COX-1 and COX-2 are members of the cyclooxygenase (COX) family, which influence tumor invasion and apoptosis. The objective of the study was to assess the relationship between COX-1 and COX-2 expression in early-stage disease and subsequent disease relapse and long-term survival. Women with FIGO stage I and II cervical carcinoma, younger than 50 years, treated between 1981 and 1990 were included. COX-1 and COX-2 expressions in the tumors were assessed by immunohistochemistry. COX-1 and COX-2 were expressed in 61% (17/28) and 57% (16/28) of tumors, respectively. COX-1 nonexpressers showed an improved overall survival compared to expressers (log-rank test, P= 0.09). There was no significant difference in the overall survival in COX-2 nonexpressers compared to expressers (P= 0.6). Out of eight women with disease relapse, COX-1 or COX-2 expression was noted in six of eight tumors, and both were expressed in five of eight tumors. Our preliminary data suggest an adverse prognosis with COX-1 expression in early-stage cervical carcinoma and a trend toward COX-1 expression in disease relapse. The association between COX-2 expression and a worse prognosis was not proven in this study.

Introduction The addition of Oncotype Dx Recurrence Score (RS) to the assessment of patients with ER positive, HER2 negative, node negative breast cancer has led to a reduction in the use of adjuvant chemotherapy. However, crude measurement of this reduction masks a more complex scenario. Prior to the introduction of routine Oncotype DX testing by NHS England, we wished to explore in more detail the potential impact of the knowledge of the RS on the therapeutic discussion. This study analyses the impact of RS on the adjuvant therapy recommendations within a UK Cancer Centre. In particular, it examines how the degree of certainty the oncologist has about the best option changes with knowledge of RS and how this influences concordance of decision making between oncologists. Methods A panel of five breast oncologists reviewed 50 consecutive cases, collected from November 2012 until November 2014, across two hospitals. Oncologists allocated each case to one of four treatment categories: chemotherapy recommended (CRec), chemotherapy discussed with a bias towards recommended (CDis), chemotherapy discussed with a bias toward endocrine therapy alone (EDis) or endocrine therapy only advised (ERec). The cases were analysed blindly and in random order without and with RS . The degree to which knowledge of RS altered treatment recommendation was analyzed. Other outcomes included the proportion of patients who were scored ERec compared with any other outcome, the trend towards definitive recommendations, the impact of RS on concordant decision making and the degree to which outcome was stratified by RS result. Chi squared and Spearman's coefficient statistical tests were used in analysis. Results Knowledge of the RS altered the recommended treatment category in 66.7% of cases (p<0.001). Alterations in treatment recommendations in response to Oncotype Recurrence Score in addition to pathological parameters CRec (n)CDis (n)EDis (n)ERec (n)Without RS2% (1)40% (20)52% (26)6% (3)With RS12% (6)16% (8)26% (13)46% (23) Overall, RS correlated significantly with treatment recommendation. Oncologists were confident to recommend endocrine therapy alone in 46% of patients when RS was known compared with only 6% of patients without RS. Complete concordance between oncologists increased with the knowledge of RS from 14% to 64%. Conclusion Discussion of adjuvant chemotherapy with patients who have ER positive, HER2 negative, node negative breast cancer can be complex and, at times, confusing for the patient, leading to increased distress. This study shows that, in addition to the previously recognised reduction in overall use of chemotherapy, the knowledge of the RS increased the proportion of patients for whom the oncologist felt confident in making a firm treatment recommendation. An added benefit was to increase concordance between different oncologists compared to that achieved when relying on standard pathological features. Citation Format: Kiernan T, Olsson-Brown AC, Innes H, Holcombe C, Thorp N, O'Hagan J, Wong H, Palmieri C, O'Reilly S. Knowledge of oncotype Dx recurrence score increases confidence and concordance in adjuvant decisions of U.K. oncologists. [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 P5-15-07.

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e12108 Background: Neoadjuvant (NA) HER2 blockade with trastuzumab (T) and pertuzumab (P) results in pathological complete response (pCR) rates of 39% to 62%. Diarrhoea is reported in up to 73% of cases. No real-world studies have explored the efficacy and toxicity of this treatment. This study aimed to determine the efficacy and toxicity of NA T-P and CT within a routine NHS clinical practice in the UK. Methods: HER2+ BC patients given NA T-P (accessed via the Cancer Drug Fund) between Oct2016-Jan 2018 at Clatterbridge Cancer Centre NHS Foundation Trust were retrospectively identified. Clinico-pathological information, treatment data, nurse led toxicity and echocardiography were reviewed. Data lock: 30th January 2019. Final pathological response data is presented. Results: 78 female patients were identified with a median age of 50 years (IQR: 44.4-60.2). Diagnosis: median tumour size 30mm (IQR 23.0-47.5mm), 62% (48/78) LN+ & 71% ER+. CT regimens: 81% (63/78) given FEC-DHP; of these 19 (30%) switched to weekly paclitaxel (wP) or nab-paclitaxel; 5% (4/78) AC/EC-DHP; 9% (8/78) TCHP of which 1 (13%) switched to wP. All patients underwent definitive surgery: 50% (39/78) mastectomy & 50% (39/78) WLE. 44% (35/78) axillary node clearance (ANC) & 56% (43/78) sentinel node biopsy (4 prior to NA therapy). 91% (32/35) undergoing ANC were LN+ at diagnosis, of which 66% (21/32) were LN- at surgery. pCR rate (ypT0/is, N0) was 47% (37/78), pCR by HR: ER+ 42% (23/55) & ER- 61% (14/23). pCR for 20 cases switched to wP was 60% (12/20). 6% (5/78) achieved pCR in the breast alone (in these LN status ITCx1, micrometsx3 & macrometsx1). Median size of the 46% (36/78) with residual breast tumour was 14.5mm (1-65mm). Outcome: Median follow up 68 weeks with one local and one distant recurrence occurring but no deaths. Toxicity: Ejection fraction did not decline beyond 10% of baseline in any patients. Diarrhoea occurred in 74% of cases, and CTCAE grade 3-4 toxicity occurring in >2% of patients: diarrhoea, fatigue, and infection. Conclusions: This data confirms 1) the real world efficacy of NA T-P 2) a significant number of LN+ patients become LN- and measures to avoid ANC are needed 3) switching to NA wP is not uncommon and may be associated with a higher pCR 4) diarrhoea rates reflect the literature and measures to mitigate it are needed. Updated outcomes will be presented.