Background: This case series follows the reflective processes undertaken, when five slim women presented with reactive oedemas of the forearm and hand, that did not respond to usual therapy. Aim: To raise awareness about Aromatase Inhibitor (AI), Letrozole. Methods: Possible causes, including Cyclin-Dependent Kinase 4 and 6 (CDK4/6) inhibitors, Ribociclib and Axillary Web Syndrome, were explored and reviewed, and potential effective treatment options were then sought. New cases presented, which discounted each theory, until Letrozole was suspected. Results: Inflammatory oedemas were explained by the mechanisms-of-action relating to Aromatase Inhibitor Associated Musculoskeletal Syndrome (AIMSS), the severity of which, especially for slim women with oestrogen deprivation, causes almost 50% of women to cease treatment within 6 months; risking disease reoccurrence. Conclusion: Permissions were gained, a table was collated and sent to referring consultants, requesting risk/benefit analysis of Letrozole with a medication review. If non-responsive, inflammatory oedemas present in clinic, AIs should be considered as a trigger.