388P Evaluation of prognosis in patients with signet ring cell breast cancer

Background: Tamoxifen reduces breast cancer mortality by 30% and prevents 40% of incident breast cancer if prescribed to healthy women with elevated breast cancer risk.Despite these profound effects adherence to tamoxifen is low because it causes quality-of-life limiting side effects in asymptomatic, healthy individuals.While tamoxifen offers only invisible future benefits, the cost feels real and the rewards abstract.We aimed to identify early signs of discontinuation using vasomotor related symptoms reported after one month of tamoxifen use at daily doses of 5, 10 and 20 mg. Methods:The KARISMA Tamoxifen trial (ClinicalTrials.govID: NCT03346200) was an investigator-driven breast cancer prevention study in healthy women.In this exploratory study we include the tamoxifen dose arms of 5 mg, 10 mg and 20 mg.We identified 'hot flash' and 'night sweats' as the most common spontaneously reported AEs in participants who discontinued.These symptoms are also included in the subscale "vasomotor symptoms", as part of the 48-item KARISMA-questionnaire.Here we used survey data to assess change in reported symptoms measured at baseline and after one month of treatment.We further evaluated discontinuation in relation to symptom worsening using simple risk ratios and unadjusted logistic and Cox regression models. Results:In total 585 participants were included in the study, of whom 94 (16%) discontinued after the one-month assessment but before the end of trial at six months.Women who reported worsening vasomotor symptom scores at one month were almost twice as likely to discontinue within the next five months compared to those reporting no worsening (21.6 % vs 11.6%, Risk ratio 1.86, Cox regression: HR 1.88, p=0.004).Discontinuation was higher in women with higher severity of vasomotor symptoms.The risk of discontinuing tamoxifen therapy after one month increased by 26% for each one-unit increase in "change in symptom score" (OR 1.26, p <0.001).No major differences in distribution of discontinuation were seen between the doses of 5, 10 and 20 mg. Conclusions:This study indicates that early reported worsening and greater severity of vasomotor symptoms predicts subsequent tamoxifen discontinuation.