Introduction: Claudins are tight junction molecules that have been associated with breast cancer prognosis. The claudin-low intrinsic subtype of invasive carcinoma was recently described and associated with high grade carcinoma, low junction molecules expression and worse response to chemotherapy. However, it is not known whether the expression of claudins may provide clues as to carcinoma in situ prognosis. The aim of study was evaluate the association between claudin–4 expression and disease-free survival and histologic type of local recurrence in carcinoma in situ after longer follow up. Methods: A tissue microarray (TMA) block was constructed from 137 pure carcinoma in situ paraffin blocks sampled from patients treated from 1999 to 2009. The TMA was submitted to immunohistochemical staining for claudin-4. A claudin-4 score calculated based on percentage and intensity of expression, categorized samples as: claudin-4-low or claudin–4-high. Clinical data, treatment data, local recurrence data and survival of each patient were reanalyzed from medical records. Kaplan-Meier curves, log-rank and Wilcoxon tests were used to analyze disease-free survival; qui-square and Fisher test were employed to compare others variables; a significance level of 5 % was used. Results: Claudin-4 expression was evaluated in 86 samples, 88.4% were claudin-4-high and 11.6% claudin-4-low. Mean follow up was 8.2 years ( and local recurrence rate was 10.5 %. There was significant difference in the disease-free survival between claudin-4-high and claudin-4-low (4.9 x 1.9 respectively, p= 0.02); however there was no difference between both in histologic type of recurrence, invasive or in situ (p=0.44). Conclusion: In our samples, claudin-4-high expression in carcinoma in situ was more frequent than low expression. Our data showed that claudin-4-low expression had a worse prognosis in carcinomas in situ (inferior disease-free survival) but it was similar to claudin-4-high in histologic type of local recurrence. Citation Format: Duarte GM, Almeida NR, Tocchet F, Espinola J, Pinto T, Barreto CT, Pinto GA, Soares FA, Marshall P, Paiva GR. Claudin-4 expression is associated with disease free survival in breast carcinoma in situ: Mean follow up of 8.2 years [abstract]. In: Proceedings of the 2016 San Antonio Breast Cancer Symposium; 2016 Dec 6-10; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2017;77(4 Suppl):Abstract nr P3-17-05.

Introduction: Claudins are tight junction molecules and have been associated to breast cancer prognosis. Claudin-low intrinsic subtype of invasive carcinoma was described recently and has been related to high grade carcinoma, low junction molecules expression and worse chemotherapy response. However, it is unknown whether Claudins expression could be associated to carcinoma in situ prognostic. The aim of this study was evaluated the Claudin – 4 expression in carcinoma in situ and its association with local recurrence, clinical and immunohistochemistry characteristics. Methods: A tissue microarray (TMA) block was constructed, using region of interesting, with 137 pure carcinoma in situ paraffin blocks of patients treated in the Women 's Hospital Prof. Dr. José Aristodemo Pinotti – UNICAMP from 1999 to 2009. The TMA was submitted to immunohistochemistry analyze to: Claudin-4, beta-catenin, e-caderin, estrogen receptor (ER), progesterone receptor (PR), HER-2 and Ki-67. It was calculated Claudin-4 score based in percentage and intensity of expression and categorized in: Claudin-4 low and Claudin – 4 high. The clinical data, treatment data (surgery, radiotherapy and tamoxifen use), local recurrence data (date and type) and death of each patient were reviewed in the medical records. The statistical analyze used Kaplan-Meier curve and log-rank test to disease free survival; qui-square and Fisher test to compare others variables; significance level of 5 % was used. Results: It was possible to evaluate Claudin-4 expression in 86 cases, 88.4% were Claudin-4 high and 11.6% Claudin-4 low. The follow up mean was 69 months and local recurrence rate was 10.5 %. There was no significant difference in local recurrence rate between Claudin-4 high and Claudin-4 low (10.0% x 10.5% , p=1.0).The disease free survival was similar between Claudin-4 low and Claudin-4 high (p=0.559). The Claudin- 4 high was significantly more frequent in beta-catenin positive patients (p=0.048). There was no association significantly between Claudin-4 expression and: age (p=0.66), histology type (p=0.75), surgery (p=0.102), radiotherapy (p=0.29), tamoxifen use (p=0.432), ER (p=0.33), PR (p=1.0), HER-2 (p=0.23) and e-caderin (p=0.21). Conclusion: Despite the Claudins are related to invasive carcinoma prognosis, our outcome did not show difference in local recurrence and disease free survival between Claudin-4 low and high in carcinoma in situ. The beta-catenin and claudin-4 expressions were significantly associated. Citation Format: Duarte GM, Toucchet F, Espinola JP, Barreto CR, Paiva Silva GR, Almeida NR, Soares F, Pinto G, Marshall P. Claudin -4 expression in carcinoma in situ and its association with local recurrence, clinical and immunohistochemistry characteristics. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-17-10.

Objective: To assess the association of MRI BPE and pathological response in women diagnosed with stage II/III breast cancer submitted to NAC. Methods: This observational and cross-sectional retrospective study was performed in consecutive women who underwent NAC and had MRI exams before and after chemotherapy. The MRI was done before and after 2 weeks of completing NAC. BPE was classified according to ACR-BIRADS 5th edition. The type of BPE before NAC, its changes and the relationship to total pathologic complete response (TpCR) were evaluated. Data were paired with patient age, size on MRI before and after NAC, features of clinical response according to the RECIST criteria, tumor grade and immunohistochemical (IHC) subtypes. MRI assessment included amount of fibroglandular tissue, symmetry of BPE and measurement of tumor at the longest diameter. All images were blinded reviewed by a radiologist. We used for the changes of the BPE the Bowker symmetry test or the McNemar test and to analyze the factors related to the clinical and pathologic responses, logistic regression analysis. The level of significance adopted was 5% (p<0.05). Results: We studied 71 women between 2009 and 2016. The medium age was 37 years old. BPE was symmetrical in 68 women (95.8%). Moderate and marked BPE was present in 28 (39.4%) of the affected breasts and in 25 (34.2%) of the contralateral breasts. After NAC all BPE were symmetrical and just 3% of them were moderate or marked. Regarding the IHC subtype, 40 women (56.3%) were triple negative or HER2 positive, and these women had a higher frequency of TpCR (55% for each, compared to 12.9% in patients with luminal subtypes). We found to be independently associated with pCR: the reduction of BPE (in the affected or contralateral breast) and the molecular subtypes triple negative and HER2 positive Table 1. Multivariate Analysis related to TpCR (n=71).VariableCategoryP-ValueO.R.*CI 95% O.R.*Tumor Size on MR pre-MAC (cm) 0.1710,8590.691-1.068Luminal subtypeLuminal B (ref.)---1.00--- Luminal A0.3120.450.10-2.11 HER2pos/ Luminal B HER20.0055.781.71-19.58 Triple negative0.0493.271.01-10.64Age (years) 0.3870.9820.942-1.023Nottingham grade1 (ref.)---1.00--- 20.0817.830.78-79.16 30.0967.100.71-71.31BPE pre-NAC (S or A)Asymmetric (ref.)---1.00--- Symmetric0.3273.030.33-27.76BPE pre-NAC affected breastMinimal (ref.)---1.00--- Mild0.8120.860.24-3.09 Moderate0.3711.890.47-7.64 Marked0.5911.570.30-8.17BPE pre-NAC contralateral breastMinimal (ref.)---1.00--- Mild0.7130.790.22-2.81 Moderate0.2502.330.55-9.77 Marked0.4701.880.34-10.43BPE ChangeSame/increased (ref.)---1.00--- Reduction0.0263.011.14-7.96* OR (Odds Ratio) = Risk ratio to pCR; (n=26 pCR, n=7 DpCR, n=31 PR e n=7 ED, where Total pCR is pathological complete response (without invasive and DCIS in the breast and axilla) DpCR is pathological response with just DCIS, PR is partial response and ED is stable disease – we haven't progression disease). CI 95% OR = Confidence interval of 95% to risk ratio. Ref.: reference level. Proportional risk models. Conclusion: BPE reduction was significantly associated with TpCR. Nevertheless, patterns of BPE pre-NAC have no association with pathological response. Citation Format: Teixeira SRC, Camargo HSAd, Ramalho S, Natal R, Machado HdC, Camargo MMAd, Azevedo J, Arruda MdS, Negrão EMS, Almeida NR, Teixeira AL, Cabello V, Cabello C. Breast cancer and magnetic resonance imaging (MRI): Background parenchymal enhancement (BPE) predicting response to neoadjuvant chemotherapy (NAC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P4-02-09.