The Proper Ki-67 Cut-Off in Hormone Responsive Breast Cancer: A Monoinstitutional Analysis with Long-Term Follow-Up.

INTRODUCTION: Breast cancer is a heterogeneous disease. Our study focuses on a monoinstitutional series of patients affected by Hormone Responsive carcinomas (luminal A and luminal B) and aims to define an optimal Ki-67 cut-off, to correctly stratify these patients into risk classes, using the ImmunoHistoChemical (IHC) surrogates of the Molecular Subtypes, according to the St. Gallen guidelines. METHODS: We analyzed 1685 patients. These patients underwent both radical and conservative surgeries with Sentinel Lymph Node Biopsy eventually followed by Axillary Dissection (AD). Furthermore, all the patients underwent adjuvant therapies according to the guidelines. A retrospective univariate analysis was performed and survival curves (Disease-Related Survival, DRS, and Disease-Free Survival, DFS) were carried out according to the following ki-67 risk classes: Low Risk (Ki-67 ≤ 14%); Intermediate Risk (Ki-67 15% ÷ 20%); High Risk (Ki-67 > 20%). RESULTS: 14 yy DRS was 98% in LA and 85% in LB with a ki-67 cut-off of 14% (p=0.037) vs 95% (LA) and 83% (LB) with a ki-67 cut-off of 20% (p=0.003). 14yy DFS was 85% in LA and 72% in LB with a ki-67 cut-off of 14% (p=0.017) vs 83% (LA) and 66% (LB) with a ki-67 cut-off of 20% (p<0.000). DISCUSSION: Our results confirmed that the 20% Ki-67 cut-off is more reliable in differentiating patients at low or high risk of recurrence and death, and stratifying patients eligible for adjuvant chemotherapy. Thus, despite its poor reproducibility, the identification of the most accurate ki-67 index assumes a pivotal relevance in guiding a tailored strategy among patients with this specific profile of breast cancer, as well as the molecular surrogates, in order to avoid harmful overtreatments.

The Emergency Surgery Frailty Index (EmSFI): development and internal validation of a novel simple bedside risk score for elderly patients undergoing emergency surgery.

BACKGROUND: Frailty assessment has acquired an increasing importance in recent years and it has been demonstrated that this vulnerable profile predisposes elderly patients to a worse outcome after surgery. Therefore, it becomes paramount to perform an accurate stratification of surgical risk in elderly undergoing emergency surgery. STUDY DESIGN: 1024 patients older than 65 years who required urgent surgical procedures were prospectively recruited from 38 Italian centers participating to the multicentric FRAILESEL (Frailty and Emergency Surgery in the Elderly) study, between December 2016 and May 2017. A univariate analysis was carried out, with the purpose of developing a frailty index in emergency surgery called "EmSFI". Receiver operating characteristic curve analysis was then performed to test the accuracy of our predictive score. RESULTS: 784 elderly patients were consecutively enrolled, constituting the development set and results were validated considering further 240 consecutive patients undergoing colorectal surgical procedures. A logistic regression analysis was performed identifying different EmSFI risk classes. The model exhibited good accuracy as regard to mortality for both the development set (AUC = 0.731 [95% CI 0.654-0.772]; HL test χ2 = 6.780; p = 0.238) and the validation set (AUC = 0.762 [95% CI 0.682-0.842]; HL test χ2 = 7.238; p = 0.299). As concern morbidity, our model showed a moderate accuracy in the development group, whereas a poor discrimination ability was observed in the validation cohort. CONCLUSIONS: The validated EmSFI represents a reliable and time-sparing tool, despite its discriminative value decreased regarding complications. Thus, further studies are needed to investigate specifically surgical settings, validating the EmSFI prognostic role in assessing the procedure-related morbidity risk.

Positive margins (R1) risk factors in breast cancer conservative surgery.

BACKGROUND: The primary goal in conservative breast cancer surgery is the complete excision of the tumor, but at the same time attempting to obtain a satisfactory postoperative esthetic result. The notion of "No Ink on Tumor" that indicates exclusively the presence of tumor cells on the inked surface of the surgical specimen is now the gold standard; however, the problem of the free margin is still a fundamental topic of debate that has not yet found a definitive solution. METHODS: Our retrospective analysis takes into account 1440 patients undergoing breast conservative surgery, from October 2004 to November 2018, all treated at the breast unit of our institution. RESULTS: Positive margins (R1) rate was 10.2% (147 cases out of 1440). Overall survival was 95% at 5 years and 89% at 10 years. No differences in mortality and local recurrence rate between R0 and R1 patients were found. Half of the R1 patients underwent secondary surgery with enlargement of margins, while in the other half we performed direct mastectomy. Among the analyzed variables, age, histological size, histological type, grading, multifocality, lympho-vascular invasion and lymph node status were significantly correlated with the R1 status. The multivariate analysis shows  the association of age and surgical technique (oncoplastic) with R1 status. CONCLUSION: Further studies will allow the creation of a statistical model, for better pre-operative prediction of patients with higher risk of R1 and better selection of patients to be candidates for conservative surgery.

Importance of perforating vessels in nipple-sparing mastectomy: an anatomical description.

BACKGROUND: Nipple-sparing mastectomy (NSM), understood as an oncologically valid procedure, is relatively new, and is an evolution of traditional mastectomy, particularly in relation to breast-conserving surgery. The anterior perforating branches are responsible for the cutaneous vascularization of the breast skin, and their preservation is a fundamental step to avoid possible postoperative necrosis. Therefore, evaluating the potential complications of cancer-related reconstructive surgical procedures such as NSM, both the distance of the tumoral lesion from the skin and the surgical incision site should be carefully considered. The preferred site of incision corresponds to the inframammary fold or possibly the periareolar area. METHODS: We retrospectively reviewed 113 patients who underwent NSM from January 2005 to October 2012 to evaluate skin complications. The anatomical study was performed by magnetic resonance imaging of the breast. RESULTS: Only one of the 113 women who had undergone a NSM procedure had total necrosis (0.9%) and six patients had partial necrosis (5.8%) of the nipple-areola complex.