Background: Patients with HER2-positive early breast cancer who have residual invasive disease after neoadjuvant chemotherapy plus HER2-targeted therapy have a high risk of recurrence and death. The current standard of care is continuation of the same HER2-targeted therapy in the adjuvant setting for one year. T-DM1 has shown activity and a favorable benefit-risk profile in metastatic patients with disease progression after prior chemotherapy plus HER2-targeted therapy. Thus, T-DM1 may also be active in patients with residual invasive disease after neoadjuvant HER2-targeted therapy. Methods: KATHERINE (NCT01772472/BO27938/NSABP B-50-I/GBG 77) is a phase III, open-label, global study of patients with centrally confirmed HER2-positive (IHC3+ or ISH+) primary breast cancer (T1–4, N0–3, M0) who received neoadjuvant chemotherapy plus HER2-targeted therapy, which had to include a taxane and trastuzumab, followed by surgery, with pathologically documented residual invasive disease in the breast and/or axillary lymph nodes. Within 12 weeks of surgery, patients were randomized 1:1 to T-DM1 (3.6 mg/kg IV q3w) or trastuzumab (6 mg/kg IV q3w), for 14 cycles. Randomization was stratified by clinical stage at presentation, hormone receptor status, single versus dual neoadjuvant HER2-targeted therapy, and pathological nodal status after neoadjuvant therapy. Patients received radiotherapy and/or endocrine therapy per local standards. The primary endpoint is invasive disease-free survival (IDFS). A single interim analysis (IA) was planned after approximately 67% of the IDFS events required for the primary analysis had occurred, with an efficacy stopping boundary of HR?0.732 or p<0.0124. The statistical plan stipulated an IA of OS if the IDFS IA boundary was crossed. Secondary endpoints include IDFS including second primary non-breast cancer, disease-free survival, distant recurrence-free interval, overall survival, and safety. Results:After review of the pre-specified IA, the IDMC recommended full analysis and disclosure of the results. With 256 IDFS events reported, administration of T-DM1 significantly improved IDFS compared with trastuzumab (unstratified HR=0.50; 95% CI: 0.39 to 0.64; p<0.0001). IDFS events occurred in 91 patients (12.2%) in the T-DM1 arm compared with 165 patients (22.2%) in the trastuzumab arm. T-DM1 treatment increased estimated three-year IDFS rates (88.3% vs 77.0% with trastuzumab). A consistent benefit was shown across all stratification subgroups. With 98 deaths reported, the OS analysis is immature (HR=0.70; 95% CI: 0.47 to 1.05; p=0.085). The safety data were consistent with the known safety profile of T-DM1, with expected increases in AEs associated with T-DM1 compared to trastuzumab alone. One grade 5 AE (0.1%) occurred in each arm. Conclusions: Adjuvant T-DM1 substantially improved IDFS in patients with HER2-positive early breast cancer with residual disease after completion of neoadjuvant therapy. Citation Format: Geyer, Jr. CE, Huang C-S, Mano MS, Loibl S, Mamounas EP, Untch M, Wolmark N, Rastogi P, Fischer HH, Redondo A, Jackisch C, Jacot W, Conlin AK, Schneeweiss A, Wapnir IL, Fasching PA, DiGiovanna MP, Wuelfing P, Arce-Salinas C, Crown JP, Shao Z, Rota Caremoli E, Wu H, Lam LH, Tesarowski D, Smitt M, Douthwaite H, Singel SM, von Minckwitz G. Phase III study of trastuzumab emtansine (T-DM1) vs trastuzumab as adjuvant therapy in patients with HER2-positive early breast cancer with residual invasive disease after neoadjuvant chemotherapy and HER2-targeted therapy including trastuzumab: Primary results from KATHERINE [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr GS1-10.

Background:Breast cancer is the most common cancer in women. While its incidence has been increasing, recurrence and mortality rates have been decreasing. Because of that, cancer can now be regarded as a transient shock that does not prevent the survivors to live normal lives, including returning to their workplace. From a social perspective, long periods of sick leave have a strong economic impact. From the patient perspective, prolonged sick leave can cause financial difficulties and emotional distress. In United States and Europe, RTW rates vary among breast cancer patients from 24-66% after 6 months and 53-82% after 36 months of diagnosis. Factors associated with the decision to return to work are: age, chemotherapy, sequelae related to cancer therapy and support from the employer and coworkers. However, these findings vary among the different populations studied, suggesting that other factors may also interfere with the decision to return to work. Data on RTW after breast cancer diagnosis is not avaliable in South America nor in developing countries – where the workforce tends to be relatively younger than average. The primary objective of this study was to evaluate RTW rates on months 12 and 24 after breast cancer diagnosis, and to evaluate factors associated with the decision to return to work. Methods: Prospective, observational study evaluating RTW rates in patients diagnosed with breast cancer, > 18 and <57 years old (in Brazil women can retire at age 60) and under remunerated work for at least 03 months at the time of diagnosis. Patients with metastatic disease were excluded. Based on previously data, we estimated that 125 patients would be required to achieve the primary endpoint. Each patient was followed for 02 years. On months 6, 12 and 24 they answered a telephone interview and the FACT-B questionnaire. Disease characteristics and treatment were collected from electronic medical records. After completion of all third row of interviews (by september, 2016) we will perform univariate and multivariate analysis by logistic regression method to determine the independent predictors of return to work. Results: Between july, 2012 and september, 2014, 125 patients were enrolled. The median age was 45.1 (range 25-57). Half of the patients (52.9%) were married at the time of diagnosis, and 96.9% received support from their life partner. Most of them reported that they liked their job (93.8%) and received support from their employer (61.5%), but only 29.1% reported adjustment offering, so that they could keep working during treatment. Almost half of patients (47.6%) had stage II disease, 75.4% and 19.7% were HR and Her 2 positive, respectively, and 92.6% received chemotherapy as part of their treatment. Overall, 22.1% and 28.8% of patients returned to work, at 6 and 12 months after breast cancer diagnosis, respectively. Conclusion: Twelve months after breast cancer diagnosis, less than 30% of the patients had returned to work. By september, 2016, we will have completed the “24 month” interviews and will present RTW rates at that time and also correlative analyses of factors that affected the RTW in this population. Citation Format: Landeiro LG, Fraile NMP, Fede AB, Fonseca LG, Testa L, Petry V, Gonçalves MS, Costa RDP, Cohn DB, Ferrari MM, Sunahara RS, de Gouveia ACC, Mano MS. Return to work after breast cancer diagnosis: An observational prospective study of 125 patients in South America [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 P4-19-06.

Introduction: Development of the nipple-sparing mastectomy (NSM) technique has constituted a significant advance in the surgical treatment of selected cases of breast cancer. The most important aspect of areolar complex preservation is the exclusion of carcinoma involving the nipple. The retroareolar surgical margin is usually sampled and subjected to an intraoperative evaluation by frozen section examination in order to avoid a second procedure. However, this method is not standardized resulting in variable rates of false-negative results. Here, a new technique is proposed for the intraoperative study of the retroareolar margin. This ex vivo study was conducted by performing a simulated NSM procedure for patients undergoing total mastectomy to assess the impact of these measures on the accuracy of retroareolar frozen section examination. Materials and Methods: Between September 2012 and April 2014, we studied 158 mastectomy specimens from patients undergoing total mastectomy for breast cancer at the Cancer Institute of the State of São Paulo. Inclusion criteria were stage Tis-T3 tumors, multifocal and multicentric breast carcinoma, unicentric carcinoma not suitable to quadrantectomy. Patients submitted to neoadjuvant chemotherapy were also included. To obtain the entire sample area, the terminal retroareolar milk duct bunch was isolated. Fragments approximately 1.5 cm in length were excised and sectioned in parallel at the base of the nipple using a cold bistoury. Three transverse histological sections (4 μm each) at 200 μm intervals that included the entire isolated fragments were subjected to frozen section examination. The sections were stained with hematoxylin-eosin (H&E) and were evaluated. The remainder of each fragment was embedded in paraffin and 4 μm sections were subsequently stained with H&E and examined. Results: A total of 158 mastectomy specimens involving mammary carcinoma of no special type were examined. These included 15 (9.5%) in situ stage tumors, 36 (22.8%) stage I tumors, 71 (44.9%) stage II tumors, and 36 (22.8%) stage IIIA tumors. Paraffin examinations identified 25 retroareolar fragments compromised by carcinoma, resulting in 16.1% prevalence. Of the frozen sections examined, 2/158 (1.3%) had false-negative results and 5/158 (3.1%) had false-positive results. For the former two cases, the corresponding paraffin examinations detected low-grade carcinoma in situ and a residual cell cluster with a diameter less than 1 mm. The latter was found in a mastectomy specimen from a patient that underwent neoadjuvant chemotherapy. For the three cases involving false-positive results, the corresponding paraffin examinations revealed no atypical ductal hyperplasia present, one sclerosing intraductal papilloma and one nipple syringomatous adenoma. Statistical analysis revealed that the frozen section examinations performed had a sensitivity rate of 92.0% and a specificity rate of 96.2%. In addition, the positive predictive value (PPV) was 82.1%, the negative predictive value (NPV) was 98.4%, and the accuracy was 95.4%. Conclusion: The frozen section examination technique described here detected nipple involvement in breast cancer with greater accuracy than the frozen section usually performed by most surgeons. Citation Format: Piato JR, Aguiar FN, Mota BS, Dória MT, Alves-Jales RD, Messias AP, Goncalves R, Mano MS, Soares JM, Ricci MD, Filassi JR, Baracat EC. Improved frozen section examination of the retroareolar margin for prediction of nipple involvement in breast cancer. [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 P3-13-09.

No abstract

Background: Access to medical care vary across the world and is related to different health systems with an impact in recurrence.Objective: To evaluate disparities in breast cancer(BC) diagnosis and treatment between public and private services in southwest Brazil and at two public safety net hospitals in Houston, Texas.Methods: Women diagnosed with BC stages I-III between 2009 to 2011, and treated at the four hospitals in Brazil and two health centers in US were included. All statistical analyses were performed in R studio software, and p<0.05 was considered significant.Results: 1245 women were included: 967 from public health system (PHS) (20.3% from Houston, Texas) and 274 from private system(PS). Recurrence rate was higher in PHS (14.6% vs. 2.6%, p<0.001) Table 1. Clinical and demographic characteristics of the patientsCharacteristicsPublic (%), n=967Private (%), n=274pDiscovery of BC   By patient530 (54.8)92 (33.5) Routine exam87 (9)109 (39.8) Screening mammography270 (27.9)23 (8.4) Other80 (8.3)50 (18.3)<0.001Initial treatment   Surgery687 (71)241 (88) Neo-adjuvant chemotherapy224 (23.2)27 (9.8) Neo-adjuvant hormone therapy23 (2.3)27 (9.8) Not available33 (3.4)3 (1.1)<0.001Clinical Stage   I293 (30.3)113 (41.2) II342 (35.4)52 (19) III271 (28)15 (5.5) Unknown61 (6.3)94 (34.3)<0.001Subtype   HR+/HER2 -561 (58)192 (70.1) HR-/HER2+108 (11.1)29 (10.6) HR-/HER2+76 (7.9)14 (5.1) Triple negative149 (15.4)28 (10.2) Unknown73 (7.6)11 (4)0.012Symptomatic at Diagnosis   Yes591 (61.1)100 (36.5) No306 (31.6)97 (35.4) Unknown70 (7.2)77 (28.1)<0.001Recurencen=772n=146 No719 (74.4)193 (70.4) Yes142 (14.6)7 (2.6) Unknown106 (11)74 (27)<0.001 . Considering the interval in weeks: symptoms to diagnosis, diagnosis to first treatment (either surgery or neoadjuvant chemotherapy), diagnosis to first systemic treatment, diagnosis to surgical treatment and diagnosis to radiotherapy were longer in public patients (24.1 vs. 8.7; 11.1 vs. 3.5; 18.6 vs. 9.8; 16.9 vs. 5.6; 51.4 vs. 26.1; p<0.001). Table 2. Delay disparities between public and private health system PublicPrivatepSymptoms to diagnosis   Number of patients575146 Time (weeks)24.1 (0.4-104.9)8.7 (0.0-43.7)<0.001Diagnosis to first treatment   Number of patients663180 Time (weeks)11.1 (2.0-31.5)3.5 (0.0-11.0)<0.001Diagnosis to first systemic treatment   Number of patients526106 Time (weeks)18.6 (2.6-44.7)9.8 (1.9-29.3)<0.001Diagnosis to surgical treatment   Number of patients657178 Time (weeks)16.9 (3.4-45.6)5.6 (0.0-32.9)<0.001Diagnosis to radiotherapy   Number of patients465127 Time (weeks)51.4 (18.7-88.4)26.1 (5.6-66.4)<0.001 In multivariate analysis, PHS (HR 1.72; 95% CI 1.34-1.88; p adj=0.003), presence of symptoms (HR 2.29; 95% CI 1.39-3.78; p adj=0.001), clinical stage III (HR 1.62; 95% CI 1.35-1.93; p adj<0.001), and triple negativity and HER2neu positivity (1.18; 95% CI 1.03-1.35; p adj=0.021) were all associated with a higher recurrence rate.Conclusions: There were significant disparities between PHS and PS. Women in the PHS presented higher rates of recurrence, advanced clinical stages at diagnosis, symptoms and more aggressive subtypes by IHC. additionally, the interval between symptoms to diagnosis and diagnosis to treatments was longer in PHS. Citation Format: NematiShafaee M, Natal RA, Ramalho S, Dória MT, Conz L, Cabello V, Pavanello M, Mano MS, Linck RDM, Batista LS, Pedro EP, Bines J, de Paula BH, Zucca-Matthes G, Bondy ML, Ellis MJ, Podany E, Debord L, Makawita S, Stewart K, Cabello C. Impact of delay in breast cancer diagnosis and treatment according to health insurance status in southwest Brazil and Houston, Texas [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 P4-10-15.