Although the implementation of new technologies is responsible for the significant improvement in the management of breast cancer over the last decades, it led to substantial increase in the cost of care. Patients worldwide are affected, but those from developing countries, such as Brazil, are substantially impacted also by the delays in updating the standard of care in the public health system. 

This thesis aims to evaluate if affordable approaches conducted in the main three breast cancer subtypes, hormonal receptor (HR)+, triple negative breast cancer (TNBC) and HER2+, can improve outcomes. 

In the metastatic setting, a phase 2 clinical trial to evaluate the clinical benefit and estrogen receptor modulation associated with Megestrol Acetate (MA), a progestin, in patients with HR+ disease was conducted. In the curative setting, an evaluation of an immunohistochemistry panel as a surrogate for genomic subtyping of TNBC for patients receiving neoadjuvant chemotherapy was performed. For HER2+ patients, ZA benefit when added to a neoadjuvant chemotherapy regimen was evaluated in a phase 2 clinical trial. 

The outputs of the MEGA trial solidify MA as a viable option after disease progression (PD) post first-line hormonal therapy, and the exploratory data generated the hypothesis that patients with reduced acetylation of H3K27 at PD might have prolonged survival in HR+HER- patients. We demonstrated that immunohistochemistry using a set panel of antibodies allowed for the definition of new molecular subtypes of TNBC, all of which show a trend for correlation between pCR rate and survival. Finally, the results of the Zo-NAnTax trial demonstrated an increase on pathological complete response (pCR) with ZA rate over a historical cohort, particularly for HR+ subgroup and was associated with provoking 5-year survival, not significantly dissimilar from pivotal studies in HER2 positive disease. 

To conclude, the evaluated approaches can improve outcomes in breast cancer with a minimum cost added, which warrants moving to confirmatory studies.