Platinum-based neoadjuvant chemotherapy in BRCA1-positive breast cancer: a retrospective cohort analysis and literature review

Sæther, Nikolai Havn; Skuja, Elīna; Irmejs, Arvids; Maksimenko, Jelena; Miklaševičs, Edvīns; Purkalne, Gunta; Gardovskis, Jānis

doi:10.1186/s13053-018-0092-2

Cited by 16 publications

(12 citation statements)

References 14 publications

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“…Standard NACT regimens continue to incorporate an anthracycline and taxane-based backbone (3). Recent evidences suggest that a dose-dense chemotherapy regimen, +/− the addition of platinum agents and immunotherapy may positively impact pCR rates in TNBC potentially longer-term outcomes (4,5).…”

Section: Introductionmentioning

confidence: 99%

Real-world assessment of the effect of impact of tumor size on pathological complete response rates in triple negative breast cancer after neoadjuvant chemotherapy

Paula¹,

Kumar²,

Morosini³

et al. 2020

Chin Clin Oncol

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Background: Triple negative breast cancer (TNBC) is characterized rapid tumor growth, and increased metastatic potential compared to other breast cancer subtypes. However, pathological complete response (pCR) to neoadjuvant chemotherapy (NACT) can predict patients with a better prognosis. Clinical predictors of pCR such as tumor size (TS) are controversial. This study aims to evaluate the influence of TS on achieving pCR, and the associated survival outcomes. Methods: Medical records from 310 TNBC patients treated with NACT between 2010 and 2013 in National Cancer Institute Brazil were screened. The aim study was to examine the impact of TS on pCR. We used descriptive statistics to organize and summarize TS data and all the other variables of interest. Logistic regression has done to assess if any of these variables were associated with pCR. Survival data were extrapolated using Kaplan-Meier analysis and log-rank tests. Results: Thirty-nine (21%) of 187 enrolled patients achieved pCR. Median age was 48 years, 50.27% were postmenopausal, 93.03% T3/T4 and 75.39% axillar clinical node-positive; 92.51% received an anthracycline regimen followed by a taxane. Age >40 years (P=0.04, OR 0.45, 95% CI, 0.20-0.95) and tumor infiltrating lymphocytes (TILs) presence (P<0.01, OR 3.71, 95% CI, 1.60-8.60) were factors significantly associated with increased rates of pCR. Neither the TS (IQR: 4; P=0.22, OR 0.93, 95% CI, 0.83-1.03) nor the other subgroups analysed demonstrated any association with achieving pCR. Median follow-up was 36 months. The 5-year OS and RFS of the study population was 71.20% and 61.10% respectively. Conclusions: Preoperative TS did not significantly impact pCR rate in our cohort of patients receiving NACT for TNBC. Characteristics associated with higher pCR rate included TILs and age >40 years. In addition, pCR, was indicative of better survival outcomes.

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Section: Introductionmentioning

confidence: 99%

Real-world assessment of the effect of impact of tumor size on pathological complete response rates in triple negative breast cancer after neoadjuvant chemotherapy

Paula¹,

Kumar²,

Morosini³

et al. 2020

Chin Clin Oncol

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“…Some retrospective studies suggested that tumors displayed higher chemosensitivity according to BRCA -mutation status [ 17 , 18 , 19 , 26 , 27 , 28 , 29 , 30 , 31 , 32 ]. Arun et al [ 30 ] compared pCR rates after NAC between BRCA1 or BRCA2 -carriers ( n = 57 and n = 23, respectively) and WT controls ( n = 237).…”

Section: Discussionmentioning

confidence: 99%

Impact of BRCA Mutation Status on Tumor Infiltrating Lymphocytes (TILs), Response to Treatment, and Prognosis in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

Grandal

Evrevin

Laas

et al. 2020

Cancers

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Introduction: Five to 10% of breast cancers (BCs) occur in a genetic predisposition context (mainly BRCA pathogenic variant). Nevertheless, little is known about immune tumor infiltration, response to neoadjuvant chemotherapy (NAC), pathologic complete response (pCR) and adverse events according to BRCA status. Material and Methods: Out of 1199 invasive BC patients treated with NAC between 2002 and 2012, we identified 267 patients tested for a germline BRCA pathogenic variant. We evaluated pre-NAC and post-NAC immune infiltration (TILs). Response to chemotherapy was assessed by pCR rates. Association of clinical and pathological factors with TILs, pCR and survival was assessed by univariate and multivariate analyses. Results: Among 1199 BC patients: 46 were BRCA-deficient and 221 BRCA-proficient or wild type (WT). At NAC completion, pCR was observed in 84/266 (31%) patients and pCR rates were significantly higher in BRCA-deficient BC (p = 0.001), and this association remained statistically significant only in the luminal BC subtype (p = 0.006). The interaction test between BC subtype and BRCA status was nearly significant (Pinteraction = 0.056). Pre and post-NAC TILs were not significantly different between BRCA-deficient and BRCA-proficient carriers; however, in the luminal BC group, post-NAC TILs were significantly higher in BRCA-deficient BC. Survival analysis were not different between BRCA-carriers and non-carriers. Conclusions: BRCA mutation status is associated with higher pCR rates and post-NAC TILs in patients with luminal BC. BRCA-carriers with luminal BCs may represent a subset of patients deriving higher benefit from NAC. Second line therapies, including immunotherapy after NAC, could be of interest in non-responders to NAC.

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“…A key question for clinicians is whether an understanding of the genetic aberrations in hereditary breast cancer can be exploited to improve patient outcomes. The genomic instability induced by mutations in HR genes potentially renders cancer cells susceptible to chemotherapeutic drugs, particularly those that act directly to damage DNA, such as anthracyclines or platinums 82‐88 . In support of this, a number pre‐clinical studies have shown that BRCA1/2 deficient breast cancer cell lines, which lack functional HR, are much more sensitive to platinum‐based drugs, which induce inter‐strand crosslinks 89‐98 .…”

Section: Hr Defects and Cancer Treatmentmentioning

confidence: 99%

Homologous recombination deficiency in breast cancer: Implications for risk, cancer development, and therapy

Ali

McIntosh

Savage

2020

Genes Chromosomes & Cancer

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An underlying cause of breast cancers has been largely attributed to defects in the DNA damage response (DDR) pathway. In particular, the homologous recombination (HR) pathway repairs double‐stranded breaks (DSBs) in DNA, ultimately protecting the cell from genomic instability and thus preventing the accumulation of transforming mutations. In line with this, mutations in a number of genes encoding HR proteins are a well‐studied cause of HR deficiency (HRD), and, at the germline level, can confer risk to breast cancer but also occur somatically, contributing to sporadic breast cancer development, progression and response to therapy. Our understanding of the biological processes involved in HR and how these become compromised during breast cancer development has led to a better understanding of how HRD cells can be targeted with specific DNA damaging agents and/or with synthetic lethal targeting approaches such as PARP inhibition. Additionally, in vitro and preclinical modeling has supported the development of clinical trials to assess targeted therapies such as PARP inhibitors (PARPis), ultimately leading to development of therapies with greater clinical benefit. A number of challenges have been encountered, including resistance to therapy; however, addressing these challenges head‐on and continually driving scientific research and clinical trials with innovative therapies will contribute to our ability to target HRD in breast cancers. Ongoing research efforts into HRD in breast cancer development are therefore essential, even in the era of targeted therapies, to provide innovative strategies for improved tumor responses.

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Platinum-based neoadjuvant chemotherapy in BRCA1-positive breast cancer: a retrospective cohort analysis and literature review

Cited by 16 publications

References 14 publications

Real-world assessment of the effect of impact of tumor size on pathological complete response rates in triple negative breast cancer after neoadjuvant chemotherapy

Real-world assessment of the effect of impact of tumor size on pathological complete response rates in triple negative breast cancer after neoadjuvant chemotherapy

Impact of BRCA Mutation Status on Tumor Infiltrating Lymphocytes (TILs), Response to Treatment, and Prognosis in Breast Cancer Patients Treated with Neoadjuvant Chemotherapy

Homologous recombination deficiency in breast cancer: Implications for risk, cancer development, and therapy

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