Abstract PO4-03-07: The impact of chemotherapy relative dose intensity on pathological complete response in patients with triple negative breast cancer treated with neoadjuvant chemotherapy
Authors: Buonaiuto Roberto , Neola Giuseppe , Caltavituro Aldo , Trasacco Paola , Mangiacotti Federica Pia , Pecoraro Giovanna , Lambertini Matteo , Pietroluongo Erica , Placido Pietro De , De Placido Sabino , Forestieri Valeria , Giuliano Mario , Arpino Grazia , De Angelis Carmine 
Published: May 2024

Abstract
Background: Neoadjuvant chemotherapy (NACT) is the preferred treatment approach for early-stage triple negative breast cancer (TNBC). Achieving pathologic complete response (pCR) after NACT is associated with improved event-free survival and overall survival in patients with TNBC. Major research efforts have been deployed to identify predictive biomarkers for pCR in TNBC. However, the values of chemotherapy (CT) relative dose intensity (RDI) in predicting pCR remain unclear.
Methods: A retrospective analysis was conducted among 96 consecutive patients with early stage TNBC who received NACT between February 2018 and January 2023 at the University of Naples Federico II (Naples, Italy). Patients’ demographics, clinical-pathological features, and type of CT schedules were retrieved from electronic medical records. pCR was defined as the absence of residual invasive or in situ carcinoma in primary tumor and/or lymph nodes, upon chemotherapy administration. RDI was calculated as the ratio of delivered to planned CT dose intensity. RDI was defined as low if &lt; 85% or high if ≥85%, respectively. Univariate and multivariate logistic regression were used to evaluate the association between age, tumor stage, RDI, CT regimen dose type, and pCR.
Results: All patients were included in the analysis. Median age at diagnosis was 51 years (range 28-75). Sixty-five (68%) and 31 (32%) patients were diagnosed with stage II and stage III TNBC, respectively. Nineteen (19%) patients received a sequential schedule of anthracycline plus cyclophosphamide (AC) and a taxane (T). Sixty-one (64%) patients received AC followed by concurrent carboplatin-paclitaxel (CaP). Sixteen (17%) patients received the anti-PD1 pembrolizumab in addition to ACCaP chemotherapy backbone (ACCaP-Pem). Fifty-four (56%) patients received a dose-dense AC-based CT. A pCR was achieved in 59 (61%) patients. Interestingly, patients who received a dose-dense AC based neoadjuvant CT had higher chance to achieve a pCR compared with those treated with a non dose-dense AC based CT (70% vs 46%, p = 0.03). Overall, 79 (82%) and 17 (18%) patients received a RDI high and RDI low CT, respectively. No difference in terms of age, body mass index, performance status, tumor stage, type of chemotherapy was observed between the two groups (Table 1). At univariate analysis RDI high (OR 5.18, 95%CI: 1.65-16.31, p=0.005) and dose dense AC-based CT (OR 2.42, 95%CI: 0.18-0.97, p=0.04) were significantly associated with pCR. In a multivariate model including RDI, age, tumor stage, and AC regimen dose type, RDI was the only variable independently associated with pCR (OR 4.60, 95% CI: 1.40-15.06, p = 0.01).
Conclusion: A chemotherapy RDI≥ 85% independently predicts pCR in early stage TNBC patients treated with standard NACT. In our cohort, one in five patients received a suboptimal chemotherapy dose intensity affecting at least in part tumor response. Studies with larger TNBC patient populations are warranted to confirm the impact of RDI on pCR and long-term outcomes.
Table 1
Citation Format: Roberto Buonaiuto, Giuseppe Neola, Aldo Caltavituro, Paola Trasacco, Federica Pia Mangiacotti, Giovanna Pecoraro, Matteo Lambertini, Erica Pietroluongo, Pietro De Placido, Sabino De Placido, Valeria Forestieri, Mario Giuliano, Grazia Arpino, Carmine De Angelis. The impact of chemotherapy relative dose intensity on pathological complete response in patients with triple negative breast cancer treated with neoadjuvant chemotherapy [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-03-07.