Long-Term Results of Intraoperative Radiation Therapy for Early Breast Cancer Using a Nondedicated Linear Accelerator.

Purpose: To present the long-term results of intraoperative radiation therapy (IORT) for early breast cancer using a nondedicated linear accelerator. Methods and Materials: The eligibility criteria were biopsy-proven invasive carcinoma, age ≥40 years, tumor size ≤3 cm, and N0M0. We excluded multifocal lesions and sentinel lymph node involvement. All patients had previously undergone breast magnetic resonance imaging. Breast-conserving surgery with margins and sentinel lymph node evaluation using frozen sections were performed in all cases. If there were no margins or involved sentinel lymph nodes, the patient was transferred from the operative suite to the linear accelerator room, where IORT was delivered (21 Gy). Results: A total of 209 patients who were followed up for ≥1.5 years from 2004 to 2019 were included. The median age was 60.3 years (range, 40-88.6), and the mean pT was 1.3 cm (range, 0.2-4). There were 90.5% pN0 cases (7.2% of micrometastases and 1.9% of macrometastases). Ninety-seven percent of the cases were margin free. The rate of lymphovascular invasion was 10.6%. Twelve patients were negative for hormonal receptors, and 28 patients were HER2 positive. The median Ki-67 index was 29% (range, 0.1-85). Intrinsic subtype stratification was as follows: luminal A, 62.7% (n = 131); luminal B, 19.1% (n = 40); HER2 enriched 13.4% (n = 28); and triple negative, 4.8% (n = 10). Within the median follow-up of 145 months (range, 12.8-187.1), the 5-year, 10-year, and 15-year overall survival rates were 98%, 94.7%, and 88%, respectively. The 5-year, 10-year, and 15-year disease-free rates were 96.3%, 90%, and 75.6%, respectively. The 15-year local recurrence-free rate was 76%. Fifteen local recurrences (7.2%) occurred throughout the follow-up period. The mean time to local recurrence was 145 months (range, 12.8-187.1). As a first event, 3 cases of lymph node recurrence, 3 cases of distant metastasis, and 2 cancer-related deaths were recorded. Tumor size >1 cm, grade III, and lymphovascular invasion were identified as risk factors. Conclusions: Despite approximately 7% of recurrences, we may infer that IORT may still be a reasonable option for selected cases. However, these patients require a longer follow-up as recurrences may occur after 10 years.

Measuring plasma levels of three microRNAs can improve the accuracy for identification of malignant breast lesions in women with BI-RADS 4 mammography.

A BI-RADS category of 4 from a mammogram indicates suspicious breast lesions, which require core biopsies for diagnosis and have an approximately one third chance of being malignant. Human plasma contains many circulating microRNAs, and variations in their circulating levels have been associated with pathologies, including cancer. Here, we present a novel methodology to identify malignant breast lesions in women with BI-RADS 4 mammography. First, we used the miRNome array and qRT-PCR to define circulating microRNAs that were differentially represented in blood samples from women with breast tumor (BI-RADS 5 or 6) in comparison to controls (BI-RADS 1 or 2). Next, we used qRT-PCR to quantify the level of this circulating microRNAs in patients with mammograms presenting with BI-RADS category 4. Finally, we developed a machine learning method (Artificial Neural Network - ANN) that receives circulating microRNA levels and automatically classifies BI-RADS 4 breast lesions as malignant or benign. We identified a minimum set of three circulating miRNAs (miR-15a, miR-101 and miR-144) with altered levels in patients with breast cancer. These three miRNAs were quantified in plasma from 60 patients presenting biopsy-proven BI-RADS 4 lesions. Finally, we constructed a very efficient ANN that could correctly classify BI-RADS 4 lesions as malignant or benign with approximately 92.5% accuracy, 95% specificity and 88% sensibility. We believe that our strategy of using circulating microRNA and a machine learning method to classify BI-RADS 4 breast lesions is a non-invasive, non-stressful and valuable complementary approach to core biopsy in women with BI-RADS 4 lesions.

IDIOPATHIC GRANULOMATOUS MASTITIS: DIAGNOSIS AND FOLLOW-UP WITH MAGNETIC RESONANCE IMAGING / Mastite granulomatosa idiopática: diagnóstico e seguimento com ressonância magnética

Granulomatous mastitis is a rare and benign condition of the breast that, in some cases, has an unknown etiology of benign inflammatory disease know as idiopathic mastitis. Your diagnosis is usually made by exclusion. Imaging tests have shown nonspecific findings that may suggest an inflammatory disease, a carcinoma, or no changes. A differential diagnosis should be made with other causes of mastitis, always alerting to the risk of inflammatory carcinoma. Imaging tests are more useful to rule out malignancy than to confirm idiopathic granulomatous mastitis. Because both imaging and physical examination can mimic a malignant lesion of the breast, the histopathological report is fundamental to establish the diagnosis. Its etiology remains unknown, so the treatment is controversial in the literature, with some authors recommending surgery, others immunosuppression, and, finally, some antibiotics. We report the case of a 21-year-old woman with a suspected lesion in the breast associated with papillary discharge. During the investigation, there was a 12 x 6 x 8.5 cm enhancement on magnetic resonance imaging associated with inflammatory signs on the skin and lymph nodes. Anatomopathological examination revealed a idiopathic granulomatous mastitis. The enhancement disappeared completely after conservative treatment with corticosteroids. Mammography and ultrasound may also demonstrate nonspecific changes, such as focal asymmetry, undefined mass, or distortion. Despite the limitations of the imaging studies, it has been demonstrated in this report that MRI can be used to monitor the clinical response to conservative treatment and follow-up by the risk of recurrence.

A mastite granulomatosa é uma condição rara e benigna da mama que, em alguns casos, possui etiologia desconhecida de doença inflamatória benigna, a mastite idiopática. Seu diagnóstico normalmente é feito por exclusão. Os exames de imagens têm demonstrado achados inespecíficos que podem sugerir uma doença inflamatória, um carcinoma ou não apresentar alterações. Deve ser realizado um diagnóstico diferencial com outras causas de mastites, sempre alertando para o risco de carcinoma inflamatório. Os exames de imagem servem mais para descartar uma malignidade do que para confirmar a mastite granulomatosa idiopática. Em função de tanto os exames de imagem como o exame físico poderem simular uma lesão maligna da mama, o laudo histopatológico é fundamental para estabelecer o diagnóstico. A sua etiologia permanece desconhecida, portanto, o tratamento é controverso na literatura, com alguns autores recomendando cirurgia, outros a imunossupressão e, por fim, alguns antibióticos. É apresentado o caso de uma paciente de 21 anos com uma lesão suspeita na mama associada à descarga papilar. Durante a investigação, houve um realce de 12 x 6 x 8,5 cm na ressonância magnética associado a sinais inflamatórios na pele e nos linfonodos. O exame anatomopatológico evidenciou um quadro de mastite granulomatosa idiopática. O realce desapareceu completamente após o tratamento conservador com corticoterapia. A mamografia e o ultrassom também podem demonstrar alterações inespecíficas, tais como assimetria focal, massa indefinida ou distorção. Apesar das limitações dos exames de imagem, demonstrou-se, neste relato, que a ressonância magnética pode ser utilizada para monitorar a resposta clínica ao tratamento conservador e o acompanhamento pelo risco de recorrência.

Magnetic resonance imaging-guided occult breast lesion localization and simultaneous sentinel lymph node mapping.

BACKGROUND: Radio-guided occult lesion localization is a valid technique for the diagnosis of suspicious non-palpable lesions. Here we determine the feasibility of pre-operative localization of occult suspect non-palpable breast lesions using radio-guided occult lesion localization, as well as for identifying the sentinel lymph node. METHODS: This is a descriptive study of data collected retrospectively. Pre-operative mapping of 34 breast lesions in 25 patients suspected of being malignant was performed using conventional imaging methods with a magnetic resonance imaging-guided radiopharmaceutical injection. RESULTS: The mean time required to perform the localization was 25 minutes. After resection of the lesions using a gamma probe, malignancy was confirmed in fifteen patients (60.0%), with nine invasive ductal carcinomas, two invasive lobular carcinomas, and four in situ ductal carcinomas The resection was confirmed by the complete removal of the radioactive material. The pathologic results and images were concordant in all but two cases, which were submitted for new magnetic resonance imaging examinations and surgery that confirmed the malignancies. Of the 15 patients with confirmed malignancies, 10 had sentinel lymph node resection. Of these, eight were negative for metastases, one had micro-metastases and one had confirmed metastases. Three patients had full axillary node dissection, with metastases found in only one. No side effects were observed with magnetic resonance-guided radiopharmaceutical injection. CONCLUSIONS: The sentinel node occult lesion localization technique is a simple, reproducible and effective alternative approach to occult lesions compared to other methods, such as mammotomy and the hook-wire localization technique, for mapping suspect breast lesions and identifying lymph node metastasis.

Intraoperative radiation therapy in early breast cancer using a linear accelerator outside of the operative suite: an "image-guided" approach.

PURPOSE: To present local control, complications, and cosmetic outcomes of intraoperative radiation therapy (IORT) for early breast cancer, as well as technical aspects related to the use of a nondedicated linear accelerator. METHODS AND MATERIALS: This prospective trial began in May of 2004. Eligibility criteria were biopsy-proven breast-infiltrating ductal carcinoma, age >40 years, tumor <3 cm, and cN0. Exclusion criteria were in situ or lobular types, multicentricity, skin invasion, any contraindication for surgery and/or radiation therapy, sentinel lymph node involvement, metastasis, or another malignancy. Patients underwent classic quadrantectomy with intraoperative sentinel lymph node and margins evaluation. If both free, the patient was transferred from operative suite to linear accelerator room, and IORT was delivered (21 Gy). Primary endpoint: local recurrence (LR); secondary endpoints: toxicities and aesthetics. Quality assurance involved using a customized shield for chest wall protection, applying procedures to minimize infection caused by patient transportation, and using portal films to check collimator-shield alignment. RESULTS: A total of 152 patients were included, with at least 1 year follow-up. Median age (range) was 58.3 (40-85.4) years, and median follow-up time was 50.7 (12-110.5) months. The likelihood of 5-year local recurrence was 3.7%. There were 3 deaths, 2 of which were cancer related. The Kaplan-Meier 5-year actuarial estimates of overall, disease-free, and local recurrence-free survivals were 97.8%, 92.5%, and 96.3%, respectively. The overall incidences of acute and late toxicities were 12.5% and 29.6%, respectively. Excellent, good, fair, and bad cosmetic results were observed in 76.9%, 15.8%, 4.3%, and 2.8% of patients, respectively. Most treatments were performed with a 5-cm collimator, and in 39.8% of the patients the electron-beam energy used was ≥12 MeV. All patients underwent portal film evaluation, and the shielding was repositioned in 39.9% of cases. No infection or anesthesia complications were observed. CONCLUSIONS: Local control with IORT was adequate, with low complication rates and good cosmetic outcomes. More than one-third of patients benefited from the "image-guidance" approach, and almost 40% benefited from the option of higher electron beam energies.