Association of <i>PIK3CA</i> Mutation Status before and after Neoadjuvant Chemotherapy with Response to Chemotherapy in Women with Breast Cancer

Abstract Purpose: The association between PIK3CA mutations and response to neoadjuvant chemotherapy in women with primary breast cancer is not fully elucidated. Experimental Design: PIK3CA mutations in breast cancer tissues that were taken prior to the initiation of neoadjuvant chemotherapy were identified in 729 operable primary breast cancer patients who received neoadjuvant chemotherapy. Among these, the PIK3CA mutations were also reassessed in tumor tissues procured following operation in 102 patients after completion of neoadjuvant chemotherapy. Results: A total of 206 out of 729 (28.3%) patients had PIK3CA mutations, and 19.5% of patients (142/729) in this cohort achieved a pathologic complete response (pCR) after neoadjuvant chemotherapy. Patients with PIK3CA mutations exhibited a lower pCR rate than did those with wild-type (14.6% vs. 21.4%, P = 0.035). No significant differences in disease-free survival (DFS) or distant disease-free survival (DDFS) were observed between PIK3CA mutant and wild-type in the entire study population. Among the 102 patients with PIK3CA mutation statuses available before and after neoadjuvant chemotherapy, 24 patients (23.5%) had PIK3CA mutations before neoadjuvant chemotherapy. Of these 24 patients, 15 patients retained their initial PIK3CA mutations and 9 patients lost their initial mutations after neoadjuvant chemotherapy. Patients who retained the initial mutations after neoadjuvant chemotherapy (n = 15) had a worse DDFS than the remaining patients (n = 87) in this subgroup [unadjusted HR, 2.34; 95% confidence interval (CI), 0.98–5.62; P = 0.050]. Conclusions: Patients with PIK3CA mutations are less likely to respond to neoadjuvant chemotherapy. Patients who retain their initial PIK3CA mutations after neoadjuvant chemotherapy have an unfavorable survival. Clin Cancer Res; 21(19); 4365–72. ©2015 AACR.</jats:p

Level III axillary lymph nodes involvement in node positive breast cancer received neoadjuvant chemotherapy

Objective: To investigate the incidence, associated factors and prognosis of level III node involvement for breast cancer with positive axillary lymph nodes after neoadjuvant chemotherapy. Methods: A consecutive series of 521 node positive T0-2 invasive breast cancer cases were included in this retrospective study. Axillary node metastases were proved by ultrasound guided needle biopsy (NB) if ultrasonographic abnormal node was detected or by sentinel node biopsy (SNB) if no abnormal node was detected. After 4 to 8 cycles of neoadjuvant chemotherapy (NCT), axillary lymph nodes dissection included level III lymph nodes were completed for each case. Results: The pathologic complete response rate of axillary nodes was 31.1% (90/289) in NB positive subgroup. The incidence of residual positive level III lymph nodes were 9.0% (47/521). Multivariate analysis showed that node NB positivity (OR 2.212, 95% CI: 1.022-4.787, P = 0.044), clinical tumor size &gt;2 cm before NCT (OR = 2.672, 95% CI: 1.170-6.098, P = 0.020), and primary tumor non-response to neoadjuvant chemotherapy (OR 1.718, 95% CI: 1.232-2.396, P = 0.001) were independent predictors of level III lymph nodes positivity. At median follow-up time of 30 months, the distant disease-free survival (DDFS) rate of level III node positive group was much lower than that of level III negative group (p = 0.011). Conclusions: About 9% of node positive T0-2 breast cancer will have residual positive node in level III region after neoadjuvant chemotherapy. Node positivity proved by NB, large tumor size, and primary tumor non-response to neoadjuvant chemotherapy are independent predictors of level III lymph nodes positivity. (C) 2013 Published by Elsevier Ltd.http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000326677500025&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701OncologyObstetrics &amp; GynecologySCI(E)PubMed1ARTICLE61161-11652

Incidence of BRCA1 somatic mutations and response to neoadjuvant chemotherapy in Chinese women with triple-negative breast cancer

Background: The prevalence of BRCA1 somatic mutations status in triple-negative breast cancer (TNBC) has not been well documented. The aims of this study were to determine the frequency of BRCA1 somatic mutations and to investigate the association between BRCA1 deleterious somatic mutation status and response to neoadjuvant chemotherapy in women with TNBC. Methods: Two hundred and five TNBC patients without BRCA1 germline mutations were enrolled in this study. Fresh tumor tissues were available for this cohort of 205 patients, including 112 patients with fresh core needle biopsy tumor tissues before treatment and 93 patients with fresh tumor tissues procured after surgery. BRCA1 somatic mutations were determined in the tumor samples using PCR-direct sequencing assay. Among the 112 patients with core needle biopsy samples, 97 patients received neoadjuvant chemotherapy. Results: Eight patients (3.9%) carried a BRCA1 pathogenic somatic mutation in this cohort of 205 TNBC patients. These eight BRCA1 deleterious somatic mutations included five frameshift or nonsense mutations (c.191_212del22, c.1664delA, c.4674_4675 + 17del, c.3671_3672insTTCC, c.1162A&gt;T), one splicing site mutation (c.134 + 2T&gt;G) and two missense mutations (c.5511G&gt;C and c.286G&gt;A). No significant differences in tumor characteristics between BRCA1 deleterious somatic mutation carriers and non-carriers were observed. The pCR (pathologic complete response) rate was 32.0% in the 97 patients who received neoadjuvant chemotherapy. BRCA1 deleterious somatic mutation carriers (n = 5) had a higher pCR rate than did non-carriers (n = 92) (BRCA1 carriers vs non-carriers, 60.0% vs 30.4%, P = 0.32), although it did not reach a significance due to a small sample size. Conclusions: A small subset of TNBC patients carried a BRCA1 deleterious somatic mutation; BRCA1 somatic mutation carriers are likely to respond to neoadjuvant chemotherapy. (C) 2016 Elsevier B.V. All rights reserved.Ministry of Science and Technology of China [2014BAI09B08]; 973 project [2013CB911004]; National Natural Science Foundation of China [81372832, 81301780]SCI(E)[email protected]

Low expression of RECQL is associated with poor prognosis in Chinese breast cancer patients

Abstract Background RECQL is a number of the RecQ DNA helicase family and plays an important role in maintaining genome stability. Although several studies have reported that RECQL mutations were correlated with the susceptibility to breast cancer, the effect on prognosis in breast cancer was not yet clarified. Here, we explored the association between RECQL expression level and survival in patients with breast cancer. Methods In the first cohort, the RECQL mRNA expression level was evaluated in 774 primary breast cancer patients using a quantitative real-time PCR assay. Then, in the second independent cohort, the level of RECQL protein expression was detected in 322 patients with breast cancer using immunohistochemistry assay. Survival curves of patients with RECQL expression were compared using the Kaplan-Meier method with log-rank test. Results In the first cohort of 774 breast cancer patients, the low expression level of RECQL mRNA was significantly correlated with aggressive clinicopathological characteristics, including the positive lymph node status (P = 0.026), HER2 overexpression (P < 0.001), ER negative status (P = 0.047) and high tumor grade (P = 0.041). Moreover, the low expression level of RECQL mRNA was significantly associated with poor distant recurrence-free survival (DRFS, unadjusted hazard ratio (HR): 2.77, 95% confidence interval (CI): 1.88–4.09, P < 0.001) and disease-specific survival (DSS, unadjusted HR: 3.10, 95% CI: 1.84–5.20,P < 0.001), and it remained an independent unfavorable factor for DRFS and DSS (DRFS: adjusted HR: 3.04, 95% CI: 1.89–4.87, P < 0.001; DSS: adjusted HR: 4.25, 95% CI: 2.12–8.46, P < 0.001). In the second cohort of 322 breast cancer patients, low expression of RECQL protein was also subject to poor survival in breast cancer, and it was an independent prognosis factor of poor DRFS by multivariate analysis (DRFS: adjusted HR: 2.12, 95% CI: 1.16–3.88, P = 0.015). Conclusions Breast cancer patients with low RECQL expression had a worse survival. The expression level of RECQL may be a potential prognosis factor for breast cancer