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.

Association Between GATA3 and Histopathological and Immunohistochemical Parameters in Early-Infiltrating Breast Carcinomas.

Objective: This study evaluated the frequency of GATA-binding protein 3 (GATA3) expression in early breast cancer and its relationship with histopathological and immunohistochemical parameters. Materials and Methods: GATA3 was analysed by immunohistochemistry in histological sections of tumors from 105 female patients, with histological diagnosis of invasive breast carcinoma (BC), at clinical stages I, II and IIIA, who underwent primary surgical treatment. GATA3 nuclear expression was determined as the percentage of positive tumor cells and further categorized as high (positive expression in more than 95% of cells) or non-high (negative or low positive expression in up to 95% of tumor cells). GATA3 expression was analysed according to the patient age, tumor and node pathological stage, histological type, histological and nuclear grade, lymphovascular invasion, and estrogen receptor (ER), progesterone receptor (PR), androgen receptor (AR), human epidermal growth factor 2 (HER2) status, and Ki-67 expression. Results: GATA3 expression was positive in 103 cases (98.1%). High expression was significantly associated with low histological and nuclear grade, positive hormonal receptors, and less proliferative activity based on Ki-67 expression. A prominent feature was that 94.7% of the ER-positive/HER2-negative cases presented high-GATA3 expression, as 94.0% of the tumors showing high-GATA3 were ER-positive. In ER-negative/HER2-positive or ER-negative/HER2- negative, high-GATA3 was present in 25% while 75% were non-high-GATA3 compared with ER-positive/HER2- negative (4.1%) and ER-positive/HER2-positive (20%). Proliferative activity in triple-negative breast cancer tended to be higher among tumors with low-GATA3, irrespective of AR expression. In the group of ER-positive/HER2-negative tumors only three cases were low-GATA3 (85% and 80%), both with high proliferative activity. Conclusion: High GATA3 expression is associated with favorable histopathologic and immunohistochemical BC prognostic factors.

Extended Sentinel Node Biopsy in Breast Cancer Patients who Achieve Complete Nodal Response with Neoadjuvant Chemotherapy.

Neoadjuvant chemotherapy (NAC) can eradicate axillary disease in breast cancer (BC) patients. Sentinel node biopsy (SNB) in patients with positive axilla who accomplish complete clinical response after NAC is a new opportunity for changing paradigms and decreasing the extension and the morbidity of axillary surgery. The aim of this article is to review the limits of SNB in this setting and present the current status of an expanded modification of this technique. False-negative rates (FNRs) of conventional SNB exceed the threshold of 10%, and are not acceptable. The extended SNB (ESNB) entails the removal of at least 3 lymph nodes (LNs) including the sentinel node (SN) mapped by dual tracers and a marked lymph node (LN) that was found previously metastatic. This node by node removal procedure greatly reduces the FNRs of the procedure. Despite that axillary lymph node dissection (ALND) is still the standard of care for patients with involved LNs before NAC, the ESNB is a valid option for selected patients in whom axillary positive disease is converted to negative. When ESNB is negative in such cases (immunohistochemistry included), the omission of ALND seems to be safe.

Nipple-sparing mastectomy for early breast cancer: the importance of intraoperative evaluation of retroareolar margins and intra-nipple duct removal.

BACKGROUND: Nipple-sparing mastectomy (NSM) is increasingly performed for breast cancer (BC) treatment. To ensure local control with this procedure, it is important to obtain clear surgical margins. Here, we aimed to estimate the confidence in intraoperative evaluation of the retroareolar margin (IERM) and the necessity of removing the intra-nipple ducts. METHODS: In this retrospective cohort study, we evaluated 224 BC (infiltrating carcinoma 178, ductal carcinoma in situ 46) patients, who underwent NSM. IERM was determined via cytology and frozen sections. Following gland removal, the intra-nipple ducts were excised and embedded in paraffin for analysis. The retroareolar tissue was also paraffin-embedded and reanalyzed for definitive evaluation of retroareolar margins (DERM). The IERM predictive capacity in relation to DERM and the frequency of intra-nipple duct involvement were estimated. RESULTS: IERM classified the sub-nipple areolar complex area as cancer-free in 219 cases (97.8%). The condition of clear retroareolar margin was confirmed by DERM in 216 cases (98.6%). The IERM accuracy was estimated as 98.6%. Ductal carcinoma in situ was detected in intra-nipple ducts using paraffin sections in 1.8% of the cases, despite clear IERM (4/219). CONCLUSIONS: In conclusion, IERM affords high accuracy and its results are suitable to manage the nipple-areolar complex. Nevertheless, some patients may retain residual disease in the intra-nipple ducts; thus, these ducts should ideally be removed during NSM.

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.

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.

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.