Search

Background: Postsurgical treatment of ductal intraepithelial neoplasia (DIN) with standard doses of tamoxifen has not reached a consensus yet. Given positive results of low-dose tamoxifen on breast cancer biomarkers modulation, we analyzed a large cohort of DIN patients treated with low-dose tamoxifen or no treatment as per institutional guidelines. Patients and methods: All consecutive women operated on at the European Institute of Oncology for estrogen receptor (ER)-positive DIN (474 treated with low-dose tamoxifen and 509 untreated patients) were followed up for a median of 7 years. Results: Compared with untreated patients, a significant 30% reduction in breast cancer risk was observed on lowdose tamoxifen with an adjusted hazard ratio (HR) = 0.70 [95% confidence interval (CI) 0.51–0.94], with a greater benefit in postmenopausal (HR = 0.57; 95% CI 0.34–0.94) than in premenopausal women (HR = 0.79; 95% CI 0.54–1.17). Treated patients with ER and progesterone receptor (PgR) >50% DIN had a lower incidence of breast events than untreated ones (HR = 0.61; 95% CI 0.40–0.94), whereas no protective effect has been observed in patients with ER or PgR

Background Breast reconstruction after mastectomy is currently considered an essential component in managing breast cancer patients, particularly those diagnosed at a young age. However, no studies have been published on the feasibility of immediate breast reconstruction in patients diagnosed and operated during the course of gestation. Method We retrospectively identified all breast cancer patients who were subjected to mastectomy and immediate breast reconstruction during pregnancy at the European Institute of Oncology between 2002 and 2012. Patient demographics, gestational age at surgery, tumor stage, adjuvant treatment, details of the surgical procedures, surgical outcomes and fetal outcomes were analyzed. Results A total of 78 patients with breast cancer diagnosed during pregnancy were subjected to a surgical procedure during the course of gestation. Twenty-two patients had mastectomy; of whom 13 were subjected to immediate breast reconstruction. Twelve out of 13 patients had a two-stage procedure with tissue expander insertion. Median gestational age at surgery was 16 weeks. No major surgical complications were encountered. Only one patient elected to have an abortion, otherwise, no spontaneous abortions or pregnancy complications were reported. Median gestational age at delivery was 35 weeks (range: 32–40 weeks). No major congenital malformations were reported. At a median follow-up of 32 months, all patients are alive with no long-term surgical complications. Conclusions This is the first study of immediate breast reconstruction in pregnant breast cancer patients. Tissue expander insertion appears to ensure a short operative time, and does not seem to be associated with considerable morbidity to the patient or the fetus. Hence, it could be considered in the multidisciplinary management of women diagnosed with breast cancer during pregnancy.

Background: The risk of developing invasive breast cancer after finding lobular carcinoma in situ (LCIS) is controversially reported in the literature. The surgeon who finds LCIS unexpectedly may be tempted to remove the breast, or even remove both breasts. Methods: From 1976 to 1991, 157 consecutive women with palpable or mammographically detected breast lesions underwent surgery to resolve doubt as to the presence of invasive cancer. We report on the women in whom LCIS was found after diagnostic breast surgery and analyze the incidence of breast cancer after a mean 5 years of follow-up in comparison with that in the normal reference population. Results: Eight patients developed infiltrating breast carcinoma (four ipsilateral, four contralateral as first events), equal to a homolateral rate of 0.00625. The expected rate in the normal reference population is 0.00152; ratio 4.11 (95% confidence interval 1.1–10.5). For a contralateral event the rate ratio is 3.0 (95% confidence interval 0.8–7.6). Conclusion: LCIS is one of many markers for later infiltrating cancer, so patients should be carefully followed. Ablative surgery is not justified.

Background: Low dose tamoxifen has shown comparable antiproliferative activity to 20 mg/day in biomarker trials, but its clinical efficacy is unclear. We assessed the effect of low dose tamoxifen, 10 mg on alternate day in most, on ipsilateral recurrence in high risk DCIS patients treated in a single institution. Methods: Following breast conserving surgery, women with DCIS received radiotherapy and/or low dose tamoxifen as per clinical judgment and patient preference. Multivariate Cox regression analyses adjusted for potential confounding variables were performed. Results: In a cohort of 1,091 women, median age was 53 years (IQR 46-62), 544 received radiotherapy versus 547 no radiotherapy. Of these, 883 had ER-positive DCIS, 467 received low-dose tamoxifen versus 416 no tamoxifen. After 7.7 years of median follow-up (IQR, 5.1-9.7), 235 ipsilateral recurrences and 62 contralateral tumors were observed. Low dose tamoxifen decreased any breast event (HR = 0.70, 95% CI, 0.54-0.91) and ipsilateral DCIS recurrence (HR = 0.66, 95% CI, 0.49-0.88), but not ipsilateral invasive recurrence (HR = 0.78, 95% CI, 0.56-1.09) or contralateral tumors (HR = 0.89, 95% CI, 0.51-1.55). Radiotherapy decreased any breast event (HR = 0.55, 95% CI, 0.42-0.72). Low dose tamoxifen was more effective in women aged >50 years for all events (HR = 0.51, 95% CI, 0.33-0.77) and ipsilateral recurrences (HR = 0.43, 95% CI, 0.26-0.72) than in women aged 50 or younger (HR = 0.84, 95% CI, 0.60-1.18 and HR = 0.80, 95% CI, 0.55-1.16, respectively, p-interaction = 0.03). Young age or premenopausal status, positive margins, high Ki67, high grade and low BMI were independent predictors of ipsilateral recurrence. No increase in endometrial cancers was observed and fewer deaths occurred in women on low dose tamoxifen. Conclusions: In high risk ER-positive DCIS, low-dose tamoxifen seems to be safe and effective in reducing ipsilateral recurrence, and represents a valuable option in women aged >50 years. A randomized clinical trial is underway to confirm these results. Supported by Lega Italiana per la Lotta contro i Tumori, AIRC, Italian Ministry of Health (RFPS-2006-1-339898), Gruppo bancario Credito Valtellinese. Citation Format: Aliana Guerrieri-Gonzaga, Ivana Sestak, Matteo Lazzeroni, Davide Serrano, Nicole Rotmensz, Massimiliano Cazzaniga, Clara Varricchio, Mangesh A. Thorat, Giancarlo Pruneri, Maria Cristina Leonardi, Viviana Galimberti, Bernardo Bonanni, Andrea DeCensi. Benefit of low-dose tamoxifen in a large, single-institution cohort of high-risk ER-positive DCIS. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1788.

10085Background: Sentinel lymph node biopsy (SLB) has been the most performed diagnostic procedure aimed at assessing nodal metastatic, helping to avoid axillary dissection (AD), which could lead t...

Plasma estradiol (E2) and progesterone vary markedly through the menstrual cycle. Data on whether these differences in hormone levels affect gene expression in oestrogen receptor-positive (ER+) tumours are inconsistent. We wished to determine whether there are substantial changes in the expression of oestrogen-regulated genes (ERGs) in ER+ breast cancer through the menstrual cycle. One hundred and seventy five paraffin-embedded ER+ breast carcinomas from premenopausal patients were analysed. Timing of the ovarian cycle was confirmed using serum progesterone levels. Patients were ascribed to one of three pre-defined menstrual cycle windows: 1 (days 27-35 + 1-6), 2 (days 7-16) and 3 (days 17-26). The RNA expression of ESR1, four ERGs (PGR, GREB1, TFF1 and PDZK1), and three proliferation genes (MKI67, TOP2A and CDC20) were compared between the windows. Gene expression of the four ERGs was 53-129 % higher in window 2 than window 1 (p = 0.0013, 0.0006, 0.022 and 0.066 for PGR, GREB1, TFF1 and PDZK1, respectively) and lower (9-41 %) in window 3 compared to window 2 (p = 0.079, 0.31, 0.031 and 0.065 for PGR, GREB1, TFF1 and PDZK1, respectively). Their average expression (AvERG) was 64 % higher in window 2 than window 1 (p < 0.0001) and 21 % lower in window 3 than window 2 (p = 0.0043). There were no significant differences between the windows for ESR1 and proliferation genes. In agreement with the gene expression data, progesterone receptor protein levels measured by immunohistochemistry (IHC) were 164 and 227 % higher in windows 2 and 3, respectively, compared to window 1 (30.7 and 37.9 % cells positive vs. 11.6 %; p = 0.0003 and 0.0004, respectively), while no difference in ER IHC score was observed. In conclusion, we observed significant differences in the expression of ERGs in ER+ breast tumours across the menstrual cycle. This variability may affect the interpretation of gene expression profiles incorporating ERGs and may be exploitable as an endogenous test of endocrine responsiveness.

Background This study assesses outcome in terms of disease-free survival (DFS) and overall survival (OS) of special types of triple-negative breast cancer (TNBC). Patients and Methods We identified 8801 women with first primary nonmetastatic breast cancer operated on at the European Institute of Oncology between 1997 and 2005. Of these patients, 781 consecutive patients with immunohistochemically defined TNBC were selected for the analyses. We explored patterns of recurrence by histologic type. Median follow-up was 5.7 years (range 0-13 years). Results The 5-year DFS was 77% for TNBC, 68% for human epidermal growth factor receptor 2 (HER2)-positive breast cancer, and 84% and 95% for luminal B and luminal A breast cancer, respectively. From 781 TNBC subtypes, 693 cases (89%) were classified as ductal not otherwise specified (NOS) (invasive ductal carcinoma [IDC]), 29 were classified as apocrine (3.7%), 18 (2.3%) were classified as lobular, 10 (1.2%) were classified as adenoid cystic, and 10 (1.2%) were classified as metaplastic. Five-year DFS and OS were 77% and 84% for patients with ductal carcinoma, 56% and 89% for patients with metaplastic carcinoma, and both 5-year DFS and OS were 100% for patients with adenoid cystic and medullary carcinomas, respectively. Conclusion Distinct prognostic implications may derive from the specific histotype of TNBC. The identification of these special types has a significant clinical utility and should be considered in therapeutic algorithms.

The most recent analysis of the results of three major trials on breast conservation carried out at the Milan Cancer Institute between 1973 and 1988 showed that breast conservation consisting of a wide breast resection (quadrantectomy) plus radiotherapy is a safe procedure, and that there are no differences in long-term survival (up to 19 years) compared with women who have undergone Halsted's mastectomy. The studies also showed that reducing the extent of surgery from quadrantectomy to lumpectomy increases the risk of local recurrence by nearly three times, as does withdrawing radiotherapy. However, in women older than 55 years, quadrantectomy alone (without radiotherapy) may yield good results. Among the risk factors for local recurrence, a young age and the presence of an extensive intraductal component are the most significant.

Electron intraoperative radiotherapy (ELIOT) has been introduced for breast conservative treatment (BCT) with promising oncological outcome. Thus, immediate breast reconstruction with prosthesis after BCT became possible due to minimal radiation effect on local tissue from ELIOT. We reported oncological and esthetical results of 29 BCT patients who had immediate implant reconstruction plus 21 Gy-ELIOT as the sole radiation treatment. All patients had prosthesis in ipsilateral breast and had simultaneous contralateral augmentation for symmetrical procedure. The average age was 52.3 years. There were stage Ia thirteen cases, stage Ib seven cases, stage IIa six cases and stage IIIb one case and two cases of intraepithelial neoplasia. From 54.2 (36-88) months follow up, the capsular contracture grading in the reconstructed breast from ELIOT-side is comparable with non-irradiated contralateral side. There was one patient who developed local recurrence (LR) and later on dead with breast related event (LR=0.76% per year). There was no primary ipsilateral carcinomas and distant metastasis.

Cryptococcus sp é um fungo saprófita, cosmopolita, que causa micose sistêmica, geralmente, subaguda ou crônica, conhecida, sobretudo, por sua localização meníngea, após aquisição da infecção por via respiratória Embora seja ubíquo, a criptococose ocorre predominantemente em indivíduos imunodeficientes e podendo ocorrer, também, em indivíduos imunocompetentes. Os estudos experimentais e em humanos avaliando a ativação do sistema complemento e a produção de anticorpos específicos mostram que a resposta inata e de anticorpos são importantes para a delimitação do processo infeccioso por Cryptococcus sp, como também, a administração de anticorpos monoclonais podem induzir uma resposta eficaz na disseminação da doença. O sistema complemento contribui para a defesa do organismo contra o Cryptococcus sp de diferentes maneiras: secretando opsoninas e fatores quimiotáticos e colaborando com a ação dos anticorpos específicos, aumentando a interação entre a imunidade inata e adquirida. Os anticorpos antiglicuroxilomanana (GXM) possuem numerosas atividades biológicas: a) opsonização para fagocitose, b) ativação da via clássica do complemento resultando na deposição precoce de fragmentos de C3 no fungo, c) supressão do excesso de acúmulo de C3 pela via alternativa; d) facilitação do clareamento do GXM do soro in vivo, resultando no maior acúmulo de GXM nos tecidos ricos em células do sistema fagocítico mononuclear; e) proteção em modelos murinos da criptococose e f) facilitação de vários aspectos da imunidade celular ao Cryptococcus sp. O objetivo desse estudo foi avaliar a resposta humoral ao GXM e às proteínas da parede celular (Ag S) avaliando a atividade do sistema complemento como também a produção de anticorpos específicos em amostras séricas de adultos com e sem neurocriptococose. Foram coletadas 106 amostras de soro e divididas em 3 grupos: grupo 1- 21 indivíduos com neurocriptococose e baixa exposição a levedura, grupo 2- foi composto por 23 indivíduos saudáveis com alta exposição ao fungo e HIV negativos, granjeiros da cidade de Jumirim localizada a 164 km de São Paulo, na região de Sorocaba e, o grupo 3- 60 indivíduos saudáveis, HIV negativos e com baixa exposição ao Cryptococcus sp. Dois pacientes foram excluídos do estudo por apresentarem tumores (timona e câncer de pulmão). O sistema complemento foi avaliado por ensaio hemolítico (CH 50 e AP 50) e, a dosagem da proteína ligadora de manose (MBL) foi feita por ELISA. Os valores de CH 50 estiveram dentro da normalidade em 17/21, 13/23, 59/60 indivíduos dos grupos 1, 2 e 3 respectivamente. A média dos valores de CH 50 foi diferente significativamente entre o três grupos (P < 0,0001). O grupo 2 mostrou níveis reduzidos significantes em comparação aos dois outros grupos. Os valores de AP 50 estiveram dentro da normalidade em 11/21; 21/23 e 60/60 indivíduos dos grupos 1, 2 e 3 respectivamente. Houve diferença nos valores de AP 50 (P = 0,0005) e apenas um paciente do grupo 1 apresentou valores indetectáveis desta via. Houve diferença significante na dosagem de MBL entre os três grupos (P = 0,0277). Anticorpos IgG anti-GXM foram quantificados por ELISA e expressos por densidade óptica (DO). IgG anti GXM foi detectado em todos os grupos com diferença significante entre eles (P= 0,0127). As médias de IgG anti- GXM (DO) foram: 1.191 (0,49 a 1.217) no grupo 1, 1.572 (0,815 a 2.479) no grupo 2 e 0,965 (0,321 a 1.295) no grupo 3. Dois indivíduos assintomáticos do grupo 2 tiveram títulos de GXM detectáveis (1/256 e 1/32). Quatro pacientes com neurocriptococose faleceram (19%) e seus resultados mostravam: CH 50 normal, 2/4 tinham valores de AP 50 baixo (12 UI/mL) e indetectável; 3/4 tinham altos níveis de MBL e apenas um tinha baixa DO de IgG anti-GXM. Baseado em nosso estudo, podemos concluir que a resposta humoral (sistema complemento e anticorpos) não é suficiente para explicar a susceptibilidade a neurocriptococose, porém a alta e constante exposição ao Cryptococcus sp pode prevenir o desenvolvimento de doença, ou seja, a constante e intensa exposição ao fungo induz a produção de anticorpos que previnem a doença clínica mas não a infecção. Por outro lado fatores genéticos que determinam as concentrações de MBL podem influenciar na susceptibilidade a neurocriptococose. Os anticorpos contribuem para o clearence de GXM, entretanto as concentrações séricas não se correlacionam com resistência à doença Cryptococcus sp is a fungal pathogen with a worldwide distribution. Although it is ubiquitous in the environment, cryptococcal disease occurs predominantly in immunocompromised hosts and can also occur in apparently immunocompetent individuals. The innate immunity is of special relevance for the antifungal reaction, as it allows an immediate reaction and recognizes a broad variety of fungal pathogens. The host immune response is a major determinant of the outcome of cryptococcal infection; however, the antibodies response is poorly understood. In addition, most of the studies are experimental and there is restricted knowledge concerning the human immune response. Complement system has soluble factors, restrictive regulator proteins and cellular receptors involved in defense mechanism. Glucuroxylomannan (GXM) monoclonal antibodies (MAbs) have numerous biological activities: a) opsonization for phagocytosis, b) activation of the classical complement pathway leading to early deposition of C3 fragments on the yeast, c) suppression overall accumulation of C3 via the alternative pathway; d) clearance facilitation of GXM from serum in vivo, leading to increased accumulation of GXM in tissues rich in mononuclear phagocyte system; e) protection in murine models of cryptococcosis and f) facilitation of various aspects of cellular immunity to Cryptococcus sp. The goal of our study was to evaluate if the antibody response to GXM and cell wall proteins regarding specific antibodies as well as complement system in sera of immunocompetent adults with and without neurocryptococcosis. The aim of our research was to evaluate classical and alternative complement system pathway, to quantify mannose-binding lectin (MBL) as well antibody response to GXM and cell wall proteins (AgS) regarding specific antibodies in sera of immunocompetent adults with and without neurocryptococcosis. One hundred and six samples were collected and classified in 3 groups: group 1- 21 individuals with neurocryptococcosis and low exposure to the yeast; group 2- was composed by 23 healthy individuals, chicken farmings from Jurumirim, a town 164 km to São Paulo, and with high exposure to Cryptoccocus spp and HIV negative. The third group included 60 healthy HIV negative individuals with presumed low exposure to Cryptococcus. Two patients were excluded by report of previous malignancies (timoma and pulmonary cancer). The complement system was evaluated by hemolytic assay and ELISA to MBL. CH 50 and AP 50 values were within the normal range in 17/21; 13/23; 59/60 patients in groups 1, 2 and 3 respectivelly. Mean CH 50 values were significantly different among the three groups (P < 0,0001). Group 2 showed significantly reduced levels in comparison with groups 1 and 3. AP 50 values were within the normal range in 11/21; 21/23; 60/60 patients in groups 1, 2 and 3 respectivelly. There was difference in the AP 50 values (P=0,0005) and one no activation of this pathway in group 1. There was significant difference in MBL among the groups (P = 0,0277). GXM antibodies IgG was measured by ELISA and expressed as optical density (OD). GXM- IgG was detected in all the groups with significant difference among them (P = 0,0127). The means of IgG anti-GXM (OD) were: 1.191 (range 0,49 to 1.217) in group 1, 1.572 (range 0,815 to 2.479) in group 2 and 0,965 (range 0,321 to 1.295) in the group 3. Two of the group 2 individuals had low GXM titers (1/256 and 1/32) and no symptoms. Four patients (4/21; 19%) with neurocryptococcosis died and the results showed: normal classical pathway activation, 2/4 had low (12 UI/mL) or undetectable alternative pathway values ; 3/4 had high MBL concentrations and only one had low OD for IgG anti-GXM. In conclusion, our results suggest that constant and high exposure to Cryptococcus sp can prevent the development of cryptococcosis, i.e. constant and intensive fungal exposition induces protective antibodies to clinical disease but not to the infection. In the other side, genetic factors which determine MBL concentrations could influence the susceptibility to neurocryptococcosis. The antibodies contribute to GXM clearance, however, the concentrations did not correlate with the resistance to the disease

The aim of this study is to evaluate the outcome of occult breast cancer (OBC) in patients with axillary presentation overall and according to the immunohistochemically defined tumour subtypes. We reviewed information on 15,490 consecutive primary breast cancer patients, who underwent surgery at the European institute of oncology between September 1997 and December 2008. Patients with OBC were compared with an equal number of patients with small invasive breast carcinomas (pT1) observed at the same institution during the same period, matched for year of surgery, age, nodal status and biological features. Eighty patients with OBC (study group) and 80 patients with early breast cancer (control group) were identified. There was no significant difference in the disease-free survival (5 years DFS 66 vs. 68% P = 0.91) and the overall survival (5 years OS 80 and 86% P = 0.99) between the OBC and control groups. A statistically significant worse outcome was observed within the group of OBC for patients with more than four involved lymph nodes and with triple negative tumours. The outcome of OBC patients is comparable with that of matched patients with small sized breast cancer. High risk of relapse and death was observed in OBC patients with triple negative tumours and extensive nodal involvement. © 2011 Springer Science+Business Media, LLC.

Dual epidermal growth factor receptor (EGFR) and HER2 targeting with the tyrosine kinase inhibitor lapatinib is approved for treating advanced HER2-positive breast cancer and can prevent estrogen receptor (ER)-negative mammary tumors in HER2 transgenic mouse models. Ki-67 labeling index (LI) has prognostic and predictive value and can be used to screen drugs' therapeutic and preventive potential in a clinical model of short-term presurgical therapy of breast cancer. We conducted a randomized, placebo-controlled trial of lapatinib (1500 mg/d) administered orally for three weeks between biopsy and surgery in 60 women with HER-2–positive breast cancer to assess lapatinib biomarker (including the primary endpoint, Ki-67 LI) and clinical activity in invasive breast cancer, adjacent ductal intraepithelial neoplasia (DIN, which comprises ductal carcinoma in situ and atypical ductal hyperplasia), and distant ductal hyperplasia without atypia (DH). Ki-67 LI increased progressively in association with disease stage, increasing in the placebo arm, for example, by medians of 3% in DH to 20% in DIN to 30% in invasive cancer. Ki-67 LI in cancer tissue decreased by a mean (±SD) of 9.3% (±34.2) in the lapatinib arm and increased by 15.1% (±30.9) in the placebo arm (P = 0.008). Compared with placebo, lapatinib reduced Ki-67 significantly more in ER-negative tumors (by 34.8%; P = 0.01) but not significantly more in ER-positive tumors (by 12.3%; P = 0.2) and reduced Ki-67 more (nonsignificantly) in cytosol PTEN-overexpressing tumors (P = 0.057). The prevalence of DIN in post-treatment surgical specimens of both arms was similar (70%–76%), with a median Ki-67 of 15% (range, 5%–35%) on lapatinib versus 20% (5%–60%) on placebo (P = 0.067). The prevalence of DH also was similar in both arms (>90%), with a median Ki-67 of 1% (1%–7%) on lapatinib versus 3% (1%–5%) on placebo (P = 0.006). Other results of lapatinib versus placebo, respectively, were as follows: Median tumor diameter at surgery of 18 mm (11 mm–57 mm) versus 24 mm (10 mm–37 mm; P = 0.009); partial response of 13.6% versus 3.7%, stable disease of 59.1% versus 40.7%, and progression of 27.3% versus 55.6% (P-trend = 0.035). In conclusion, short-term lapatinib decreased cell proliferation in DIN, DH, and invasive HER-2–positive (especially ER-negative) breast cancer, thus providing the rationale for further clinical development of lapatinib for breast cancer prevention in high-risk patients, including those with HER-2–positive DIN. Cancer Prev Res; 4(8); 1181–9. ©2011 AACR.

Objective: We analyzed 382 patients with pure lobular carcinoma treated up to 2002 with sufficient follow-up to draw prognostic conclusions, all treated by conservative surgery. Our aim was to evaluate the influence of margin status on outcomes with a view assessing the appropriateness of conservative surgery in this breast cancer subtype. Methods: We assessed locoregional relapse, distant metastasis, contralateral breast cancer, breast cancer-related event free survival, disease-free survival and overall survival according to margin status categorized as at least 10 mm versus less than 10 mm (usually considered negative). Results: The proportions of patients with less than 10 mm margins varied significantly with age (P = 0.02), menopausal status (P = 0.006), and tumor size (P = 0.02) but no other characteristic was significantly related to margin status. As regards unfavorable events during follow-up, none differed significantly between at least 10 mm and less than 10 mm margin groups. In particular, there were 11 (3.7%) local relapses in the same quadrant in at least 10 mm margin group compared to 4 (4.6%) in the less than 10 mm margin group, and 7 (2.4%) ipsilateral breast cancers in the 10 mm or more margin group but none in the less than 10 mm group. These findings indicate that minimal residual disease as evidenced by margins less than 10 mm is eradicated by radiotherapy (backed up in selected cases by reexcision, which in this series was always conservative). The rate of contralateral breast cancer was low at 2.9% indicating that prophylactic contralateral mastectomy is not justified. Conclusions: We conclude that the surgical approach and criteria for adjuvant hormonal and systemic treatment in lobular carcinoma should be the same as for ductal carcinoma, provided that adequate preoperative investigations exclude extensive multifocal and contralateral disease.

We followed 777 consecutive patients with breast carcinoma and positive axillary nodes for a mean of 60 months to evaluate the prognostic weight of both the total number of involved nodes and their distribution by level. Quadrantectomy was performed in 223 cases and mastectomy in 552. Complete axillary dissection was performed in all cases with identification and removal of the three levels of lymph nodes. Metastases at level I were identified in 420 patients (54%), at levels I and II 175 patients (22.5%), and at all 3 levels in 173 (22.3%). In 9 patients (1.2%) there was involvement of level II nodes in the absence of level I involvement (skip metastases). In 18 other patients (2.3%) axillary involvement was discontinuous in that the first and third levels were involved while the second level was free. Overall survival for patients with 1–3, 4–10 and >10 metastatic nodes was 80%, 62% and 35% respectively; and when level I only, levels I and II, and all 3 levels were involved, overall survival was 82%, 52% and 38% respectively. Both the total number of involved axillary nodes and the extent of axillary invasion by level had strong prognostic significance. Multivariate analysis showed that the prognostic power of levels of nodal involvement, measured as hazard ratios, is superior to that of the number of involved nodes. It is therefore recommended that surgeons and pathologists record this important information whenever axillary dissection is performed.

Background and Methods Conservative surgery and radiotherapy have become well-established treatments for breast cancer, and many trials in progress are attempting to define the most acceptable type of procedure. Between 1987 and 1989 we randomly assigned 567 women with small breast cancers (

There is considerable interest in foregoing axillary dissection (AD) when the sentinel node (SN) is positive in early breast cancer, particularly when involvement is minimal (micrometastases or isolated tumor cells). To address this issue we analyzed outcomes in patients with a single micrometastatic SN who did not receive AD. We selected 377 consecutive patients treated at the European Institute of Oncology between 1999 and 2007 for invasive breast cancer. Classical and competing risks survival analyses were performed to estimate prognostic factors for axillary recurrence, first events and overall survival. Median age was 53 years (range 26–80); median follow-up was 5 years (range 1–9). Most (91.8%) patients received conservative surgery; 209 (55.4%) had only one SN (range 1–8). Five-year overall survival was 97.3%. There were 10 local events, 2 simultaneous local and axillary events, 6 axillary recurrences and 12 distant events. The cumulative incidence of axillary recurrence was 1.6% (95% CI 0.7–3.3). By multivariable analysis, tumor size and grade were significantly associated with axillary recurrence. The high five-year survival and low cumulative incidence of axillary recurrence in this cohort provide justification for the increasingly common practice of foregoing AD in women with minimal SN involvement, and suggest in particular that AD can safely be avoided in women with small, low-grade tumors. Nevertheless, a subset of patients might be at high risk of developing overt axillary disease and efforts should be made to identify such patients by ancillary analyses of the results of ongoing or recently published clinical trials.

International audience; Intraoperative radiotherapy with electrons (ELIOT) after conservative surgery for breast carcinoma was introduced at the IEO in 1999 as a research programme. The results on 1,822 patients treated from January 2000 to December 2008 are reported. Women with unicentric primary breast carcinoma of less than 2.5 cm in the largest diameter were assessed by imaging. All patients were treated with breast-conserving surgery (quadrantectomy). ELIOT was delivered by two mobile linear accelerators immediately after breast resection with a single dose of 21 Gy. Local side effects of ELIOT were mainly liponecrosis (4.2%) and fibrosis (1.8%). After a mean follow-up of 36.1 months, 42 women (2.3%) developed a local recurrence, 24 (1.3%) a new primary ipsilateral carcinomas and 26 (1.4%) distant metastases as first event. Forty-six women died (2.5%), 28 for breast carcinoma and 18 for other causes. Five- and ten-year survivals were, respectively, 97.4 and 89.7%. ELIOT appears a promising feature in early breast cancer treated with breast conserving surgery, reducing the exposure of normal tissues to radiations and shortening the radiation course from 6 weeks to one single session.

Total mastectomy is usually indicated after breast conservative treatment cancer recurrence. Breast reconstruction in this group can be performed with many options. We did 63 latissimus dorsi flap with implants reconstructions between 2001-2007. All of them were performed in breast cancer recurrence cases after breast conservative treatment and preceded for total mastectomy. The patient age range from 31 to 71 years old (50.1 ± 7.3 years). The follow-up was 36.5 ± 14.9 months (22-141 months). Neither flap loss nor significant major donor-site complication was recorded. The capsular contraction Baker's grade III was observed in 2 cases (3.1%). The rest were grade I-II and there was no grade IV contracture. We purpose that LD flap with implant can be performed in irradiated breast with low capsular contracture rate. It is suitable in total mastectomy reconstruction after conservative breast cancer surgery recurrence.

Introduction. In recent decades, a steady improvement in imaging diagnostics has been observed together with a rising adherence to regular clinical breast examinations. As a result, the detection of small clinically occult (nonpalpable) lesions has progressively increased. At present in our institution some 20% of the cases are treated when nonpalpable. The aim of the present study is to analyze the characteristics and prognosis of such tumors treated in a single institution. Methods. The analysis focused on 1,258 women who presented at the European Institute of Oncology with a primary clinically occult carcinoma between 2000 and 2006. All patients underwent radioguided occult lesion localization (ROLL), axillary dissection when appropriate, whole breast radiotherapy, or partial breast intraoperative irradiation and received tailored adjuvant systemic treatment. Results. Median age was 56 years. Imaging showed a breast nodule in half of the cases and a breast nodule accompanied by microcalcifications in 9%. Microcalcifications alone were present in 17.1% of the cases, whereas suspicious opacity, distortion, or thickening represented the remaining 24.6%. Most tumors were characterized by low proliferative rates (68.9%), positive estrogen receptors (92.3%), and non-overexpressed Her2/neu (91.3%). After a median follow-up of 60 months, we observed 19 local events (1.5%), 12 regional events (1%), and 20 distant metastases (1.6%). Five-year overall survival was 98.6%. Conclusions. Clinically occult (nonpalpable) carcinomas show very favorable prognostic features and high survival rates, showing the important role of modern imaging techniques.

Purpose: Sentinel lymph node biopsy (SLNB) is currently not recommended in pregnant patients with breast cancer due to radiation concerns. Methods: Twelve pregnant patients with breast cancer received low-dose (10 MBq on average) lymphoscintigraphy using 99mTc human serum albumin nanocolloids. Results: The sentinel lymph node (SLN) was identified in all patients. Of the 12 patients, 10 had pathologically negative SLN. One patient had micrometastasis in one of four SLN. One patient had metastasis in the SLN and underwent axillary clearance. From the 12 pregnancies, 11 healthy babies were born with no malformations and normal weight. One baby, whose mother underwent lymphatic mapping during the 26th week of gestation, was operated on at the age of 3 months for a ventricular septal defect and at 43 months was in good health. This malformation was suspected at the morphological US examination during week 21, well before lymphoscintigraphy, and was confirmed a posteriori by a different observer based on videotaped material. No overt axillary recurrence appeared in the patients with negative SLNs after a median follow-up of 32 months. Conclusion: Our experience supports the safety of SLNB in pregnant patients with breast cancer, when performed with a low-dose lymphoscintigraphic technique. © 2009 Springer-Verlag.

Purpose The main objective of this study was to determine the role of [ 18F]-2-fluoro-2-deoxy-D-glucose positron emission tomography (FDG PET) in the selection of patients with breast cancer as candidates for sentinel node biopsy (SNB) after neoadjuvant therapy. Methods Forty-four patients with primary breast cancer clinically classified as cT2, cT3 or cT4 a-c cN0-N2 or cN3 M0 and with a baseline FDG PET scan positive both in the site of primary tumour and axillary lymph nodes underwent neoadjuvant therapy and then a second FDG PET scan. In the case of axillary FDG PET uptake, patients underwent axillary lymph node dissection (ALND). If the second FDG PET scan was negative for axillary involvement, SNB was performed in order to evaluate axillary lymph node status. Only in the case of SN positivity did total ALND follow. Results Specificity and positive predictive value of FDG PET for detection of axillary lymph node metastases after neoadjuvant therapy were as high as 83% (95% confidence interval: 51-97%) and 85% (95% confidence interval: 54-97%), respectively, whereas sensitivity, negative predictive value and diagnostic accuracy were inadequate for a correct staging (34, 32 and 48%, respectively). Conclusion The poor sensitivity of FDG PET in detecting axillary lymph node metastases makes SNB mandatory in cases of a negative scan. The relatively high positive predictive value seems to suggest a role of FDG PET in selecting patients who, after neoadjuvant therapy, are candidates for ALND, avoiding SNB. However, this issue requires confirmation in a larger series of patients. © Springer-Verlag 2010.

Background. Sixty cases of axillary metastases from clinically occult breast cancer were analyzed. All cases had histologic evidence of metastatic nodes compatible with breast carcinoma. Methods. Thirty-three patients underwent breast surgery at the time of histologic diagnosis of the axillary metastases, 6 patients were treated with radiation therapy to the breast, and 17 patients did not receive any immediate treatment of the breast carcinoma (9 of these subsequently had a primary breast carcinoma) during the follow-up. Thirty-seven of 60 patients underwent adjuvant therapy (29 underwent chemotherapy and 8 underwent tamoxifen therapy). From the histologic point of view, the number of metastatic nodes was 1 in 13 patients, 2 to 3 in 10 patients, and 4 or more in 23 patients; the number of metastatic nodes was not evaluable in 14 cases. Invasion was extranodal in 92% of cases. Eightysix percent of cases were histologically classified as Grade 3 according to Bloom and Richardson. Results. The 5-year and 10-year survival rates were 77% and 58%, respectively. The comparison between the survival curves of the patients treated with immediate surgery/radiation therapy and of the patients whose cases were followed-up without treatment to the breast showed no difference. Adjuvant treatments did not improve prognoses. The coexistence of a minimal (or unidentifiable) primary carcinoma with an extensive involvement of axillary nodes and a predominance of the undifferentiated histologic type, together with an unexpectedly good prognosis, makes this type of presentation an interesting example of a dissociated host resistance. Cancer 1992; 70:504-508. The metastatic enlargement of axillary nodes may be the first sign of clinically occult carcinoma of the breast. This particular presentation of the disease occurs in approximately 1 % of all breast cancers,'-'0 and the prognosis of these cases is better than that generally reported for Stage I1 breast carcin~ma."-'~ Conclusions.

Mondor's disease or thrombophlebitis of the subcutaneous veins of the chest region is an uncommon condition and is rarely associated with breast cancer. From January 1980 to June 1990, 63 cases of Mondor's disease were diagnosed (57 women and 6 men). In 31 patients, no apparent cause was determined (primary disease), whereas in 32 cases, the disease was secondary because the etiopathogenesis could be discerned. The identified potential causes were three cases of myentasis (all in men), eight cases of accidental local trauma (seven in women), seven cases of iatrogenic origin (three surgical breast biopsies, one skin biopsy, one needle biopsy, one mastectomy, and one reconstruction operation), six cases of inflammatory process, and eight cases associated with breast cancer (all females). Three of the tumors were less than 1 cm in diameter. The authors performed conservative surgery in four patients and demolitive in the other four. In this series, the incidence of breast cancer in association with Mondor's disease was the highest yet reported (12.7%). It was concluded that Mondor's disease may at times be caused by breast carcinoma. This association is by no means exceptional and implies that mammography should always be performed for Mondor's disease, even when the results of a physical examination are negative.

216 consecutive female patients with histologically confirmed phyllode tumour, the largest series yet reported, were operated on from 1970 to 1989 at our institute and followed-up for a mean period of 118 months. The type of surgery in relation to tumour histotype and natural history were investigated in order to identify the best treatment for this rare breast neoplasm when found unexpectedly at the final histological examination. For the 140 benign tumours, 55 enucleations, 52 enucleoresections, 29 wide resections and 4 mastectomies were performed; the 30 malignant lesions were treated with 3 enucleations, 7 enucleoresections, 9 wide resections and 11 mastectomies; the 46 borderline cases received 11 enucleations, 12 enucleoresections, 18 wide resections and 5 mastectomies. 28 underwent radical surgery following histological diagnosis. There were 27 relapses: 11 (7.9%) in benign, 7 (23.3%) in malignant and 9 (19.6%) in borderline cases. The average disease-free intervals were 32 months for benign, 22 months for malignant and 18 months for borderline phyllode tumours. It is concluded that a wide resection in healthy tissue is indispensable for malignant and borderline phyllode tumours, while, where benign phyllode tumour is encountered unexpectedly, even if a limited resection was performed, a wait-and-see policy is justified.

Although it has been shown that axillary dissection (AD) is unnecessary and without a rational basis in patients with pure ductal intraepithelial neoplasia (DIN), it is evident from the literature that AD (i.e., in the USA and in the UK) has been still recently performed. Furthermore sentinel lymph node biopsy (SLNB) is not usually required in all cases of DIN, but may be indicated in certain specific cases. Even if the SLNB is positive, AD should not be performed immediately but only in cases where an invasive component is found on definitive pathological examination of the DIN lesions.

It is still controversial whether the identification of micrometastases and isolated tumor cells in the axillary lymph nodes of patients with breast cancer has any prognostic value. We evaluated the prognostic role of isolated tumor cells and micrometastases in the axillary lymph nodes in 3,158 consecutive patients pT1-2 pN0-N1mi (with a single involved lymph node) and M0, referred to the Division of Medical Oncology after surgery performed at the European Institute of Oncology from April 1997 to December 2002. Median follow-up was 6.3 years (range 0.1-11 years). Sentinel lymph node biopsy (SLNB) and axillary lymph node dissection (ALND) were performed in 2,087 and 1,071 patients, respectively. A worse metastasis-free survival was observed for patients with micrometastatic disease compared to node-negative patients, if staged with ALND (log-rank P < .0001; HR: 3.17; 95% CI 1.72-5.83 at multivariate analysis), but not for patients who underwent SLNB (log-rank P = 0.36). The presence of a single micrometastatic lymph node is associated with a higher risk of distant recurrence as compared to node-negative disease only for patients undergoing ALND for staging purposes. Treatment recommendations for systemic therapy should not take into account the presence of a single micrometastatic lymph node identified during complete serial sectioning of sentinel node(s).

Approximately 10% of patients with breast cancer who are treated with breast-conserving surgery (BCS) develop an ipsilateral-breast tumor recurrence (IBTR). The optimal local therapy for women with BRCA-associated breast carcinoma remains controversial. We report the outcome of BCS in BRCA mutation carriers followed at a single institution.A total of 54 women with BRCA1/2-associated breast cancer treated with BCS and whole breast radiotherapy were matched for age, tumor size, and time of surgery with 162 patients with sporadic breast cancer who had the same treatment between February 1994 and October 2007. Primary end points were cumulative incidence of IBTR and contralateral breast cancer (CBC). Median follow-up was 4 years for both groups.Median age was 36 and 37 years for mutation carriers and controls, respectively; mean tumor size was 1.8 cm in carriers and 1.9 cm in controls. Ten-year cumulative incidence of IBTR was 27% for mutation carriers and 4% for sporadic controls (hazard ratio 3.9; 95% confidence interval 1.1-13.8; P = 0.03). Ten-year cumulative incidence of CBC was 25% for mutation carriers and 1% for sporadic controls (P = 0.03).Our data suggest that IBTR risk after BCS in BRCA1/2 mutation carriers is increased compared with patients who have sporadic breast cancer. Likewise, the risk of CBC seems to be increased in this group. These risks and the likelihood of developing new primary tumors should be discussed with carriers interested in breast conservation as well as when choosing risk-reducing strategies.

Background: In the case of ipsilateral breast tumour recurrence (IBTR) after breast-conserving surgery (BCS), a second conservative surgical approach maybe considered in some motivated patients whereas in others mastectomy is unavoidable. Patients and methods: From 1997 to 2004, 282 patients presented at the European Institute of Oncology with an operable invasive IBTR after BCS. One hundred and sixty-one (57%) underwent a second conservative surgery, whereas 121 patients (43%) were given a mastectomy and represent the study population. We investigated the prognosis and determined predictive factors of outcome. Results: Median time from primary breast cancer to IBTR was 41 months (range 5–213). Recurrences were T2–T4 and/or multifocal in 83 cases (68.6%). With a median follow-up of 5 years after mastectomy, 5-year overall survival (OS) and disease-free survival (DFS) were 73.3% [95% confidence interval (CI) 65.0% to 81.6%] and 50.4% (95% CI 40.9% to 59.8%), respectively. At the multivariate analysis, early onset of IBTR, presence of vascular invasion and Ki67 ≥20 of the recurrent tumour were found to significantly affect both DFS and OS. Conclusions: In women who need mastectomy for IBTR, early onset of the relapse, high proliferation index and presence of vascular invasion represent the worst prognostic factors.

Background: We aimed to predict disease-free survival (DFS) in patients who failed to achieve a pathologic complete remission (pCR) after preoperative chemotherapy (PC). Patients and methods: Data from 577 patients treated with PC and operated at the European Institute of Oncology (EIO) were used to develop a nomogram using Cox proportional hazards regression model based on both categorical (pT, positive nodes, human epidermal growth factor receptor 2 (HER2) status, vascular invasion) and continuous histological variables (estrogen receptors and Ki-67 expression) at surgery. The nomogram was tested on a second patient cohort (343 patients) treated in other institutions and subsequently operated at the EIO. Results: The nomogram for DFS based on both categorical and continuous variables had good discrimination in the training and the validation sets (concordance indices 0.73, 0.67). Conclusion: The use of a nomogram based on the degree of selected histopathological variables can predict DFS and might help in the adjuvant therapeutic algorithm design.

Electron beam intraoperative radiotherapy (ELIOT) is a new technique permitting breast radiotherapy to be completed in a single session. Since ELIOT is associated with much reduced irradiation to nontarget tissues, we carried out a study on nonpregnant breast cancer patients to estimate doses to the uterus during ELIOT to better evaluate the possible use of ELIOT in pregnant breast cancer patients. We performed in vivo dosimetry with thermoluminescence radiation detectors (TLDs) in 15 premenopausal patients receiving ELIOT to the breast (prescribed dose 21 Gy) using two mobile linear accelerators. The TLDs were positioned subdiaphragmatically on the irradiated side, at the medial pubic position, and within the uterus. A shielding apron (2 mm lead equivalent) was placed over the viscera from the subcostal to the subpubic region. TLDs showed mean doses of 3.7 mGy (range 1-8.5 mGy) at subdiaphragm, 0.9 mGy (range 0.3-2 mGy) pubic, and 1.7 mGy (range 0.6-3.2 mGy) in utero, for beam energies in the range 5-9 MeV. These findings indicate that ELIOT with a mobile linear accelerator and shielding apron would be safe for the fetus, as doses of a few mGy are not associated with measurable increased risk of fetal damage, and the threshold dose for deterministic effects is estimated at 100-200 mGy. We conclude that studies on the use of ELIOT in pregnant women treated with conservative breast surgery are justified.

Premises Sentinel node biopsy (SNB) in patients with breast carcinoma accurately predicts the axillary node status. However, in some 4–7% of patients with negative sentinel nodes, the remaining axillary nodes harbour cancer cells. Objective Our purpose was the long-term observation of a large number of patients who did not receive axillary dissection after a negative sentinel node biopsy, in order to evaluate the incidence of overt axillary metastases. Methods Patients (3548) treated from 1996 to 2004, with negative sentinel nodes not submitted to axillary dissection, were followed up to 11 years with a median follow-up of 48 months. Results Three hundred and sixteen unfavourable events occurred among the 3548 patients, 196 of which (5.5%) related to primary breast carcinoma. Thirty one cases of overt axillary metastases were found (0.9%): they received total axillary dissection and 27 of them are at present alive and well. The 5-year overall survival rate of the whole series was 98%. Conclusions Patients with negative sentinel node biopsy not submitted to axillary dissection show, at follow-up, a rate of overt axillary metastases lower than expected.

BACKGROUND. Although invasive lobular carcinoma (ILC) is the second most common histotype of breast cancer, the prognostic implications of its clinicopathologic characteristics remain controversial. METHODS. The authors undertook a retrospective analysis of a large series of cases treated and followed at a single institution, with the objective of assessing the prognostic/predictive value of distinct clinicopathologic features of the tumors, after revision of the original histopathologic preparations and statistical analyses. RESULTS. Overall, 530 patients with pure ILC (57% with the classic type; 19% with the alveolar type; 11% with the solid type; and the remaining 13% characterized by pleomorphic, signet ring cell, histiocytoid, or apocrine features) were included in the study. Tumor size, lymph node metastatic involvement, and hormonal status were confirmed to be significant prognostic factors. In addition, statistically significant correlations were demonstrated between the ‘classic’ histotype of ILC and a lower risk of axillary lymph node metastases (P = .0005), a reduced number of metastatic lymph nodes (P = .04), and lower tumor grade (P < .0001). Patients with ILC of the ‘nonclassic’ subtype demonstrated significantly increased breast-related events (hazards ratio of 1.80; 95% confidence interval, 1.04-3.10) and a trend toward reduced disease-free survival and overall survival. CONCLUSIONS. The results of the current study confirm the clinical usefulness of several traditional clinicopathologic features of ILC as prognostic parameters but also emphasize the prognostic role of the histopathologic subtyping of these tumors, documenting the more favorable outcome of the classic subtype of ILC. Cancer 2008. © 2008 American Cancer Society.

International audience; In order to reduce mutilation, nipple-areola complex (NAC) conservation can be proposed for the treatment of breast cancer when mastectomy is indicated. To reduce the risk of retro areolar recurrence, a novel radiosurgical treatment combining subcutaneous mastectomy with intraoperative radiotherapy (ELIOT) is proposed. One thousand and one nipple sparing mastectomies (NSM) were performed from March 2002 to November 2007 at the European institute of oncology (EIO), for invasive carcinoma in 82% of the patients and in situ carcinoma in 18%. Clinical complications, aesthetic results, oncological and psychological results were recorded. A comparison was performed between the 800 patients who received ELIOT and the 201 who underwent delayed one-shot radiotherapy on the days following the operation. The median follow up time was 20 months (range 1–69) for a follow up performed in 83% of the patients. The NAC necrosed totally in 35 cases (3.5%) and partially in 55 (5.5%) and was removed in 50 (5%). Twenty infections (2%) were observed and 43 (4.3%) prostheses removed. The median rate of the patients for global cosmetic result on a scale ranging from 0 (worst) to 10 (excellent) was 8. Evaluation by the surgeon in charge of the follow-up gave a similar result. Only 15% of the patients reported a partial sensitivity of the NAC. Of the fourteen (1.4%) local recurrences, ten occurred close to the tumour site, all far from the NAC corresponding to the field of radiation. No recurrences were observed in the NAC. In a group of patients characterized by a very close free margin under the areola, no local recurrence was observed. Overall, 36 cases of metastases and 4 deaths were observed. No significant outcome difference was observed between the 800 patients receiving intraoperative radiotherapy (ELIOT) and the 201 patients receiving delayed irradiation.

International audience; Whether invasive lobular carcinoma of the breast per se constitutes a prognostically favorable type has been debated. The present series comprises 301 consecutive “classic” lobular breast carcinomas seen at one institution between 1994 and 2001, compared to an equal number of invasive ductal carcinomas at the same institution during the same period, matched for year of surgery, age, menopausal status, primary tumor size, nodal involvement, hormone receptor status and where possible histological grade. Despite matching, the lobular carcinomas were more frequently multifocal, had more involved nodes, lower grade and lower proliferative fraction. There was no significant difference in disease-free or overall survival, locoregional relapse or time to distant metastasis between the lobular and ductal groups overall or within any examined subset, though the lobular group showed a trend to earlier appearance of contralateral breast cancer. Classical lobular histology is not an independent factor in the prognosis of early breast cancer.

Background GBC is a rare disease and chemotherapy in this setting lacks a standardized approach. Patients and Methods Patients 16–30 weeks pregnant with locally advanced/metastatic disease or with high risk of recurrence after surgery were evaluated. Results Twenty patients received weekly epirubicin 35 mg/m2. Median maternal age was 37 years (23–42). Median gestational age at chemotherapy was 19 weeks. Thirteen patients were treated after surgery while 7 had locally advanced tumours of which one had liver metastases. Mean total epirubicin dose was 420 mg/m2 with a median number of 12 administrations (4–16). No grade 3–4 toxicities were observed. No foetal adverse events were observed except 1 premature delivery at 28 weeks. Births were induced by caesarean section in 12 patients at a median gestational age of 35 weeks. No malformations were reported except 1 newborn with polycystic kidney. At a median age of 2 years, neurological, cardiological and immunological development was normal in all children as reported by their parents. In 7/20 patients with evaluable disease, five had an objective response. At a median follow-up of 38 months, 17 patients are alive; 14 are disease free. Conclusions Weekly epirubicin appears safe and effective with low foetal toxicity and could be considered in GBC.

Aims and background Although some guidelines recommend adjuvant radiotherapy (RT) to the axilla and supraclavicular nodes if 4 or more axillary nodes are involved, the current practice at our Institute is not to irradiate the axilla but to perform complete axillary dissection in which all 3 Berg levels are removed. We performed a retrospective analysis of patients with 4 or more axillary nodes involved and sufficient follow-up to provide indications as to whether our current treatment is adequate. Methods We retrospectively analyzed 287 T1–T3 patients with a median follow-up of 5 years and 4 or more involved nodes treated by quadrantectomy and breast RT but no axillary RT; supraclavicular RT was given only when prognostic factors were unfavorable. Results A total of 170 (59.2%) patients did not receive supraclavicular RT, while 117 (40.8%) patients received supraclavicular irradiation. No patient received axillary RT. After a median follow-up of 5 years (range, 4–105 months), 4.7% had died and 13.5% had developed distant metastases in the no supraclavicular RT group, compared to 12.0% dead (P = 0.028 log rank) and 24.8% (P = 0.201 log rank) in the supraclavicular RT group. No patients with supraclavicular RT developed supraclavicular metastases compared to 4 in the no supraclavicular RT group. There were no axillary recurrences. Conclusions Complete axillary dissection appears adequate treatment in patients with 4 or more involved nodes. The low breast recurrence rate also suggests that breast conservation is adequate treatment in such patients. Supraclavicular RT appears to reduce the number of supraclavicular metastases but confers no survival advantage. Although a small number of cases were examined in this retrospective single-center series, all received highly uniform treatment.

Background When the conservative treatment is not recommended, Nipple Sparing Mastectomy (NSM) is proposed more and more frequently for the surgical treatment of breast cancer. The risk of local recurrence behind the nipple areolar complex (NAC) is the main limiting factor of the NSM procedure. To minimize such risk, we proposed in 2002 a intraoperative radiotherapy of the preserved NAC. Patients and methods From March 2002 to November 2006, 579 cases (in 570 patients) of NSM were performed for carcinoma. The median follow up time was 19 months (Range: 1–60). The subcutaneous mastectomy was performed through an incision removing a portion of the skin overlying the tumour. An extemporaneous histological examination was performed on the retroareolar glandular tissue. If the histology was positive the patient was not considered eligible. Then an intraoperative radiotherapy with electrons (ELIOT) of 16 Gy in one shot was delivered on the NAC area. An immediate breast reconstruction was done using implants in most cases and in several cases a musculocutaneous flaps, usually in large breast. The number of local recurrences was recorded and the correlation between their occurrence and the clinical and histological criteria were analysed using the Gray test statistical method in a competing framework. Results In 516 cases the negative retroareolar frozen section biopsy was confirmed by the final histology, while in 63 cases, the final histology showed foci of carcinoma. Seven out of these 63 cases underwent a secondary NAC removal. In the 56 cases which preserved areolas we did not observe any local recurrence after 19 months follow up. The probability of retro areola positive histology increases with the tumour size. and was not related to the nodal status. The rate of local relapses was 0.9% per year. We didn’t find any significant difference in the local relapse rate according to different patient’s and tumour’s features. Most relapses were located close to the tumour bed but never in the NAC area. Conclusion Our study confirms that the local recurrence rate in the NSM completed with local radiotherapy on the NAC is not higher than the usual rate observed in the literature and the preservation of the NAC does not increase the risk. The absence of local recurrence in the region where a portion of glandular tissue has been purposely preserved is a good argument in favour of ELIOT.

Purpose Many physicians recommend mastectomy in case of multifocal (MF) or multicentric (MC) breast cancer due to a theoretical risk of poor local control with less extensive surgery. We retrospectively evaluate outcome of patients with MF/MC cancers who had breast conservation with specific attention on local control and predictive factors of recurrence. Patients and methods Four hundred and seventy six patients with either MF (n = 421) or MC (n = 55) breast cancer, underwent breast-conserving surgery between 1997 and 2002 in a single institution. Median follow up was 73 months (range 11–118). Results Median age was 53 years (range 23–86). Invasive lobular carcinoma was found in 88 patients (18.5%) and mixed ductal-lobular cancer in 27 (5.7%) patients. Two hundred and sixty-seven patients (76.7%) had two identified tumor foci, 55 patients (15.3%) had three and 29 patients (8.0%) had four or more. Two hundred and sixty-one patients (55.3%) had nodal involvement. The 5-year cumulative incidence of local relapse was 5.1%. At the multivariate analysis, over-expression of HER2/neu and lack of both estrogen and progesterone receptors (HR: 3.2, 95% C.I. 1.01–10.0, and HR: 2.7, 95% C.I. 1.06–7.7, respectively) were associated with a higher ipsilateral breast cancer reappearance rate. Involvement of four or more lymph nodes and lack of estrogen and progesterone receptors (HR: 2.7, 95% C.I. 1.06–6.7, and HR: 4.7, 95% C.I. 2.1–10.4, respectively) were associated with poorer overall survival. Conclusions In selected patients with MF/MC breast cancer, wide conservative surgery is not associated with poor local disease control and can be considered whenever acceptable cosmetic results can be achieved.

Background: Previous studies showed that after breast-conserving surgery for breast cancer, radiotherapy may be applied to the portion of the breast where the primary tumour was removed (partial breast irradiation (PBI), avoiding the irradiation of the whole breast. We developed a procedure of PBI consisting of a single high dose of radiotherapy of 21 Gy with electrons equivalent to 58–60 Gy in fractionated doses, delivered during the surgical session by a mobile linear accelerator, positioned close to the operating table. Patients and methods: From July 1999 to December 2006, 1246 patients with primary carcinoma of less than 2.5-cm maximum diameter, mostly over 48 years, were treated with electron intra-operative radiotherapy (ELIOT) at a single dose of 21 Gy. Results: After a follow-up from 0.3 to 94.7 months (median 26), 24 (1.9%) patients showed a local recurrence and 22 developed distant metastases. Sixteen patients died, seven from breast carcinoma and nine from others causes. The five-year crude survival was 96.5%. Six (0.5%) developed severe breast fibrosis, which resolved in 2–3 years. An additional 40 patients suffered for mild fibrosis. Cosmetic results were good. Conclusions: Electron intra-operative radiotherapy is a safe method for treating conservatively operated breasts and avoids the long period of post-operative radiotherapy, greatly improving the quality of life and reduces the cost of radiotherapy. ELIOT markedly reduces the radiation to normal surrounding tissues and deep organs. Results on short- and medium-term toxicity are good. Data on local control are encouraging.

This study compares sentinel lymph-node biopsy carried out at the time of removal of the primary breast tumour, under general anaesthetic, with sentinel lymph-node biopsy carried out under local anaesthetic prior to the main operation. It compares the total cost of the two treatment approaches, in terms of average income and of their impact on the subsequent programming of operations and hence on waiting lists and income.

Purpose: In a continuous effort to seek for anticancer treatments with minimal side effects, we aim at proving the feasibility of the Intraoperative Avidination for Radionuclide Therapy, a new procedure for partial breast irradiation. Experimental Design: To assess doses of 90Y-DOTA-biotin to target (i.e., breast tumor bed) and nontarget organs, we did simulation studies with 111In-DOTA-biotin in 10 candidates for conservative breast surgery. Immediately after quadrantectomy, patients were injected with 100-mg avidin in the tumor bed. On the following day, patients were given 111In-DOTA-biotin (∼111 MBq) i.v. after appropriate chase of biotinylated albumin (20 mg) to remove circulating avidin. Biokinetic studies were done by measuring radioactivity in scheduled blood samples, 48-h urine collection, and through scintigraphic images. The medical internal radiation dose formalism (OLINDA code) enabled dosimetry assessment in target and nontarget organs. Results: Images showed early and long-lasting radioactive biotin uptake in the operated breast. Rapid blood clearance (75% at 24 h) were observed. Absorbed doses, expressed as mean ± SD in Gy/GBq, were as low as 0.15 ± 0.05 in lungs, 0.10 ± 0.02 in heart, 0.06 ± 0.02 in red marrow, 1.30 ± 0.50 in kidneys, 1.50 ± 0.30 in urinary bladder, and 0.06 ± 0.02 in total body, whereas in the targeted area, they increased to 5.5 ± 1.1 Gy/GBq (50% ISOROI) and 4.8 ± 1.0 Gy/GBq (30% ISOROI). Conclusion: Our preliminary results suggest that Intraoperative Avidination for Radionuclide Therapy is a simple and feasible procedure that may improve breast cancer patients' postsurgical management by shortening radiotherapy duration.

Clinically occult breast lesions are found with increasing frequency by breast screening, and several methods have been used to locate suspicious occult lesions prior to excision. We have developed a new localization technique called ROLL (radioguided occult lesion localization) in which a small quantity of 99m Tc-labelled colloidal serum albumin is injected into the lesion during mammographic or ultrasonic examination. Correct positioning is checked by scintigraphy. A gamma detecting probe is then used to locate the lesion and guide its surgical removal. We report on the first 225 patients in whom we have employed this technique; all had non-palpable breast lesions identified by mammography or ultrasound as clusters of microcalcifications or small opacities. Pathology revealed 134 cancers, 133 of which were treated by breast-conserving surgery. In all but 2 cases (99%), radiolabelling coincided with the lesion site. X-radiography verified that the specimen removed contained all of the lesion. Removal of clinically occult breast lesions is greatly facilitated by the gamma probe, which locates the skin projection accurately, allowing choice of the most appropriate incision, and which can be employed continuously during surgery.

In a consecutive series of 241 women with operable breast cancer and clinically negative axillary lymph nodes, 99m Tc was injected on the day before surgery, and scintigraphic images were taken. During breast surgery a handheld gamma ray detector was used to locate the sentinel node and facilitate its removal separately via a small axillary incision. Complete axillary lymphadenectomy was then performed. The sentinel node accurately predicted axillary lymph node status in 232 (97.5%) of the 238 patients in whom a sentinel node was identified, and in all of the cases with a tumour

Sentinel node biopsy (SNB) has become a standard treatment in staging axillary lymph nodes in early breast cancer. SNB, however, is an invasive procedure and is time-consuming when the sentinel node is analysed intra-operatively. Breast cancer is frequently characterised by increased 2-fluoro-2-deoxy-D-glucose uptake and many studies have shown encouraging results in detecting axillary lymph node metastases. The aim of this study was to compare SNB and -positron emission tomography (-PET) imaging, to assess their values in detecting occult axillary metastases.In all, 236 patients with breast cancer and clinically negative axilla were enrolled in the study. 18-FDG-PET was carried out before surgery, using a positron emission tomography (PET)/computed tomography scanner. In all patients, SNB was carried out after identification through lymphoscintigraphy. Patients underwent axillary lymph nodes dissection (ALND) in cases of positive FDG-PET or positive SNB. The results of PET scan were compared with histopathology of SNB and ALND.In all, 103 out of the 236 patients (44%) had metastases in axillary nodes. Sensitivity of FDG-PET scan for detection of axillary lymph node metastases in this series was low (37%); however, specificity and positive predictive values were acceptable (96% and 88%, respectively).The high specificity of PET imaging indicates that patients who have a PET-positive axilla should have an ALND rather than an SNB for axillary staging. In contrast, FDG-PET showed poor sensitivity in the detection of axillary metastases, confirming the need for SNB in cases where PET is negative in the axilla.

A new procedure, known as Intraoperative Avidination for Radionuclide Therapy (IART), is described in breast cancer patients. In this paper, we provide proof of the principle that intraoperative injection of avidin in the tumour bed after quadrantectomy allows homing in of intravenously (IV) administered radioactive biotin to the target site. This approach of targeted therapy consists of two steps: (i) "avidination" of the anatomical area of the tumour with avidin injected by the surgeon, into and around the tumour bed; (ii) targeting the anatomical area of the tumour by IV injection of radiolabelled biotin. The scintigraphic images demonstrated fast and stable uptake of labelled biotin at the site of operated breast. The radiation dose released to the index quadrant was more than 5 Gy/GBq, consistent with a boost of 20 Gy for an activity of 3.7 GBq 90Y-biotin (100mCi). A further large clinical trial facing IART in combination with reduced external-beam radiotherapy is, in our opinion, fully justified.

Breast sarcoma is a rare entity that accounts for less than 1% of all breast malignancies; it may spread by direct invasion and/or through the blood. Axillary lymph node involvement is extremely rare and usually associated with advanced-stage disease. In the surgical treatment of this neoplasm, complete axillary lymphadenectomy is important for the local clearance of the clinically involved lymph nodes. We report a case of a 65-year-old woman affected by follicular dendritic cell sarcoma of the left breast. Six months after breast surgery she developed an axillary metastasis from the same disease.

Over recent decades, breast carcinoma surgery has witnessed a considerable evolution. The extent of surgery undertaken has progressively reduced, leading to less disfigurement and a significant improvement in quality of life, thereby offering women considerable motivation to seek early diagnosis. From an oncological perspective, outcome was found to be equally effective, and this key observation provided us with significant impetus to investigate the effects of reducing the radiotherapy field.We present the achievements made so far in the conservative treatment of breast carcinoma, based on experiences at the European Institute of Oncology in Milan and, prior to 1994, at the Milan Cancer Institute.Conservative surgery of breast carcinoma, both in the breast and in the axillary nodes, has yielded very good results in terms of overall survival and impact on quality of life. The reduction of the radiation field, conducted in our Institute by means of electron intraoperative radiotherapy (ELIOT), is currently the subject of evaluation via a randomised trial.