapy, surgery, or a combination of the above. In the near future, a better knowledge of the biology of these tumors will hopefully provide new therapeutic targets for personalized treatment. In this review, we discuss the current evidence and the future perspectives on diagnosis and treatment of neuroendocrine carcinoma of the breast. IMPLICATIONS FOR PRACTICE Neuroendocrine carcinoma of the breast (NECB) is a distinct entity of breast cancer. Clinical features and morphology are not helpful to distinguish NECB from other subtypes of breast cancer; therefore, immunohistochemistry markers for neuroendocrine differentiation, mainly chromogranin and synaptophysin, should be routinely used to confirm the diagnosis, especially in cases of mucinous or solid papillary carcinoma in which the suspicion of NECB may be relevant. Adjuvant treatment should be offered according to the same recommendations given for the other types of invasive breast cancer. An accurate diagnosis of NECB is also important in the metastatic setting, in which a multimodality approach including specific therapies such as peptide receptor radionuclide therapy can be considered.

Triple-negative breast carcinomas represent a tumor group of pivotal clinical importance given the lack of target therapies. The prognostic significance of triple-negative breast carcinomas remains unclear because of their histological and molecular heterogeneity. Currently, neither prognostic nor predictive factors are available for these tumors. Retinoblastoma (Rb) pathway loss has been linked to clinical outcome in various cancer types, including breast cancer. We investigated the association between Rb and p16 protein expression and clinical outcome in no-special-type triple-negative breast carcinomas. Immunohistochemical staining for Rb, p16, p53 and CK5 was carried out on a section from archival specimens of 117 no-special-type triple-negative breast carcinomas. Immunopositive p16 (p16+) and immunonegative Rb (Rb-) staining were seen in 49.5% and in 24.8% of tumors, respectively. There was an inverse correlation between p16+ and Rb- (P0.001). P16+ was correlated with G3 grade (P0.001), high Ki-67 (P=0.03), p53 overexpression (P0.001) and CK5 immunopositivity (P=0.01). Rb- was not associated with any clinicopathologic variable. Follow-up and therapy data were available in 95 patients. In 20 patients treated with surgery only, neither p16+ nor Rb- immunostaining were associated with disease-free survival and overall survival. In 75 patients treated with adjuvant chemotherapy, p16+ was associated with good response to therapy with significant increased disease-free survival (P=0.001) and showed a trend towards a statistical significance for increased overall survival (P=0.056); Rb- were not associated with disease-free survival and overall survival. In multivariate analysis, p16+ was independently associated with disease-free and overall survival, with a hazard ratio of 0.18 (95% CI: 0.06-0.51; P=0.001) and 0.21 (95% CI: 0.06-0.74; P=0.015), respectively. In patients with no-special-type triple-negative breast carcinomas, p16+ is related to good response to adjuvant chemotherapy and can be considered the best surrogate marker for Rb pathway loss.

We compared the anti–estrogen receptors (ER) SP1, 6F11, and 1D5 antibodies in breast carcinoma cases with different ranges of positive cells to evaluate whether this could generate different therapies for patients. We selected 66 cases of breast cancer, each of which was immunostained with the 3 antibodies. 1D5 was less sensitive than SP1 and 6F11, as seen in 26, 20, and 21 negative cases, respectively. Nine cases showed differences in endocrine-therapy indications, of which 8 1D5-negative cases showed low positivity for SP1 and/ or 6F11. However, these cases were prevalently G3, progesterone receptor–negative or low-positive, with high Ki-67 and positive HER-2 findings, all biological features associated with endocrine resistance. Finally ER values obtained with these 3 antibodies had no implications for chemotherapy. Estrogen receptors (ER) are powerful predictors of breast cancer response to endocrine therapy. In addition, chemotherapy is significantly more beneficial in patients with ERnegative than in ER-positive breast cancer. 1 Therefore it is of paramount importance to use reliable assays for determining ER status to ensure adequate therapy for patients. From the 1970 to the early 1990s, a ligand-binding assay (LBA) was used, which allowed ER levels to be quantitatively assessed. The availability of ER antibodies and the advent of heatmediated antigen retrieval made it possible to assess ER with immunohistochemistry (IHC) on paraffin sections in a procedure that is less laborious and less expensive than

Differences in hormone receptor and HER-2 status between primary tumour and corresponding relapse could have a substantial impact on clinical management of patients. The aim of this study was to evaluate change in expression of hormone receptors and HER-2 status between primary tumour and corresponding local recurrence or distant metastasis. We analysed 140 primary tumours and related recurrent or metastatic samples. Hormone receptors status was evaluated by immunohistochemistry, while HER-2 status by immunohistochemistry and silver in situ hybridisation. A change in HER-2 was rare; 3.7% of cases by immunohistochemistry and only 0.7% by silver in situ hybridisation analysis. A change in estrogen and progesterone receptors was seen in 6.4% and 21.4% of cases, respectively. Estrogen receptor change was not affected by adjuvant therapy, whereas progesterone receptor was influenced by adjuvant chemotherapy associated to hormone therapy (P = 0.0005). A change in progesterone receptor was more frequent in distant metastases than in local recurrences (P = 0.03). In the setting of estrogen receptor positive tumours, patients with progesterone receptor loss in local recurrence had a statistically significant lower median metastasis free survival compared to others patients; progesterone receptor positive, 112 months; progesterone receptor negative, 24 months (P = 0.005). A change between primary tumour and corresponding relapse is frequent for progesterone receptor, infrequent for estrogen receptor and rare for HER-2. In cases with changes in HER-2, it is worthwhile reassessing HER-2 status with both immunohistochemistry and in situ hybridisation analysis. Progesterone receptor loss seems to be influenced by therapy and to correlate with a worse prognosis.

Objective—To compare the eVectiveness of the Infant Flow Driver (IFD) with single prong nasal continuous positive airway pressure (nCPAP) in preterm neonates aVected by respiratory distress syndrome. Design—Randomised controlled study. Patients—Between September 1997 and March 1999, 36 preterm infants who were eligible for CPAP treatment were randomly selected for either nCPAP or IFD and studied prospectively for changes in oxygen requirement and/or respiratory rate. The requirement for mechanical ventilation, complications of treatment, and eVects on mid-term outcome were also evaluated. Results—Use of the IFD had a significantly beneficial eVect on both oxygen requirement and respiratory rate (p < 0.0001) when compared with nCPAP. Moreover,O2 requirement and respiratory rate were significantly decreased by four hours (p < 0.001 and p < 0.03 respectively). The probability of remaining supplementary oxygen free over the first 48 hours of treatment was significantly higher in patients treated with the IFD than with nCPAP (p < 0.02). IFD treated patients had a higher success (weaning) rate (94% v 72 %) and shorter duration of treatment (49.3 (31) v 56 (29.7) hours respectively; mean (SD)), although the diVerence was not significant. Conclusions—IFD appears to be a feasible device for managing respiratory distress syndrome in preterm infants, and benefits may be had with regard to oxygen requirement and respiratory rate when compared with nCPAP. The trend towards reduced requirement for mechanical ventilation, shorter clinical recovery time,and shorter duration of treatment requires further evaluation in a multicentre randomised clinical trial. (Arch Dis Child Fetal Neonatal Ed 2001;85:F86‐F90)

Retrospective analysis of 17 cases of phyllodes tumor with a follow-up of almost 1 year revealed no close correlation between histological pattern and clinical course, since local relapse occurs even after histological findings of benign lesion in the primary tumor. Phyllodes and fibroadenoma patterns are often associated in the same patient and extensive surgery is not recommended owing to the fact that recurrences are observed both after subcutaneous mastectomy and after simple resection. We conclude that local control of the disease by wedge resection and strict follow-up may be the most rational approach.

Summary— The plasma level profile of SA and SUA after a single oral dose of ASA was studied in 8 children with juvenile rheumatoid arthritis, aged 3.5–15.0 years. Pharmacokinetic parameters were on average similar to those reported in the literature for adult subjects, although a somewhat larger intersubject variability was found.