Prognostic impact of the 8th edition of American Joint Committee on Cancer (AJCC) cancer staging system on clinically negative lymph nodes (cN0) breast cancer patients.

In 2017, the 8th edition of American Joint Committee on Cancer (AJCC) Staging Manual released the updating of TNM. The new edition introduces changes concerning tumor classification that could have a real innovative and useful clinical impact. The purpose of the study is to compare anatomic vs. prognostic stage group introduced in the new edition of AJCC staging system and its importance in clinical practice. We retrospectively analyzed the prognostic stage group introduced by the 8th edition of the AJCC staging system for breast cancer. We restaged a large series of patients with infiltrative breast cancer from 2004 to 2017 applying the AJCC 8th Edition prognostic stage group criteria. This study included 1575 patients with all molecular subtypes of breast cancer. Our follow-up included disease-free survival (DFS), disease-related survival (DRS), and overall survival (OS) data. Kaplan-Meier test was used for statistical analysis. The median follow-up was 7 years. The 5-year and 10-year OS were 96% and 90%, respectively. From our analysis, according to the 8th edition, the majority of patients included in the cohort had a down-staging to a better prognostic group except the triple-negative tumors. Most of the anatomic stage IIA turned into IA and IB. This new staging system seems to better relate to prognosis. Therefore, the prognostic stage represents an important support in breast cancer management since it could avoid unnecessary and ineffective therapies; in contrast, it could help realize the global evaluation of the risk of relapse/response to specific treatments, leading to a significant reduction in the national health cost.

Role of frozen section in sentinel lymph node biopsy for breast cancer in the era of the ACOSOG Z0011 and IBCSG 23-10 trials.

BACKGROUND: Intraoperative frozen sections (FS) of sentinel lymph nodes (SLN) were evaluated to avoid the need for deferred axillary lymph node dissection (ALND) in patients with early breast cancer (EBC). However, FS has low sensitivity for detecting micro-metastases (<2 mm), resulting in patients who later undergo deferred ALND. The aim of the study was to determine the best clinical approach for selecting patients who would derive real benefit from ALND, as well as to minimize the functional and psychological damage caused by delayed surgery, and the risk of undertreating EBC patients. METHODS: This study evaluated 1453 patients with early breast cancer (EBC) who underwent SLN biopsy, FS and definitive evaluation. Causes of discrepancies between SLN biopsy and FS results and the need for further surgery were evaluated. RESULTS: A total of 1226 (86%) patients underwent FS; of these patients, 146 (11.9%) were false negatives. The global sensitivity of FS in detecting both macro and micrometastases was 53.7%. Although ACOSOG Z0011 criteria found that ALND could be avoided in 236 patients, 40 (17%) of these had >3 positive axillary lymph nodes. In contrast, application of the IBCSG 23-10 trial criteria, found that only three patients (3.1%) had >3 positive axillary lymph nodes. CONCLUSIONS: FS has a low sensitivity in detecting micrometastases (19%), but a reasonable sensitivity for macrometastases (75%). Most false negatives were smaller metastases (mean 2.1 mm) and more likely in patients with infiltrating lobular carcinoma. Retrospective modelling of the IBCSG 23-10 criteria reduced the percentage of patients requiring deferred surgery from 12% to 4%. Guidelines recommend irradiation of lymph node drainage stations in patients with ≥4 axillary metastatic lymph nodes. Omission of ALND from 40% of patients who met Z0011 criteria would have resulted in their undertreatment. This risk decreases to 3% by omitting axillary clearing only in patients with micrometastases.

High-resolution, handheld camera use for occult breast lesion localization plus sentinel node biopsy (SNOLL): a single-institution experience with 186 patients.

BACKGROUND: Sentinel node and occult lesion localization (SNOLL) calls for a combination of two specific procedures: intraoperative detection of sentinel lymph node (SLN) via gamma probe and radioguided occult lesion localization (ROLL). This applies to nonpalpable invasive breast cancer or high-grade in situ carcinoma. As opposed to standard techniques, today's handheld gamma cameras enable intraoperative scintigraphic images. METHODS: A cohort (N = 186) of consecutive patients with breast cancer was subjected to radioguided conservative surgery (quadrantectomy and SLN biopsy), using a standard gamma probe and a high-resolution handheld camera. Intraoperative SLN frozen section was also performed. RESULTS: Neoplastic lesions were removed in 99.4% of all patients, and SLN biopsy was achieved in 99%. Of the 137 patients with invasive cancer, SLN metastasis was confirmed in 21. In 12% of patients, a second operation was required for close or tumor-positive surgical margins. DISCUSSION: This combination of procedures represents an improvement in the surgical management of occult breast carcinomas and is the method of choice for accurate tumor localization and SLN biopsy. Handheld cameras have the potential to become highly useful intraoperative aids.

Radiation therapy after breast reconstruction: outcomes, complications, and patient satisfaction.

PURPOSE: The aim of this study was to evaluate treatment-related complications, outcomes, and patient satisfaction in women with locally advanced breast cancer who received post-mastectomy radiation therapy (PMRT) after breast reconstruction (BR). MATERIALS AND METHODS: Between October 2007 and November 2010, 46 patients with locally advanced breast cancer who underwent mastectomy followed by BR received PMRT at our Department. Radiotherapy was delivered to the chest wall with a dose of 50 Gy in 25 fractions over 5 weeks. RESULTS: The median follow-up was 19 months. Skin erythema grade 1 and 2 was seen in 44 (96%) and two (4%) patients, respectively. Major complications, requiring additional corrective surgical procedure, occurred in three (7%) patients (one patient with prosthesis, one patient with tissue expander and one patient with deep inferior epigastric perforator flap). At univariate analysis, smoking, chemotherapy, hormone therapy with tamoxifen and reconstruction with implant were associated with overall complications (capsular contracture and reconstruction failure). Forty (86%) patients were very satisfied or satisfied with the cosmetic outcome of reconstruction. CONCLUSIONS: Radiotherapy can be safely delivered after BR, with a low complication rate and good patient satisfaction. Further randomised studies are needed to better define the optimal timing of breast reconstruction and post-mastectomy radiation therapy.

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 "Type V" skin-sparing mastectomy for upper quadrant skin resections.

Skin-sparing mastectomies (SSMs) are classified according to the type of incision and breast size. In large breasts, if cancer is superficially located in the upper quadrants, SSM type IV is not indicated, because tumor resection interferes with skin flap pattern. For these patients, a modified Wise-pattern SSM has been developed to achieve immediate breast reconstruction. Twenty-four patients, 14 with tumor in the superior-lateral, 7 in the superior-medial, and 3 in the inferior-lateral quadrant, were operated on with modified SSM incisions. To replace the skin area removed with mastectomy from the upper quadrants, a similar size area from the lower pole was used. No local or distant recurrences occurred, with a mean follow-up of 27 months. Natural breast shape was achieved in all cases. Our procedure allows for a skin-sparing mastectomy (SSM type V) with immediate reconstruction, achieving a natural breast shape also in this group of patients previously excluded.

Beyond BRCA1 and BRCA2: Deleterious Variants in DNA Repair Pathway Genes in Italian Families with Breast/Ovarian and Pancreatic Cancers.

The 5-10% of breast/ovarian cancers (BC and OC) are inherited, and germline pathogenic (P) variants in DNA damage repair (DDR) genes BRCA1 and BRCA2 explain only 10-20% of these cases. Currently, new DDR genes have been related to BC/OC and to pancreatic (PC) cancers, but the prevalence of P variants remains to be explored. The purpose of this study was to investigate the spectrum and the prevalence of pathogenic variants in DDR pathway genes other than BRCA1/2 and to correlate the genotype with the clinical phenotype. A cohort of 113 non-BRCA patients was analyzed by next-generation sequencing using a multigene panel of the 25 DDR pathways genes related to BC, OC, and PC. We found 43 unique variants in 18 of 25 analyzed genes, 14 classified as P/likely pathogenic (LP) and 28 as variants of uncertain significance (VUS). Deleterious variants were identified in 14% of index cases, whereas a VUS was identified in 20% of the probands. We observed a high incidence of deleterious variants in the CHEK2 gene, and a new pathogenic variant was detected in the RECQL gene. These results supported the clinical utility of multigene panel to increase the detection of P/LP carriers and to identify new actionable pathogenic gene variants useful for preventive and therapeutic approaches.

Is complete axillary dissection necessary for all patients with positive findings on sentinel lymph node biopsy? Validation of a breast cancer nomogram for predicting the likelihood of a non-sentinel lymph node.

AIM AND BACKGROUND: Axillary dissection in patients positive for sentinel lymph nodes is currently under discussion in the literature, since approximately only 50% of such patients has metastases in the remaining lymph nodes. To identify patients at risk for non-sentinel lymph nodes metastases, a nomogram was developed by the Breast Service of the Memorial Sloan-Kettering Cancer Center. The aim of this study was to assess the nomogram's predictive accuracy in a population of Italian breast cancer patients in our hospital. MATERIALS AND METHODS: The system of calculation used as variables prognostic factors of breast cancer: pathologic size, tumor type and nuclear grade, lymphovascular invasion, multifocality, estrogen receptor status, method of detection of the sentinel lymph nodes metastases (frozen section, serial hematoxylin-eosin, routine hematoxylin-eosin, and immunohistochemistry), number of positive and number of negative sentinel lymph nodes. RESULTS AND CONCLUSIONS: To measure the discrimination of the nomogram, a receiver-operating characteristic curve was construed, and the area under the curve was calculated. However, the area under the curve was 0.72, a very high value considering that the limit of acceptability is 0.70-0.80. The calculation system developed by the Memorial Sloan-Kettering Cancer Center provides a predictive value on the histopathologic state of sentinel lymph nodes.

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.

High-resolution, hand-held camera for sentinel-node detection.

BACKGROUND: The imaging probe (IP) is a high-resolution (HR), 1-in(2) field-of-view hand-held gamma camera. We used it to detect breast cancer sentinel node (SN). PATIENTS AND METHODS: We divided 120 T1 breast cancer patients, who underwent Anger camera lymphoscintigraphy (ACL), in two subgroups of 60 patients who were age, body mass index, and cancer size matched: subgroup A (SA) and B (SB). SN was detected with a common gamma probe (GP) in SA, with IP plus GP in SB. RESULTS: Surgeons removed radioactive nodes without exceeding four nodes. Eighty-two (82) SNs were taken off in SA and 105 in SB (p<0.01). Of SA, 22 of 60 patients and 36 of 60 patients of SB showed more than 1 node, and 3 of them showed 3 nodes and 1 showed 4 nodes. Thirteen (13) patients resulted N(+) (21.6%) in SA. Ten (10) patients of SA showed an invasion on the hottest nodes and 3 on the second nodes. In the SB, 18 patients (25%) showed invasion. Sixteen (16) invasions were on hot, 4 on second, and 1 on the third node. Withdrawal time of SN was 11.25+/-4.7 minutes for SA and 7.4+/-2.8 minutes for SB (p<0.025). CONCLUSIONS: SN biopsy with IP is fast and discovers more SNs and more invasions than ACL.

Rapid detection of copy number variations and point mutations in BRCA1/2 genes using a single workflow by ion semiconductor sequencing pipeline.

Molecular analysis of BRCA1 (MIM# 604370) and BRCA2 (MIM #600185) genes is essential for familial breast and ovarian cancer prevention and treatment. An efficient, rapid, cost-effective accurate strategy for the detection of pathogenic variants is crucial. Mutations detection of BRCA1/2 genes includes screening for single nucleotide variants (SNVs), small insertions or deletions (indels), and Copy Number Variations (CNVs). Sanger sequencing is unable to identify CNVs and therefore Multiplex Ligation Probe amplification (MLPA) or Multiplex Amplicon Quantification (MAQ) is used to complete the BRCA1/2 genes analysis. The rapid evolution of Next Generation Sequencing (NGS) technologies allows the search for point mutations and CNVs with a single platform and workflow. In this study we test the possibilities of NGS technology to simultaneously detect point mutations and CNVs in BRCA1/2 genes, using the OncomineTM BRCA Research Assay on Personal Genome Machine (PGM) Platform with Ion Reporter Software for sequencing data analysis (Thermo Fisher Scientific). Comparison between the NGS-CNVs, MLPA and MAQ results shows how the NGS approach is the most complete and fast method for the simultaneous detection of all BRCA mutations, avoiding the usual time consuming multistep approach in the routine diagnostic testing of hereditary breast and ovarian cancers.

Current trends and outcomes of breast reconstruction following nipple-sparing mastectomy: results from a national multicentric registry with 1006 cases over a 6-year period.

BACKGROUND: Reconstruction options following nipple-sparing mastectomy (NSM) are diverse and not yet investigated with level IA evidence. The analysis of surgical and oncological outcomes of NSM from the Italian National Registry shows its safety and wide acceptance both for prophylactic and therapeutic cases. A further in-depth analysis of the reconstructive approaches with their trend over time and their failures is the aim of this study. METHODS: Data extraction from the National Database was performed restricting cases to the 2009-2014 period. Different reconstruction procedures were analyzed in terms of their distribution over time and with respect to specific indications. A 1-year minimum follow-up was conducted to assess reconstructive unsuccessful events. Univariate and multivariate analyses were performed to investigate the causes of both prosthetic and autologous failures. RESULTS: 913 patients, for a total of 1006 procedures, are included in the analysis. A prosthetic only reconstruction is accomplished in 92.2 % of cases, while pure autologous tissues are employed in 4.2 % and a hybrid (prosthetic plus autologous) in 3.6 %. Direct-to-implant (DTI) reaches 48.7 % of all reconstructions in the year 2014. Prophylactic NSMs have a DTI reconstruction in 35.6 % of cases and an autologous tissue flap in 12.9 % of cases. Failures are 2.7 % overall: 0 % in pure autologous flaps and 9.1 % in hybrid cases. Significant risk factors for failures are diabetes and the previous radiation therapy on the operated breast. CONCLUSIONS: Reconstruction following NSM is mostly prosthetic in Italy, with DTI gaining large acceptance over time. Failures are low and occurring in diabetic and irradiated patients at the multivariate analysis.

Nipple sparing mastectomy: Surgical and oncological outcomes from a national multicentric registry with 913 patients (1006 cases) over a six year period.

BACKGROUND: Nipple sparing mastectomy is deemed surgically and oncologically safe based on a long lasting literature data from reviews of single institution series. This study aims at evaluating surgical and oncological outcomes of NSM on a large multi-institutional scale, by means of the Italian National registry. METHODS: In July 2011 a panel of Italian specialists agreed upon and designed a National database of NSM. Centers with at least 150 cancers per year and following the National follow-up schedule guidelines could participate inserting any NSM case performed, retrospectively and prospectively from that moment on. In March 2015 analysis of data was accomplished. Dataset for this study consists of cases performed in the period between January 1st 2009 and December 31st 2014. RESULTS: 913 Women were included in the analysis, for a total of 1006 procedures. Prophylactic mastectomies were 124 (12.3%). MRI utilization increased over time. NSM failure rate, with NAC removal for any reason was 11.5%. NAC necrosis rate was 4.8%. Larger skin-flap necrosis rate was 2.3%. Major surgical complications rate was 4.4%. Oncological outcomes were calculated among primitive EBC cases only: locoregional recurrences rate was 2.9%, NAC recurrence 0.7%. Systemic recurrence rate was 1.0%. Five deaths (0.7%) were registered. CONCLUSIONS: More than 10% of NSM procedures are prophylactic mastectomies. MRI is gaining more importance over time. Surgical and oncological results show that NSM is effective. This National multicentric analysis enables a comparison of results with no geographical differences and a "safe" state of the art of NSM in Italy.

Alpha- and beta-tubulin expression in rectal cancer development.

BACKGROUND: Microtubules are involved in cell growth and division, motility, signalling and in the development and maintenance of cell shape. Consequently, the non-equilibrium dynamics of these microtubules can be crucial to cellular function, including cancer development. Although the involvement of tubulins in human development has been well investigated, the role of alpha- and beta-tubulins in human tumorigenesis still remains controversial. The aim of this study was to investigate alpha- and beta-tubulin protein expression in rectal cancer development. PATIENTS AND METHODS: By immuno-histochemistry, using alpha- and beta-tubulin monoclonal antibodies, 66 patients were examined, 32 of whom (22 male, 10 female; range 31-60 years, mean age 49.5 years) had preneoplastic lesions discovered during endoscopic surveillance, which were classified as mild, moderate and severe dysplastic polyps of the rectum, and 34 had invasive adenocarcinomas (24 male, 10 female; range 39-60 years, mean 52 years) of the rectum, with no local or distant metastases at the time of surgical resection. RESULTS: In preneoplastic lesions, no statistically significant relationship was found among alpha- and beta-tubulin protein expression, grade of dysplasia, or other clinical data. Statistical association among alpha- and beta-tubulin immunoreactivity and Dukes' stages B and C was found with p = 0.017 and p = 0.009, respectively. No statistical relationship was found between alpha- and beta-tubulin protein expression among different grades of dysplasia. On the contrary, a significant relationship was detected among tubulins in different stages of cancer. CONCLUSION: In this preliminary study a significant difference of alpha- and beta-tubulin protein expressions was found in polyps and invasive cancer of the rectum, indicating a possible role of tubulins in invasive, but not in preinvasive cancer development. This preliminary data suggest the possibility of performing alpha- and beta-tubulin protein expression in order to identify B stage versus C stage rectal cancer, before surgical treatment.

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.

[Vascular malformations: the need for a multidisciplinary treatment. Considerations on a clinical case]. / Le malformazioni vascolari: necessità di un trattamento multidisciplinare. Considerazioni su di un caso clinico.

The case reported here is a paradigm of a complex vascular malformation with a therapeutic approach which involved both vascular radiology and surgery. The case came to our attention in 1999 and consisted in a tumefaction of the left gluteal region in a 14-year-old female. The lesion had previously been evaluated by ultrasonography and magnetic resonance imaging. The lesion was described as a dysplastic malformation with a high vascular factor. After angiography, we decided to embolize the mass. A second embolization also yielded no result, and therefore we decided to remove the dysplasia surgically. The dysplasia, however, was resolved only in 2001 after a third embolization. Because of the multiple types of symptoms, a multidisciplinary approach is required to obtain both a correct classification and treatment of the vascular malformations.

Cytokines, fatigue, and cutaneous erythema in early stage breast cancer patients receiving adjuvant radiation therapy.

We investigated the hypothesis that patients developing high-grade erythema of the breast skin during radiation treatment could be more likely to present increased levels of proinflammatory cytokines which may lead, in turn, to associated fatigue. Forty women with early stage breast cancer who received adjuvant radiotherapy were enrolled from 2007 to 2010. Fatigue symptoms, erythema, and cytokine levels (IL-1ß, IL-2, IL6, IL-8, TNF-α, and MCP-1) were registered at baseline, during treatment, and after radiotherapy completion. Seven (17.5%) patients presented fatigue without associated depression/anxiety. Grade ≥2 erythema was observed in 5 of these 7 patients. IL-1ß, IL-2, IL-6, and TNF-α were statistically increased 4 weeks after radiotherapy (P < 0.05). After the Heckman two-step analysis, a statistically significant influence of skin erythema on proinflammatory markers increase (P = 0.00001) was recorded; in the second step, these blood markers showed a significant impact on fatigue (P = 0.026). A seeming increase of fatigue, erythema, and proinflammatory markers was observed between the fourth and the fifth week of treatment followed by a decrease after RT. There were no significant effects of hormone therapy, breast volume, and anemia on fatigue. Our study seems to suggest that fatigue is related to high-grade breast skin erythema during radiotherapy through the increase of cytokines levels.

Exclusive electron intraoperative radiotherapy in early-stage breast cancer: a monoinstitutional experience.

AIM: To evaluate the effectiveness of intra-operative radiotherapy (IORT) in breast cancer in terms of local control, esthetic results and disease-free survival. PATIENTS AND METHODS: From June 2007 to October 2011, 110 patients with early-stage breast cancer were submitted to quadrantectomy and IORT. A total dose of 21 Gy prescribed at 90-100% isodose was delivered in all cases. Patients were evaluated after surgery for early and late complications. RESULTS: Median follow-up was 27 (range: 2-54) months. In 10 patients (9.1%), breast ultrasound showed liponecrosis. Six patients (5.5%) developed grade 2 fibrosis. Disease-free survival rates at 2 and 3 years were 96.8% and 92.9 %. Three patients (2.7%) developed local recurrence, two patients (1.8%) distant metastasis. Two patients died. The 2- and 3-year overall survival rates were 100% and 97.3%, respectively. CONCLUSION: IORT could be an appropriate therapeutic alternative in selected patients although it remains investigational; longer follow-up to confirm these results is required.

Non-sentinel lymph node metastases in breast cancer patients with a positive sentinel lymph node: validation of five nomograms and development of a new predictive model.

AIMS AND BACKGROUND: Discordance of intraoperative analysis with definitive histology of the sentinel lymph node in breast cancer leads to completion axillary lymph node dissection, which only in 35-50% shows additional nodal metastases. The aim of the study was to identify individual patient risk for non-sentinel lymph node metastases by validating several statistical methods present in the recent literature and by developing a new tool with the final goal of avoiding unnecessary completion axillary lymph node dissection. METHODS: We retrospectively evaluated 593 primary breast cancer patients. Completion axillary lymph node dissection was performed in 139 with a positive sentinel lymph node. The predictive accuracy of five published nomograms (MSKCC, Tenon, Cambridge, Stanford and Gur) was measured by the area under the receiver operating characteristic curve. We then developed a new logistic regression model to compare performance. Our model was validated by the leave-one-out cross-validation method. RESULTS: In 53 cases (38%), we found at least one metastatic non-sentinel lymph node. All the selected nomograms showed values greater than the 0.70 threshold, and our model reported a value of 0.77 (confidence interval = 0.69-0.86 and error rate = 0.28) and 0.72 (confidence interval = 0.63-0.81, error rate = 0.28) after the validation. With a 5% cutoff value, sensitivity was 98% and specificity 9%, for a cutoff of 10%, 96% and 2%, respectively. CONCLUSIONS: All the nomograms were good discriminators, but the alternative developed model showed the best predictive accuracy in this Italian breast cancer sample. We still confirm that these models, very accurate in the institution of origin, require a new validation if used on other populations of patients.