Pathological complete response to neoadjuvant chemotherapy, but not the addition of carboplatin, is associated with improved survival in Chilean triple negative breast cancer patients: a report of real world data

Abstract

Background: Breast cancer (BC) is the leading cause of cancer death for Chilean women. About 11% of cases are triple-negative (TN) BC. These are characterised by poor prognosis, higher risk of early recurrence and visceral dissemination versus other BC subtypes. Current standard treatment for early-stage non-metastatic TNBC patients consists of neoadjuvant chemotherapy (NACT) followed by surgery and radiotherapy. Pathological complete response (pCR) to NACT is associated with an increase in survival rates. In general, NACT and adjuvant regimens involve similar cytotoxic drugs. Recent studies have postulated that the use of platinum compounds in TNBC would increase response rates. However, their effects on patient survival remain uncertain. Materials and methods:We retrieved and analysed medical records from a total of 156 Chilean stage I-III TNBC female patients that received NACT and compared survival rates using carboplatin (Cb)-containing versus non-Cb-containing regimens at two health cancer centres.Results: Median age was 51 years (range: 24-81); 13.5% (n = 21) received Cb-containing regimens, 80.1% (n = 125) received sequential anthracyclines plus taxanes; 29.5% (n = 46) of the total group achieved pCR, 28% for the standard treatment and 35% (n = 8) for the Cb-containing group (p = 0.59). We confirmed pCR was associated with prolonged overall survival, invasive and distant disease-free survival (Log-rank p = 0.0236). But the addition of Cb was not associated with differences in survival measures (Log-rank p = 0.5216). Conclusions:To the best of authors' knowledge, this is the first report on real-world data in the Chilean population assessing the effect of Cb-containing NACT in TNBC. The authors' results suggest no survival benefit by the addition of Cb to standard NACT. However, we confirm an increase in survival associated to pCR regardless of treatment.

Real-life analysis of neoadjuvant-therapy-associated benefits for pathological complete response and survival in early breast cancer patients - role of trastuzumab in HER2+ BC and platinum in TNBC

“…An apparent difference in the OS following neoadjuvant treatment between TNBC patients with and without attaining pCR was shown in this study, with an aHR of 0.27 (CI: 0.15-0.51) for favoring the pCR population. Unfortunately, an increased chance of achieving pCR (adjusted OR: 2.60, CI: 1.59-4.26) following platinum-based therapy did not translate to a long-term survival benefit among both the pCR and non-pCR populations, despite great effort being made in this study to address the methodology concerns that have been raised in previous real-world studies (14)(15)(16)(17). That is, we adjusted for potential confounding effects attributable to patient baseline conditions using multivariate regression models and stratified the analyses by patients' pCR status to generate precise study estimates for the pCR and non-pCR populations separately.…”

“…Considering that the platinum-associated benefit for pCR did not translate to better survival outcomes in both trial ( 11 , 12 , 28 ) and real-world TNBC populations ( 15 – 17 ), novel agents such as immunotherapy should be considered in the neoadjuvant setting for this population ( 29 , 30 ). Specifically, the KEYNOTE-522 trial as an example demonstrated that the addition of pembrolizumab, an immune checkpoint inhibitor targeting programmed death 1, to conventional chemotherapy including carboplatin not only increased the pCR rate but also provided a longer event-free survival than the use of chemotherapy alone ( 31 ).…”

“…For TNBC, the benefit of adding platinum agents, which have cytotoxic DNA-damaging effects, to neoadjuvant therapy to enhance pCR rates has been observed in trial ( 11 – 13 ) and real-world populations ( 14 , 15 ), while an insignificant difference in OS associated with the use of platinum-based therapy has been reported by retrospective studies ( 15 – 17 ). However, the interpretation of previous findings should be done with caution because 1) a single-center design with a small number of platinum users may attenuate statistical power and limit the generalizability of study findings ( 14 , 17 ), 2) the lack of adjustment for potential confounding effects attributable to patient baseline and comorbid conditions may have biased the study estimates ( 15 , 17 ), and 3) analyses conducted without considering patient pCR status may lead to mixed estimates that cannot be differentiated for pCR and non-pCR populations ( 15 – 17 ). The use of platinum-based neoadjuvant regimens in TNBC remains inconclusive in the scientific community, as evident in international clinical practice guidelines ( 18 ).…”

Efficacy of platinum-based and non-platinum-based drugs on triple-negative breast cancer: meta-analysis

“…Lastly, the first report concerning real-world data on the Chilean population covered that females of TNBC in the phase of I–III received NAT of contained platinum. The result showed that the PCR rate was associated with extended overall survival, invasiveness, and disease-free survival, however whether the Cb exists or not was irrelevant to variability in survival indicators [ 37 ]. Similarly, other 2 studies suggest that whether patients of TNBC use platinum agents or not was related to PCR rate, which can induce the incidence of adverse reactions in the blood system increased markedly, such as febrile neutropenia [ 38 , 39 ].…”

Cytoplasmic Colocalization of RXRα and PPARγ as an Independent Negative Prognosticator for Breast Cancer Patients

“…Breast cancer (BC) is the most common malignant tumor in women. One of the greatest challenges for clinicians remains to control BC invasiveness and dissemination in order to improve patient survival [ 1 , 2 ]. Indeed, although the treatment options of BC with surgery, chemotherapy, aromatase inhibitors, hormone receptor modulators, and anti-Human Epidermal Growth Factor Receptor 2 (HER2)-Therapy [ 3 , 4 , 5 ] have developed tremendously in recent years, consistently high mortality rates due to tumor metastasis remain [ 6 , 7 ].…”