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There is increased understanding of the heterogeneity of breast tumors, with greater emphasis now being placed on histological and molecular profiles and, in particular, their implications for prognosis and therapy. This review addresses breast cancers of unusual histological subtype with an approximate incidence ≤1%. Given the rarity of these tumors, the literature contains primarily case reports, small series, and population-based studies. Data are heterogeneous and almost entirely retrospective, frequently gathered over long time periods, in the context of changing pathological techniques and reporting. In addition, our understanding of the disease biology and therapeutic context has also evolved significantly over this time. There is often limited information about the specific therapies used and the rationale for choosing such an approach. Meaningful comparisons of treatment modalities are not feasible and it is not possible to define management guidelines. Instead, this review correlates the available information to give an impression of how each subgroup behaves—of the favored surgical technique, responses to therapy, and prognosis—as well as the emerging molecular data, highlighting new research areas for potential target in clinical trials. Each tumor subtype described represents a small but real cohort of patients with breast cancer, and although inferences may be made from this review, we are mindful of the paucity of data. The management of each patient must be considered in the context of their unique clinical presentation and correlated with the evidence-based principles that apply to more common breast cancer histologies.

TPS5610 Background: Approximately 75% of women with epithelial ovarian cancer (OC) present with advanced disease. Most of these women will ultimately recur and require life-long treatment for their cancer. Well tolerated therapies for treatment in the recurrent setting are needed. The AR is expressed in greater than 60% of cases of OC and is more prevalent than the estrogen or progesterone receptor. All past clinical studies of AR inhibition in OC have focused on unselected populations of heavily pretreated women; however preclinical data suggests that AR expression decreases in OC cells with increasing lines of therapy. Enzalutamide is a small molecule androgen receptor-antagonist that is FDA approved for treatment of prostate cancer and is currently being investigated as treatment for breast and ovarian cancer. Methods: This is a phase II, single-institution trial of enzalutamide 160mg po QD in patients with AR+ ovarian, fallopian tube or primary peritoneal cancer. Eligible patients must be found to have greater than or equal to 5% AR staining by IHC on FFPE tumor tissue and been treated with only 1,2 or 3 prior cytotoxic therapies. Patients must have RECIST 1.1 defined measurable disease. Enrolled patients are treated with enzalutamide until progression of disease or unacceptable toxicity. The primary endpoint is to estimate the proportion of women who achieve a complete or partial response by RECIST 1.1 criteria or survive progression free for at least 6 months. Secondary objectives include the retrieval of optional tumor biopsies at time of progression to evaluate the effect of enzalutamide on AR expression and to observe the effect of enzalutamide on serum testosterone and estradiol levels. This study will enroll 58 patients at Memorial Sloan Kettering Cancer Center and its regional sites. The study utilizes a safety lead-in phase and a two-stage design. The first patient enrolled in April 2015. The safety lead-in phase has been completed. The prespecified activity goal for the first stage was met; second stage accrual began in October 2016. Thus far, 35 patients have initiated treatment. Clinical trial information: NCT01974765.

e13019 Background: High grade gliomas(HGG) are aggressive primary brain tumors. Most patients relapse following adjuvant therapy and treatment options are limited. Novel therapies have impacted little on overall survival (OS). Bevacizumab is approved for use following recurrence. We aimed to evaluate the extent of clinical benefit derived from this treatment, as defined by decreased steroid usage and median OS. Methods: We retrospectively reviewed medical records of consecutive patients with recurrent HGG treated with single agent Bevacizumab from May 2009 to Dec 2012 at our institution. We recorded patient demographics, histological features, therapeutic interventions, OS, steroid use and radiological response. Results: 29 patients with recurrent glioma were identified, 19 male and 10 female, with a median age at diagnosis of 47 years (16-72). All patients developed tumour recurrence following various combinations of multimodal therapies including 1-3 partial debulking surgeries, radiotherapy and chemotherapy. The median time from diagnosis of HGG to commencement of bevacizumab was 15 months (6-42). Patients received a median of 7 cycles (1-22) of therapy on a variable dosing schedule. 4 patients are alive, 2 continue on Bevacizumab. 19 patients were on steroid therapy when commencing therapy. There was a significant reduction in mean daily steroid use during therapy (7.65mg vs 3.97mg, p = 0.012). However, daily steroid use ultimately increased in some patients following treatment failure. Interval imaging appearances improved in 6 cases, deteriorated in 15, were stable in 4 and 1 patient had a mixed response. 1 patient was not re-imaged due to deterioration in performance status on therapy. The median OS was 5.5 months (0.5-16 months) from commencement of bevacizumab. Conclusions: The management of patients with recurrent HGG is challenging and prognosis remains dismal. In our unselected cohort, Bevacizumab therapy resulted in temporary or sustained steroid reduction in a majority. However, only a small number of patients demonstrated an objective radiological response and median OS was poor. Tumour response was variable and the addition of a predictive biomarker to establish which patients are likely to benefit from treatment may be helpful.

10530 Background: Chemotherapy in the treatment of osteosarcoma has improved 5 year overall survival (OS) from 20% with surgery alone to 60-70%. However, poor tumor necrosis following neoadjuvant chemotherapy (NAC) is associated with decreased survival, therefore strategies to improve outcomes are required for these patients. Methods: Records from all adult patients diagnosed with osteosarcoma between 1986 and 2012 were retrospectively reviewed. Patients were stratified according to age at diagnosis (40yrs), stage (localised or metastatic) and tumor necrosis post NAC (90%). All patients received 2 cycles of methotrexate alternating with cisplatin/doxorubicin (MAP) preoperatively. Following surgery, patients with >90% tumor necrosis continued MAP whilst those with 40 yrs (N=12) (p=0.05). 2/13 patients with metastatic disease at diagnosis are disease free >10 years post diagnosis. 65 of 73 patients with localised disease < 40 yrs had histology reviewed post neoadjuvant MAP. 34/65 (52%) had >90% tumor necrosis and continued on MAP, 5 yr OS 79%, 31 patients (48%) had

e12533 Background: Cancer in pregnancy accounts for ~1 in 1,000 pregnancies. Studies show that cytotoxic agents are safe from the second trimester. Long-term follow up has not shown increased malformations or malignancies in children exposed to chemotherapy in utero. There is no evidence of worse outcomes among women diagnosed in pregnancy. Methods: We retrospectively identified women diagnosed with cancer in pregnancy over a 25-year period. Medical records were reviewed for demographics, diagnosis, gestation, timing of treatment and outcomes. We assessed if all cancers need to be treated in pregnancy or if treatment could be safely deferred to allow normal delivery. Results: Twenty-five women were diagnosed with cancer in pregnancy and referred to medical oncology. Of 25 women, 16 (64%) received chemotherapy during pregnancy. These included 13 cases of breast cancer, one Ewing’s sarcoma, one ovarian cancer, and one small cell of cervix. All 16 women received doxorubicin and cyclophosphamide. There were 15 live births and no abnormalities seen in children who received chemotherapy in utero. At a median follow-up of 6 years 11 mothers (69%) are disease free and 4 (25%) have recurrent disease. Of nine mothers who did not receive chemotherapy in pregnancy, seven received chemotherapy immediately post-partum. Six (86%) were diagnosed in early pregnancy (median gestation 13 weeks). There were three cases of Hodgkin lymphoma, two breast cancers, and one ovarian cancer. At a median follow-up of 12 years, all mothers remain disease free. There were no abnormalities seen in these children. Conclusions: We did not identify any adverse outcomes in mothers or infants exposed to chemotherapy during pregnancy. We identified a cohort of patients that do not need immediate treatment during pregnancy. In selected cases, it is safe and appropriate to delay chemotherapy until delivery of the baby. There were no adverse outcomes to mothers due to delayed treatment and no adverse outcomes to babies not exposed to chemotherapy in utero. A multi-disciplinary team is essential to individualize treatment planning. [Table: see text]

1543 Background: Breast cancer is not among the recognised malignant manifestations of Lynch Syndrome which include colorectal, endometrial, gastric, ovarian and upper urinary tract tumours. In this study we report the prevalence of breast cancer in Irish Lynch Syndrome families and determine immunohistochemical (IHC) expression of mismatch repair proteins (MMR) in available breast cancer tissue. Methods: Breast cancer prevalence was determined among Lynch Syndrome kindreds from two institutions in Ireland. One kindred was omitted due to a biallelic MMR and BRCA1 mutation.The clinicopathological data that was collected on breast cancer cases included age of onset, morphology, and hormone receptor status, and a genotype phenotype correlation was investigated. Immunohistochemical staining was performed for MLH1, MSH2, MSH6, and PMS2 on all available breast cancer tissue from affected individuals. Results: The distribution of MMR mutations seen in sixteen pedigrees were as follows; MLH1 (n=5), MSH2 (7), MSH6 (3), PMS2 (1). Sixty cases of colorectal cancer and 14 cases of endometrial cancer were seen. Seven breast cancers (5 invasive ductal and 2 invasive lobular cancers) and 1 case of ductal carcinoma in situ were reported in 7 pedigrees. This compared with 4 cases of prostate cancer. Of the 7 LS kindreds containing breast cancer, 6 MSH2 mutations and 1 MSH6 mutations were identified. Median age of breast cancer diagnosis was 49 years (range 38-57). Hormone receptor status is available on 3 breast cancer cases at time of abstract submission; all were ER positive and HER 2 negative. All cases had grade 2 or 3 tumours. 5 samples were available for IHC evaluation. 3 out of 5 cases showed loss of MMR expression, all showed loss of MSH2 and MSH6 expression. One of the two cases with normal IHC expression in breast tissue belonged to a kindred where 3 siblings with colorectal cancer and documented deleterious mutations demonstrated no IHC loss. Conclusions: Breast cancer occurred at an early age and was more common than prostate cancer in Irish Lynch Syndrome pedigrees. All identified breast cancer were in kindreds with MSH2 or MSH6 mutations. Enhanced breast cancer screening may be warranted in certain Lynch Syndrome kindreds.

e19516 Background: Anthracycline based chemotherapy is the treatment of choice for aggressive primary lymphomas of the GI tract, with surgery reserved for management of complications. We report long term follow up of 71 cases of primary GI NHL treated with chemotherapy and/or surgery. Methods: Cases were identified from the institutional histology database & records reviewed. Results: 71 patients over an 24 year period were identified; 43 (61%) male, 28 (39%) female. Median age at diagnosis was 60 (15–83). 52 (73%) were DLBCL, 11 (16%) were T-cell, 8 (11%) were MALT. The 8 patients with MALT were treated with single agent chemotherapy; 7 (88%) are alive at median follow up of 8.5 years (2–16). Of the aggressive lymphomas (63), all patients with T cell lymphoma had small bowel as primary site and histological evidence of celiac associated enteropathy, even in the absence of known celiac disease. Primary sites of DLBCL were stomach 35 (67%), small bowel 11 (21%) & colon 6 (12%). 39 (62%) patients underwent surgery at diagnosis due to acute presentation with perforation, bleeding or obstruction, or to obtain histology. Following confirmed diagnosis, 61 patients received anthracycline based chemotherapy. 2 patients with T cell lymphoma presented with perforation, were treated with surgery only and died of rapid disease progression. Of the 63 patients with aggressive NHL, 37 (59%) remain alive & disease free at median follow up of 13 years (1–24). 35 (67%) patients with DLBCL are alive & disease free. Only 2 (18%) of the T cell lymphomas are alive & disease free. 5 deaths in the DLBCL group were not related to cancer or treatment. All deaths in the T cell group were due to progressive disease. There was no difference in survival between patients treated with chemotherapy only and those who also underwent surgery. Conclusions: Patients with aggressive primary B cell GI NHL have almost 70 % survival following anthracycline based chemotherapy. However, in contrast, coeliac enteropathy associated T-cell lymphomas present with rapidly progressive disease & have a survival of < 20% with chemotherapy and/or surgery. A novel therapeutic approach is required to improve outcome in this group. No significant financial relationships to disclose.