Preoperative MRI evaluation of lesion-nipple distance in breast cancer patients: thresholds for predicting occult nipple-areola complex involvement.

AIM: To identify clinically occult nipple-areola complex (NAC) involvement using preoperative magnetic resonance imaging (MRI), to inform selection of patients eligible for nipple-sparing mastectomy (NSM) or skin-sparing mastectomy (SSM). MATERIAL AND METHODS: This was a retrospective study of 195 patients, who had preoperative breast MRI (February 2011 to January 2017) before undergoing surgical treatments (NSM or SSM) for newly diagnosed breast cancer. Tumour features at MRI (mass or non-mass lesion, diameter, lesion-NAC distance [LND]) and pathology (lesion diameter, histopathological type, receptor status) were recorded, as well as the type of surgery (NSM/SSM) and presence (NAC+) or absence (NAC-) of tumour at intraoperative evaluation of retroareolar tissue. Mann-Whitney test, Fisher's exact test, logistic regression, and receiver operating characteristic (ROC) curve analysis were used for analysis of NAC+ versus NAC- to assess variables that predict NAC tumoural involvement. RESULTS: Over the study period, NAC+ was proven histologically in 71/200 (35.5%) surgical treatments, while there were 129/200 NAC- (72 NSM and 128 SSM performed). LND at MRI was statistically (p<0.001) lower in NAC+ patients than in NAC- patients. The area under the ROC curve (0.82, 95% confidence interval [CI]: 0.76-0.88) indicated 10 mm as the best cut-off, with sensitivity of 82%, specificity of 72%, and accuracy of 79%. A 5-mm cut-off enhanced sensitivity, whereas a 15-mm cut-off favoured specificity. CONCLUSIONS: MRI is a useful tool for identifying NAC+ patients; a 10-mm cut-off for LND assists selection of patients for NSM, although intraoperative retroareolar tissue examination remains mandatory.

Neoadjuvant systemic treatment for breast cancer in Italy: The Italian Society of Surgical Oncology (SICO) Breast Oncoteam survey.

The Italian Society of Surgical Oncology (SICO) Breast Oncoteam developed a survey to explore the state of the art of neoadjuvant treatment for breast cancer in Italy, specifically focusing on cases treated during the two-year period 2014-2015. A questionnaire was sent to Italian Breast Units with a minimum of 150 new breast cancer cases treated/year according to the Senonetwork directory and to the SICO Breast Oncoteam Breast Unit network. A total of 23/107 Breast Units submitted the survey, reporting a total amount of 20156 cases of breast carcinoma (17241 invasive, 2915 in situ) treated in the biennium, corresponding approximately to 20% of newly diagnosed breast cancers in Italy. In the United States, medical treatment before surgery for breast cancer is indicated in about 22.7% of newly diagnosed cases according to the National Cancer Database, while a German study reported approximately 20% of cases treated with neoadjuvant therapy. In our survey, a total of 1673/17241 cases (9.7%) were treated with neoadjuvant therapy, ranging from 2.9% to 23.6% according to different centres, showing heterogeneity in neoadjuvant treatment indications, even in multidisciplinary breast units. Better resources should be engaged to achieve a standardised quality indicator for neoadjuvant treatment, and this indicator could be included among the European Society of Breast Cancer Specialists (EUSOMA) quality indicators. In the near future, we plan to develop a second survey to better test improvements in the employment of neoadjuvant therapy after the expiry of the 2016 European Parliament deadline and after the 2017 St. Gallen Conference recommendations.

Electrochemotherapy in the Treatment of Cutaneous Metastases from Breast Cancer: A Multicenter Cohort Analysis.

BACKGROUND: The management of breast cancer (BC) skin metastases represents a therapeutic challenge. Electrochemotherapy (ECT) combines the administration of bleomycin with temporary permeabilization induced by locally administered electric pulses. Preliminary experience with ECT in BC patients is encouraging. METHODS: A total of 125 patients with BC skin metastases who underwent ECT between 2010 and 2013 were enrolled onto a multicenter retrospective cohort study. The treatment was administered following the European Standard Operative Procedures of Electrochemotherapy. Tumor response was clinically assessed adapting the Response Evaluation Criteria in Solid Tumors, and toxicity was evaluated according to Common Terminology Criteria for Adverse Events 4.0. Cox regression analysis was used to identify predictive factors. RESULTS: Response was evaluable in 113 patients for 214 tumors (median 1 per patient, range 1-3). The overall response rate after 2 months was 90.2 %, while the complete response (CR) rate was 58.4 %. In multivariate analysis, small tumor size (P < 0.001), absence of visceral metastases (P = 0.001), estrogen receptor positivity (P = 0.016), and low Ki-67 index (P = 0.024) were significantly associated with CR. In the first 48 h, 10.4 % of patients reported severe skin pain. Dermatologic toxicity included grade 3 skin ulceration (8.0 %) and grade 2 skin hyperpigmentation (8.8 %). Tumor 1-year local progression-free survival was 86.2 % (95 % confidence interval 79.3-93.8) and 96.4 % (95 % confidence interval 91.6-100) in the subgroup of those with CR. CONCLUSIONS: In this study, small tumor size, absence of visceral metastases, estrogen receptor positivity, and low Ki-67 index were predictors of CR after ECT. Patients who experienced CR had durable local control. ECT represents a valuable skin-directed therapy for selected patients with BC.

Role and efficacy of intraoperative evaluation of resection adequacy in conservative breast surgery.

In the present study we considered the histology of 51 patients who have undergone breast conservative surgery and the related 54 re-excisions that were performed in the same surgical procedure or in delayed procedures, in order to evaluate the role of intraoperative re-excisions in completing tumor removal. In 13% of the cases the re excision obtained the resection of the target lesion. In this study, the occurrence of residual neoplastic lesions in intraoperative re-excisions (24%) is lower than in delayed re-excisions (62%; P = .03). The residual lesions that we could find with definitive histology of re excision specimens are related with lesions with ill defined profile. In 77% of the cases of re excision with tumoral residual the lesion was close to the new resection margin, thus the re-excisions couldn't achieve an adequate ablation of the neoplasm. Invasive or preinvasive nature of the main lesion resected for each case and the approach to the evaluation of the first resection specimen adequacy (surgical or radiological) don't affect the rate of tumoral residual in intraoperative re-excisions. In conclusion, our data are consistent with a low efficacy of intraoperative re excision in obtaining a complete removal of the tumor; intraoperative radiologic evaluation of the first resection specimen is however imperative in defining the effective removal of the target lesion.

Radiography of the surgical specimen in early stage breast lesions: diagnostic reliability in the analysis of the resection margins.

PURPOSE: The purpose of this study was to evaluate the diagnostic reliability of specimen radiography in the assessment of the status of resection margins in early stage breast lesions. MATERIALS AND METHODS: The study involved 123 consecutive patients who underwent breast-conserving surgery for early stage breast lesions. Specimen radiography in the two orthogonal views and with direct magnification was obtained in all cases to assess presence or absence of the lesion, position of the lesion within the surgical specimen and direction in which to extend the excision in cases of lesions located close to the margin. Diagnostic reliability was evaluated for only 102 patients with malignant lesions. RESULTS: Comparison between the radiological and histological diagnoses before immediate reexcision had 66% sensitivity, 86% specificity, 74% positive predictive value and 81% negative predictive value. Definitive histological assessment of margin status, including status after reexcision, was infiltrated margins in 23 patients (23%) and clear margins in 79 patients (77%). Definitive histological assessment in 12/19 patients (63.15%) with intraoperative reexcision, confirmed margin infiltration of the first specimen. Twenty patients (20%) underwent a second surgical procedure. CONCLUSIONS: Specimen radiography was reliable in identifying clear margins (74% positive predictive value) and reduced the rate of reintervention from 31% to 20%. Better results will be provided by digital mammographic equipment.

Lymphatic mapping in early stage breast cancer: comparison between periareolar and subdermal injection.

The combination of preoperative lymphatic mapping with intra-operative probe detection is becoming the standard procedure for identifying tumour lymphatic spread at the time of initial treatment in breast cancer. There are a number of identification techniques for sentinel lymph nodes, but the concordance of the results of a sentinel lymph node biopsy with axillary lymph node dissection did not vary significantly among them. Periareolar (p.a.) injection of tracer is a new procedure specifically studied to overcome some limitations of other techniques; in two groups of patients with early breast cancer we compared the periareolar with the subdermal technique. One hundred and fifty biopsy proven breast cancer patients were consecutively enrolled in this study. This population was divided into two groups: (1) group A, including 100 cancers; lymphatic mapping was performed by s.d. injection of both blue dye and radiotracer; and (2) group B, including 50 cancers; lymphatic mapping was performed with a combination of blue dye injected p.a. and radiotracer injected s.d. For group A, with both techniques we identified one or more SLNs in 100/100 tumours; blue dye detected the SLNs in 99/100 cancers (99%), lymphoscintigraphy in 93/100 cancers (93%). The concordance rate was 92%. For group B, with both techniques we identified one or more SLNs in 49/50 cancers (98%); blue dye detected the SLNs in 48/50, lymphoscintigraphy in 46/50 cancers (92%). The concordance rate was 92%. In the present study p.a. and s.d. injection of blue dye give similar and comparable results. The periareolar technique is simpler and has several advantages over the subdermal technique.

Sentinel node detection in breast carcinoma.

AIMS AND BACKGROUND: The standard procedure for the evaluation of axillary nodal involvement in patients with breast cancer is still complete lymph node dissection. However, about 70% of patients are found to be free of metastatic disease while axillary node dissection may cause significant morbidity. Lymphatic mapping and sentinel lymph node (SLN) biopsy are changing this situation. METHODS AND STUDY DESIGN: In a period of 18 months we studied 201 patients with breast cancer, excluding patients with palpable axillary nodes, tumors > 2.5 cm in diameter, multifocal or multicentric cancer, pregnant patients and patients over 80 years of age. Before surgery 99mTc-labeled colloid and vital blue dye were injected into the breast to identify the SLN. In lymph nodes dissected during surgery the metastatic status was examined by sections at reduced intervals. Only patients with SLNs that were histologically positive for metastases underwent axillary dissection. RESULTS: We localized one or more SLNs in 194 of 201 (96.5%) patients; when both techniques were utilized the success rate was 100%. Histologically, 21% of patient showed SLN metastases (7.8% micrometastases) and 68% of these had metastases also in other axillary nodes. None of the patients with negative SLNs developed metastases during follow-up. CONCLUSIONS: At present there is no definite evidence that negative SLN biopsy is invariably correlated with negative axillary status; however, our study and those of others demonstrate that SLN biopsy is an accurate method of axillary staging.

Sentinel lymph node and breast cancer staging: final results of the Turin Multicenter Study.

AIM OF THE STUDY: Validation of the sentinel node (SN) technique in breast cancer by means of lymphoscintigraphy. MATERIALS AND METHODS: From December 1996 to January 1999 102 T1-T2 breast carcinoma cases were recruited in Turin. 99mTc-human serum albumin colloids were injected subdermally the day before surgery (mean activity, 5.2 +/- 2.5 MBq). Scintigraphic imaging was performed after injection. After identification of the SN during surgery by a hand-held gamma probe, the SN was excised and sent for histologic examination. SN histology was compared with that of other axillary nodes. RESULTS: The SN detection rate was 86.3%; among 88 cases with an identified SN, 37 (42%) had axillary metastases; the SN was metastatic in 35 cases (sensitivity, 94.6%); in 51.3% of pN+ cases (19/37) the SN was the only metastatic site. In two of the 53 negative SNs, SN histology did not match with that of the remaining axilla (negative predictive value, 96.2%; staging accuracy, 97.7%). CONCLUSIONS: Our results agree with those reported in the literature; however, except in clinical trials and experienced structures axillary lymph node dissection should not be abandoned when mandatory for prognostic purposes, considering that at present SN biopsy alone is not completely accurate for axillary staging, especially in the absence of an adequate learning period.

Extended lymph node dissection for gastric cancer: results of a prospective, multi-centre analysis of morbidity and mortality in 118 consecutive cases.

This study reports interim data on post-operative morbidity, hospital mortality and duration of hospital stay of Italian patients undergoing extended lymph-node dissection combined with a pancreas-preserving technique for gastric cancer. Of the 218 patients admitted to one of eight general and/or university hospitals in North Italy, 118 were enrolled in the trial. Eligible patients presented with proven primary adenocarcinoma of the stomach without clinical evidence of distant, peritoneal and/or liver metastasis, or metastasis in para-aortic and retropancreatic nodes at intraoperative biopsy. Patients underwent the extended procedure as described by the Japanese Research Society for the Study of Gastric Cancer, following the Maruyama pancreas-preserving technique. A strict quality control system was used to ensure the performance of a standard surgical treatment. A surgeon of the reference centre (M.D.), who stayed at the National Cancer Center Hospital in Tokyo to learn the D2 technique from a specialist Japanese surgeon, became the trial supervisor and assisted each surgeon in all the Italian participating centres. The patients were staged according both to the TNM system and to the General Rules for the Gastric Cancer Study in Surgery and Pathology. Post-operative surgical complications developed in 21 patients (17.8%). The non-surgical complication rate was 2.5%. Reoperation was necessary in six patients (5%), all of whom survived. The 30-day mortality rate for the eligible group was 2.5%. The overall hospital mortality was the same. Total gastrectomy was associated with a slightly higher operative mortality (4.5% vs 1.3%). Only one patient died from an anastomotic leak. The rate of leakages was higher after total than after distal gastrectomy (15.9 vs 5.4%); the association of splenectomy and pancreatectomy worsened the morbidity rate. D2 lymphadenectomy with pancreas-preserving technique, when performed at experienced centres, seems a feasible and safe technique for the radical treatment of gastric cancer in selected Western patients.

Prognostic value of CEA and ferritin assay in breast cancer: a multivariate analysis.

The prognostic significance of preoperative serum carcinoembryonic antigen (CEA) and ferritin levels was evaluated in 191 women operated for breast cancer. The influence of CEA, ferritin and another 11 clinical and pathological features on the disease-free survival was investigated in a multivariate analysis, using Cox's proportional hazard model. Axillary node status (P = 0.004), CEA level (P = 0.011), and the histological grade of the tumor (P = 0.029) emerged as independent prognostic factors. By contrast, no significant relationship was found between ferritin and disease-free survival. These three parameters were used to derive a prognostic index (I) for each patient. Multivariate analysis showed that its prognostic value was better than the value of any single factor (P less than 0.0001). The I score was used to divide patients into groups at different risk of recurrence: low, moderate and high (97.5%, 45% and 22.5% of recurrence-free patients at 3 years respectively). The data showed that the prognosis of patients with different combinations of node status and tumor grade was related to the level of CEA. Only women with very good (node-negative with well-differentiated tumors) or very bad prognosis (node-positive with four or more metastatic nodes and poorly differentiated tumors) had a disease-free survival independent of CEA values. These findings suggest that the preoperative measurement of CEA enhances the possibility of correctly predicting outcome and hence could be of assistance in the planning of adjuvant therapies.

Pelvic and para-aortic lymph nodal positivity in the ovarian carcinoma: its prognostic significance.

Our study is based on 29 patients with ovarian carcinoma in early stage (IA-IIB) having undergone total abdominal hysterectomy, with bilateral salpingo-oophorectomy, omentectomy, appendectomy and pelvic and paraaortic lymphadenectomy selective and bioptic. Out of the 29 patients 11 were classified I stage and 18 II stage. Within 3 years, out of 10 patients with node metastases, 1 is alive and free of disease, 6 deceased from the tumor and 3 are alive with residual tumor at various stages of invasion. Out of the 19 patients without nodes metastases 14 are alive and free of disease, 4 deceased from the tumor and 1 is alive with residual carcinoma. Survival related to histological type shows no statistically significant differences. Grading III has a survival of 27.6%, while the other two grades have a survival of 70% without significant differences. We can affirm that lymph nodes metastases represent the most reliable marker of high risk patients among the 3 risk factors (grading, histotype and nodes metastases) even if considered on a limited number of patients on the basis of preliminary data so obtained.

The correlation between the spread of metastases by level in the axillary nodes and disease-free survival in breast cancer. A multifactorial analysis.

Axillary lymph nodes were separated from 492 radical or modified radical mastectomies for primary breast cancer and examined according to their anatomical level corresponding to their position along the theoretical pathway of lymph drainage from the breast. The patterns of metastasis and the relationship between metastatized levels and disease-free survival were investigated to see whether complete axillary dissection is necessary for the staging and the planning of adjuvant therapy in breast cancer. Progressive involvement from level I (proximal) to level III (distal) was found in 206 specimens (80.8% of tumors with axillary metastases), while discontinuous or "skip" metastases were present in 49 (19.2%), including 38 (14.9%) with positive nodes at level II or III but not at level I. "Skip" metastasis was more frequent when fewer than four nodes were positive, and not related to either the size of the primary tumor or its location. The effect of age, menopausal status, tumor size, node status, number of positive nodes, anatomic level of axillary node involvement, estrogen and progesterone receptors, and adjuvant therapies on disease-free survival was evaluated using a multivariate proportional hazard model and life table analysis. This showed that disease-free survival was strongly related to the number of positive nodes (P less than 0.001), tumor size (P = 0.001) and level of node involvement (P = 0.01) as independent prognostic factors. Moreover, the subset of patients with four or more positive nodes and involvements of level III had a higher risk of recurrence (25% recurrence-free patients 5 years after mastectomy). The high frequency of "skip" metastases and the prognostic value of both the level of involvement and the number of metastatic nodes suggest that a complete axillary dissection is needed in the surgical management of breast cancer to obtain all the data useful in the planning of adjuvant therapy.