Clinical and pathological response to neoadjuvant chemotherapy (NCT) in patients with triple-negative breast cancer (TNBC).

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12616-e12616
Author(s):  
Petr Krivorotko ◽  
Elena Zhiltsova ◽  
Larisa Gigolaeva ◽  
Alexander Emelyanov ◽  
Roman Pesotskiy ◽  
...  

e12616 Background: Neoadjuvant chemotherapy (NCT), Triple-negative breast cancer (TNBC) including anthracyclines and taxanes for early stages of TNBC, allows to achieve pathological complete response (pCR) in 25-36% of patients. Pathological complete response (pCR) significantly correlates with an increase in disease-free survival (DFS) and overall survival (OS). Methods: Randomized, monocentric trial was conducted in NN Petrov National Medical Research Center of Oncology from 2016 to 2019. 99 patients aged from 28 to 68 years with confirmed TNBC were included in trial: 96 had invasive ductal carcinoma G3, 3 - metaplastic cancer, negative BRCA mutations (a test for Founder mutations was performed).Patients were randomized in 3 groups, depending on the NCT regimen:1st subgroup (24 patients) - Eribulin in combination with Carboplatin AUC 5 x 4 cycles 2nd subgroup (37 patients) - Paclitaxel in combination with Carboplatin AUC 5 x 4 cycles 3rd subgroup (38 patients) –Carboplatin AUC5 + Doxorubicin + Paclitaxel x 6 cycles. Patients 1 and 2 subgroups in an adjuvant mode received 4 cycles of AC. Results: Clinical complete response (cCR) by physical examination (palpation) was achieved in 44 out of 99 patients (44.4%). Clinical complete response (cCR) by ultrasound and MG - in 27 (27.2%) patients. Miller-Payne V regression stage was achieved in 55 out of 99 cases (55.6%). In clinical cT1-T2 stage (n = 70), ypCR was achieved in 49 cases (70%), cT3-T4 (n = 29) ypCR in 6 patients (20.68%). Before NCT, 71 patients had status cN0-N1. Conversion to ypN0 occurred in 57 patients (80.2%). In 28 patients with cN2-N3 status, conversion to ypN0 occurred in 7 patients (25%). The median follow-up was 58 months. Progression was observed in 15.1% of patients, mortality – 6%. Local recurrence - 6 patients (6%), all patients were with residual tumor after NCT. Distant recurrence – 8 patients (8.1 %). Local recurrence rate and distant recurrence rate did not correlate with type of surgery (BCS or ME), but correlated with ypCR. Conclusions: NCT for TNBC is advisable both for locally advanced breast cancer and early breast cancer BC. De-escalation of BC surgery is possible in the future, especially in cT1-T2 stage patients (n = 70) where ypCR rate reaches 70%. It is planned to continue the trial with the vacuum aspiration biopsy of the tumor bed and SLNB after NCT.SLNB after NCT is advisable only in cN0-N1 group of patients (n = 71), since conversion to ypN0 was achieved in 57 patients - 80.2%.

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1586
Author(s):  
Milos Holanek ◽  
Iveta Selingerova ◽  
Ondrej Bilek ◽  
Tomas Kazda ◽  
Pavel Fabian ◽  
...  

Pathological complete response (pCR) achievement is undoubtedly the essential goal of neoadjuvant therapy for breast cancer, directly affecting survival endpoints. This retrospective study of 237 triple-negative breast cancer (TNBC) patients with a median follow-up of 36 months evaluated the role of adding platinum salts into standard neoadjuvant chemotherapy (NACT). After the initial four standard NACT cycles, early clinical response (ECR) was assessed and used to identify tumors and patients generally sensitive to NACT. BRCA1/2 mutation, smaller unifocal tumors, and Ki-67 ≥ 65% were independent predictors of ECR. The total pCR rate was 41%, the achievement of pCR was strongly associated with ECR (OR = 15.1, p < 0.001). According to multivariable analysis, the significant benefit of platinum NACT was observed in early responders ≥45 years, Ki-67 ≥ 65% and persisted lymph node involvement regardless of BRCA1/2 status. Early responders with pCR had a longer time to death (HR = 0.28, p < 0.001) and relapse (HR = 0.26, p < 0.001). The pCR was achieved in only 7% of non-responders. However, platinum salts favored non-responders’ survival outcomes without statistical significance. Toxicity was significantly often observed in patients with platinum NACT (p = 0.003) but not for grade 3/4 (p = 0.155). These results based on real-world evidence point to the usability of ECR in NACT management, especially focusing on the benefit of platinum salts.


2020 ◽  
Vol 52 (3) ◽  
pp. 689-696 ◽  
Author(s):  
Sanxing Guo ◽  
Sibylle Loibl ◽  
Gunter von Minckwitz ◽  
Silvia Darb-Esfahani ◽  
Bianca Lederer ◽  
...  

Purpose<i>PIK3CA</i>, encoding for subunit p110a of phosphatidylinositol 3 kinase, is frequently mutated in breast cancer. <i>PIK3CA</i>mutation was predictive for pathological complete response (pCR) in human epidermal growth factor 2 positive breast cancer. This study explores the association of <i>PIK3CA</i> mutation and pCR in triple-negative breast cancer (TNBC) treated with neoadjuvant chemotherapy.Materials and MethodsA total of 92 patients with TNBC derived from a prospectively randomized phase II trial GeparSixto study (NCT01426880). Exon 9 and exon 20 of <i>PIK3CA</i> mutations were evaluated by using classical Sanger method with formalin-fixed paraffin-embedded tumor tissues.ResultsSeven of 90 tumors (7.8%) were detectable with a <i>PIK3CA</i> H1047R mutation. Overall, <i>PIK3CA</i> H1047R mutation was significantly associated with a lower pCR rate (14.3% vs. 56.6%; odds ratio, 0.128; 95% confidence interval [CI], 0.015 to 1.108; p=0.047). In carboplatin- containing treatment patients, H1047R mutation trended to predict a lower pCR rate (20% vs. 62.5%; p=0.146). In a multivariable analysis, H1047R mutation trended to predict a lower pCR rate (hazard ratio, 0.1; 95% CI, 0.01 to 1; p=0.056).ConclusionTNBC with a <i>PIK3CA</i> H1047R mutation was less likely to achieve pCR after anthracyclinebased neoadjuvant chemotherapy. Development of H1047R mutant selective inhibitors might be helpful to conquer this subtype of breast cancer.


2011 ◽  
Vol 29 (27_suppl) ◽  
pp. 274-274
Author(s):  
E. A. Ibrahim

274 Background: Primary systemic chemotherapy is a standard approach to treating women with locally advanced breast cancers, with higher survival rates reported among patients who attain a pathologic complete response. Triple-negative breast cancer is a special biological entity that remains major challenge to oncologist. Around 12%-20% of breast cancers are triple negative. The current phase II study was conducted to evaluate the pathological complete response (pCR) using cis-platinum containing regimen as neoadjuvant chemotherapy in locally advanced triple negative breast cancer. Methods: Eighteen women with stage III triple negative breast cancer who were recruited between July 2007 and February 2010 at King Fahad Specialist Hospital, Dammam, Saudi Arabia. Neoadjuvant chemotherapy consisted of 4 cycles of AC or FEC 100, followed by 4 cycles consisted of docetaxel-cisplatin every 3 weeks. Primary end point was pathological complete response. Results: Median age: 49 y (24-70); premenopausal: 16; 25% were below 35 years of age; Median tumor size: 9 cm (3.5-19); Grade III: 15; Stage IIIA: 3, IIIB:14, IIIC:1; all but 2 had positive nodes at diagnosis (89%). Clinical evaluation of response by RECIST criteria pre surgery: OR: 17/18 (94%), CR: 9 (50%); PR: 8 (44%).The second sequence with D-Cis-T doubled the rate of clinical CR obtained with AC/FEC. One patient was not operated due to disease progression. Pathological assessment, revealed that 8 (47%) pts had no residual invasive carcinoma in the breast; 3 (18%) had residual occasional scattered tumor cells less than 5 mm (pT1a); 10 (59%) had negative nodes; 8 achieved CpR and 2 nCpR. Patients with residual invasive component and/or nodal involvement had high baseline Ki 67 level. After a median follow up of 24 months, cumulative overall survival at 24 months is 88.9% for whole group. Cumulative overall survival in relation to response was 100% for patients who achieved pCR while overall cumulative survival rate for patients without pCR was 83.3% without statistical significance. Conclusions: This cisplatin based neoadjuvant chemotherapy regimen was well tolerated and achieved a high rate of pCR/npCR.


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