Circulating tumor DNA in patients with locally advanced rectal cancer treated with multimodal treatment.

Background: The management of locally advanced rectal cancer (LARC) relies on a multimodal approach. Neither instrumental work-up nor molecular biomarkers are currently available to identify a risk-adapted strategy. Objectives: We aim to investigate the role of circulating tumor DNA (ctDNA) and its clearance at different timepoints during chemo-radiotherapy (CRT) and correlate them with clinical outcomes. Design: Between November 2014 and November 2019, we conducted a monocentric prospective observational study enrolling consecutive patients with LARC managed with neoadjuvant standard CRT (capecitabine and concomitant pelvic long-course radiotherapy), followed by consolidation capecitabine in selected cases and surgery. Methods: Blood samples for ctDNA were obtained at pre-planned timepoints. We evaluated the correlation of baseline variant allele frequency (VAF) with pathologic complete response (pCR) down-staging, node regression (pN0), event-free survival (EFS), and overall survival (OS). Results: Among 112 screened patients, 61 were enrolled. In all, 38 (62%) had a positive ctDNA at baseline with VAF > 0 and 23 had negative ctDNA (VAF = 0). Among patients with negative ctDNA, 30% had a complete response, while only 13% of positive ctDNA patients had pCR [odds ratio (OR) 0.35 (95% confidence interval (CI): 0.10-1.26), p = 0.11]. Similarly, 96% and 74% of pN0 were observed among negative and positive ctDNA patients, respectively [OR 0.13 (95% CI: 0.02-1.07), p = 0.058]. The presence of a baseline VAF > 0 was associated with a trend toward a lower EFS compared with VAF = 0 patients [hazard ratio (HR) = 2.30, 95% CI: 0.63-8.36, p = 0.21]. Within the limitations of small sample size, no difference in OS was observed according to the baseline ctDNA status (HR = 1.18, 95% CI: 0.35-4.06, p = 0.79). Conclusion: Within the limitations of a reduced number of patients, patients with baseline negative ctDNA seem to show a higher probability of pN0 status and a trend toward improved EFS. Prospective translational studies are required to define the role of ctDNA analysis in the multimodal treatment of LARC.

Role of microsatellite instability and HER2 positivity in locally advanced esophago-gastric cancer patients treated with peri-operative chemotherapy.

PURPOSE: Neoadjuvant chemotherapy (NAC) significantly improved the prognosis of patients with locally advanced gastric cancer (LAGC). Several biomarkers, including HER2 and MMR/MSI are crucial for treatment decisions in the advanced stage but, currently, no biomarkers can guide the choice of NAC in clinical practice. Our aim was to evaluate the role of MSI and HER2 status on clinical outcomes. METHODS: We retrospectively collected LAGC patients treated with NAC and surgery +/- adjuvant chemotherapy from 2006 to 2018. HER2 and MSI were assessed on endoscopic and surgical samples. Pathologic complete response (pCR) rate, overall survival (OS), and event-free survival (EFS) were estimated and evaluated for association with downstaging and MSI. RESULTS: We included 76 patients, 8% were classified as MSI-H, entirely consistent between endoscopic and surgical samples. Six percent of patients were HER2 positive on endoscopic and 4% on surgical samples. Tumor downstaging was observed in 52.5% of cases, with three pCR (5.1%), none in MSI-H cancers. According to MSI status, event-free survival (EFS) and overall survival (OS) were higher for MSI-H patients to MSS [EFS not reached vs 30.0 months, p = 0.08; OS not reached vs 39.6 months, p = 0.10]. CONCLUSION: Our work confirms the positive prognostic effect of MSI-H in the curative setting of LAGC, not correlated with pathologic tumor downstaging. Prospective ad-hoc trial and tumor molecular profiling are eagerly needed.

Correlations between Molecular Alterations, Histopathological Characteristics, and Poor Prognosis in Esophageal Adenocarcinoma.

Esophageal adenocarcinoma (EAC) is a severe malignancy with increasing incidence, poorly understood pathogenesis, and low survival rates. We sequenced 164 EAC samples of naïve patients (without chemo-radiotherapy) with high coverage using next-generation sequencing technologies. A total of 337 variants were identified across the whole cohort, with TP53 as the most frequently altered gene (67.27%). Missense mutations in TP53 correlated with worse cancer-specific survival (log-rank p = 0.001). In seven cases, we found disruptive mutations in HNF1alpha associated with other gene alterations. Moreover, we detected gene fusions through massive parallel sequencing of RNA, indicating that it is not a rare event in EAC. In conclusion, we report that a specific type of TP53 mutation (missense changes) negatively affected cancer-specific survival in EAC. HNF1alpha was identified as a new EAC-mutated gene.

Malignancies in Patients with Celiac Disease: Diagnostic Challenges and Molecular Advances.

Celiac disease (CD) is a multiorgan autoimmune disorder of the chronic intestinal disease group characterized by duodenal inflammation in genetically predisposed individuals, precipitated by gluten ingestion. The pathogenesis of celiac disease is now widely studied, overcoming the limits of the purely autoimmune concept and explaining its hereditability. The genomic profiling of this condition has led to the discovery of numerous genes involved in interleukin signaling and immune-related pathways. The spectrum of disease manifestations is not limited to the gastrointestinal tract, and a significant number of studies have considered the possible association between CD and neoplasms. Patients with CD are found to be at increased risk of developing malignancies, with a particular predisposition of certain types of intestinal cancer, lymphomas, and oropharyngeal cancers. This can be partially explained by common cancer hallmarks present in these patients. The study of gut microbiota, microRNAs, and DNA methylation is evolving to find the any possible missing links between CD and cancer incidence in these patients. However, the literature is extremely mixed and, therefore, our understanding of the biological interplay between CD and cancer remains limited, with significant implications in terms of clinical management and screening protocols. In this review article, we seek to provide a comprehensive overview of the genomics, epigenomics, and transcriptomics data on CD and its relation to the most frequent types of neoplasms that may occur in these patients.

Colorectal cancer, Vitamin D and microbiota: A double-blind Phase II randomized trial (ColoViD) in colorectal cancer patients.

BACKGROUND: Several studies suggest a role of gut microbiota in colorectal cancer (CRC) initiation and progression. Vitamin D (vitD) blood levels are also inversely correlated with CRC risk and prognosis. However, these factors' interplay remains unknown. METHODS: 74 CRC patients after standard treatment were randomized to 1-year 2000 IU/day vitD or placebo.  Baseline and post-treatment fecal microbiota for shotgun metagenomics sequencing was collected. Coda-lasso and Principal Component Analysis were used to select and summarize treatment-associated taxa and pathways. Associations between vitD and taxa/pathways were investigated with logistic regression. Mediation analysis was performed to study if treatment-associated taxa mediated the effect of supplementation on 25(OH)D levels. Cox proportional-hazards model was used for disease-free survival (DFS). RESULTS: 60 patients were analyzed. Change in alpha diversity (Shannon: p = 0.77; Simpson: p = 0.63) and post-treatment beta diversity (p = 0.70) were comparable between arms. Post-treatment abundances of 63 taxa and 32 pathways differed between arms. The 63 taxa also mediated the effect of supplementation on 25(OH)D (p = 0.02). There were sex differences in vitD levels, microbiota and pathways. Pathways of essential amino acids' biosynthesis were more abundant in supplemented women. Fusobacterium nucleatum presence at baseline was associated with worse DFS (p = 0.02). Those achieving vitD sufficiency (25(OH)D≥30 ng/ml) had lower post-treatment abundances (p = 0.05). Women were more likely to have F. nucleatum post-treatment (p = 0.02). CONCLUSIONS: VitD supplementation may contribute shaping the gut microbiota and the microbiota may partially mediate the effect of supplementation on 25(OH)D. The observed sex-specific differences highlight the necessity of including sex/gender as a variable in microbiome studies.

HER2 in Metastatic Colorectal Cancer: Pathology, Somatic Alterations, and Perspectives for Novel Therapeutic Schemes.

HER2 is an emerging biomarker in colorectal cancer (CRC). This oncogene plays an essential role in regulating cell proliferation, differentiation, migration, and, more in general, tumorigenesis and tumor progression. The most frequent types of HER2 alterations in CRC include gene amplification and missense mutations in 7-8% of CRC, often being mirrored by HER2 protein overexpression, representing founder events in solid tumors, including CRC. There are currently no approved HER2-targeted therapy guidelines for CRC; however, several studies have shown that HER2 can be effectively targeted in meta-static CRC settings. In this review, we discuss the current knowledge of HER2 testing in CRC and the immediate future perspectives for HER2 targeting in the metastatic setting.

A Randomized Trial of Robotic Mastectomy Versus Open Surgery in Women With Breast Cancer or BrCA Mutation.

OBJECTIVE: The aim of this study was to compare robotic mastectomy with open classical technique outcomes in breast cancer patients. SUMMARY BACKGROUND DATA: As the use of robotic nipple sparing mastectomy continues to rise, improved understanding of the surgical, oncologic, and quality of life outcomes is imperative for appropriate patient selection as well as to better understand indications, limits, advantages, and dangers. METHODS: In a phase III, open label, single-center, randomized controlled trial involving 80 women with breast cancer (69) or with BRCA mutation (11), we compared the outcome of robotic and open nipple sparing mastectomy. Primary outcomes were surgical complications and quality of life using specific validated questionnaires. Secondary objective included oncologic outcomes. RESULTS: Robotic procedure was 1 hour and 18 minutes longer than open (P < 0.001). No differences in the number or type of complications (P = 0.11) were observed. Breast-Q scores in satisfaction with breasts, psychosocial, physical and sexual well-being were significantly higher after robotic mastectomy versus open procedure. Respect to baseline, physical and sexual well-being domains remained stable after robotic mastectomy, whereas they significantly decreased after open procedure (P < 0.02). The overall Body Image Scale questionnaire score was 20.7 ±â€Š13.8 versus 9.9 ±â€Š5.1 in the robotic versus open groups respectively, P < 0.0001. At median follow-up 28.6months (range 3.7-43.3), no local events were observed. CONCLUSIONS: Complications were similar among groups upholding the robotic technique to be safe. Quality of life was maintained after robotic mastectomy while significantly decrease after open surgery. Early follow-up confirm no premature local failure.ClinicalTrials.gov NCT03440398.

The Prognostic Impact of Histology in Esophageal and Esophago-Gastric Junction Adenocarcinoma.

Stage significantly affects survival of esophageal and esophago-gastric junction adenocarcinomas (EA/EGJAs), however, limited evidence for the prognostic role of histologic subtypes is available. The aim of the study was to describe a morphologic approach to EA/EGJAs and assess its discriminating prognostic power. Histologic slides from 299 neoadjuvant treatment-naïve EA/EGJAs, resected in five European Centers, were retrospectively reviewed. Morphologic features were re-assessed and correlated with survival. In glandular adenocarcinomas (240/299 cases-80%), WHO grade and tumors with a poorly differentiated component ≥6% were the most discriminant factors for survival (both p < 0.0001), distinguishing glandular well-differentiated from poorly differentiated adenocarcinomas. Two prognostically different histologic groups were identified: the lower risk group, comprising glandular well-differentiated (34.4%) and rare variants, such as mucinous muconodular carcinoma (2.7%) and diffuse desmoplastic carcinoma (1.7%), versus the higher risk group, comprising the glandular poorly differentiated subtype (45.8%), including invasive mucinous carcinoma (5.7%), diffuse anaplastic carcinoma (3%), mixed carcinoma (6.7%) (CSS p < 0.0001, DFS p = 0.001). Stage (p < 0.0001), histologic groups (p = 0.001), age >72 years (p = 0.008), and vascular invasion (p = 0.015) were prognostically significant in the multivariate analysis. The combined evaluation of stage/histologic group identified 5-year cancer-specific survival ranging from 87.6% (stage II, lower risk) to 14% (stage IVA, higher risk). Detailed characterization of histologic subtypes contributes to EA/EGJA prognostic prediction.

Ten-year outcome results of cT4 breast cancer after neoadjuvant treatment.

BACKGROUND AND OBJECTIVES: cT4 breast cancer (BC) is classified as noninflammatory breast cancer (non-IBC) or inflammatory breast cancer (IBC). The outcome often is considered worse. The purpose of this study was to determine recurrence and outcomes in overall survival (OS), invasive disease-free survival (IDFS), distant disease-free survival (DDFS) according to pathological complete response (pCR), and inflammatory status. METHODS: From 2000 to 2015 we selected 634 nonmetastatic cT4 BC patients treated with neoadjuvant therapy followed by surgery at the European Institute of Oncology. OS, IDFS, and DDFS were estimated with the Kaplan-Meier method. RESULTS: The median follow-up was 9.0 years. Twenty patients underwent only sentinel node biopsy (SNB), 13 SNB + AD, and 601 only AD. Considering the 614 patients with AD, only 2.5% of non-IBC patients reported pCR compared to 15% of IBC cases. Only two axillary recurrences were reported. Ten-year results were 52.3% (95% confidence interval [CI]: 47.8-56.5) for OS, 37.0% (95% CI: 32.6-41.3) for IDFS, and 49.8% (95% CI: 45.0-54.4) for DDFS. OS, IDFS, and DDFS were better in all BC with pCR (irrespective of inflammatory status). CONCLUSION: Our long-term results demonstrated that pCR significantly improves survival, reducing locoregional and distant recurrence risk in cT4 tumors with respect to patients with no pCR and according to inflammatory status of cT4 BC.

Long-term standard sentinel node biopsy after neoadjuvant treatment in breast cancer: a single institution ten-year follow-up.

INTRODUCTION: In patients with positive lymph nodes (cN+) prior to neoadjuvant treatment (NAT), which convert to a clinically negative axilla (cN0) after treatment, the use of sentinel node biopsy (SNB) is still debatable, since the false-negative rate (FNR) is significantly high (12.6-14.2%). The objective of this retrospective mono-institutional study, with a long follow-up, aimed to evaluate the outcome in patients undergoing NAT who remained or converted to cN0 and received SNB independent of target axillary dissection (TAD) or the removal of at least 3 sentinel nodes (SNs). METHODS: This study analyzed 688 consecutive cT1-3, cN0/1/2 patients, operated at the European Institute of Oncology, Milan, from 2000 to 2015 who became or remained cN0 after NAT and underwent SNB with a least one SN found. Axillary dissection (AD) was not performed if the SN was negative. Nodal radiotherapy (RT) was not mandatory. RESULTS: Axillary failure occurred in 1.8% of the initially cN1/2 patients and in 1.5% of the initially cN0 patients. After a median follow-up of 9.2 years (IQR 5.3-12.3), the 5- and 10-year overall survival (OS) were 91.3% (95% CI, 88.8-93.2) and 81.0% (95% CI, 77.2-84.2) in the whole cohort, 92.0% (95% CI, 89.0-94.2) and 81.5% (95% CI, 76.9-85.2) in those initially cN0, 89.8% (95% CI, 85.0-93.2) and 80.1% (95% CI, 72.8-85.7) in those initially cN1/2. CONCLUSION: The 10-year follow-up confirmed our preliminary data that the use of standard SNB is acceptable in cN1/2 patients who become cN0 after NAT and will not translate into a worse outcome.

Metaplastic breast cancer: Prognostic and therapeutic considerations.

INTRODUCTION: Metaplastic breast cancer (MBC) is a rare condition of breast tumor with different subtypes, considered a disease with worse prognosis; treatments and survival are often unclear and conflicting. METHODS: We consecutively collected 153 primary MBCs of different subtypes. Breast surgery, neoadjuvant or adjuvant treatment, clinic-pathological factors, number and type of events during follow-up were considered to evaluate overall survival (OS) and invasive disease-free survival (IDFS). RESULTS: The majority of MBC was triple-negative (TN) subtype (88.7%), G3 (95.3%), pN0 (70.6%), and with high levels of Ki-67 (93.5%). For OS and IDFS, no significant associations were seen between the different MBC subtypes. The matched triple-negative MBC (TNMBC) and ductal TNBC cohorts had similar prognosis both in terms of OS (p = .411) and IDFS (p = .981). We observed a positive trend for TNMBC patients treated in the adjuvant setting with the cyclofosfamide, methotrexate, 5-fluorouracil protocol for better OS (p = .090) and IDFS (p = .087). A poor or absent response rate was observed in the neoadjuvant setting. CONCLUSION: Our results demonstrate that metaplastic and ductal breast cancers with TN phenotype are similar in terms of overall and disease-free survival. Metaplastic cancers are poorly responsive to neoadjuvant treatment, and in the absence of novel targeted therapies, surgical treatment remains the first choice.

Cisplatin plus capecitabine concomitant with intensity-modulated radiation therapy in non-metastatic anal squamous cell carcinoma: the experience of a single research cancer center.

BACKGROUND AND AIMS: The standard treatment of non-metastatic anal squamous cell carcinoma (ASCC) consists of chemotherapy with mitomycin (MMC) plus 5-fluorouracil (5FU) for 1-2 cycles concomitant with pelvic radiotherapy. Subsequent studies introduced cisplatin (CDDP) combined with 5FU, with unclear results. We evaluated the doublet capecitabine (C) and CDDP as a possible alternative to MMC-5FU regimen concomitant with intensity-modulated radiation therapy (IMRT). PATIENTS AND METHODS: We carried out a retrospective study on 67 patients affected by stage I-III ASCC, treated with CDDP (60-70 mg/m2 every 21 days for two courses) plus C (825 mg/m2 twice daily for 5 days/week) chemotherapy concomitant with IMRT for curative intent. RESULTS: At a median follow up of 41 months, the clinical complete response calculated at the 6-month time-point (6-moCR), the 6-month objective response rate and the 6-month disease control rate were 93%, 94%, and 99%, respectively.Disease-free survival rates at 1, 2, and 3 years were 89%, 87%, and 85%, while the overall survival rates at 1 and 2 years were 100% and 95%. The colostomy-free survival rates were 90% at 1 year and 88% at 2 years. Grade 3-4 acute adverse events were reported in 61% of patients; predominantly skin toxicity (46%) and limited hematological toxicity (12%). CONCLUSION: In this retrospective study, chemotherapy with C plus CDDP concomitant with IMRT proved safe and effective, and may represent a possible alternative option to standard MMC-containing regimen for curative intent.

Update on the Feasibility and Progress on Robotic Breast Surgery.

BACKGROUND: Robotic nipple-sparing mastectomy (RNSM) may allow for more precise anatomic dissection and improved cosmetic outcomes over conventional open nipple-sparing mastectomy; however, data regarding the feasibility and safety of the procedure are limited. OBJECTIVE: The aim of this study was to present and discuss perioperative surgical outcomes and early oncologic follow-up data on consecutive patients undergoing RNSM from June 2014 to January 2019. METHODS: Patients underwent RNSM and immediate robotic breast reconstruction through an axillary incision at a single institution. Perioperative data, complications at 3 months postoperatively, pathological data, and adjuvant therapies were recorded. Local recurrence-free, disease-free, and overall survival were analyzed. RESULTS: Overall, 73 women underwent 94 RNSM procedures. Indications were invasive breast cancer in 39 patients, ductal carcinoma in situ in 17 patients, and BRCA mutation in 17 patients. Mean surgery time was 3 h and 32 min. One-step reconstruction with implant occurred in 89.4% of procedures. The rate of complications requiring reoperation was 4.3%, and the rate of flap or nipple necrosis was 1.1%. Median follow-up was 19 months (range 3.1-44.8). No local recurrences occurred. Overall survival at 12, 24, or 60 months was 98% (95% confidence interval 86-100%). CONCLUSION: We observed a low complication rate in 94 consecutive RNSM procedures, demonstrating the procedure is technically feasible and safe. We found no early local failures at 19 months follow-up. Long-term follow-up is needed to confirm oncologic safety. Future clinical trials to study the advantages and disadvantages of RNSM are warranted.

Hereditary diffuse gastric cancer in two families: A case report.

Hereditary diffuse gastric cancer (HDGC) is associated with E-cadherin 1 (CDH1) germline mutations. In the present study, two unusual HDGC cases are described. Case 1 was a female with no family history of gastric cancer who developed Hodgkin's lymphoma at 19 years of age, and DGC at 32 years of age. Due to her young age (32 years), the patient was examined for CDH1 abnormalities and a deleterious mutation was identified. Her father and younger sister were identified to be carriers of the mutation. Case 2 was a 36-year-old female diagnosed with lobular breast cancer (LBC); her mother had LBC, and her grandmother had LBC and DGC. The molecular test was wild-type for breast cancer susceptibility genes 1 and 2; however, a large deletion in CDH1 was identified. At prophylactic gastrectomy, early DGC was identified. Early onset of DGC and LBC justifies testing for CDH1. A better knowledge of tumor natural history in carrier subjects is important to aid genetic counseling, in order to assess the surveillance time required prior to carrying out prophylactic surgery.

Human papillomavirus in anal squamous cell carcinoma: an angel rather than a devil?

Anal cancer is a rare disease with an increasing incidence worldwide but, unfortunately, even today the scientific community still has a limited knowledge and limited options of treatment. More than 50% of patients with anal cancer presenting at diagnosis with locoregional disease have good chances of cure with chemoradiotherapy (CT-RT). However, once patients develop metastatic spread, the prognosis is very poor. Human papillomavirus (HPV) is present in more than 80% of anal cancers and while multiple etiologic connections between HPV infection and anal cancer have already been well elucidated, its prognostic and/or predictive role is currently under investigation, especially among immunocompetent patients affected by this disease. In a single-institutional set, we have retrospectively analysed clinical data of 50 consecutive cases homogeneously treated with CT-RT for stage I-III anal squamous cell carcinoma. We found that HPV-positive anal cancers had a statistically significant improved five-year disease-free survival (DFS) compared to HPV-negative group. These findings could be explained by an increased chemo/radiosensitivity of HPV-positive tumours. Further efforts should be directed towards a better understanding of HPV-related oncogenesis and towards designing novel tailored strategies for the management of this disease both in terms of prevention and treatment.

Breast phyllodes tumor: a review of literature and a single center retrospective series analysis.

PURPOSE: Complete surgical resection is the standard treatment for localized breast phyllodes tumors. Post-surgical treatments are still a matter of debate. We carried out an overview of the literature to investigate the clinical outcome of patients with phyllodes tumor. A retrospective analysis of mono-institutional series has been included as well. METHODS: We reviewed all the retrospective series reported from 1951 until April 2012. We analyzed cases treated at our institution from 1999 to 2010. RESULTS: Eighty-three articles (5530 patients; 1956 malignant tumors) were reviewed. Local recurrences were independent of histology. Distant recurrences were more frequent in the malignant tumors (22%). A total of 172 phyllodes tumors were included in the retrospective analysis. DISCUSSION: Prognosis of phyllodes tumors is excellent. There are no convincing data to recommend any adjuvant treatment after surgery. Molecular characterization may well provide new clues to permit identification of active treatments for the rare poor prognosis cases.

Heterogeneity of triple-negative breast cancer: histologic subtyping to inform the outcome.

BACKGROUND: This study assesses outcome in terms of disease-free survival (DFS) and overall survival (OS) of special types of triple-negative breast cancer (TNBC). PATIENTS AND METHODS: We identified 8801 women with first primary nonmetastatic breast cancer operated on at the European Institute of Oncology between 1997 and 2005. Of these patients, 781 consecutive patients with immunohistochemically defined TNBC were selected for the analyses. We explored patterns of recurrence by histologic type. Median follow-up was 5.7 years (range 0-13 years). RESULTS: The 5-year DFS was 77% for TNBC, 68% for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and 84% and 95% for luminal B and luminal A breast cancer, respectively. From 781 TNBC subtypes, 693 cases (89%) were classified as ductal not otherwise specified (NOS) (invasive ductal carcinoma [IDC]), 29 were classified as apocrine (3.7%), 18 (2.3%) were classified as lobular, 10 (1.2%) were classified as adenoid cystic, and 10 (1.2%) were classified as metaplastic. Five-year DFS and OS were 77% and 84% for patients with ductal carcinoma, 56% and 89% for patients with metaplastic carcinoma, and both 5-year DFS and OS were 100% for patients with adenoid cystic and medullary carcinomas, respectively. CONCLUSION: Distinct prognostic implications may derive from the specific histotype of TNBC. The identification of these special types has a significant clinical utility and should be considered in therapeutic algorithms.

Sarcoma of the breast: outcome and reconstructive options.

INTRODUCTION: Surgery is the mainstay of treatment for all breast sarcomas. The role of adjuvant chemotherapy and radiation therapy has not been clearly defined. The aim of this single-center retrospective study was to analyze prognostic factors, outcome, and recent advances. MATERIALS AND METHODS: Data from 203 patients with all breast sarcomas treated in a single center were collected from 1996 to 2010. Phyllodes tumors and metastatic disease at presentation were excluded from the population. Thirty-six women and 1 man were included in the analysis. Local recurrence, metastatic disease, survival, and reconstructive outcome were evaluated. RESULTS: Thirty-four patients out of 37 (91.9%) had an angiosarcoma and 3 had a stromal sarcoma (8.1%). Twenty-one patients (56.8%) had previously undergone breast radiation therapy for breast carcinoma or lymphoma. Twenty-six patients (70.3%) underwent mastectomy, 14 of whom (53.8%) with breast reconstruction. Thirty-six patients (97.3%) had free margins, 1 (2.7%) had a microscopically focally involved margin after surgery. Five patients received adjuvant chemotherapy and 6 received adjuvant radiation therapy. Median follow-up was 58 months (range, 4-146 months). Twelve sarcoma-related deaths were observed with a 5-year cumulative incidence of 43.4%. Twenty-four sarcoma-related events were observed with a 5-year cumulative incidence of 70.8%. The same figure was 49.7% in patients affected by primary sarcoma and 85.7% in patients with secondary sarcoma (P = .06). CONCLUSION: Secondary sarcomas were associated with a higher risk of events. Patients undergoing breast conservative surgery or reconstruction after mastectomy did not show a worse prognosis compared with patients undergoing mastectomy.

Invasive lobular breast cancer: subtypes and outcome.

Invasive lobular carcinoma (ILC) is the most common "special type" of breast cancer. Although conflicting literature data are available on the outcome of ILC, recently reported data indicate that ILC carries a poorer prognosis if compared to invasive ductal carcinomas. We evaluated clinical and biological features of 981 consecutive patients with pT1-3, pN1-3 M0 ILC. Median follow-up was 7.4 years for survival. A total of 541 patients were classified as classic (55.8%), 146 alveolar (14.9%), 145 mixed non-classic (14.8%), 104 solid (10.6%), and 38 trabecular (3.9%). A statistically significant difference in the outcome was observed at multivariate analysis for patients with solid (HR 2.44, 95% CI 1.39-4.29 for OS; HR 1.92, 95% CI 1.29-2.88 for DFS) and mixed non-classic (HR 1.99, 95% CI 1.12-3.53 for OS) versus patients with classical ILC. A statistically significant difference in the risk of distant metastases was observed at multivariate analysis for patients with Luminal B (HR 2.56, 95% CI 1.38-4.76), HER2 positive (HR 7.80, 95% CI 1.55-39.3), and triple negative (HR 7.61, 95% CI 2.63-22.1) subtypes versus patients with Luminal A ILC. Age ≥70 years, tumor size and degree of nodal involvement were additional independent predictors of reduced overall survival. The outcome of ILC significantly correlated with histological and immunohistochemically defined molecular subtypes. New tailored strategies should be explored in these subgroups of patients with poor outcome.