Background: L and T “beyond progression” (TBP) for MBC pts who progressed on 1^st line therapy with T, are both reimbursed in Israel since 1/2010. The relative efficacy of L vs. T when combined with chemotherapy in 2^nd line therapy for HER2+ MBC is unknown. In this retrospective database study we compared outcomes of 2^ndline L or TBP, in the daily practice ("real life") in Israel. Methods: Using the computerized databases of Clalit Health Services' (CHS), Israel's largest health care provider, we identified all MBC pts that received 2^nd line anti HER2 therapy, with either L or TBP after a 1^stline protocol containing T, between 1/1/2010 and 31/12/2011. Pts characteristics and treatments were retrieved. The primary end point was overall survival (OS) defined as the time interval between date of initiation of 2^nd line anti HER2 therapy and death or last day of follow-up. Secondary endpoint was progression free survival (PFS), defined as duration of 2^nd line therapy. Results: The study population included 83 pts (28 L and 55 TBP). Mean age (59.9 vs. 61.4) and average Charlson co-morbidity index score (6.54 vs. 6.13) were similar between the cohorts. The groups differed in rates of prior adjuvant T (32.1% vs. 10.9%, p=0.017). The interim cutoff date for analysis was 31/12/2012 (allowing at least 12 months of follow-up). Median OS was 10.0 months for L pts (95% CI: 7.41–12.59) and was not reached for TBP, with a total of 31 deaths: 19 [67.9%] in the L group and 22 [40.0%] in the TBP group. A Cox regression showed an adjusted hazard ratio (HR) of 1.44 (95% CI 0.74-2.81), not significant (p=0.28).Prior adjuvant therapy with T was found to be a significant cofounder; HR=3.16 (95% CI 1.52-6.56). Median PFS was 6.0 months (95% CI: 4.31–7.69) for L and 7.0 months (95% CI: 4.30-9.70) for TBP, with a Cox regression adjusted HR of 0.87 (95% CI: 0.50-1.52), not statistically significant (p=0.87). Conclusions: In this retrospective database analysis, our interim results suggest no statistically significant difference in OS and PFS between L and TBP, as 2nd line therapy for HER2+ MBC, however the data showed a strong trend toward a survival benefit with TBP. A longer follow-up is required.