Abstract Introduction: Retrospective data from institutional series and population-based databases have suggested a potential benefit of the primary tumor (PT) surgery in de novo metastatic breast cancer (MBC) patients (pts). Recently reported prospective data from 2 randomized trials and a multicenter registry questioned the real role of the local approach in the modern individualized systemic treatment era. Methods: The ALAMO (A) is a retrospective analysis of pts diagnosed with BC between 1990 and 2001 across 56 GEICAM hospitals in Spain. Patterns of BC presentation (tumor and host characteristics), treatment and survival were recorded in 3 cohorts, AI (1990-93, 4529 pts, closed by 2000), AII (1994-97, 10453 pts, closed by 2003) and AIII (1998-2001, 10675 pts, closed by 2007). MBC pts at first diagnosis excluding those without complete information about their PT surgery were included. Descriptive, Kaplan-Meier and Cox regression analyses were carried out. Results: 5.5% (N=1415) of the ALAMO database pts were initially diagnosed with MBC, 1331 fulfilled the present analysis criteria (327 from AI, 619 from AII and 385 from AIII). Median age was 63.1 years (range: 21.6-96.0), 51.8% had single-organ metastasis, and their distribution according to the predominant site of disease was skin/soft tissue (16.2%), bone (33.7%), and visceral (48.4%). Surgery of the PT was done in 44.5% (N=592) of pts (512 with radical procedures, 46 with palliative procedures and 34 unknown); besides, 427 pts underwent axillary dissection. Initial local treatment was the choice for 380 pts (358 surgery and 22 radiotherapy), 722 received initial systemic therapy (480 chemotherapy, 214 endocrine treatment and 28 both), 29 received best supportive care and for 200 pts the treatment sequence could not be established. Pts in the surgery (S) group were younger (19.5% vs 11.8% were <44 years-old in the S vs non-S group respectively), with oligometastatic disease (61.9% vs 43.9% with single-organ involvement in the S vs non-S group respectively) and with different sites of disease (40.2% vs 54.3% with visceral and 39% vs 29.8% with bone metastasis in the S vs non-S group respectively). With a median follow-up of 1.9 years, the 5-yr overall survival (OS) was 25.4% in the entire de novo MBC population, with a median OS of 3.3 yrs in the S-group vs 1.9 yrs in the non-S-group (HR 1.69, p<0.0001). Subgroup analyses showed a benefit of PT surgery in OS regardless the number of metastasis and site of disease, but didn't show this benefit analyzing pts according to BC subtypes. The multi-adjusted HR for surgery was 1.38 (p=0.037). The multivariate Cox regression analysis model included the site of disease (p=0.028), the histopathologic grade (p=0.019) and the hormone receptor status (p=0.007). Discussion: The Alamo data line up with previously reported population-based registries, which highlight the better survival outcome of de novo MBC pts undergoing PT surgery. However, the consideration of the biological heterogeneity of BC has changed the landscape of systemic treatment. Only well designed randomized controlled trials will have the power to discriminate between a consistent bias and a real biologic effect of the PT surgery. Citation Format: Sara López-Tarruella, María José Escudero, Miguel Martín, Carlos Jara, Ángel Guerrero, Ana Lluch, Ana Santaballa, Purificación Martínez del Prado, Juan Lao, Emilio Alba, Antonio Fernández, Raquel Andrés, Antonio Llombart, Norberto Batista, Ignacio Porras, José Manuel López-Vega, Encarna Adrover, Lourdes Calvo, Marina Pollán, Eva Carrasco. Impact on survival of primary tumor resection in women with de novo metastatic breast cancer. The GEICAM Alamo I-III breast cancer registry (1990-2001) [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P2-13-17.