Abstract Background: NCCN guidelines recommend that premenopausal women with HR+/HER2- metastatic breast cancer (MBC) be rendered postmenopausal and then treated accordingly. After its approval in February 2015, the CDK4/6 inhibitor palbociclib (P), in combination with endocrine therapy (ET), has become a standard of care in the first-line or pretreated settings for women with HR+/HER2- MBC. Specialty pharmacy prescription data indicate that 12% of all women with HR+/HER2- MBC treated with P in the United States are younger than 50 years of age. We assessed the real world treatment patterns and outcomes before and after approval of P in women with HR+/HER2- MBC. We further sought to assess the impact of the NCCN guidelines for premenopausal women on treatment patterns and outcomes. Methods: This retrospective cohort study utilized electronic health record (EHR) data from Flatiron Health (Fl) from 1/2012 through 4/2017 to evaluate patient characteristics and first-line ET treatment patterns among women with HR+/HER2- MBC prior to and after P approval. Menopausal status was defined by age (< 50 vs >50 yrs). Additional datasets of > 13,000 pts with MBC in the Truven Health MarketScan and Optum Clinformatics claims and Humedica EHR databases will be included to represent a more comprehensive dataset and evaluate clinical outcomes. Results and Discussion: Initial results include 4,537 pts in the FI database who initiated a first-line ET regimen. Overall, 30% of pts < 50 yrs used P compared to 29% of women age >50. Treatment patterns for initial endocrine therapy are shown in the table. Initial Endocrine Therapy Women <_50 yrs N (%) women > 50 yrs N(%) cohort01.2012-01.201502.2015-04.2017Absolute Change01.2012-01.201502.2015-04.2017Absolute ChangeN (%)296 (%0273 (100%) 2062 (100%)1906 (100%) ET monotx +/- LHRH296 (100%)192 (70%)-30%2062 (100%)1345 (71%)-29%TAM108 (36%)75 (27%)-9%161 (8%)78 (4%)-4%AI139 (47%)80 (29%)-18%1326 (64%)866 (45%)-19%FUL49 (17%)37 (14%)-3%575 (28%)401 (21%)-7%ET + P +/- LHRHNA81 (30%)+30%NA561 (29%)+29%% of concurrent LHRH77 (26%)92 (34%)+8%20 (1%)28 (1%)0% Decreased use of tamoxifen as 1st line ET was observed in pts <_50 yrs over the observed time. 47% of young pts initiated endocrine based treatment with AI monotherapy in the pre-P era, consistent with the NCCN guidelines. About 26% (pre-P) and 34% (post-P) of pts ≤50 yrs initiated first ET with ovarian suppression in the analyzed treatment eras. The concurrent use of LHRH increased 8%. Conclusions: The treatment paradigm for women with HR+/HER2- MBC has evolved over the last >5 years. Consistent with NCCN guidelines, more young pts are receiving ovarian suppression as part of initial therapy, and pts regardless of age are receiving treatment with P. There has been a related decrease in use of tamoxifen for younger pts and overall. These data illustrate rapid incorporation of palbociclib into standard care for US pts with HR+/HER2- MBC. Further treatment patterns and therapy outcome data for these groups reflecting real world use ET regimens of over 17,000 pts in the combined cohort, will be reported. Citation Format: Burstein HJ, Mayer EL, DeMichele A, Harnett J, Mardekian J, McRoy L, Huang Bartlett C, Koehler M, Fahed Rimawi M. Treatment patterns for young women with HR+/HER2- metastatic breast cancer in the United States in the era of CDK 4/6 inhibitors [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-11-01.