Background: The lengthening of the lifespan led to an increase in breast cancer (BC) diagnosed in very old age, but the treatment recommendations in this patient group usually lack evidence-based practice. We conducted a prospective observational monocentric study specifically targeting patients diagnosed with invasive BC at 80 years of age or older. Methods: We enrolled 88 patients consecutively observed for a new BC diagnosis at 80 years or older. The aim was to investigate progression-free (PFS) and overall survival (OS), with a long follow-up period, along with clinico-pathological characteristics of the population. Results: At the end of the 5-year follow-up, the estimated OS and PFS probabilities were 82.9% (95% CI: 71.3–95.3%) and 64.0% (95% CI: 51.7–79.2%), respectively. After 8.5 years from the BC diagnosis, 48.9% died. The cause of death was BC in 32.6% of patients, different from BC in 13.9%, and unknown in the remaining. Surgery was performed in 69.3% of the cases and was associated with improved 12-month PFS (p < 0.001). Adjuvant systemic therapy and radiotherapy were omitted in 32% and 93% of eligible patients, respectively. A higher rate of metastatic disease at the diagnosis was observed in comparison with data described in younger people, as well as a significantly high rate of drop-out (27.3%). Conclusions: Ultra-old patients have a not negligible life expectancy; therefore, the oncologic treatment should be optimal and should adequately fight BC, always considering the quality of life of these frail patients. Future research should focus on developing personalized treatment protocols that incorporate comprehensive geriatric assessments and quality-of-life metrics. Additionally, larger, multicentric studies are needed to validate our findings and explore the role of emerging therapies in this age group.
