Abstract Background: Oncoplastic breast conserving surgery (OPBCS) may allow women with early breast cancer to avoid mastectomy leading to fewer complications and better quality of life. High quality comparative evidence, however, is lacking. The UK ANTHEM study (ISRCTN18238549) aimed to explore the feasibility of undertaking a large-scale multicentre study comparing the clinical and patient reported outcomes (PROs) of OPBCS as an alternative to mastectomy +/- immediate breast reconstruction (IBR) in women offered both options. Methods: Women aged 18 and over with invasive breast cancer or DCIS not suitable for standard breast conserving surgery, who were offered OPBCS as an alternative to mastectomy +/- IBR were eligible to participate in the study. Demographic, operative, oncological data were collected and the numbers of women experiencing complications at 3 months following surgery compared by procedure type. Participants completed the validated BREAST-Q at baseline and 3 months post-operatively. Questionnaires were scored according to the developers’ instructions and scores compared across timepoints by procedure group. Analysis of covariance, adjusting for baseline scores was used to explore factors influencing patient-reported outcomes after surgery. Results: 361 women from 32 UK centres participated in the study. When offered both options, the majority (n=284, 78.7%) elected to undergo OPBCS with either a therapeutic mammaplasty (TM) (n=207, 57.3%) or a chest wall perforator flap (CWPF) (n=77, 21.3%). The remaining 77 (21.3%) women chose mastectomy with (n=40, 11.1%) or without IBR (n=37, 10.3%). Women having mastectomy + IBR were significantly younger than those choosing other procedure types (p=0.002) and those choosing TM had higher BMIs (P=0.008), but there were no other differences between the groups. By 3 months post-operatively, 23.0% (n=83) women had experienced at least one complication, but there were no differences between the groups (p=0.50). The BREAST-Q was completed by 329 (91.1%) and 282 (78.1%) women at baseline and 3 months respectively. Although their scores were initially the lowest, women undergoing TMs reported clinically meaningful and statistically significant increases in ‘Satisfaction with Breasts’ (baseline 53.7 [95% confidence interval [CI] 50.4-57.0] to 3 months 68.9 [95% CI 65.5-72.2], p< 0.001) and ‘Psychosocial Well-being’ scores (baseline 62.1 [95% CI 59.2-65.0] to 3 months 70.4 [95% CI 66.9-73.8] p< 0.001) from baseline to 3 months. Women having CWPF and mastectomy +/- IBR did not report any significant changes in either ‘Satisfaction with Breasts’ or ‘Psychosocial Well-being’ scores over time. ‘Physical Well-being’ scores significantly decreased from baseline to three months in all treatment groups (p< 0.001) but were lowest after mastectomy only (56.5 [95% CI 47.4-65.5]) and highest in the TM group (68.6 [95% CI 65.9-71.3], p< 0.001). ‘Sexual Well-being’ decreased in all groups except for women having mastectomy + IBR. Adjusting for baseline, women undergoing OPBCS with TM (13.2, 95% CI 4.2-22.2, p< 0.001) or CWPF (11.4, 1.6-21.2, p=0.02) reported significantly higher ‘Satisfaction with Breasts’ scores at 3 months than those undergoing mastectomy. Receipt of IBR did not appear to lead to significantly higher scores compared with mastectomy alone (6.47, 95% CI -6.19 to 19.12, p=0.32). Women undergoing TM reported significantly higher ‘Psychosocial’ and ‘Physical well-being’ at 3 months compared with those having other procedure types. Experiencing a post-operative complication resulted in significant decreases in all BREAST-Q domains. Conclusions: When offered OPBCS as an alternative to mastectomy, most women choose breast conservation. This option is safe and appears to be associated with improved short-term PROs, particularly in the TM group. Further work is needed to establish the long-term outcomes of these techniques to support informed decision-making. Citation Format: Charlotte Davies, Leigh Johnson, Carmel Conefrey, Nicola Mills, Patricia Fairbrother, Chris Holcombe, Lisa Whisker, William Hollingworth, Joanna Skillman, Paul White, Douglas MacMillan, Charles Comins, Shelley Potter. Short-term clinical and patient-reported outcomes of oncoplastic breast conserving surgery and mastectomy with and without immediate breast reconstruction: The UK ANTHEM multicentre prospective cohort study [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO3-23-06.