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Breast metastasis originating from a primary lung tumor is exceedingly rare and can present challenges in distinguishing it from primary breast cancer. This case report discusses the management of a 64-year-old woman who initially presented with a nodule in her left breast. A biopsy revealed an infiltrating ductal carcinoma. Despite negative BRCA genetic testing, her significant family history of cancer and the presence of a newly detected right breast lesion led to a bilateral mastectomy. Post-operative imaging identified multiple hypodense nodules and a spiculated pulmonary nodule, necessitating further investigation. An endoscopic lung biopsy confirmed a primary pulmonary carcinoma with histological features similar to the breast carcinoma, suggesting the lung as the primary source. This case highlights the complexity of differentiating breast metastasis originating from a lung tumor and primary breast cancer. It underscores the importance of comprehensive diagnostic evaluations and the consideration of extramammary origins in metastatic cases. The findings emphasize the role of multidisciplinary teams in managing such rare and challenging cases and highlight the necessity for thorough and repeated assessments in atypical breast cancer presentations.

Locally advanced breast cancer (LABC) is a complex disease that requires a multidisciplinary approach. Neoadjuvant chemotherapy (NAC) is usually performed in order to achieve loco-regional radical resection; although its importance in the multidisciplinary approach to LABC is well recognized, a small number of patients show Progressive Disease (PD). No standard salvage treatment (ST) has been defined and different strategies can be adopted, such as second-line systemic therapies, radiation therapy, and surgery. Herein, a case of LABC in PD during NAC is reported with a literature review, with the aim of highlighting the importance of a tailored multidisciplinary treatment for each patient.

Oncoplastic breast-conserving surgery (OBCS) is increasingly used to treat breast cancer with the dual purpose of performing a radical oncological resection while minimizing the risk of post-operative deformities. The aim of the study was to evaluate the patient outcomes after Level II OBCS as regards oncological safety and patient satisfaction. Between 2015 and 2020, a cohort of 109 women consecutively underwent treatment for breast cancer with bilateral oncoplastic breast-conserving volume displacement surgery; patient satisfaction was measured with BREAST-Q questionnaire. The 5-year overall survival and disease-free survival were 97% (95%CI 92, 100) and 94% (95%CI 90, 99), respectively. In two patients (1.8%), mastectomy was finally performed due to margin involvement. The median patient-reported score for "satisfaction with breast" (BREAST-Q) was 74/100. Factors associated with a lower aesthetic satisfaction index included: location of tumour in central quadrant (p = 0.007); triple negative breast cancer (p = 0.045), and re-intervention (p = 0.044). OBCS represents a valid option in terms of oncological outcomes for patients otherwise candidate to more extensive breast conserving surgery; the high satisfaction index also suggests a superiority in terms of aesthetic outcomes., (© 2023. The Author(s).)

Background/aim: Clinicopathological features of patients undergoing margin enlargement after lumpectomy for early breast cancer with positive/close excision margins were analyzed in order to define whether a re-operative procedure could have been avoided. Furthermore, a standardized protocol of specimen orientation was adopted in order to optimize both the widening procedure as well as the oncologic outcome., Patients and Methods: A retrospective analysis was performed including pre-, peri-, and post-operative parameters, and a predictive score by means of a multivariate model was developed using all clinically and statistically significant variables associated with residual disease (RD)., Results: RD was significantly related to positive tumor margins, hormone receptor negative, HER2-positive, and tumors with high Ki67 proliferation index (p<0.001); the corresponding contribution to the prognostic score was as follows: close margins, 3 points; hormone receptor positive disease, 2 points; low Ki67, 2 points; HER2 negativity, 1 point. In 102 patients with a score >3, only 2 patients (2.0%) had RD, while in 81 patients with a score ≤3, 55 patients (67.9%) had RD (p<0.001)., Conclusion: This predictive model might aid in clinical-decision making of patients with positive margins who actually require a widening procedure after intraoperative and/or definitive histology., (Copyright© 2022, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Competing Interests: None

Background/aim: The perspective validation of a selective approach in patients undergoing breast cancer surgery was performed in order to assess whether patients as well as Health Care Workers (HCWs) were exposed to any undue risk of COVD-19 infection., Patients and Methods: From March 9 th to June 9 th 2020, 207 patients were phone-triaged by a dedicated Breast Care Nurse; a patient-tailored program was adopted with the aim of avoiding hospitalization of SARS-CoV-2 symptomatic patients, with a careful prioritization of surgical procedures according to specific disease features., Results: Two hundred and three out of 207 patients underwent operation; seven patients were temporarily excluded because they tested positive at phone triage (n=3), or in-hospital triage (n=3); another asymptomatic patient with negative NP swab tested IgM Ab-positive so that surgery was re-scheduled two weeks later. Four patients had no surgery; one of them was reconsidered for neoadjuvant chemotherapy (NAC) after testing positive at phone triage; three patients were excluded because they were already hospitalized for COVID-19. Overall, mean in-hospital stay was 2.2 days (±SD, 0.7) and, after hospital discharge, no patient required readmission., Conclusion: This preventive program avoided any COVID-19 infection among patients and HCWs, so that an elective breast cancer surgical procedure can be safely and timely pursued without affecting the oncologic outcome., (Copyright© 2021, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background: COVID-19 pandemic required a marked re-allocation of healthcare resources, including at Breast Units. A patient-tailored program was developed to assess its efficacy regarding prevention of COVID-19 infection among patients with breast cancer undergoing surgery and healthcare workers (HCWs)., Patients and Methods: From March 9th to April 9th 2020, 91 patients were selected for elective surgery by means of: i) Pre-hospital screening aimed at avoiding hospitalization of symptomatic or suspicious COVID-19 patients, and ii) prioritisation of surgical procedure according to specific disease features., Results: Eighty-five patients (93.4%) were fit for surgery, while five patients (5.5%) were temporarily excluded through 'telephone triage'; another two patients were excluded at in-hospital triage. A total of 71 out of 85 patients (83.5%) were diagnosed with invasive cancer, most of whom were undergoing breast-conserving surgery (61 out of 85 patients, 71.8%). The mean in-hospital stay was 2.2 days (SD=0.7 days). After hospital discharge, no patient needed re-admission due to post-operative complications; moreover, no COVID-19 infection among patients or HCWs was detected., Conclusion: Safe breast cancer surgery was accomplished for both patients and HCWs by means of a careful preoperative selection of patients and in-hospital preventative measures. This screening program can be transferred to high-volume Breast Units and it may be useful in implementing European Community recommendations for prevention of COVID-19 infection., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: A retrospective study was performed in 246 breast cancer patients to define whether tumor-to-nipple distance (TND) assessment by breast MRI may select patients eligible to nipple-sparing mastectomy (NSM) as compared to permanent section assessment of retroareolar margin., Patients and Methods: Pre- and post-operative parameters including imaging data, histology of the primary tumor, biologic prognostic factors, and adjuvant regimens were retrieved; patients with close/positive retroareolar margins underwent nipple or NAC excision. The primary endpoint was loco-regional recurrence (LRR)., Results: Patients with TND ≤2 cm had a significantly higher rate of invasive ductal carcinoma (p<0.003) and excision margins less than 2 mm (p<0.000). Eleven retroareolar specimens were positive at definitive pathology; final re-excision specimen examination showed residual disease in seven patients (63.6%). At a median follow-up of 31 to 33 months, no NAC recurrence did occur; disease-free survival was more than 96%, and LRR was homogeneously distributed among TND subgroups., Conclusion: Therapeutic NSM is a safe procedure independently of TND assessed at preoperative breast MRI. Permanent section assessment of retroareolar tissue is more accurate and cost-effective than frozen section. Furthermore, delayed nipple and/or NAC excision did not impair local disease control., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: The histopathological assessment of the B5c category may sometimes be hampered by simple artifacts that may lead to over- or underestimation of that particular breast cancer so that its management is still controversial, especially with regard to the decision to proceed immediately to sentinel lymph node (SLN) biopsy. Hence, a retrospective study was performed in 174 patients undergoing breast-conserving surgery with a preoperative diagnosis of B5c in order to assess the usefulness of axillary node staging by means of SLN biopsy., Patients and Methods: Pre- and post-operative parameters including imaging data, histology of the primary tumor and SLN biopsy, biological prognostic factors, type of operation, and adjuvant regimens were computed., Results: Invasive carcinoma and carcinoma in situ were diagnosed in 46 (26.5%) and 128 patients (73.5%), respectively. Preoperative tumor size was significantly related to post-operative diagnosis of invasive carcinoma (p=0.020), retaining its predictive value at logistic regression analysis (p=0.046). Post-operative predictive factors of invasion were represented by tumor stage (p=0.008) and grading (p=0.008)., Conclusion: B5c preoperative diagnosis in patients undergoing breast conservative surgery would suggest an immediate wide local excision avoiding any further preoperative histologic assessment. Conversely, one-stage SLN biopsy might be suggested for patients eligible to mastectomy, similar to patients with carcinoma in situ, although its impact on the therapeutic and prognostic assessment seems negligible., (Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Background/aim: A retrospective analysis of 388 patients with pure ductal carcinoma in situ (DCIS) was performed in order to test the correlation of clearance margin of resection and other host-, tumor- and treatment-related factors with ipsilateral breast tumor recurrence (IBTR)., Materials and Methods: The pathological analysis was performed according to a standardized protocol: positive margins had DCIS at the inked margin; close margins had tumor between 0.1 to 0.9 mm, or 1 to 1.9 mm, and negative margins were ≥2 mm., Results: At a median follow-up of 90 months there were 26 IBTR (10 invasive and 16 DCIS). Both in univariate and multivariate analysis a significant difference was observed in IBTR by comparing positive versus close/negative margins of excision (p=0.05) and the number of re-operations (p=0.000). Moreover, the actuarial IBTR rates were significantly different in patients with a positive compared to close/negative margins (log-rank test, p=0.042) while the stratification by the margin width (0.1-0.9 mm; 1.0-1.9 mm; ≥2 mm) was not significant (log-rank test, p=0.243)., Conclusion: The policy of "no ink on the tumor" can be translated from invasive to DCIS, because the actuarial IBTR rates were significantly different only in patients with a positive, compared to close/negative margins., (Copyright© 2019, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objective: A prospective observational clinical study was undertaken to assess the accuracy of preoperative Axillary Ultrasound (AUS) plus Fine-Needle Aspiration Cytology (FNAC) as well as and its clinical utility, that is the capacity of the information supplied by the test to guide the clinical decision-making., Materials and Methods: from January 2013 to August 2015, 400 female patients with pT1-3 cN0 operable breast cancer underwent AUS with FNAC at the Breast Unit of the "IRCCS San Martino-IST" in Genoa (Italy)., Results: 127 out of 400 patients (31.7%) had axillary lymph node metastases; in 69 out of 127 node-positive patients (54.3%) AUS detected at least one abnormal lymph node, and in 56 out of 127 patients (44.1%) the abnormal sonographic pattern of the lymph node was coupled with a positive FNAC finding. No false-positive finding by both AUS-alone or combined AUS/FNAC was observed. AUS-alone had sensitivity of 54.3% (69/127), specificity of 100% (273/273), PPV of 100% (69/69), NPV of 82.5% (273/331), and accuracy of 85.5% (342/400). Combined AUS/FNAC had sensitivity of 44.1% (56/127), specificity of 100% (273/273), PPV of 100% (56/56), NPV of 79.4% (273/344), and accuracy of 82.2% (329/400)., Conclusions: AUS-alone or combined AUS/FNAC had a high accuracy rate coupled with a more than satisfactory efficiency due to their low costs and easy access for the preoperative staging of the axilla. Notably, AUS-alone might be suggested for the preoperative staging of patients with early stage breast cancer because FNAC did not increased the specificity but reduced the sensitivity of the technique. Patients with negative findings might undergo either SLNB or close observation while waiting for the definitive results of ongoing SOUND randomized clinical trial., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Background: Fine-needle aspiration cytology (FNAC) is a simple and reliable technique to assess breast lesions, although a definitive differential diagnosis (benignity vs. cancer) is achieved approximately in 60-70% of cases because an inadequate (C1), atypical (C3) or suspicious (C4) category is otherwise reported., Patients and Methods: A retrospective analysis of 763 cases with C3 or C4 reports was performed to define their positive predictive value (PPV), as well as the practical implications of clinical and imaging findings as for clinical decision-making. FNACs were collected from January 2003 to September 2012 at the Breast Unit of IRCCS "A.O.U. San Martino-IST" Genoa, with each being received later to definitive histology. The PPV for cancer of C3/C4 categories were computed to measure the accuracy of FNAC; moreover, the PPV was also stratified according to clinical, mammography and sonography data alone or by their combination., Results: The PPV of C3 and C4 was 21.1% (80/380) and 84.1 % (322/383), respectively. Within each C3/C4 category, a significant direct correlation (p<0.001) between the suspicion index of clinical, mammography and sonography data and cancer detection rate was always observed. The PPV of C3/C4 stratified by the combination of clinical and imaging findings showed satisfactory values in the C3 category only when there was an agreement between clinical and imaging findings, whereas the PPV of the C4 category was always remarkably high (ranging from 92.3% to 100%)., Conclusion: the diagnostic work-up in C4 reports or in patients with a C3 report but with an high suspicion index at clinical or imaging examination should be preferably implemented by means of a core biopsy to optimize the therapeutic planning; given a C3 report with dubious clinical and/or imaging findings, an excisional biopsy (or in alternative vacuum-assisted breast biopsy with complete removal of the nodule) should be preferably performed in order to reach a definitive histological dia gnosis with no further delay., (Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.)

Patient-related, tumor-related, and sentinel node (SN)-related factors have been identified with the aim of predicting non-SN status in patients with SN micrometastases. According to our previous experience, primary tumor size (p=0.005) and the presence of lymphovascular invasion (LVI) (p=0.000) significantly predicted non-SN status in patients with SN micrometastasis; moreover, non-SN metastases were never detected in patients with pT1a-1b, G1, and no LVI. A prospective assessment was undertaken in a validation set of 126 patients to confirm these findings. Univariate analysis indicated that primary tumor size (p=0.05), Scarff-Bloom-Richardson (SBR) grade (p=0.008), LVI (p=0.001), and the number of mitoses/mm(2) (p=0.01) were significant predictors of non-SN status. By logistic regression analysis, tumor size (p=0.03), LVI (p=0.001), grade (p=0.003) and the number of mitoses/mm(2) (p=0.01) were the only variables remaining in the model. Three subsets of patients were identified: i) 18.3% of patients (pT1, G1, and no LVI) had tumor-negative non-SN (no risk group); ii) 37.3% of patients (number of mitoses/mm(2) <10, SBR grade II-III) had a rate of tumor-positive non-SN <15% (intermediate risk); iii) 44.4% of patients had a mean rate of non-SN involvement of 46% (high risk). By these parameters, more than 50% of patients could be selectively spared unnecessary axillary lymph node dissection without staging or therapeutic benefit, especially in patients with well-differentiated pT1 tumors without LVI.

Background: Sentinel lymph node (SLN) staging is currently used to avoid complete axillary dissection in breast cancer patients with negative SLNs. Evidence of a similar efficacy, in terms of survival and regional control, of this strategy as compared with axillary resection is based on few clinical trials. In 1998, we started a randomized study comparing the two strategies, and we present here its results., Materials and Methods: Patients were randomly assigned to sentinel lymph node biopsy (SLNB) and axillary dissection [axillary lymph node dissection (ALND arm)] or to SLNB plus axillary resection if SLNs contained metastases (SLNB arm). Main end points were overall survival (OS) and axillary recurrence., Results: One hundred and fifteen patients were assigned to the ALND arm and 110 to the SLNB arm. A positive SLN was found in 27 patients in the ALND arm and in 31 in the SLNB arm. Overall accuracy of SLNB was 93.0%. Sensitivity and negative predictive values were 77.1% and 91.1%, respectively. At a median follow-up of 5.5 years, no axillary recurrence was observed in the SLNB arm. OS and event-free survival were not statistically different between the two arms., Conclusions: The SLNB procedure does not appear inferior to conventional ALND for the subset of patients here considered.

Aim: To identify by means of clinical and histopathological features a subset of breast cancer patients with sentinel lymph-node (sN) micrometastases and metastatic disease confined only to the sN in order to spare them an unnecessary axillary lymph node dissection (ALND)., Materials and Methods: From January 1998 to December 2004, 116 patients with sN micrometastases underwent standard ALND for early-stage (T1-2 N0 M0) invasive breast cancer; clinical and histopathologic parameters were prospectively collected and evaluated by means of univariate and logistic regression analysis in order to identify which patients with sN micrometastases were free of metastasis in axillary non-sN., Results: Sixteen of 116 patients with sN micrometastases had tumour involvement of non-sN, with six and 10 patients having non-sN micrometastases and macrometastases, respectively. None of 19 patients with primary tumour measuring

Background and Objectives: Literature review suggests that the sentinel lymph node (sN) represents a reliable predictor of axillary lymph node status in breast cancer patients; however, some important issues, such as the optimisation of the technique for the intraoperative identification of the sN, the role of intraoperative frozen section examination of the sN, and the clinical implications of sN metastasis as regards the surgical management of the axilla, still require further confirmation. The authors aimed (1) to assess the feasibility of sN identification with a combined approach (vital blue dye lymphatic mapping and radioguided surgery, RGS) and the specific contribution of either techniques to the detection of the sN, (2) to determine the accuracy and usefulness of intraoperative frozen section examination of the sN in order to perform a one-stage surgical procedure, and (3) to define how the sN might modulate the therapeutic planning in different stages of disease., Materials and Methods: From October 1997 to June 2001, 334 patients with early-stage (T(1-2) N(0) M(0)) invasive mammary carcinoma underwent sN biopsy; the average age of patients was 61.5 years (range, 39-75 years). In a subset of 153 patients, both vital blue dye (Patent Blue-V) lymphatic mapping and RGS were used to identify the sN, and the relative contribution of each of the two techniques was assessed., Results: In the whole group, the sN was identified in 326 of 334 patients (97.6%), and 105 of 326 patients (37.3%) had positive axillary lymph nodes (pN+). In 9 of 105 pN+ patients, the definitive histologic examination of the sN did not show metastases but these were detected in non-sN, thus giving an 8.6% false-negative rate, a negative predictive value of 94.5% (156/165), and an accuracy of 96.5% (252/261). As regards the specific contribution of the two different techniques used in the identification of the sN, the detection rate was 73.8% (113/153) with Patent Blue-V alone, 94.1% (144/153) with RGS alone, and 98.7% (151/153) with Patent Blue-V combined with RGS (P < 0.001). Noteworthy, whenever the sN was identified, the prediction of axillary lymph node status was remarkably similar (93-95% sensitivity; 100% specificity; 95-97% negative predictive value, and 97-98% accuracy) whichever of the three procedures was adopted (Patent Blue-V alone, RGS alone, or combined Patent Blue-V and RGS). Intraoperative frozen section examination was performed in 261 patients, who had at least one sN identified, out of 267 patients who underwent complete axillary dissection; 170 patients had histologically negative sN (i.o. sN-) and 91 patients histologically positive sN (i.o. sN+). All 91 i.o. sN+ were confirmed by definitive histology, whereas in 14 of 170 i.o. sN- patients (8.2%) metastases were detected at definitive histology. As regards the correlation between the size of sN metastasis, the primary tumour size, and the status of non-sN in the axilla, micrometastases were detected at final histology in 23 patients and macrometastases in 82 patients. When only micrometastases were detected, the sN was the exclusive site of nodal metastasis in 20 of 23 patients (86.9%) while in 3 patients with tumour size larger than 10 mm micrometastases were detected also in non-sN. Macrometastases were never detected in pT(1a) breast cancer patients; the sN was the exclusive site of these metastases in 30 patients (36.6%), while in 52 patients (63.4%) there were metastases both in sN and non-sN., Conclusions: Sentinel lymphadenectomy can better be accomplished when both procedures (lymphatic mapping with vital blue dye and RGS) are used, because of the significantly higher sN detection rate, although the prediction of axillary lymph node status remains remarkably similar whichever method is used. The intraoperative frozen section examination proved to be rather accurate in predicting the actual pathologic status of the sN, with a negative predictive value of 91.8%; in 35% of patients it allowed sN biopsy and axillary dissection to be performed in a one-stage surgical procedure. Finally, specific clinical and histopathologic features of the primary tumour and sN might be used to tailor the loco-regional and systemic treatment in different clinical settings, such as in ductal carcinoma in-situ (DCIS), early-stage invasive breast cancer, and patients with large breast cancer undergoing neo-adjuvant CT for breast-saving surgery as well as elderly patients with operable breast cancer.

The concept of sentinel lymph node biopsy in breast cancer surgery relates to the fact that the tumor drains in a logical way via the lymphatic system, from the first to upper levels. Therefore, (1) the first lymph node met (the sentinel node) will most likely be the first one affected by metastasis, and (2) a negative sentinel node makes it highly unlikely that other nodes are affected. Sentinel lymph node biopsy would represent a significant advantage as a mini-invasive procedure, considering that, after operation, about 70% of patients are found to be free from metastatic disease, yet axillary node dissection can lead to significant morbidity. Although the pattern of lymphatic drainage from a breast cancer can be very variable, the mammary gland and the overlying skin can be considered as a biologic unit in which lymphatics tend to follow the vasculature. Considering that tumor lymphatics are disorganized and relatively ineffective, subdermal, and peritumoral injection of small aliquots of radiotracer is preferred to intratumoral administration. (99m)Tc-labeled colloids with most of the particles in the 100-200 nm size range would be ideal for radioguided sentinel node biopsy in breast cancer. Lymphoscintigraphy is an essential part of radioguided sentinel lymph node biopsy, as images are used to direct the surgeon to the site of the node. The sentinel lymph node should have a significantly higher count than background. After removal of the sentinel node, the axilla must be re-examined to ensure all radioactive sites are identified and removed for analysis. The success rate of radioguidance in localizing the sentinel lymph node in breast cancer surgery is about 94-97% in Institutions where a high number of procedures are performed, approaching 99% when combined with the vital blue dye technique. At present, there is no definite evidence that a negative sentinel lymph node biopsy is invariably correlated with a negative axillary status, except perhaps for T(1a-b) breast cancers, with size < or =1 cm. Randomized clinical trials should elucidate the impact of avoiding axillary node dissection in patients with a negative sentinel lymph node on the long-term clinical outcome of patients., (Copyright 2004 Wiley-Liss, Inc.)

Background and Objectives: Recent studies have demonstrated that the sentinel lymph node (sN) can be considered a reliable predictor of axillary lymph node status in breast cancer patients. However, some important issues, such as optimization of the technique for the intraoperative identification of the sN, and the clinical implications of sN metastasis as regards the surgical management of the axilla still require further elucidation. The objectives of this study was to assess (1) the feasibility of sN identification with a combined approach (vital blue dye lymphatic mapping and radioguided surgery, RGS) and the specific contribution of either techniques to the detection of the sN, and (2) the correlation between the size of sN metastasis (micrometastasis < or = 2 mm; macrometastasis > 2), primary tumour size, and the status of nonsentinel nodes (nsN) in the axilla., Methods: Between October of 1997 and December of 1999, 212 patients with breast cancer (average age: 61 years; range, 40-79 years) underwent sN biopsy before performing standard axillary dissection. In a subset of 153 patients, both vital blue dye (Patent Blue-V) lymphatic mapping and RGS were used to identify the sN, and the relative contribution of each of the two techniques was assessed., Results: Overall, the sN was identified in 206 of 212 patients (97.1%); at histologic examination of all dissected nodes, 77 of 206 patients had positive nodes (37.3%). The false-negative rate was 6.5% (5/77), the negative predictive value was 96.3% (129/134), and accuracy was 97.6% (201/206). Among 72 patients with positive sN, micrometastases were detected in 21 cases and macrometastases in 51. When micrometastases only were observed, the sN was the exclusive site of nodal metastasis in 17 of 21 cases (80.9%); in the remaining 4 cases (19.1%), nsN metastases were detected in 3 of 14 pT1c patients (21.5%), and 1 of 5 pT2 patients (20%). Macrometastases were detected in patients with tumors classified as pT1b or larger: the sN was the exclusive site of metastasis in 3 of 4 pT1b patients (75%), in 14 of 29 pT1c patients (48.2%), and in 3 of 18 pT2 patients (16.6%). The specific contribution of the two different techniques used in the identification of the sN was evaluated; the detection rate was 73.8% (113 of 153) with Patent Blue-V alone, 94.1% (144 of 153) with RGS alone, and 98.7% (151 of 153) with Patent Blue-V combined with RGS (P < 0.001). Noteworthy, whenever the sN was identified, the prediction of axillary lymph node status was remarkably similar (93-95% sensitivity; 100% specificity; 95-97% negative predictive value, and 97-98% accuracy) with each of the three procedures (Patent Blue-V alone, RGS alone, or combined Patent Blue-V and RGS)., Conclusions: Sentinel lymphadenectomy can better be accomplished when both procedures (lymphatic mapping with vital blue dye and RGS) are used, due to the significantly higher sN detection rate, although the prediction of axillary lymph node status remains remarkably similar with each one of the methods assessed. That patients with small tumours (<1 cm) and sN micrometastasis are very unlikely to harbour metastasis in nsN should be considered when planning randomised clinical trials aimed at defining the effectiveness of sN guided-axillary dissection., (Copyright 2001 Wiley-Liss, Inc.)

Several studies have been published describing the techniques of identification of the "sentinel lymph node" (SN). There are marked differences in the techniques used by different investigators. Although agreement exists about the tracer particle size and the volume of injection, it is unknown what is the best site where to inject the tracer or the vital dye. The aim of the present study was to define the influence of different sites of injection on imaging of the lymphatic ducts and their SNs. We performed a pilot study in 30 consecutive patients with breast cancer who underwent SN biopsy by means of radioguided surgery and vital blue dye mapping. The patients were divided into six groups of five patients each; each patient was given a subdermal (ID) or peritumoral (IP) injection of radiotracer (300 microCi in 150 mL of 99mTc-HSA microcolloids; Albures, Amersham Sorin) above the tumor site in order to localize the SN. After the identification of the SN, a second injection of radiotracer was performed, which was different in each patient subset. In some cases more than one lymph node appeared on the lymphoscintigraphic scans after the second injection of radiotracer. When the peritumoral route was used it took longer to visualize the lymphatic pathways. For the ID route, injection at the exact skin projection over the tumor is optimal. Internal mammary lymph nodes were identified by both IP (2) and ID (1) injection, irrespective of the quadrant in which the tracer was injected. Our findings support the hypothesis of a precise topographic correspondence between the primary tumor and its specific SN. The subdermal route is more accurate than the intraparenchymal route, as it allows faster identification of the lymphatic vessels and SN. We believe these observations should be taken into account for the proper selection of the injection site of either vital dye or radiopharmaceuticals.

Axillary lymph node status represents the most important prognostic factor in patients with operable breast cancer. A severe limitation of this technique is the relatively high rate of false negative sentinel lymph nodes (>5%). We studied 284 patients suffering from breast cancer; 264 had T1 tumors (16 T1a, 37 T1b and 211 T1c), while 20 had T2 tumors. All patients underwent lymphoscintigraphy 18-h before surgery. At surgery, 0.5 mL of patent blue violet was injected subdermally, and the sentinel lymph node (SN) was searched by gamma probe and by the dye method. The surgically isolated SN was processed for intraoperative and delayed examinations. The SN was successfully identified by the combined radioisotopic procedure and patent blue dye technique in 278/284 cases (97.9%). Analysis of the predictive value of the SN in relation to the status of the axillary lymph nodes was limited to 191 patients undergoing standard axillary dissection irrespective of the SN status. Overall, 63/191 (33%) identified SNs were metastatic, the SN alone being involved in 37/63 (58.7%) patients; a positive axillary status with negative SN was found in 10/73 (13.7%) patients with metastatic involvement. In T1a-T1b patients the SN turned out to be metastatic in 9/53 patients (17.0%). In 7/9 patients the SN was the only site of metastasis, while in 2/9 patients other axillary lymph nodes were found to be metastatic in addition to the SN. None of the 44 patients in whom the SN proved to be non-metastatic showed any metastatic involvement of other axillary lymph nodes. Our results demonstrate a good predictive value of SN biopsy in patients with breast cancer; the predictive value was excellent in those subjects with nodules smaller than 1 cm.

The purpose of the present work was two-fold: 1) to evaluate the predictive value of the sentinel lymph node (sLN) versus the axillary-node status in patients with T1-T2 breast cancer, and 2) to form an experimental basis for a randomized trial in which one group of patients with non-metastatic sLN will not have axillary dissection. Of a group of 284 patients considered for this analysis, 264 had a T1 cancer (16 T1a, 37 T1b and 211 T1c), while 20 had a T2 cancer; 243 patients were in clinical stage N0 and 41 were N1. All patients underwent lymphoscintigraphy 18 hr before surgery: 10 MBq in 0.15 mL of 99mTc-human albumin nanocolloids (particle size between 50-80 nm) was injected subdermally at the cutaneous projection of the tumor. Static gamma-camera images were acquired every 10-15 minutes until scintigraphic identification of the sLN. At surgery, 1-2 mL of Patent-Blue Violet was injected subdermally, and the sLN was searched by gamma-probe and by the dye method. The surgically isolated sLN was processed for intraoperative Hematoxylin & Eosin (H&E) histology, then for delayed histological and immunohistochemical examinations. The sLN was successfully identified by the combined radioisotopic procedure and Patent-Blue dye technique in 278/284 cases (97.9%). The Patent-Blue dye technique alone identified fewer sLNs than the radioisotopic procedure alone (56.3% versus 97.2%). Analysis of the predictive value of the sLN as to the status of axillary lymph nodes was limited to 197 patients undergoing standard axillary dissection irrespective of the sLN status. Overall, 63/191 (33%) identified sLNs were metastatic, the sLN alone being involved in 37/63 (58.7%) patients; a positive axilla status with negative sLN was found in 10/73 patients with metastatic involvement (13.7% false-negative rate). In conclusion, subdermal lymphoscintigraphy was confirmed to be an effective technique for sLN mapping; the addition of Patent-Blue dye minimally improved intra-surgical identification of the sLN. There was a high, but not absolute, correlation between a negative sLN and a negative axilla.

Background and Objective: We performed a pilot study on 30 consecutive patients undergoing sentinel node (sN) biopsy by radioguided surgery and vital blue dye mapping to determine whether there is a single sN for each breast independent of tumor site or an sN specifically related to the site of the breast neoplasm., Methods: There were 6 groups of 5 patients; each patient had a subdermal injection of radiotracer on the tumor site plus a second injection of radiotracer that was changed in every subset of patients to test whether modifying the site or the route of injection could have impaired the proper detection of the sN., Results: "False" sN were detected only in patients who had a second injection of radiotracer away from the tumor site; this occurred in 2 of 5 patients (40%) in group I, in 3 of 5 patients (60%) in group II, in all patients in group III, and in 3 of 5 patients (60%) in group IV. The different route of injection (peritumoral or subdermal) always on the tumor site that was tested in groups V and VI did not impair the proper detection of the sN., Conclusions: Our findings support the hypothesis of a precise topographic correspondence between the primary tumor and its specific sN more than the existence of a first sN in the axillary basin, which indiscriminately drains all quadrants of the breast, like "a neck of a bottle." This should be considered for the proper selection of the injection site of either vital blue dye or radiopharmaceuticals., (Copyright 2000 Wiley-Liss, Inc.)

Background and Objectives: Axillary lymph node status is the most important prognostic factor in patients with operable breast cancer. Recent studies have demonstrated the possibility of identifying the sentinel lymph node (sN) as a reliable predictor of axillary lymph node status in both cutaneous melanoma and breast cancer. Sentinel lymph node identification proved feasible by either peritumoral dye injection (Patent Blue-V) or radiodetection, with identification rates of 65-97% and 92-98%, respectively. However, some important issues need further definition, namely (a) optimization of the technique for intraoperative detection of the sN, (b) predictive value of the sN with regard to axillary lymph node status, and (c) reliability of intraoperative histology of the sN. We reviewed our experience in sN detection in patients with stage I-II breast cancer to assess the feasibility and accuracy of lymphatic mapping, by vital blue dye or radioguided surgery, and sN histology as a predictor of axillary lymph node status., Methods: Two groups of patients (55 and 48) were recruited between May 1996 and May 1997 and between October 1997 and February 1998; the patients of the first series underwent vital blue dye lymphatic mapping only, whereas those of the second series had a combined approach with both vital blue dye mapping and radioguided detection of the sN., Results: In the first set of patients, the sN was identified in 36/55 patients (65.4%); sN histology predicted axillary lymph node status with a 77% sensitivity (10/13), a 100% specificity (23/23), an 88.5% negative predictive value (23/26), and an overall 91.5% accuracy (33/36). The sN was the quasi-elective site of lymph node metastases because in clinically N0 patients nodal involvement was 20-fold more likely at histology in sN than in non-sN (30% and 1.5%, respectively). In the second set of patients, 49 lymphadenectomies were performed because 1 patient had bilateral breast cancer; the sN was identified in 45/49 lymphadenectomies (92%). The sN was intraoperatively negative at frozen-section examination in 33 cases, and final histology confirmed the absence of metastases in 31/33 cases (94%), whereas in 2 cases (6%) micrometastases only were detected. Final histology of the sN predicted axillary lymph node status with an 87.5% sensitivity (14/16), a 100% specificity (29/29), a 93.5% negative predictive value (29/31), and an overall 95.5% accuracy (43/45)., Conclusions: Sentinel lymphadenectomy can be better accomplished when both mapping techniques (vital blue dye and radioguided surgery) are used. In this group of patients, agreement of intraoperative histology of the sN with the final diagnosis was 94%, and sN histology accurately predicted axillary lymph node status in 43/45 lymphadenectomy specimens (95.5%) in which an sN was identified., (Copyright 2000 Wiley-Liss, Inc.)

Recent studies have demonstrated the possibility of identifying the sentinel lymph node (sN) as a reliable predictor of axillary lymph node status in both cutaneous melanoma and breast cancer. However, some important issues need further definition: (1) optimization of the technique for intraoperative detection of the sN; (2) predictive value of the sN as regards axillary lymph node status, and (3) reliability of intraoperative histology of the sN. We report our experience in sN mapping in patients with Stage I-II breast cancer, with the aim of assessing: (1) the feasibility of lymphatic mapping with a combined approach (vital blue dye lymphatic mapping and radioguided surgery); (2) the agreement of the intraoperative histologic examination of the sN, by means of hematoxylin and eosin staining with final histology, and (3) the accuracy of sN histology as a predictor of axillary lymph node status.

Aims: Clinical records of patients undergoing surgery for breast cancer were reviewed in order to evaluate the prognostic role of lymph-node level involvement., Methods: From 1982 to 1991, 1143 patients had radical mastectomy or conservative surgery with total axillary dissection: 461 patients of mean age 57.1 years (range: 25-89 years) were lymph-node positive (pN1); 369 patients (80%) had radical mastectomy; and 92 patients (20%) had conservative treatment plus post-operative radiotherapy, with the same mean number (n = 16) of lymph nodes collected in the surgical specimen. Data were analysed for the number of positive lymph nodes and level of involvement., Results: Level I, Levels I + II and Levels I + II + III were involved in 44.9, 18 and 21.4% of patients, respectively; 'skip metastases' occurred in 72 of 461 pN1 patients (15.5%). A univariate analysis showed that prognosis was directly related to the number of levels involved (P < 0.001), and skip metastases had the same prognostic role as Level I involvement. The numbers of involved lymph-node levels and metastatic lymph nodes were well correlated; multivariate analysis showed that involvement of Levels I and III was independently correlated with prognosis. After adjustment for age and number of positive lymph nodes, the number of involved lymph-node levels was an independent prognostic factor, with highest predictability when all three lymph-node levels were positive (P = 0.009)., Conclusions: The prognostic value of lymph-node status should be defined not only by the number of metastatic lymph nodes, but also by the number of levels of involvement.

From 1981 to 1990, 1003 stage I-II breast cancers underwent surgery at the Division of Surgical Oncology of National Institute for Cancer Research of Genoa. This study described the clinical and pathologic features of these breast cancers. Radical mastectomy was performed in 73.8% of cases and conservative surgery in 26.2% of cases. In the last years the number of conservative treatment has increased. Related to size of tumour, in 1991 80.4% of pT1 performed a conservative surgery. The choice of type of surgery for pT2 tumours depended on the choice of patient and the ratio breast size and tumour size. The five-year overall survival was 85.8% in the group of conservative surgery and 65.3% in the group of radical surgery. The overall survival and relapse free survival have been calculated by Kaplan-Meyer method. Actuarial survival curves were computed according to type of surgery, tumor size, nodal status, hormonal receptors. In our experience the size of tumour was an important prognostic factor. The five years, overall survival was 80.7% in pT1 tumours and 67% in pT2-pT3 tumours (p = 10(-6)). The five-year overall survival in negative nodes patients was 80.5%. Conversely in patients with more than ten nodal metastases was 29.5%. The data reported in the present study were no different as in previous studies.

From May 1985 to June 1992, 375 patients were enrolled in a prospective controlled randomized clinical trial of peri-operative adjuvant chemotherapy (PAC) associated with long-term adjuvant chemo-endocrinotherapy in order to test the effectiveness of reducing the time interval between surgery and chemotherapy. The short-term surgical complications related to PAC are reported in order to verify whether such treatment might negatively affect the results of breast cancer surgery. One hundred and eighty-nine patients were randomly assigned to the peri-operative treatment, and 186 to the control group. Patients undergoing PAC received one course of cyclophosphamide (600 mg/sqm), epidoxorubicin (60 mg/ sqm), and 5-fluorouracil (600 mg/sqm) (CEF) within 48-72 h following surgery. Pathologically node-positive (N+) patients, who were given peri-operative CEF, had five further cycles of CEF alternated with six cycles of CMF (cyclophosphamide 600 mg/sqm, methotrexate 40 mg/sqm, and 5-fluorouracil 600 mg/sqm). All the other N+ patients received six cycles of CEF alternated with six cycles of CMF, starting within 30 days of surgery. No significant difference in post-operative morbidity was observed as regards median hospital stay (8 days), number of outpatient dressings (3.5 vs 3), seroma (51 (26.9%) vs 45 (24.2%)), lymphatic drainage (400 ml vs 409 ml), and post-operative infections, both local (10 vs 9) and in extraoperative foci (6 vs 7), in the study and control group, respectively. The toxicity of the peri-operative CEF was mainly gastrointestinal (nausea and vomiting, 55%; stomatitis, 3%), with only a small percentage (9%) reaching grades III-IV. Hair loss was the other main side effect (55%) with baldness in only 3%. Post-operative complications following radical breast cancer surgery seem to be primarily related to operative details (type of incision, accurate nerve-sparing technique, bleeding control, closure of subcutaneous and skin, drainage, aseptic technique) rather than to the one course of PAC.

The new combination of ifosfamide and vinorelbine was evaluated in a phase II study of patients with metastatic breast cancer. All the patients had evaluable or measurable lesions resistant to the combination of cyclophosphamide, epidoxorubicin and 5-fluorouracil. Out of 25 patients entered the trial, 7 achieved an objective response (28%) (95% C.I. 12-49.3). Ten patients (40%) experienced stable disease and the remaining patients (30%) progressive disease. The median time to progression was 4 months (range 2-12+). The activity of the ifosfamide-vinorelbine combination has been demonstrated and the toxicity was acceptable.

Purpose: To assess the role of radioimmunoguided surgery (RIGS) using a handheld intraoperative gamma-detecting probe (GDP) to identify neoplastic disease after primary chemotherapy in locally advanced breast cancer (LABC) patients injected with iodine 125-labeled monoclonal antibodies (MAbs)., Patients and Methods: Twenty-one patients with histologically documented LABC were treated with a combined modality approach. After three courses of primary chemotherapy and before modified radical mastectomy, the 125I-radiolabeled MAbs B72.3 (anti-TAG72) and FO23C5 (anti-carcinoembryonic antigen [CEA]) were administered to 11 patients (group A) and 10 patients (group B), respectively. At surgery, a GDP was used to locate the primary tumor and to assess possible tumor multicentricity and the presence of ipsilateral axillary metastases. Routine pathologic examination was performed in neoplastic and normal tissue specimens of all 21 patients. In addition, immunohistochemical assay for TAG72 and CEA expression was performed., Results: In group A patients, RIGS identified primary tumor in seven of 11 patients (63.3%) and unpalpable multicentric tumor lesions were located in two of four (50%). Positive axillary lymph nodes were histologically documented in eight of 11 patients (72.7%) and RIGS identified three of eight (37.5%). In group B, RIGS located the primary tumor lesion in four of 10 patients (40%); in two cases, the tumor was not clinically evident. Multicentricity was observed in one of two patients and lymph node involvement in three of nine (33.3%). No false-positive results were observed in either group A or B., Conclusion: RIGS appears to be a safe and reliable technique. However, the MAbs used in this study are not sufficiently specific. RIGS represents a technique for which the full potential for intraoperative assessment of breast cancer lesions can be reached when more specific antibodies become readily available.