C. Amanti

Conservative surgery with and without radiotherapy in elderly patients with early-stage breast cancer: a prospective randomised multicentre trial.

Breast conserving therapy (BCT) including postoperative irradiation of the remaining breast tissue is generally accepted as the best treatment for the majority of patients with early-stage breast cancer. The question is whether there is a necessity for irradiating all patients. Between 2001 and 2005, 749 women aged 55-75 years with infiltrating breast carcinoma were randomly assigned to breast conservative surgery, with or without radiotherapy (RT), to evaluate the incidence of in-breast recurrence (IBR). After 5 years of median follow-up, the cumulative incidence of IBR was 2.5% in the surgery-only arm and 0.7% in the surgery plus RT arm. There are no differences in terms of overall survival and distant disease-free survival. The preliminary evaluation suggests that breast irradiation after conservative surgery can be avoided without exposing these patients to an increased risk of distant-disease recurrence. Prolonged follow-up will further clarify the possible risks and late sequelae potentially induced by breast RT.

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.

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-1β, 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-1β, 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.

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 nomograms 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.

Bullous Pemphigoid Induced by Radiation Therapy

A rare complication occurring in a female patient who underwent conservative surgery and radiation therapy for breast cancer is described. Three weeks after the completion of radiotherapy, a diffuse bullous pemphigoid eruption developed in the irradiated area, spreading thereafter to the whole body. Although systemic cutaneous side effects have been reported after radiation therapy, this is the first occurrence of bullous pemphigoid ever reported in a female patient following treatment for breast cancer. Having made the diagnosis, an effective therapeutic regimen including nicotinamide and tetracycline was started. As the conservative management of breast cancer is now widely adopted, oncologists and physicians should be aware of such rare side effects due to radiation therapy.

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

PurposeThe aim of this study was to evaluate treatmentrelated 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 methodsBetween 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.ResultsThe 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.ConclusionsRadiotherapy 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.RiassuntoObiettivoScopo del nostro lavoro è stato valutare le complicanze del trattamento e il livello di soddisfazione del risultato in pazienti con tumore della mammella localmente avanzato sottoposte a trattamento radioterapico post-mastectomia e ricostruzione mammaria.Materiali e metodiTra ottobre 2007 e novembre 2010, presso il nostro Dipartimento, 46 pazienti affette da neoplasia della mammella sono state sottoposte a trattamento radioterapico dopo intervento di mastectomia radicale e ricostruzione mammaria. La dose totale somministrata sulla parete toracica è stata di 50 Gy in 25 frazioni.RisultatiA un follow-up mediano di 19 mesi, si è osservata la comparsa di eritema cutaneo di grado 1 e 2 rispettivamente in 44 (96%) e in 2 (4%) pazienti. Complicanze maggiori, che hanno richiesto un ulteriore intervento chirurgico correttivo, sono state osservate in 3 pazienti (7%). All’analisi univariata il fumo, la chemioterapia, il tamoxifene e la ricostruzione con protesi risultano associate a un maggior rischio di complicanze generali (contrattura capsulare e fallimento della ricostruzione). Quaranta pazienti (86%) si sono mostrate soddisfatte o molto soddisfatte dei risultati estetici.ConclusioniLa radioterapia dopo ricostruzione mammaria è un trattamento sicuro associato a una bassa incidenza di complicanze e a un buon livello di soddisfazione da parte delle pazienti. Sono necessari ulteriori studi per definire meglio la sequenza ottimale di trattamento tra ricostruzione mammaria e radioterapia.

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.

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, todays 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.

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.

Clinical use of an imaging probe in breast cancer surgery

Aim Portable cameras allow easy transfer of the detector, and thus of radioisotope imaging, to the operating room. In this paper we describe our preliminary experience in radionuclide imaging of breast cancer with a 22.8 × 22.8 mm2 field-of-view minicamera called “Imaging Probe” (IP). Methods Breast cancer detection by IP was performed to guide biopsy, in particular open biopsy, or help fine-needle or core-needle positioning when the main guidance method was ultrasonography or digital radiography. 99mTc Sestamibi (MIBI) was injected 1 h before imaging and biopsy to 14 patients with suspected or known breast cancer. Scintigraphic images were acquired before and after biopsy in each patient. The surgeon was allowed to take into account scintigraphic images as well as previously performed mammograms and ultrasonography. Results High-resolution IP images were able to guide biopsy toward cancer or toward washout zones of cancer, which are thought to be chemoresistant, in seven patients out of 10. Four patients in whom IP and MIBI were unable to guide biopsy were found not to have cancer. Conclusions Our study confirms the ability of IP to guide breast biopsy even when our minicamera has to be handled manually by trained physicians during surgery.