Abstract
In the absence of identified therapeutic targets, chemotherapy is the main systemic treatment option for triple-negative breast cancer (TNBC). The achievement of a pathological complete response (pCR) after neoadjuvant chemotherapy leads to good outcome, whereas patients not achieving a pCR are at high risk of relapse. Various trials have evaluated the inclusion of platinum in neoadjuvant chemotherapy regimens for TNBC, leading to non-univocal results. The panel of the Italian Association of Medical Oncology (AIOM) Guidelines on Breast Cancer developed a clinical recommendation on the addition of platinum to anthracycline/taxane-based neoadjuvant chemotherapy for TNBC by using the Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) methodology and the Evidence to Decision framework (EtD). Five studies were eligible. The panel identified the following outcomes of benefit: pCR (critical), disease/event-free survival (DFS/EFS, critical), and overall survival (OS, critical). The panel identified febrile neutropenia (critical), serious adverse events (critical), anemia grade 3–4 (important), thrombocytopenia grade 3–4 (important) as outcomes of harms. The probability of pCR was higher in the platinum-based chemotherapy group versus control group (RR = 1.45, 95%CI 1.28–1.64); however, no impact on long-term outcome was observed. Neoadjuvant treatment regimens containing platinum resulted in a non-significant increase in the risk of febrile neutropenia and in a significant increase in the risk serious adverse events, G3–G4 anemia and G3–G4 thrombocytopenia: 11.3% versus 0.8%, RR = 15.66 (95%CI 6.38–38.44). The panel judged uncertain/favorable the benefit/harms balance. The panel’s final recommendation was conditional in favor of the inclusion of platinum in anthracycline/taxane-based neoadjuvant regimens for TNBC.
Highlights
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer (BC) subtype, accounting for around 15% of all diagnoses
+ veliparib followed by doxorubicin and cyclophosphamide; paclitaxel + carboplatin + veliparib placebo followed by doxorubicin and cyclophosphamide; paclitaxel + carboplatin placebo + veliparib placebo followed by doxorubicin and cyclophosphamide [17]
The final recommendation highlights the relevance that was attributed by the panel to the effect on pathological complete response (pCR), which has the strongest association with long-term outcome in the challenging and hard-to-treat triple-negative breast cancer (TNBC) subtype
Summary
Triple-negative breast cancer (TNBC) is the most aggressive breast cancer (BC) subtype, accounting for around 15% of all diagnoses. Up to one-third of patients diagnosed with TNBC may experience disease recurrence, with the highest peak within 1–3 years from diagnosis. The pattern of recurrence often involves visceral sites, leading to high mortality rates and short survival. Triple-negative breast cancer lacks recognized therapeutic targets; cytotoxic agents represent the only option of systemic treatment [1,2]. TNBC is highly chemosensitive [3]. This paradox is evident in the neoadjuvant setting [4]. TNBC is associated with higher pathological complete response (pCR) rates (~30–40%) after neoadjuvant chemotherapy (NACT) as compared to other BC subtypes
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