Giuseppe Canavese

Sentinel lymph node mapping in early-stage breast cancer: Technical issues and results with vital blue dye mapping and radioguided surgery

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.

Sentinel lymph node mapping opens a new perspective in the surgical management of early‐stage breast cancer: A combined approach with vital blue dye lymphatic mapping and radioguided surgery

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.

Pattern of lymphatic drainage to the sentinel lymph node in breast cancer patients

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.

Mapping sentinel lymph node in breast cancer by combined lymphoscintigraphy, blue-dye, and intraoperative gamma-probe.

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.

Surgical complications related to peri-operative adjuvant chemotherapy in breast cancer. Results of a prospective, controlled, randomized clinical trial.

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.

Radioimmunoguided surgery after primary treatment of locally advanced breast cancer.

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.

USE OF RADIOIMMUNOGUIDED SURGERY AFTER INDUCTION CHEMOTHERAPY IN LOCALLY ADVANCED BREAST CANCER

Twenty-one patients with histologically proven locally advanced breast cancer (LABC) were treated with a combined modality approach based on primary chemotherapy and radical modified mastectomy followed by adjuvant chemotherapy. Surgery was performed by using radioimmunoguided surgery (RIGS) technique with the preoperative injection of Iodine-125 labeled monoclonal antibodies (MoAbs) B72.3 anti-TAG (11 patients, Group A) and FO23C5 anti-carcinoembryonic antigen (CEA; 10 patients, Group B). The role of RIGS was defined at surgery by using an intraoperative hand-held gamma-detecting probe (GDP) to locate the primary tumor, possible clinically occult multicentric foci and ipsilateral lymph node metastases. In Group A, RIGS correctly defined the primary tumor in seven out of 11 patients (63.3%) and was able to find multicentric tumors in two out of four patients (50%). Positive lymph nodes were identified by RIGS in three out of eight patients (37.5%). In Group B, patients RIGS correctly located the primary in 4/10 cases (40%); in two RIGS-positive cases, the tumor was clinically not evident after primary chemotherapy (yT0). RIGS correctly identified multicentric foci of tumor in one out of two cases (50%). Correct lymph nodal RIGS assessment was observed in three out of nine patients (33.3%). No RIGS false-positive findings occurred in the 21 patients included in the study. RIGS appears to be a reliable technique for the intraoperative diagnosis and staging of breast cancer with a potential role especially when conservative surgery is planned after primary chemotherapy in LABC.

SINODAR ONE, an ongoing randomized clinical trial to assess the role of axillary surgery in breast cancer patients with one or two macrometastatic sentinel nodes

Sentinel lymph node biopsy alone is the current surgical axillary treatment for early-stage breast cancer patients with a negative sentinel lymph node (SLN). The possibility to omit axillary dissection also in presence of positive SLNs has been promoted by the American College of Surgeons Oncology Group (ASOCOG) Z0011 randomized trial. Several limitations and evidences of potential selection bias made this trial fairly controversial. Stronger evidence than currently available is needed on the safety of foregoing axillary dissection in well-defined populations of patients with positive SLNs. The Italian multicentre SINODAR ONE randomized trial here presented was designed with this aim.

Accelerated partial breast irradiation via the mammosite® catheter: Preliminary reports of a single-institution experience

Abstract:  Several studies have shown that the majority of in‐breast recurrences following lumpectomy are at or near the original tumor site while ipsilateral breast recurrences further afield occur rarely. This suggests that the radiation dose could be delivered exclusively to the tumor bed, allowing larger fractions to be used without increasing toxicity and shortening the total treatment time. We investigated the use of the MammoSite irradiation system with a view to analyzing complications, cosmesis and patient comfort. Between 2004 and 2007 intracavity brachytherapy was given to 30 patients using the MammoSite device. The reference isodose was prescribed to the lumpectomy cavity with a 1 cm margin. Geometric parameters and anatomic position of the applicator after implantation were checked via CT, x‐ray and ultrasound. Analysis was done for patient quality of life, cosmesis, early and late complications. Forty‐nine patients received a proposal for MammoSite brachytherapy. Nine declined, 40 enrolled while 10 were excluded for various reasons ( Table 5 ). A total of 30 patients were actually treated to 34 Gy (2 × 3.4 Gy) in 5 days. We observed 3 cases (10%) of infection within 3 months of implantation. Symptomatic seroma was seen in five patients (16.6%) at 6 months, in three (10%) at 12 months, and in just one patient (3.3%) at 18 months. Good to excellent cosmetic results were achieved in 75% by patient and physician ratings. Accelerated partial breast irradiation using the MammoSite catheter produces favorable short‐term outcomes, limited toxic effects on skin, and optimal cosmetic results. Patient tolerance for the treatment is very high. Critical issues may regard the importance of good cavity conformance and adequate balloon‐skin distance in avoiding possible dose excesses to the skin. For a selected patient group, this could be a valid alternative to conventional whole breast irradiation.

Use in current clinical practice of 70-gene signature in early breast cancer

on 21 early breast cancer patients. All patients gavewritten informed consent approved by the Ethic Committee.After the breast tumor was removed, a tumor sample wasstored by pathologist and sent to Agendia for MammaPrint test.Nine patients had a MammaPrint result which is not use-ful for clinical decision about adjuvant chemotherapy because3 were ductal carcinoma in situ, 4 (22%) had quality of sam-ples not sufficient to perform the MammaPrint assay and 2had both oestrogen- and progesterone-receptors negative andthen patients were candidates for chemotherapy regardlessthe MammaPrint results.In the remaining 12 cases (67%) both clinical risk (definedby clinical-pathological parameters) and MammaPrint riskwere considered for decision-making about adjuvant treat-ment. All cases were discussed in the Breast Disease Manage-ment Team with the presence of medical oncologists, sur-geons and pathologists. Characteristics of the 12 patients areshowed in Table 1.In five (42%) cases (2, 4, 5, 6, 11) clinical risk was dis-cordant with the risk estimated by MammaPrint. In thesecases decision about chemotherapy was based on clinical-pathological factors and disagreed with MammaPrint risk. Infact, in our Institute we recommend chemotherapy in endo-crine-responsive patients with node-positive (2 and 5) or T2tumor or G3 or age 35 years. Conversely, we do not recom-mend usually chemotherapy in endocrine-responsive patientswith age 70 years (4 and 6). Patient 11 had a lobular inva-sive carcinoma and, although she had a T2, we did not rec-ommend chemotherapy because lobular invasive carcinomaappeared to be less responsive to chemotherapy.