Preservation of Axillary Lymph Nodes Compared with Complete Dissection in T1-2 Breast Cancer Patients Presenting One or Two Metastatic Sentinel Lymph Nodes: The SINODAR-ONE Multicenter Randomized Clinical Trial.

BACKGROUND: The SINODAR-ONE trial is a prospective noninferiority multicenter randomized study aimed at assessing the role of axillary lymph node dissection (ALND) in patients undergoing either breast-conserving surgery or mastectomy for T1-2 breast cancer (BC) and presenting one or two macrometastatic sentinel lymph nodes (SLNs). The endpoints were to evaluate whether SLN biopsy (SLNB) only was associated with worsening of the prognosis compared with ALND in terms of overall survival (OS) and relapse. METHODS: Patients were randomly assigned (1:1 ratio) to either removal of ≥ 10 axillary level I/II non-SLNs followed by adjuvant therapy (standard arm) or no further axillary treatment (experimental arm). RESULTS: The trial started in April 2015 and ceased in April 2020, involving 889 patients. Median follow-up was 34.0 months. There were eight deaths (ALND, 4; SNLB only, 4), with 5-year cumulative mortality of 5.8% and 2.1% in the standard and experimental arm, respectively (p = 0.984). There were 26 recurrences (ALND 11; SNLB only, 15), with 5-year cumulative incidence of recurrence of 6.9% and 3.3% in the standard and experimental arm, respectively (p = 0.444). Only one axillary lymph node recurrence was observed in each arm. The 5-year OS rates were 98.9% and 98.8%, in the ALND and SNLB-only arm, respectively (p = 0.936). CONCLUSIONS: The 3-year survival and relapse rates of T1-2 BC patients with one or two macrometastatic SLNs treated with SLNB only, and adjuvant therapy, were not inferior to those of patients treated with ALND. These results do not support the use of routine ALND.

Surgical management of BRCA-mutation carriers: A single institution experience.

INTRODUCTION: The optimal surgical management of BRCA-mutation carriers remains a subject of debate. To evaluate the appropriateness of breast cancer (BC) treatment, the oncological outcomes of BRCA-mutation carriers treated either with breast-conserving therapy (BCT) or mastectomy were compared. Additionally, the role of bilateral salpingo-oophorectomy (BSO) and potential independent predictive factors for BC treatment were analyzed. MATERIALS AND METHODS: We retrospectively reviewed all the consecutive patients with a pathogenic germline mutation in the BRCA1/2 genes tested at our Institution between July 2008 and October 2018. Primary end-points were disease-free survival (DFS), distant disease-free survival (DDFS), and overall survival (OS). RESULTS: The characteristics and outcomes of 124 BRCA-associated BC patients were analyzed. Overall, 69 (55.7%) and 55 (44.3%) patients underwent BCT and mastectomy, respectively; 72 (58.1%) patients underwent BSO. After a median interval of 13.3 months, 24 patients underwent mastectomy after primary BCT. There was no significant difference in terms of DFS, DDFS, and OS between patients treated with BCT or mastectomy (p = 0.39,p = 0.27,p = 0.265, respectively). Patients treated with BSO had significantly better DDFS and OS compared to ovarian conservation (p = 0.033,p = 0.040, respectively). Three independent predictive factors for BCT were identified: age ≤41 years, genetic testing performed post-operatively, and breast tumors ≤21 mm. CONCLUSIONS: Our data suggest that BRCA-mutation carriers treated with BCT present similar oncological outcomes compared to mastectomy. Ovarian preservation decreases survival. Young BRCA-mutated patients with small BCs may not need up-front mastectomy, and BSO might be performed when ovarian cancer risk epidemiologically rises and potential reproductive desire is fulfilled.

Single-cell profiling defines the prognostic benefit of CD39high tissue resident memory CD8+ T cells in luminal-like breast cancer.

Luminal-like breast cancer (BC) constitutes the majority of BC subtypes, but, differently from highly aggressive triple negative BC, is poorly infiltrated by the immune system. The quality of the immune infiltrate in luminal-like BCs has been poorly studied, thereby limiting further investigation of immunotherapeutic strategies. By using high-dimensional single-cell technologies, we identify heterogeneous behavior within the tissue-resident memory CD8+ T (Trm) cells infiltrating luminal-like tumors. A subset of CD127- CD39hi Trm cells, preferentially present in the tumor compared to the adjacent normal breast tissue or peripheral blood, retains enhanced degranulation capacity compared to the CD127+ CD39lo Trm counterpart ex vivo, and is specifically associated with positive prognosis. Nevertheless, such prognostic benefit is lost in the presence of highly-suppressive CCR8hi ICOShi IRF4+ effector Tregs. Thus, combinatorial strategies aiming at boosting Trm function and infiltration while relieving from Treg-mediated immunosuppression should be investigated to achieve proper tumor control in luminal-like BCs.

Internal mammary lymph node siliconoma in absence of prosthesis rupture: a case series that raises concern for potential risk of overdiagnosis.

BACKGROUND: Silicon migration after rupture is an adverse event of breast implant, whose risk increases with the aging of prosthesis. The exact prevalence of this complication remains unclear and reported data are inconsistent. In addition, microscopic diffusion of silicone gel through intact implant, known as gel bleeding, might verify thus complicating diagnosis. Although high cohesive gel has reduced the occurrence of gel bleeding, this phenomenon is still possible and its occurrence rate remains underestimated. If silicon droplets migrate in locoregional lymph node, a swelling that mimics recurrence can arise. Therefore, a risk of overdiagnosis is possible when clinicians rely only on imaging techniques. The aim of this study is to evaluate the actual prevalence of metastasis in internal mammary lymph node (IMLN) in presence of PET positive uptake and no prosthesis rupture. METHODS: We retrospectively evaluated our patient's records and selected those with intact breast implants and suspected relapse in IMLN that underwent biopsy, either surgical or imaging guided. All patients performed PET/CT scan showing pathological uptake in IMLNs. A breast magnetic resonance (MRI) or ultrasound (US) imaging confirmed a suspicious adenopathy and excluded prosthesis rupture. From 2015 to 2019 a total of nine patients underwent biopsy of the IMLN and only six of them met inclusion criteria. RESULTS: Four biopsies were CT-guided, two were surgical. Three patients (50%) were diagnosed with breast cancer relapse while two (33.3%) were found with siliconoma and one (16.7%) was inflammatory. CONCLUSIONS: Siliconoma can occur even without evidence of capsule rupture, challenging the clinicians and leading to a risk of relapse over diagnosis. Echographic, MRI and nuclear medicine imaging criteria may be not sufficient in differential diagnosis. To overcome the issue, we suggest introducing into the clinical practice the biopsy of suspicious enlarged IMLN with minimally invasive technique.

Insights for the application of TILs and AR in the treatment of TNBC in routine clinical practice.

Triple negative breast cancer (TNBC), usually presenting with a very aggressive phenotype, is a heterogeneous entity. We aim to discuss new biomarkers, suitable for prognostic and predictive purposes. We retrospectively collected clinical variables and immunohistochemical characteristics of early TNBCs, specifically focusing on the prognostic and predictive significance of tumor infiltrating lymphocytes (TILs) and androgen receptor (AR) expression, assessing their correlation with clinical variables. Among 159 patients, TILs were significantly higher in younger patients and with lower BMI, and in tumors with higher ki-67 and greater nodal involvement; conversely, AR was significantly higher in older patients and in tumors with lower ki-67. Interestingly and in line with literature, both TILs level and ARs expression were lower within metastatic sites, in patients who developed distant metastases, compared to those found in the primary site. Small (pT1) and node negative tumors were highly represented and no correlation of either TILs or AR with prognosis could be observed. Our findings support the use of stromal TILs to identify a more aggressive, but chemo-sensitive phenotype, mostly represented in younger women, while AR may identify a less aggressive, slow-growing luminal TNBC subtype, more common among older patients. TILs and AR are worth implementing in routine clinical practice to refine prognosis even if, in our case series, we couldn't identify a significant correlation of the two variables with either disease-free and overall survival.

Mucinous breast cancer: A narrative review of the literature and a retrospective tertiary single-centre analysis.

Mucinous carcinoma (MC) is a rare breast cancer characterized by the presence of large extracellular mucin amount. Two main subtypes can be distinguished: pure (PMC) and mixed (MMC). We conducted a retrospective MC analysis in our prospective maintained database, calculating disease-free survival (DFS) and 5-year overall survival (OS). We found a global 92.1% OS (higher in MMC group and statistically significative) and a DFS of 95.3% (higher in MMC group but not statistically significative).

Survival Outcome and Prognostic Factors After Pulmonary Metastasectomy in Sarcoma Patients: A 18-Year Experience at a Single High-volume Referral Center.

BACKGROUND: Metastatic sarcoma patients have a poor prognosis with 3-year survival rate of 25%. About 30% of them present isolated lung metastases. We aimed to analyze the clinical outcome of sarcoma patients undergoing pulmonary metastasectomy (PM) and prognostic factors associated with local control, disease-free, and overall survival (OS). PATIENTS AND METHODS: All sarcoma patients undergoing PM at Humanitas Cancer Center were retrospectively reviewed. Analyzed variables included clinicopathologic, surgical, and survival data. Exclusion criterion comprised a follow-up period inferior to 1 year. A univariable and multivariable Cox regression analysis was performed (P<0.05). RESULTS: In total, 154 patients underwent PM from 1997 to 2015. Total complication rate was 7.1%. The median follow-up was 24 months. The median OS was 35.4 months from initial metastasectomy. In univariable analysis, we identified as significant negative prognostic factors a disease-free interval of <18 months, male sex, grading G3, and bilateral metastases. Three histology risk groups were defined according to OS: high risk (myxofibrosarcoma, malignant peripheral nerve sheath tumor, and Ewing sarcoma), intermediate risk (leiomyosarcoma, liposarcoma, and undifferentiated pleomorphic sarcoma), and low risk (synovial and chondrosarcoma) with a 3-year OS of 21.4%, 45.7%, and 74.1%, respectively. In multivariable analysis, male sex (P=0.042), bilateral metastases (P=0.004), and histology (intermediate vs. low-risk group, P=0.021; high vs. low-risk group, P<0.001) were identified as independent predictors of survival. CONCLUSIONS: PM for sarcoma is a valid therapeutic option. High-risk histologies and bilaterality of lung metastases are independent negative prognostic factors. A prognostic score to improve patient selection is proposed.

CXCR4/CXCL12 Signaling and Protumor Macrophages in Primary Tumors and Sentinel Lymph Nodes Are Involved in Luminal B Breast Cancer Progression.

Luminal B breast cancers (BC) have a more aggressive behavior associated with a higher rate of tumor relapse and worse prognosis compared to luminal A tumors. In this study, we evaluated the involvement of specific epithelial-to-mesenchymal transition- (EMT-) and immune-related pathways in the dissemination of luminal B BC cells. The expression of 42 EMT- and immune-related genes was evaluated in matched sentinel lymph nodes (SLNs) analyzed by the one-step nucleic acid amplification assay (OSNA) and primary tumors of 40 luminal B BC patients by gene array and immunohistochemistry. The results were validated in an independent group of 150 luminal B tumors by immunohistochemistry and immunofluorescence and using gene expression data from 315 luminal B BC patients included in the Metabric dataset. We found that the expression of CXCR4 (p = 3.28E - 02) and CD163 (p = 6.92E - 03) was significantly upregulated in SLNs of recurrent luminal B BC patients. Luminal B primary tumors overexpressing CXCR4 were characterized by an increased expression of vimentin and a high content of CD163-positive macrophages. Bioinformatics analysis confirmed the correlation of CXCR4 with CXCL12, VIM, and CD163 expression and LN involvement. Our results suggest that the upregulation of the CXCR4/CXCL12 pathway and the presence of protumor macrophages in the primary tumor and SLNs sustain the aggressiveness of an important subgroup of luminal B BC.

Multicentric castleman's disease resembling metastatic lung carcinoma. A case report.

A 67-year-old patient presented for persistent cough. Computed tomography showed right lower lung opacity associated with mediastinal adenopathy. On suspicion of metastatic pulmonary neoplasm, the patient was submitted to right lower lobectomy with lymphadenectomy. Postoperative histopathology led to the diagnosis of multicentric Castleman's disease.

Pseudoangiomatous stromal hyperplasia - a benign and rare tumor of the breast in an adolescent: a case report.

BACKGROUND: Pseudoangiomatous stromal hyperplasia is an uncommon mesenchymal breast neoplasm. CASE PRESENTATION: Here we present a case of an 11-year old hispanic girl affected by bilateral mammary nodular pseudoangiomatous stromal hyperplasia, an uncommon breast disease, with a review of the literature related to diagnostic workup, differential diagnosis, and management. A rapidly growing mass in the breast may be stressful for both parents and child as the suspicion of malignancy arises. Multiple wide excisions of both breasts were performed. CONCLUSIONS: The purpose of this case report is to draw attention to the fact that most emerging lesions of the breast in girls during puberty are benign diseases.

Robotic approach in case of thymoma involving the left anonymous vein: a case report.

The robotic system has several technical advantages over the manual video thoracoscopic approach. It offers a high definition three-dimensional view and robotic arms are more comfortable to use, because they allow more precise, flexible, and intuitive movements. This case report describes a locally advanced thymoma in a 75-year-old male patient, excised through a robotic-assisted thymectomy with atypical resection of the infiltrated left upper lobe, the preservation of the left phrenic nerve and partial resection of the left anonymous vein involved, without necessity of reconstruction. Clinical staging was thymoma T3 B1-2, while the postoperative histological classification and radiation was thymoma T3, B3, Masaoka-Koga stage IIB. The postoperative course was uneventful and the patient was discharged in second postoperative day. This case remarks that robotic devices are of great help in the intraoperative recognition and precise management of infiltrated structure, like important vessels and nerves, avoiding conversion to an open approach, which until now was the main surgical indication in these situations.

Comorbidity, postoperative morbidity and survival in patients undergoing radical surgery for malignant pleural mesothelioma.

OBJECTIVES: We examined a series of malignant pleural mesothelioma (MPM) patients who underwent radical surgery to explore relationships among comorbidity, postoperative morbidity and survival. METHODS: A retrospective analysis was carried out of all MPM patients operated on in a single centre from 2000 to 2015. The Charlson Comorbidity Index (CCI) was used to classify patients according to their underlying condition. Postoperative complications were scored according to WHO-derived criteria. Survival comparisons were performed by Cox analysis. RESULTS: Ninety-one patients underwent extrapleural pneumonectomy (EPP), 47 underwent pleurectomy decortication (PD) and 25 underwent palliative pleurectomy. The mean CCI of PD patients was significantly higher compared with that of EPP patients (P= 0.044). The frequency of grade 3+ complications was similar between EPP and PD (27 vs 26%). However, EPP patients had a 6-fold higher frequency of pleural sepsis (24 vs 4%, P= 0.002) occurring up to 695 days postoperatively. Median overall survival was 19 months (95% CI 13-25) after EPP, 30 months (95% CI 20-35) after PD and 13 months (95% CI 5-32) after palliative pleurectomy. At multivariate analysis, CCI (P< 0.001), histology (P= 0.014) and pleural sepsis (P= 0.001), but not complete resection, were significantly associated with survival. There was a trend in favour of PD over palliative resection after adjusting for histology and CCI. CONCLUSIONS: The CCI is an independent predictor of survival in MPM patients undergoing radical surgery. Owing to its significant frequency and adverse impact, pleural sepsis may contribute to a reduced life expectancy after EPP. Surgical treatment of MPM remains debatable.

Prognostic and diagnostic potential of local and circulating levels of pentraxin 3 in lung cancer patients.

There is a well-established link between inflammation and cancer of various organs, but little data are available on inflammation-associated markers of diagnostic and prognostic clinical utility in pulmonary malignancy. Blood samples were prospectively collected from 75 resectable lung cancer patients before surgery and in a cohort of 1,358 high-risk subjects. Serum levels of long pentraxin 3 (PTX3) were determined by high-sensitivity ELISA. PTX3 immunostaining was evaluated by immunohistochemistry in cancer tissue. Serum PTX3 levels in the high-risk population were not predictive of developing subsequent lung cancer or any other malignancy; however, serum PTX3 values in patients with lung cancer were significantly higher compared with cancer-free heavy smokers. With a cutoff of 4.5 ng/ml, specificity was 0.80, sensitivity 0.69, positive predictive value 0.15 and negative predictive value 0.98. The receiver operating curve (ROC) for serum PTX3 had an area under the curve (AUC) of 83.52%. Preoperative serum PTX3 levels in lung cancer patients did not correlate with patient outcome, but high interstitial expression of PTX3 in resected tumor specimens was a significant independent prognostic factor associated with shorter survival (p < 0.001). These results support the potential of serum PTX3 as a lung cancer biomarker in high-risk subjects. Furthermore, PTX3 immunohistochemistry findings support the role of local inflammatory mechanisms in determining clinical outcome and suggest that local expression of PTX3 may be of prognostic utility in lung cancer patients.

Huge malignant phyllodes breast tumor: a real entity in a new era of early breast cancer.

Phyllodes tumor is an extremely rare tumor of the breast. It occurs in females in the third and fourth decades. The difficulty in distinguishing between phyllodes tumors and benign fibroadenoma may lead to misdiagnosis. Lymph node involvement is rarely described in phyllodes tumors; for this reason, sentinel node biopsy may be warranted. We present a case of a 33-year-old woman affected by huge tumor of the right breast with ulceration in the skin with a rapid tumor growth and with omolateral axillary metastasis.

Long-Term Follow-up Results of the DANTE Trial, a Randomized Study of Lung Cancer Screening with Spiral Computed Tomography.

RATIONALE: Screening for lung cancer with low-dose spiral computed tomography (LDCT) has been shown to reduce lung cancer mortality by 20% compared with screening with chest X-ray (CXR) in the National Lung Screening Trial, but uncertainty remains concerning the efficacy of LDCT screening in a community setting. OBJECTIVES: To explore the effect of LDCT screening on lung cancer mortality compared with no screening. Secondary endpoints included incidence, stage, and resectability rates. METHODS: Male smokers of 20+ pack-years, aged 60 to 74 years, underwent a baseline CXR and sputum cytology examination and received five screening rounds with LDCT or a yearly clinical review only in a randomized fashion. MEASUREMENTS AND MAIN RESULTS: A total of 1,264 subjects were enrolled in the LDCT arm and 1,186 in the control arm. Their median age was 64.0 years (interquartile range, 5), and median smoking exposure was 45.0 pack-years. The median follow-up was 8.35 years. One hundred four patients (8.23%) were diagnosed with lung cancer in the screening arm (66 by CT), 47 of whom (3.71%) had stage I disease; 72 control patients (6.07%) were diagnosed with lung cancer, with 16 (1.35%) being stage I cases. Lung cancer mortality was 543 per 100,000 person-years (95% confidence interval, 413-700) in the LDCT arm versus 544 per 100,000 person-years (95% CI, 410-709) in the control arm (hazard ratio, 0.993; 95% confidence interval, 0.688-1.433). CONCLUSIONS: Because of its limited statistical power, the results of the DANTE (Detection And screening of early lung cancer with Novel imaging TEchnology) trial do not allow us to make a definitive statement about the efficacy of LDCT screening. However, they underline the importance of obtaining additional data from randomized trials with intervention-free reference arms before the implementation of population screening.

A very elderly lung cancer patient: case report of a long disease free survival.

Despite the fact that non-small-cell lung cancer (NSCLC) is very common in the older population, these patients are frequently underrepresented in clinical and surgical trials and thus it is difficult to reach evidence-based recommendations for this special population. We present a case of a surgical treatment of asymptomatic lung cancer in a very elderly patient. The patient had no recurrence for 4 years after a complete resection.

Surgical procedures in the DANTE trial, a randomized study of lung cancer early detection with spiral computed tomography: comparative analysis in the screening and control arm.

BACKGROUND: The patient population derived from lung cancer screening programs with low-dose spiral computed tomography (LDCT) is different from the general population accessing thoracic surgical services. METHODS: Retrospective review of all surgical cases in the DANTE trial, a randomized study of lung cancer screening with LDCT. Patient characteristics, workup, procedures, resections for benign disease, complications, tumor features, and final outcomes have been analyzed in the LDCT and in the control arm. RESULTS: In the LDCT arm, 77 suspicious lesions were surgically managed in 72 patients. A benign lesion was diagnosed in 17 cases (22%). Major video-assisted thoracoscopic surgery resection was carried out in five lung cancer cases (7%) and segmentectomy in 11 (19%). Complete resection was achieved in 93%, and stage I rate was 73%. Two patients had a local recurrence after open lobectomy, and three had a resectable new primary. In the control group, 28 patients underwent 31 surgical procedures, in five cases (16%) for benign lesions. No major video-assisted thoracoscopic surgery resections were carried out. Resectability rate was 88%, and stage I rate was 52%. Five patients had a local recurrence and two had a second primary. CONCLUSIONS: Surgery for benign lesions is a relevant issue in screening-derived patients. Local control may be achieved by minimally invasive techniques or segmentectomy; however, developing the necessary skills requires an effort by the surgical team. Long-term survivors have a noticeable chance of developing second primary cancers or resectable recurrences and may benefit from a second resection.

A randomized study of lung cancer screening with spiral computed tomography: three-year results from the DANTE trial.

RATIONALE: Screening for lung cancer with modern imaging technology may decrease lung cancer mortality, but encouraging results have only been obtained in uncontrolled studies. OBJECTIVES: To explore the effect of screening with low-dose spiral computed tomography (LDCT) on lung cancer mortality. Secondary endpoints are incidence, stage at diagnosis, and resectability. METHODS: Male subjects, aged 60 to 75 years, smokers of 20 or more pack-years, were randomized to screening with LDCT or control groups. All participants underwent a baseline, once-only chest X-ray and sputum cytology examination. Screening-arm subjects had LDCT upon accrual to be repeated every year for 4 years, whereas controls had a yearly medical examination only. MEASUREMENTS AND MAIN RESULTS: A total of 2,811 subjects were randomized and 2,472 were enrolled (LDCT, 1,276; control, 1,196). After a median follow-up of 33 months, lung cancer was detected in 60 (4.7%) patients receiving LDCT and 34 (2.8%) control subjects (P = 0.016). Resectability rates were similar in both groups. More patients with stage I disease were detected by LDCT (54 vs. 34%; P = 0.06) and fewer cases were detected in the screening arm due to intercurrent symptoms. However, the number of advanced lung cancer cases was the same as in the control arm. Twenty patients in the LDCT group (1.6%) and 20 controls (1.7%) died of lung cancer, whereas 26 and 25 died of other causes, respectively. CONCLUSIONS: The mortality benefit from lung cancer screening by LDCT might be far smaller than anticipated.