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Platinum is essential in neoadjuvant treatment of triple-negative breast cancer: a network meta-analysis

Cancer Biology & Medicine 2022年第5期19卷 742-754页

作者： Junjie Li Li Chen Wei Tan Fang Qi Yang Zhang Zhonghua Wang Zhimin Shao Key Laboratory of Breast Cancer in Shanghai Department of Breast SurgeryFudan University Shanghai Cancer CenterShanghai 200032China Department of Oncology Shanghai Medical CollegeFudan UniversityShanghai 200032China Nottingham Clinical Trials Unit University of NottinghamNottingham NG72RDUK Academic Department Systematic Review Solutions LtdShanghai 201400China

Objective:This study aimed to assess the efficacy and safety of various neoadjuvant regimens for patients diagnosed with early-stage or locally advanced triple-negative breast cancer(TNBC).Methods:Medline,EMBASE,Cochrane Library,and Web of Science were searched in May 2020 to identify randomized controlled trials(RCTs).Bayesian network meta-analysis(NMA)was performed(Registration:PROSPERO CRD42020223012).Results:A total of 35 RCTs involving 8,424 participants were reviewed,of which 22 RCTs with 5,203 patients were included in this NMA focusing on pathologic complete response(pCR).An anthracycline-taxane-based(AT)regimen combined with a platinum(ATPt)[odds ratio(OR)=2.04,95%credible interval(CrI):1.69,2.48]regimen,and a docetaxel regimen combined with a carboplatin(TCb;OR=2.16,95%CrI:1.20,3.91)regimen improved pCR beyond that with AT only.AT and ATPt combined with targeted therapy[including bevacizumab(Bev),veliparib,atezolizumab,or pembrolizumab]also improved pCR.Five RCTs included in this NMA reported serious adverse events(SAEs)or grade≥3 AEs.TCb was associated with fewer grade≥3 AEs than was AT(OR=0.66,95%CrI:0.23,1.72)alone.In contrast,ATPt,AT+Bev,ATPt+Bev,ATPt+veliparib,and ATPt+pembrolizumab were associated with more SAEs than was AT alone.Conclusions:In patients with TNBC,platinum-based neoadjuvant regimens ATPt and TCb increase pCR beyond that with AT alone,but TCb appears to be better tolerated than either AT or ATPt.Platinum-based regimens combined with targeted therapies(Bev,PARPi,and PD-1/PD-L1 inhibitor)also improve the pCR rate beyond that with AT alone,but this benefit is accompanied by greater toxicity.

关键词： Breast cancer triple negative neoadjuvant network meta-analysis

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Non-anthracycline-containing docetaxel and cyclophosphamide regimen is associated with sustained worse outcome compared with docetaxel, anthracycline and cyclophosphamide in neoadjuvant treatment of triple negative and HER2-positive breast cancer patients:

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Chinese Journal of Cancer Research 2016年第6期28卷 561-569页

作者： Xiaosong Chen Guolin Ye Chenfang Zhang Xinzheng Li Kunwei Shen Comprehensive Breast Health Center Rui Jin Hospital Shanghai Jiao Tong University School of Medicine Department of Breast Surgery The First People’s Hospital of Foshan Department of Breast Surgery General Hospital of Guangzhou Military Command of PLA Department of Breast Surgery Shanxi Provincial Cancer Hospital

Objective： A previous study demonstrated that non-anthracycline-containing docetaxel plus cyclophosphamide（TC） regimen was inferior to docetaxel, anthracycline and cyclophosphamide（TAC） in neoadjuvant treatment of triple-negative breast cancer（TNBC） and human epidermal growth factor receptor-2-（HER2）-positive breast cancer in a short-term follow-up. Herein, long-term follow-up survival outcomes have been investigated.Methods： TNBC or HER2-positive patients were randomized to receive 6 cycles of TC or TAC neoadjuvant treatment. The primary endpoint was pathological complete remission（p CR）. Secondary endpoints included clinical response rate, event-free survival（EFS）, and overall survival（OS）.Results： A cohort of 96 patients consisted of 45 in TC and 51 in TAC arm. With a median follow-up period of53（range, 8-76） months, the patients achieving p CR post neoadjuvant chemotherapy exhibited superior EFS and OS than patients without p CR（P〈0.05）. TAC treatment resulted in consistently better EFS than TC treatment：the estimated 5-year EFS was 66.1% vs. 29.8%（P=0.002）. Moreover, the estimated 5-year OS was also in favor of TAC： 88.4% vs. 51.6%（P〈0.001）. Multivariable analysis demonstrated that the treatment regimen was an independent prognostic factor, and patients treated with TAC had a superior EFS [hazard ratio（HR）, 0.48; 95%confidence interval（95% CI）, 0.26-0.90; P=0.021] and OS（HR, 0.20; 95% CI, 0.08-0.60; P=0.003）.Conclusions： The updated long-term follow-up data demonstrated a sustained benefit in EFS and OS from anthracycline-containing TAC treatment, indicating that anthracycline is an essential and effective drug in this clinical trial.

关键词： Breast cancer neoadjuvant chemotherapy anthracycline survival triple negative HER2

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Efficacy of platinum in advanced triple-negative breast cancer with germline BRCA mutation determined by next generation sequencing

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Chinese Journal of Cancer Research 2020年第2期32卷 149-162页

作者： Nan Wang Kun Li Wenfa Huang Weiyao Kong Xiaoran Liu Weijie Shi Feng Xie Hanfang Jiang Guohong Song Lijun Di Quanren Wang Jianjun Yu Huiping Li Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing) Department of Breast OncologyPeking University Cancer Hospital and InstituteBeijing 100142China Huidu Shanghai Medical Sciences Shanghai 201499China Jiangsu Hengrui Medicine Shanghai 200120China

Objective:To compare the efficacy of platinum-and non-platinum-based regimens as first-line treatment for advanced triple-negative breast cancer(TNBC)and analyze the relationship between their efficacy and BRCA gene status.Methods:Retrospectively analyze clinical data of 220 patients diagnosed pathologically with advanced TNBC and treated at the Department of Breast Oncology,Peking University Cancer Hospital from 2013 to 2018 and evaluate the efficacy of chemotherapy.A total of 114 patients had BRCA1/2 gene tested by next generation sequencing(NGS)using peripheral blood,and we analyzed the correlation between their efficacy and BRCA1/2 gene status.Results:Non-platinum-based chemotherapy(NPCT)was administered to 129 and platinum-based chemotherapy(PBCT)to 91 study patients.The clinical benefit rate(CBR)and median progression-free survival(PFS)were not statistically different between NPCT and PBCT groups.The median overall survival(OS)was 30.0 and 22.5 months for PBCT and NPCT group,respectively[P=0.090,hazard ratios(HR)=0.703].BRCA status was assessed in 114 patients,14 of whom had deleterious germline BRCA1/2(g BRCA)mutations(seven in each group).In PBCT group,the CBR was 85.7%and 35.1%for patients with and without deleterious g BRCA mutations,respectively(P=0.039).The median PFS were 14.9 and 5.3 months and median OS were 26.5 and 15.5 months for patients with and without deleterious g BRCA mutations,respectively(P=0.001,P=0.161,respectively).Patients in PBCT group had significantly greater rates of grade 3-4 anemia(5.5%vs.0%)and thrombocytopenia(8.8%vs.0%),whereas palmar-plantar erythrodysesthesia(12.4%vs.0%)and peripheral neuropathy(8.6%vs.1.1%)occurred more frequently in NPCT group.Conclusions:Platinum-based regimens are more effective in patients with deleterious g BRCA mutations,but no difference in patients without BRCA gene mutations,so non-platinum is an option in patients without BRCA gene mutations considering the toxicity and side effect.And we recommend that patients with advanced TNBC should have BR

关键词： Advanced breast cancer triple negative BRCA mutation next-generation sequencing platinum efficacy

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Pattern of Failure and Treatment Results in triple negative Breast Cancer Patients

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Advances in Breast Cancer Research 2022年第2期11卷 75-88页

作者： Sherif Zawawy Gehan Khedr Clinical Oncology Department Faculty of Medicine Alexandria University Alexandria Egypt

Background: triple negative breast cancer (TNBC) tends to present aggressively with rapid progression and poor survival. Methods: We retrospectively reviewed patients’ files to define TNBC patients’ characteristics, predictive and prognostic factors, pattern of recurrence and survival. Results: 965 cases were identified. 147 patients (15.2%) were TNBC. 71.1% patients were premenopausal. T2, T3, T4 tumors represented 46.1%, 32% and 14.1%, respectively. N0, N1, N2, N3 disease represented 18.5%, 50.9%, 27.8% and 2.8%, respectively. Stages II, III & IV constituted 34.1%, 44.2% and 15.5%, respectively. 31.5% patients received neoadjuvant chemotherapy with 17.7% complete pathological response. 19.5%, 35.9%, 44.6% patients had unknown, ≤20 and >20 Ki67, respectively. Among non-metastatic patients (n = 108), 21.3% patients developed relapse with median time to relapse of 11 months. 78.3% of them had visceral (88.3% lung) metastasis, 13% bone metastasis, 21.7% brain metastasis and 13% LRR. There is significantly high risk of relapse in patients with large tumor size [T4: 66.75%, T3: 22.9%, T2: 16.7%, T1: 0% (p = 0.002)], positive LNs [N3: 100%, N2: 37.9%, N1: 15.1%, N0: 4.3% (p 0.001)] and Ki67 [>20: 31.6% versus 10.8% for Ki67 ≤ 20 (P = 0.007)]. Multivariate analysis revealed only T4 and N2-3 were significantly associated with high probability for relapse (P = 0.022 & 0.038). The 3-year DFS and OS were 73.2% and 75% respectively. For metastatic patients (n = 20), the m PFS was 7 months and m OS 1.5 years. Conclusion: Our data confirms the aggressive nature of TNBC with significant risk of relapse for patients with large tumor and positive lymph nodes. Maintenance metronomic capecitabine, neoadjuvant/adjuvant immunotherapy could be beneficial for non-metastatic patients. Lungs and brain were the most common sites of distant failure with poor survival that necessitates administration of molecular biomarkers (BRCA mutations, PD-L1 expression and microsatellite instability) for patients’ selection for novel targeted therapy.

关键词： Metastatic Breast Cancer triple negative Pattern of Failure

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Clinicopathological Characters of triple negative Breast Cancer

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Chinese Journal of Cancer Research 2010年第1期22卷 17-20页

作者： Xin Zhou Qian Liu Chongqing Cancer Institute Chongqing 400030 China

Objective： To study the clinicopathological characters Methods： A total of 629 patients with breast cancer of triple negative breast cancer （TNBC）. were reviewed, who were treated from 2003 to 2007 in Chongqing Cancer Institute. The comparison of clinicopathological features including TNM classification, histological type, tumor location, axillary lymphonodes status and neoadjuvant chemotherapy between TNBC and nontriple negative breast cancer （NTNBC） was performed. The overall response was evaluated by whether the patients achieve complete remission （CR） and partial remission （PR） after chemotherapy. Results： There were 69 TNBCs in the 629 patients with breast cancer. The premenopausal patients, which was found in 49/69 of TNBCs, was more than NTNBCs. The average diameter of tumor in TNBC group was 4.1 cm, lager than NTNBC group. TNBC with axillary nodes metastasis occurred in 21 cases, and the axillary nodes metastasis rate was lower than NTNBC. The positive expression rate of p53 in TNBC was 44.9%, and the overall response （CR＋PR） was 72.2%. No statistical differences were found regarding the positive expression rate of p53 and the overall response between TNBC and NTNBC. Conclusion： TNBC were a group of primary breast cancers with triple negative, tending to occur in premenopausal women, with larger tumors, lower axillary nodes metastasis rate. TNBC had worse clinical prognosis and currently lacked effective targeted therapies.

关键词： Breast cancer triple negative Prognosis

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Epidemiological, Diagnosis, Therapeutic and Evolving Profile of triple negative Breast Cancer in Senegal

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Advances in Breast Cancer Research 2021年第3期10卷 100-109页

作者： Papa Macoumba Gaye Mouhamed Diouf Mouhamadou Bachir Ba Doudou Diouf Fatimatou Néné Sarr Maimouna Mané Mamadou Sarr Mamadou Moustapha Dieng Sidy Ka Ahmadou Dem Radiotherapy Department of Dalal Jamm Hospital Dakar Senegal Cheikh Anta Diop University of Dakar Dakar Senegal Oncological Surgery Department of Dalal Jamm Hospital Dakar Senegal Joliot Curie Institute in Dakar Aristide Ledantec Hospital Dakar Senegal

Objective: Describe the epidemiological, diagnostic, therapeutic and evolutionary profile of triple negative breast cancer at the Dakar Cancer Institute in Senegal. Patients and Methods: This was a retrospective study between January 1, 2011 and December 31, 2014. All patients with a triple negative molecular profile were included. The data were collected from the medical records of the patients. The data were entered and analyzed with SPSS edition 16 software under Windows 7. Results: Two hundred and twenty-five patients were selected. The mean age was 47.9 ± 12.5 years with extremes of 25 and 90 years. The main reason for consultation was dominated by the finding of a breast lump. The mean clinical tumor size was 8, 54 cm with a large majority of T3-T4 tumors 26% and 63% respectively, lymph node involvement in one hundred and seventy-two cases (76.4%);twenty eight patients (12.4%) were metastatic from the outset. Non-specific invasive carcinoma was the most common histologic type (78.2%), and more than half of the patients (53.3%) had an aggressive tumor (Scarff-Bloom-Richardson grading III). Neoadjuvant chemotherapy was performed in 65.78% of cases. We noted 27.7% total response and 41.7% partial response in patients who have received this neoadjuvant chemotherapy. The surgery was radical in 77% of cases, conservative in 14% and clea

关键词： Breast Cancer triple negative Senegal

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An unusual case of encapsulated papillary carcinoma of breast

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Journal of Cancer Metastasis and Treatment 2016年第1期2卷 224-227页

作者： Kriti Chauhan Monika Garg Department of Pathology Maharishi Markandeshwar Institute of Medical Sciences and ResearchMullanaAmbalaHaryana 133203India

Intracystic(encapsulated)papillary carcinoma of breast is a rare variant of breast cancer.It is usually a low-grade tumor showing estrogen,progesterone positivity.The authors report an unusual case of intracystic papillary carcinoma showing high nuclear grade,brisk mitosis,and necrosis with triple negativity for estrogen,progesterone,and Her-2/neu receptors,as well as negative axillary lymph nodes.Such cases need to be reported to increase awareness so that they will be managed conservatively,avoiding any overtreatment despite being high grade and triple negative.

关键词： Intracystic papillary carcinoma high grade triple negative

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