Valentina Rossi

Background: Triple-negative breast cancer (TNBC) is associated with poor prognosis and a high risk of early relapse. The incorporation of platinum-based agents into neoadjuvant chemotherapy (NACT) regimens has been linked to improved pathological complete response (pCR) rates. However, the clinical benefit of carboplatin (CBDCA) remains debated due to variable long-term survival outcomes and concerns over cumulative toxicity. This meta-analysis evaluates the efficacy of adding CBDCA to NACT in early-stage TNBC (eTNBC). Methods: A systematic review and meta-analysis were conducted by searching MEDLINE, PubMed, and major oncology conference proceedings (2014–2024), with no language restrictions. Randomized phase II–III trials assessing the addition of CBDCA to standard NACT in eTNBC and reporting pCR and survival outcomes were included. The systematic review followed the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). The protocol has not been registered. The primary endpoint was pCR; the secondary endpoint was disease-free survival (DFS). For pCR, a random-effects model was used, and odds ratios (OR) were log-transformed. For DFS, a mixed-effects model was applied, extracting hazard ratios (HR) and converting them into logHR values. Heterogeneity was assessed using I² statistics, and publication bias was evaluated through the Fail-Safe N method and Egger’s regression test. Statistical analyses were performed using Jamovi v2.4.11. Results: Of 30 studies identified, 9 randomized clinical trials were eligible; 6 (BrighTNess, GeparSixto, GS5-01, BR-15-1 PEARLY, NACATRINE, CALGB 40603) met all inclusion criteria, totaling 3402 patients. The addition of CBDCA to NACT significantly improved pCR (OR 1.63; 95% CI: 1.38–1.92; p < 0.001), with low heterogeneity (I² = 0.81%) and no publication bias. DFS was also significantly improved (SHR 0.81; 95% CI: 0.63–0.91; p = 0.003), with moderate heterogeneity (I² = 27.95%) and no bias detected. Conclusions: Adding carboplatin to NACT significantly improves pCR and DFS in patients with early-stage TNBC.

Aromatase inhibitors (AIs), with or without gonadotropin-releasing hormone analogs, are the cornerstone of adjuvant endocrine therapy for women with hormone receptor-positive early-stage breast cancer, offering significant reductions in recurrence risk and improving long-term survival. Their use is frequently accompanied by treatment-related toxicities that can adversely affect patients’ quality of life (QoL) and adherence to therapy. Commonly reported side effects include vasomotor symptoms, such as hot flashes; musculoskeletal disorders, such as arthralgia and myalgia; mood disorders; and genitourinary discomfort, such as vaginal dryness and dyspareunia. Additionally, AIs are associated with a heightened risk of bone loss, leading to osteoporosis and fractures, and may have implications for cardiovascular health. Effective management of these adverse events is pivotal in maintaining treatment adherence and preserving QoL. Evidence-based strategies to address these toxicities include pharmacological interventions, such as analgesics for joint pain, bisphosphonates or denosumab for bone health, and hormonal or non-hormonal approaches for vasomotor and genitourinary symptoms. Non-pharmacological measures, including physical activity, dietary adjustments, and complementary therapies, can also help mitigate symptoms. This review examines the broad spectrum of AI-associated toxicities, discusses their clinical implications, and provides an overview of evidence-based management strategies. These insights aim to support clinicians in optimizing patient care while minimizing the toxicities of therapy.