A Randomized Trial of Robotic Mastectomy Versus Open Surgery in Women With Breast Cancer or BrCA Mutation.

OBJECTIVE: The aim of this study was to compare robotic mastectomy with open classical technique outcomes in breast cancer patients. SUMMARY BACKGROUND DATA: As the use of robotic nipple sparing mastectomy continues to rise, improved understanding of the surgical, oncologic, and quality of life outcomes is imperative for appropriate patient selection as well as to better understand indications, limits, advantages, and dangers. METHODS: In a phase III, open label, single-center, randomized controlled trial involving 80 women with breast cancer (69) or with BRCA mutation (11), we compared the outcome of robotic and open nipple sparing mastectomy. Primary outcomes were surgical complications and quality of life using specific validated questionnaires. Secondary objective included oncologic outcomes. RESULTS: Robotic procedure was 1 hour and 18 minutes longer than open (P < 0.001). No differences in the number or type of complications (P = 0.11) were observed. Breast-Q scores in satisfaction with breasts, psychosocial, physical and sexual well-being were significantly higher after robotic mastectomy versus open procedure. Respect to baseline, physical and sexual well-being domains remained stable after robotic mastectomy, whereas they significantly decreased after open procedure (P < 0.02). The overall Body Image Scale questionnaire score was 20.7 ±â€Š13.8 versus 9.9 ±â€Š5.1 in the robotic versus open groups respectively, P < 0.0001. At median follow-up 28.6months (range 3.7-43.3), no local events were observed. CONCLUSIONS: Complications were similar among groups upholding the robotic technique to be safe. Quality of life was maintained after robotic mastectomy while significantly decrease after open surgery. Early follow-up confirm no premature local failure.ClinicalTrials.gov NCT03440398.

Ductal carcinoma in situ of the male breast: clinical radiological features and management in a cancer referral center.

PURPOSE: To present an overview of the management of male patients with Ductal Carcinoma In Situ of the breast (male DCIS). METHODS: We retrospectively studied all male patients with a diagnosis of pure DCIS from January 1999 to December 2018: 20 patients were identified in our cancer referral center. We collected data regarding clinical presentation, age of onset, radiological features, receptor status of the neoplasm, histological type, and the follow-up of those patients. RESULTS: The median age was 62 years (range 21-80). All patients underwent surgery, in 15/20 (75%) cases a mastectomy was carried out. Two patients (10%) underwent endocrine treatment and 1/20 (5%) underwent radiotherapy. The receptor status for 15/20 patients was documented: 13/15 patients were ER+/Pr+. In 3 cases the Ki 67% was positive (i.e., > 20%). All cases were negative for Her2. The median follow-up time was 9.0 years (IQR 4.0-13.7). Only one patient had an ipsilateral recurrence with the finding of an infiltrating carcinoma in the same breast after 14 years. The 5-year disease-free survival was 92.9%. CONCLUSION: Pure DCIS in men is an extremely rare disease: proper diagnosis and management allow an excellent prognosis.

Update on the Feasibility and Progress on Robotic Breast Surgery.

BACKGROUND: Robotic nipple-sparing mastectomy (RNSM) may allow for more precise anatomic dissection and improved cosmetic outcomes over conventional open nipple-sparing mastectomy; however, data regarding the feasibility and safety of the procedure are limited. OBJECTIVE: The aim of this study was to present and discuss perioperative surgical outcomes and early oncologic follow-up data on consecutive patients undergoing RNSM from June 2014 to January 2019. METHODS: Patients underwent RNSM and immediate robotic breast reconstruction through an axillary incision at a single institution. Perioperative data, complications at 3 months postoperatively, pathological data, and adjuvant therapies were recorded. Local recurrence-free, disease-free, and overall survival were analyzed. RESULTS: Overall, 73 women underwent 94 RNSM procedures. Indications were invasive breast cancer in 39 patients, ductal carcinoma in situ in 17 patients, and BRCA mutation in 17 patients. Mean surgery time was 3 h and 32 min. One-step reconstruction with implant occurred in 89.4% of procedures. The rate of complications requiring reoperation was 4.3%, and the rate of flap or nipple necrosis was 1.1%. Median follow-up was 19 months (range 3.1-44.8). No local recurrences occurred. Overall survival at 12, 24, or 60 months was 98% (95% confidence interval 86-100%). CONCLUSION: We observed a low complication rate in 94 consecutive RNSM procedures, demonstrating the procedure is technically feasible and safe. We found no early local failures at 19 months follow-up. Long-term follow-up is needed to confirm oncologic safety. Future clinical trials to study the advantages and disadvantages of RNSM are warranted.

Ipsilateral Breast Tumor Reappearance and Contralateral Breast Cancer after Primary Breast Cancer Treatment: A Comprehensive Retrospective Study of 15,168 Patients.

OBJECTIVE: The aim of this retrospective study was to assess the risk factors for developing ipsilateral breast tumor reappearance (IBTR) and de novo contralateral breast cancer (BC) after primary BC treatment. METHODS: Retrospectively, 15,168 consecutive patients with primary monolateral BC were enrolled in this monocentric study (from June 1994 to December 2006). Clinicopathological features, follow-up, and survival at 15 years were considered for statistical analysis. RESULTS: Significant associations of increased risk for IBTR were verified with metastatic axillary lymph nodes (HR 1.37 [1.15-1.62], p = 0.0004), high tumor grade G2 (HR 1.35 [1.05-1.74], p = 0.02) and G3 (HR 1.35 [1.01-1.79], p = 0.04), luminal B (HR 1.51 [1.25-1.82], p < 0.0001), and HER2-positive (HR1.66 [1.14-2.41], p = 0.008) and triple-negative subtype (HR 1.54 [1.07-2.21], p = 0.02). Older age (HR 1.44 [1.08-1.91], p = 0.01) and positive family history (HR 1.85 [1.47-2.32], p < 0.0001) were risk factors for contralateral BC. Significant protective factors for IBTR were hormonotherapy (HR 0.71 [0.59-0.85], p = 0.0003), chemotherapy (HR 0.72 [0.60-0.87], p = 0.001), and radiotherapy (HR 0.73 [0.61-0.87], p = 0.0005). Hormonotherapy was also confirmed as a protective factor for contralateral second BC (HR 0.43 [0.30-0.60], p < 0.0001). CONCLUSIONS: We classified factors for IBTR and contralateral BC in high- and low-risk groups. In the high-risk group, breast surgery still remains more important than in the low-risk group, which seems to benefit more from adjuvant treatments.

Nomograms for Predicting Axillary Response to Neoadjuvant Chemotherapy in Clinically Node-Positive Patients with Breast Cancer.

BACKGROUND: Many patients with clinically node-positive breast cancer receive neoadjuvant chemotherapy (NAC). Recent trials suggest the potential for limiting axillary surgery in patients who convert to pathologically node-negative disease. The authors developed a nomogram to predict axillary response to NAC in patients with cN1 disease that can assist clinicians in treatment planning. METHODS: Patients with cT1-4N1M0 breast cancer who received NAC and underwent axillary lymph node dissection from 2001 through 2013 were identified (n = 584). Uni- and multivariate logistic regression analyses were performed to determine factors predictive of nodal conversion. A nomogram to predict the likelihood of nodal pathologic complete response (pCR) was constructed based on clinicopathologic variables and validated using an external dataset. RESULTS: Axillary pCR was achieved for 217 patients (37 %). Patients presenting with high nuclear grade [grade 3 vs. 1, odds ratio (OR) 13.4], human epidermal growth factor receptor 2-positive (OR 4.7), estrogen receptor (ER)-negative (OR 3.5), or progesterone receptor-negative (OR 4.3) tumors were more likely to achieve nodal pCR. These factors, together with clinically relevant factors including presence of multifocal/centric disease, clinical T stage, and extent of nodal disease seen on regional nodal ultrasound at diagnosis were used to create nomograms predicting nodal conversion. The discrimination of the nomogram using ER+ status (>1 % staining) versus ER- status [area under the curve (AUC) 78 %] was improved slightly using the percentage of ER staining (AUC 78.7 %). Both nomograms were validated using an external cohort. CONCLUSION: Nomograms incorporating routine clinicopathologic parameters can predict axillary pCR in node-positive patients receiving NAC and may help to inform treatment decisions.

The clinical relevance of micropapillary carcinoma of the breast: a case-control study.

AIMS: To ascertain the prognostic relevance of micropapillary carcinoma, a specific type of breast tumour. METHODS AND RESULTS: We interrogated the clinical records of a series of 49 pure micropapillary carcinoma patients and 13 487 invasive ductal carcinoma patients, diagnosed and treated consecutively in our institution over a 9-year time-frame. Compared with invasive ductal carcinoma, patients with micropapillary carcinoma more frequently had moderately differentiated tumours (P = 0.02) with extensive peritumoral vascular invasion (P < 0.0001), associated with a significantly higher rate of axillary lymph node involvement (P < 0.0001). Survival data obtained by comparing 49 micropapillary carcinoma patients with a set of 98 invasive ductal carcinoma patients matched for age, tumour size and grade, peritumoral vascular invasion, immunohistochemically defined molecular subtype, number of positive lymph nodes and year of surgery showed that the micropapillary histotype did not add any independent information to the risk of locoregional (P = 0.48) or distant (P = 0.79) relapse, or overall survival (P = 0.60). CONCLUSIONS: Our data reinforce the notion that micropapillary carcinoma usually arises as a locally advanced disease, and provide evidence that micropapillary histology does not add any additional information on clinical outcome independent of clinicopathological characteristics such as lymph node status and immunohistochemically defined molecular subtype.

A Model to Predict Upstaging to Invasive Carcinoma in Patients Preoperatively Diagnosed with Low-Grade Ductal Carcinoma In Situ of the Breast.

BACKGROUND: We aimed to create a model of radiological and pathological criteria able to predict the upgrade rate of low-grade ductal carcinoma in situ (DCIS) to invasive carcinoma, in patients undergoing vacuum-assisted breast biopsy (VABB) and subsequent surgical excision. METHODS: A total of 3100 VABBs were retrospectively reviewed, among which we reported 295 low-grade DCIS who subsequently underwent surgery. The association between patients' features and the upgrade rate to invasive breast cancer (IBC) was evaluated by univariate and multivariate analysis. Finally, we developed a nomogram for predicting the upstage at surgery, according to the multivariate logistic regression model. RESULTS: The overall upgrade rate to invasive carcinoma was 10.8%. At univariate analysis, the risk of upgrade was significantly lower in patients with greater age (p = 0.018), without post-biopsy residual lesion (p < 0.001), with a smaller post-biopsy residual lesion size (p < 0.001), and in the presence of low-grade DCIS only in specimens with microcalcifications (p = 0.002). According to the final multivariable model, the predicted probability of upstage at surgery was lower than 2% in 58 patients; among these 58 patients, only one (1.7%) upstage was observed, showing a good calibration of the model. CONCLUSIONS: An easy-to-use nomogram for predicting the upstage at surgery based on radiological and pathological criteria is able to identify patients with low-grade carcinoma in situ with low risk of upstaging to infiltrating carcinomas.

Advances and controversies in management of breast ductal carcinoma in situ (DCIS).

Ductal carcinoma in situ (DCIS) is a non-obligate precursor of invasive breast cancer. It accounts for 25% of all breast cancers diagnosed, as a result of the expansion of breast cancer screening and is associated with a high survival rate. DCIS is particularly clinically challenging, due to its heterogeneous pathological and biological traits and its management is continually evolving towards more personalized and less aggressive therapies. This article suggests evidence-based guidelines for proper DCIS clinical management, which should be discussed within a multidisciplinary team in order to propose the most suitable approach in clinical practice, taking into account recent scientific studies. Here we include updated multidisciplinary treatment protocols and techniques in accordance with the most recent contributions published on this topic in the peer-reviewed medical literature, and we outline future perspectives.

The management of ductal intraepithelial neoplasia (DIN): open controversies and guidelines of the Istituto Europeo di Oncologia (IEO), Milan, Italy.

The management of ductal intraepithelial neoplasia (DIN) has substantially changed over the past 30 years, as its incidence has increased (from 2-3% to more than 20%), mainly due to the widespread use of mammography screening. This article describes not only the more widespread theoretical concepts on DIN but also the differences in the practical applications of the theory between different countries, different oncology specialists, and different cancer centers. Papers related to the international multicentre-randomized trials and retrospective studies were analyzed. We include articles and papers published between 1993 and 2010 related to patients with DIN, and abstracts and reports from MEDLINE and other sources were indentified. The standard of care for DIN consists of (a) breast conservative surgery (mastectomy is still indicated in large lesions--masses or microcalcifications--in about 30% of cases); (b) radiotherapy (RT) after conservative surgery, and (c) medical treatment in estrogen receptors-positive patients. However, most studies have shown significant differences between theory and practical application. Moreover, there are differences regarding (a) the indications of sentinel lymph node biopsy, (b) the definition and identification of low-risk DIN subgroups that can avoid RT and tamoxifen, and (c) the research into new alternative drugs in adjuvant medical therapy. A general agreement on the best management of DIN does not exist as yet. New large trials are needed in order to define the best management of DIN patients which is (in most respects) still complex and controversial.

Breast-conserving surgery in BRCA1/2 mutation carriers: are we approaching an answer?

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

A new option for early breast cancer patients previously irradiated for Hodgkin's disease: intraoperative radiotherapy with electrons (ELIOT).

INTRODUCTION: Patients who have undergone mantle radiotherapy for Hodgkin's disease (HD) are at increased risk of developing breast cancer. In such patients, breast conserving surgery (BCS) followed by breast irradiation is generally considered contraindicated owing to the high cumulative radiation dose. Mastectomy is therefore recommended as the first option treatment in these women. METHODS: Six patients affected by early breast cancer previously treated with mantle radiation for HD underwent BCS associated with full-dose intraoperative radiotherapy with electrons (ELIOT). RESULTS: A total dose of 21 Gy (prescribed at 90% isodose) in five cases and 17 Gy (at 100% isodose) in one case were delivered directly to the mammary gland without acute complications and with good cosmetic results. After an average of 30.8 months of follow up, no late sequelae were observed and the patients are free of disease. CONCLUSION: In patients previously irradiated for HD, ELIOT can avoid repeat irradiation of the whole breast, permit BCS and decrease the number of avoidable mastectomies.

No more axillary dissection in patients with ductal intraepithelial neoplasia (DIN).

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.

Novo TNM: classificação do câncer de mama proposta pelo Instituto Europeu de Oncologia de Milão, Itália / New TNM: classification of breast cancer proposed by the European Institute of Oncology, Milan, Italy

O estadiamento TNMuicc classifica a neoplasia mamária de acordo com o tamanho tumoral, comprometimento linfonodal e metástases à distância. O tratamento da neoplasia mamária é influenciado por esses parâmetros, porém, também é necessário conhecimento sobre uma série de outros fatores. Na realidade, o tratamento eficaz depende da extensão da doença, do status dos receptores hormonais e de outras características biológicas do câncer. Nós propomos uma nova classificação(TNM), que não apenas inclui características biológicas relevantes e amplia o estadiamento para incluir outros fatores quando validados, mas também especifica o tamanho exato do tumor (T2,3 indica um tumor com diâmetro maior que 2,3 cm), fornece mais dados sobre o envolvimento linfonodal e especifica sítio(s) de metástases a distância. Propomos também abolir o termo "carcinoma" quando se trata de condição neoplásica não-invasiva e o termo "infiltrante" para carcinomas. A nova classificação é suficientemente similar à classificação TNMuicc para permitir comparações válidas entre pacientes classificados por ambos os sistemas, porém é mais lógica, fornece informações úteis para guiar a terapia e é flexivel o suficiente para satisfazer as necessidades de pesquisas no presente e no futuro.

The TNMuicc classification of breast cancer categorizes tumor size, regional lymph node involvement, and distant metastases. Treatment is influenced by these characteristics, but requires knowledge of several other factors. In fact, effective treatment is dependent on disease extent, hormone receptor status, and other biologic characteristics of the cancer. We propose a new classification (tumor node metastasis, TNM), that not only includes relevant biologic characteristics and can expand to include others as they are validated but also specifies tumor size exactly (T2,3 indicates a cancer of maximum diameter 2,3 cm), provides more information on regional lymph node involvement, and specifies the site(s) of distant metastases. We also propose abolishing the term "carcinoma" for non-invasive neoplastic conditions and the term "infiltrating" for carcinomas. The new classification is sufficiently similar to the TNMuicc classification to permit valid comparison of patients classified by both systems, but is more logical, provides useful information for guiding therapy, and is flexible enough to satisfy present and future clinical and research needs.

Abdomen agudo ginecológico traumático / Traumatic gynecological acute abdomen

El abdomen agudo ginecológico traumático (AAFT), verdadera emergencia médico-quirúrgica ginecológica, está representado en la gran mayoíra de los casos, por la Perforación Uterina (PU), la cual está provocada por muy diversos métodos y elementos, que pueden ocasionar variadas lesiones y complicaciones abdominopelvianas. El objetivo de este trabajo ha sido analizar los 41 casos de P.U. tratados en el Hospital de Urgencias de Córdoba, entre 1967 y 1984, que configuran el 33% de los 1.230 casos correspondientes a emergencias médico-quirúrgicas ginecológicas (internados en el mismo Hospital y períodos de tiempo). Alrededor de un 80% de la P.U. se produjeron en pacientes entre los 21 y 35 años. En el 83% de las pacientes, la P.U. fue provocada durante el primer trimestre de embarazo (el 56%, entre las 8 y 12 semanas de amenorrea). Desde el punto de vista clínico, destacamos que el dolor se localizó en hipogastrio y hemiabdomen inferior en un 70%; y tuvo características de leve o ausente, en casi un 5-% de los casos. El abdomen se presentó blando en un 65% de las pacientes. La terapéutica varió según la P.U. haya sido "simple" (53,6%) o "complicada" (46,4%). En la primera se realizó tratamiento médico; en la segunda, tratamiento quirúrgico. La evolución fue en todos los casos satisfactoria y la mortalidad, nula; enfatizando que, en su mayor porcentaje, las P.U. fueron producto de maniobras "clandestinas"

Conceptualización y clasificación del abdomen agudo ginecologico (A.A.G.): nuestra experiencia / Conceptualization and classification of the gynecologic acute abdomen (G.A.A): our experience

El objetivo de la presente comunicación es analizar los 1230 pacientes internados en el Hospital de Urgencias de Córdoba, entre 1967 y 1984, que configuraron emergencias ginecológicas médico-quirúrgicas, de las cuales 973 (79,11%) correspondieron a genuinos abdómenes agudos ginecológicos (A.A.G.). Para un diagnóstico certero de A.A.G. (cuyo sindrome clínico mínimo se caracteriza, por la rápida aparición del dolor, las modificaciones del abdomen y la afectación del estado general) enfatizamos la conveniencia de una completa semiología y la laparoscopía como maniobra instrumental de gran valor. La etiología dominante en el A.A.G. infeccioso fue la enfermedad pelviana inflamatoria aguda (EPIA), en su gran mayoría pelviperitonitis. El embarazo ectópico representó el 94% del A.A.G. hemorrágico. La torsión de tumor de ovario, el 50% del A.A.G. mecánico. La perforación uterina, el 83% del A.A.G. traumático. La rotura del cuerpo amarillo y folículo, el 81% del A.A.G. funcional y hormonal. Clasificamos, a los fines didácticos, los A.A.G. según: a) Criterio clínico etiopatogénico; b) Enfoque terapéutico; c) Incidencia etaria; d) Estrato sociocultural. El tratamiento de todo A.A.G. debe ser lo suficientemente conservador para mantener el órgano o la función, cuando el cuadro clínico lo permita, y lo bastante agresivo como para erradicar la enfermedad. Es de trascendencia vital determinar si el A.A.G. es quirúrgico o no, pues es preferible una laparotomía diagnóstica a la certidumbre de una autopsia

HPR y cáncer de mama / HPR and breast neoplasm

Desde hace años se conoce que la vitamina A juega un total esencial en varios procesos bioquimicos y fisiológicos como la reproducción, el crecimiento, el desarrollo embrionario y la diferenciación de los tejidos epiteliales. El nuevo interés hacia esta vitamina y hacia los retinoides en general se basa en el hecho de que estas sustancias pueden inhibir el desarrollo de tumores en muchos sistemas experimentales. En efecto se ha demostrado que los retinoides bloquean in vitro la transformación neoplásica producida por cancerigenos químicos, y que, in vivo, pueden prevenir la inducción de tumores por parte de dichos compuestos. Por tanto, los retinoides pueden considerarse potenciales agentes de prevención. El tratamiento con retinoides, sin embargo, se ve dificultado por su toxicidad, especialmente a nivel hepático. La única excepción está representada actualmente por la N-(4-Hydroxy Phenil) Retinamida (HPR), un análogo sintético de la Vitamina A que, a diferencia de muchos otros retinoides, no se acumula en el hígado y puede ser eficaz y al mismo tiempo relativamente no tóxico. La HPR, objeto de un estudio actualmente en curso, con su fase I concluida, en pacientes tratadas por carcinoma mamario en el Istituto Nazionali de Tumori de Milan, merece ser tenida en cuenta por los oncólogos clínicos

Tratamento cirúrgico conservador do câncer de mama / Conservative surgical treatment of breast cancer

Nos últimos 15 anos o tratamento cirúrgico do câncer de mama foi revolucionado por alguns novos conceitos na história natural destes tumores. A impossibilidade de controlar a doença com uma cirurgia alargada, a identificaçäo de tumores cada vez menores com o uso da mamografia, a possibilidade da "paciente atual" participar da escolha do tratamento , criaram as condiçöes para um tratamento conservador. Os resultados retrospectivos e, especialmente, prospectivos, dos estudos sobre o tratamento conservador têm demonstrado que a terapia de combinaçäo pode fornecer um adequado controle local do tumor. O Trial I de Miläo, comparando a mastectomia de Halsted versus a QUART (quadrantectomia, dissecçäo axilares e radioterapia), forneceu uma importante contribuiçäo mostrando näo existir diferenças na sobrevida global, período livre de doença e recidivas locais entre os dois tipos de tratamento