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Introduction: The addition of Trastuzumab(T) to chemotherapy (CT) revolutionized HER2-positive breast cancer(BC) and changed its natural history. We reviewed the efficacy of T outside clinical trials in a cancer comprehensive center. Methods: Ambiespective and descriptive study was conducted in Catalan Institute of Oncology (ICO-Barcelona). Estimates of progression-free survival (PFS) and overall survival (OS) were obtained with the Kaplan-Meier method and compared with LogRank test. The association of clinic-pathological variables and outcome was studied by χ2and Cox proportional hazard analysis. Results: 430 consecutive early HER2-positive BC patients (pts) were treated with adjuvant/neoadjuvant T and CT from Jan 2005 to Dec 2012. Pt basal characteristics are reported in Table 1. Neoadjuvant treatment was administrated in 230pts (54%) and in 200 (46%) in adjuvancy. Pathological complete response (pCR) in breast and nodes (ypT0/isypN0) was achieved in 48% of pts, with higher rates in hormone receptor (HR)-negative pts (62 vs 37% p=0.0005). Median duration of T: 10.6 months (m). 28%pts treated with neoadjuvant T+CT who achieved a pCR did not receive adjuvant T. Treatment discontinuation: 38pts (8.8%): 27pts due to cardiac toxicity and 4 relapsed during adjuvant T. In 87%pts, neoadjuvant CT was based on anthracyclines(A) and taxanes. Adjuvant CT: A and taxanes in 57.4%; 14%pts FAC, 15.4% A-CMF and 12% TCH. At a median follow-up of 70m (3-135), 44pts (10.4%) had relapsed: 33pts with distant M1, 9pts with only loco-regional disease and 2pts contralateral HER2-positive BC. M1 location: 46% visceral, 34% bone/lymph nodes and 20% in central nervous system (CNS). PFS was 23.4m(0-88); median OS was not reached; estimated 10 years-OS was 86.5%. Pts treated with A and taxanes had a significantly better OS compared to those treated with other CT (113 vs 98m, p= 0.009). Kaplan-Meier curve showed numerically higher relapses at 10 years in HR-positive pts (83 vs 90% p=0.8). Pts with pCR had significantly better OS (113 vs 104m, p=0.006). Pts with CNS-metastases had a significantly worse OS (13 vs 26m,p=0,02) and those with HR-negative (49 vs 24m, p= 0.033). Conclusion: In everyday clinical practice, recurrences after adjuvant/neoadjuvant trastuzumab in HER2-positive BC were less than described in the T-pivotals trials, with 10% of recurrences at a median of FU of 70m. In our series, estimated 10 years-OS was 86.5%. Pts treated with A and taxanes had a significantly better OS as well as those pts who achieved a pCR. On the contrary, pts with CNS M1 and those with HR-negative had worse prognosis. Table 1Median age51.9y (27-83)Stage I/II/III106 (25%)/ 226 (52%)/ 97 (23%)HR Positive/ Negative249 (58%)/181 (42%) Citation Format: Ortega A, Domenech M, Falo C, Gil M, Stradella A, Fernandez A, Morilla I, Villanueva R, Castany R, Vazquez S, Molina K, Bergamino M, Navarro V, Pernas S. Treatment of early HER2-positive breast cancer in trastuzumab era in everyday clinical practice: An overview after 10 years of its approval [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 P4-21-32.

e12112 Background: Pathological complete response (pCR) after neoadjuvant chemotherapy for BC has been related with survival, and the sequence of anthracyclines followed by taxanes (AT) has been the strategy to achieve this response. Some studies suggest that the reverse sequence (TA) might improve cancer outcomes. The aim of our study was to compare clinical response, toxicity and efficacy in terms of pCR rate (ypT0/pTis, ypN0) between both sequences Methods: A retrospective cohort study was designed. TA cohort received Docetaxel (100 mg/m2) x 4, followed by AC (60/600 mg/m2) x 4. AT cohort received the reverse sequence at the same doses. To be included, it was necessary to have received at least one cycle in the planned sequence. Logistic regression analysis was performed to obtain a model adjusted by age, menopausal status, tumor size, nodal status, grade, estrogen receptor (ER), progesterone receptor, and Ki67 Results: From June 2008 to December 2015, 135 consecutive patients with stage II – III HER2 negative BC were treated: TA (n = 48) and AT (n = 87). No significant differences in patient characteristics between groups were found, except for histological grade 3 (63.2% to AT vs. 35.4% to TA), and ER negative (41.4% to AT vs. 22.9% to TA). The pCR rate for TA was 16.7% (8 of 40) vs. 14.9% (13 of 74) for AT. Multivariate logistic regression analysis found OR = 3.65 to achieve pCR for TA (95%CI 1.03 – 12.94; p = .045). We also performed the same analysis for two clinical parameters of response: Neoadjuvant response index (NRI) with cut-off > 0.5 (OR 3.96, 95%CI 1.42-11.08; p = .009) and Clinical response (CR) > 50% (OR 3.65, 95%CI 1.03 – 12.94; p = .045). These parameters were correlated in our series with DFS (p = .011 to NRI and p = .00023 to CR) and OS (p = .034 to NRI and p = .0014 to CR) using the Kaplan-Meier method. No significant differences between rates of either, hospitalizations, neutropenia or dose intensity were found Conclusions: Sequence of T followed by A was slightly significantly more effective to achieve pCR as well as better clinical outcomes in our series of HER2 negative BC than classical sequence of A followed by T, and support the design of large prospective studies to confirm these results

This provides a contemporary look at the current trends of breast-conserving therapy. Though outcomes are improving, such as local control and survival, the rate of lumpectomy versus mastectomy in breast cancer patients continues to decline. Evolving techniques for the critical roles of tumor localization, margin assessment, and margin control are described. Novel complementary therapies, such as cryoablation, radiofrequency ablation, intraoperative radiation therapy, brachytherapy, partial breast irradiation, and various forms of external beam radiation deployment, are discussed. The concept of oncoplastic breast surgery, combining oncologic principles with plastic surgery techniques, has emerged as an important part of breast-conserving therapy. The combination of oncoplastic repair with partial breast radiation is changing the face of breast conservation. Neoadjuvant chemotherapy, with tumor size reduction, is allowing breast conservation in patients who would traditionally not be eligible. These advances continue to redefine breast conservation therapy.

e13530Background: brain metastases (BM) occur in 15-30% of patients with metastatic breast cancer (MBC). In spite of improvements in the treatment, the development of BM is still being a major limi...

One of the most efficacious primary therapies in HER2-positive breast cancer was published by the M.D. Anderson group in 2005. This randomized trial evaluated the addition of trastuzumab to a taxane-anthracycline based chemotherapy. Despite largely significant differences in pathological complete response (pCR) in the trastuzumab group (65 vs. 26 %) this regimen did not become a common standard due to toxicity concerns and its premature closure with a small sample size. In order to evaluate the efficacy and safety of this regimen in an off-trial setting we conducted a prospectively monitorized series of consecutive patients with early or locally advanced Her-2 positive breast cancer following the same treatment strategy. Stage II-IIIC HER2-positive breast cancer patients, including inflammatory disease, were treated with weekly-trastuzumab for 24 weeks administered concurrently with all primary chemotherapy containing paclitaxel (80 mg/m(2)) for 12 weeks and 4 cycles of FEC-75 (fluorouracil 500 mg/m(2), epirubicine 75 mg/m(2), and cyclophosphamide 500 mg/m(2)) followed by surgery. The objectives were efficacy, in terms of pCR in both the breast and lymph nodes, and safety, with close cardiac monitoring during and after treatment. From August 2004 to February 2009, 83 patients were included. Most patients (73.5 %) had node involvement and 13.2 % had inflammatory disease. Fifty-one patients (61.4 %) achieved a pCR in breast and axilla (95 % CI 50-72 %). HR-negative tumors were associated with higher pCR rate than HR-positive tumors (77 vs. 48 %, P = 0.006). At a median follow-up of 50.2 months no patient developed symptomatic cardiac failure, and 9 patients (10.8 %) presented a transient asymptomatic decrease in left ventricular ejection fraction. Primary therapy with concurrent trastuzumab plus paclitaxel-FEC for HER2-positive breast cancer in everyday practice is highly effective and safe confirming the results observed in a randomized trial stopped prematurely.

This section focuses on different aspects of the individualization of hormone treatment in breast cancer. This includes tumor-related biological factors such as expression of hormone receptors, HER-2, and Ki-67; host-related factors such as CYP2D6 or body mass index, and risk and/or development of specific toxicities and treatment adherence. The best predictor of response to hormonal interventions is the expression of hormone receptors, in particular, estrogen receptors. Treatment adherence and compliance are key factors and strategies aiming to identify and intervene when patients are at risk of abandoning treatment. Currently, routine assessment of CYP2D6 is not recommended to guide tamoxifen treatment. Likewise, there are no criteria regarding bone mass density, lipid profile, or arthralgias to recommend one class of agent versus another. Aromatase inhibitors should not be administered to patients who are pre- or perimenopausal.

Lymphangioleiomyomatosis (LAM) is a rare lung-metastasizing neoplasm caused by the proliferation of smooth muscle-like cells that commonly carry loss-of-function mutations in either the tuberous sclerosis complex 1 or 2 (TSC1 or TSC2) genes. While allosteric inhibition of the mechanistic target of rapamycin (mTOR) has shown substantial clinical benefit, complementary therapies are required to improve response and/or to treat specific patients. However, there is a lack of LAM biomarkers that could potentially be used to monitor the disease and to develop other targeted therapies. We hypothesized that the mediators of cancer metastasis to lung, particularly in breast cancer, also play a relevant role in LAM. Analyses across independent breast cancer datasets revealed associations between low TSC1/2 expression, altered mTOR complex 1 (mTORC1) pathway signaling, and metastasis to lung. Subsequently, immunohistochemical analyses of 23 LAM lesions revealed positivity in all cases for the lung metastasis mediators fascin 1 (FSCN1) and inhibitor of DNA binding 1 (ID1). Moreover, assessment of breast cancer stem or luminal progenitor cell biomarkers showed positivity in most LAM tissue for the aldehyde dehydrogenase 1 (ALDH1), integrin-beta 3 (ITGB3/CD61), and/or the sex-determining region Y-box 9 (SOX9) proteins. The immunohistochemical analyses also provided evidence of heterogeneity between and within LAM cases. The analysis of Tsc2-deficient cells revealed relative over-expression of FSCN1 and ID1; however, Tsc2-deficient cells did not show higher sensitivity to ID1-based cancer inhibitors. Collectively, the results of this study reveal novel LAM biomarkers linked to breast cancer metastasis to lung and to cell stemness, which in turn might guide the assessment of additional or complementary therapeutic opportunities for LAM. This work was funded by the Government of Catalonia grant SGR 2014-364, the "Red Tematica de Investigacion Colaborativa en Cancer" grant RD12/0036/0008, the Telemaraton 2014 "Todos Somos Raros, Todos Somos Unicos" grant P35, the Spanish Ministry of Health "Instituto de Salud Carlos III Fondo de Investigacion Sanitaria" grant PI12/01528, and a Spanish Society of Pneumology and Thoracic Surgery (Sociedad Espanola de Neumologia y Cirugia Toracica, SEPAR) grant for 2012. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.