Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomised controlled superiority trial with a parallel HER2-negative cohort

e11034 Background: Neoadjuvant chemotherapy(NAC)is one of the treatment options for locally advanced breast cancer. In this study, we evaluated the efficacy and safety of 4 cycles of NAC doxorubicine,docetaxel and cyclophosphamide(TAC),correlation between the response to NAC and molecular classification sub-groups and between the pCR and the time to progression(TTP). Methods: This is a prospective study from January 2005 to December 2008.110 pts with locally advanced breast cancer stage III.All pts have received 4 cycles of NAC based on docetaxel 75 mg/m², doxorubicine 50 mg/m² and cyclophosphamide 500 mg/m² every 3 weeks, followed by surgery.101 pts were assessed, since 9 of them have progressed on treatment and came out of the study. Pts were stratified according to age, menopausal status, histopathological analysis (luminal tumors(ER-positive and HER2-negative), triple-negative tumors (TN)and HER2-positive tumors), response to the treatment and survival. The median follow up of patients was 39 months. The statistical study was done using SPSS 17. Results: The median age was 41(23–65).30% of pts were younger than 35 and 80% were premenopausal. 55% luminal tumors(56 pts), 33% HER2 positive(33 pts) and 12 % TN(12 pts).CRR was estimated at 89%(37% of CR and 63% of PR).There were 23, 7% of pCR according to Chevallier’s classification. In luminal, TN and HER2-positive pCR rates were 16%(9 of 56), 66,6%(8 of 12), and 21,2%(7 of 33) respectively. Multivariate analysis showed that the ER status was the only significant predictor of pCR(P = 0.025).HER2 status was not significantly associated with pCR(P= 0,423).TTP was 50 months. In luminal tumors, TN and HER2-positive tumors the TTP was respectively 59, 52 and 49 months. There was not a significant difference in TTP between the pCR(51 months) and the non-pCR group(44 months)(CI 95, p= 0.109).Grade III/IV toxicity included neutropenia(22%), febrile neutropenia(6,5%), mucositis(13%), and diarrhea(4%). Conclusions: Breast cancer occurs in young women in Algeria. In this study, neoadjuvant TAC was effective and well tolerated. The ER status was the only significant predictor of pCR. The molecular classification group with the highest percentage of pCR was the TN group. pCR was not associated with a better prognosis.

Download Full-text

Prognostic significance of estrogen, progesterone and HER2 receptors’ status conversion following neoadjuvant chemotherapy in patients with locally advanced breast cancer: Results from a tertiary Cancer Center in Saudi Arabia

PLoS ONE ◽

10.1371/journal.pone.0247802 ◽

2021 ◽

Vol 16 (3) ◽

pp. e0247802

Author(s):

Khalid Al-Saleh ◽

Tareq Salah ◽

Maria Arafah ◽

Sufia Husain ◽

Ammar Al-Rikabi ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Advanced Breast Cancer ◽

Locally Advanced Breast Cancer ◽

Univariate Analysis ◽

Locally Advanced ◽

Receptor Expression ◽

Advanced Breast ◽

Her2 Positive ◽

Receptor Conversion

Background The prognostic impact of neoadjuvant chemotherapy (NAC) on the receptor expression status in patients with locally advanced breast cancer (LABC) is still not fully understood. We aimed to evaluate the changes in hormone (estrogen and progesterone) receptor (HR) and human epidermal growth factor receptor 2 (HER2) status post-NAC and their correlation with survival. Methods Patients with LABC who have received NAC between 2008 and 2015 and have been followed up till December 2019 at the Oncology Center, King Saud University, KSA were analyzed retrospectively. biomarker analysis of ER, PR & HER2 were done using immunohistochemistry (IHC) and Fluorescent in situ hybridization. Results Ninety-one patients fulfilled the inclusion criteria. HR status changed in 21(23.1%) patients, with a significant difference between patients with stable receptors and those with any receptor conversion; p = 0.000. Five (5.5%) initially HER2 negative tumors became HER2 positive and 10 (11%) initially HER2 positive tumors became HER2 negative after NAC. The difference in HER2 expression level before and after NAC was not statistically significant (p = 0.302). Univariate analysis relating patients’ characteristics and 10-years disease-free survival (DFS) showed only significant correlations with the expressions of ER, PR, and any receptor conversion, (ER and/or PR) p< 0.001, p< 0.001, and p = 0.001; respectively. In the univariate analysis, none of the clinicopathological features showed a significant correlation with the OS except for the molecular subtypes P<0.001. Conclusions Patients with LABC have significant changes in the ER and PR receptor status following NAC. Post-NAC expressions change of ER and PR (ER and/or PR) are correlated to DFS. Retesting of the hormone receptors should be considered after NAC in Saudi patients with LABC.

Download Full-text

Prognostic biomarker candidates of neoadjuvant chemotherapy for luminal B-positive locally advanced breast cancer.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e12638 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e12638-e12638

Author(s):

Zhaoyun Liu ◽

Jinjin Wang ◽

Chenxi Yuan ◽

Zhiyong Yu ◽

Wendy Wu ◽

...

Keyword(s):

Breast Cancer ◽

Neoadjuvant Chemotherapy ◽

Advanced Breast Cancer ◽

Locally Advanced Breast Cancer ◽

Locally Advanced ◽

Neoadjuvant Treatment ◽

Advanced Breast ◽

Luminal A ◽

Her2 Positive ◽

Luminal B

e12638 Background: In the last decade, the treatment approach for locally advanced breast cancer (BC) patients has partly shifted from adjuvant treatment to neoadjuvant treatment. Systemic neoadjuvant treatment can downstage the tumor for less extensive surgery and improve cosmetic outcomes. Differential subtypes of BC responded unevenly to neoadjuvant chemotherapy. Luminal B type with the relatively higher prevalence (40% in all 4 subtypes) had better therapeutic effect to neoadjuvant treatment than luminal A type, but worse than HER2-positive patients. Methods: We enrolled 87 BC patients for genotyping with multiple cancer-related genes. Among them, 17 patients were luminal A, 21 were HER2-negative luminal B, 23 were HER2-positive luminal B, 17 were HER2-positive and 9 were triple-negative. According to the RECIST, the patients were divided into 1-4 and 5 grades. Fisher test was used to analyze the difference of SNV and CNV between the two primary tumors, as well as TMB difference between post-neoadjuvant chemotherapy and past-neoadjuvant chemotherapy. Results: Base mutations in all patients showed discrepant preference between 1-4 grades and 5 grade groups, G-to-A in 1-4 grades, while A-to-G, A-to-T and G-to-T in 5 grade. In luminal B group (combine liminal B-negative and luminal B-positive groups), FLT4 gene mutation occurred more frequent in 5 grade than 1-4 grades (4/16 vs 0/28, P = 0.01). CNV analysis in NFKBIA and ZNF217 distinguished the two therapeutic efficiency groups in luminal B-positive group. The amplification of NFKBIA and ZNF217 was higher in 1-4 grades than 5 grade (8/14 vs 1/9, P = 0.036; 9/14 vs 1/9, P = 0.017). TMB difference between post and past neoadjuvant chemotherapy in luminal B-positive group was also significant in 5 grade (4.36 vs 1.99, P = 0.002). Conclusions: NFKBIA and ZNF217 amplification notably differentiated the 1-4 grades and 5 grade groups in luminal B-positive patients, suggesting the potential prognostic biomarkers of neoadjuvant chemotherapy in this locally advanced breast cancer subtype, which would be improved by further large-scale cohort study. The differences of TMB and FLT4 gene mutation were also found between the two therapeutic efficiency groups.

Download Full-text