e21695 Background: Patients on chemotherapy often fail to develop a robust response to influenza vaccine. We had previously demonstrated that HD vaccine improved immunogenicity in cancer patients receiving chemotherapy. The present subgroup analysis evaluates immunogenicity & tolerability of HD to SD vaccine specifically in breast cancer pts <65 yrs receiving chemotherapy. Methods: 35 breast cancer pts were randomized to receive either SD or HD (17 vs 18) vaccine on day1 of chemotherapy during 2 influenza seasons. HAI titers were measured prior to & 4-wks after vaccination. HAI were summarized as geometric mean titer (GMT) and seroconversion (>4-fold titer rise) & seroprotection (GMT ≥40) rates calculated. t-test was used to compare log2-transformed GMT titers between groups and χ2 for comparison of seroconversion and seroprotection rates. Results: 2 pts were included only once (yr 1) as they received study vaccine both yrs. Mean age (50.4 vs 51.3 yrs) and baseline HAI titers were equivalent; 81 vs 88% were receiving therapy with curative intent in SD vs HD arms, respectively. Both vaccines were well tolerated with no SAEs. Post vaccination GMT were greater after HD vaccine, but was statistically significant only for H3N2 virus. Seroconversion rates for B strain was significantly improved with HD vaccine while seroprotection was excellent for all antigens in both arms. Conclusions: Trivalent HD influenza vaccine can be safely administered with increased seroconversion over SD vaccine. Most patients with breast cancer should be offered vaccination even if they are receiving chemotherapy, as they demonstrate robust response to either influenza vaccine. A larger study is needed to show clinical benefits with HD vaccine. Clinical trial information: NCT01666782. [Table: see text]