. 2017 Dec;19(1).
doi: 10.1016/S1470-2045(17)30777-5.

Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials

Early Breast Cancer Trialists' Collaborative Group (EBCTCG)  
  • PMID: 29242041
  •     29 References
  •     116 citations


Background: Neoadjuvant chemotherapy (NACT) for early breast cancer can make breast-conserving surgery more feasible and might be more likely to eradicate micrometastatic disease than might the same chemotherapy given after surgery. We investigated the long-term benefits and risks of NACT and the influence of tumour characteristics on outcome with a collaborative meta-analysis of individual patient data from relevant randomised trials.

Methods: We obtained information about prerandomisation tumour characteristics, clinical tumour response, surgery, recurrence, and mortality for 4756 women in ten randomised trials in early breast cancer that began before 2005 and compared NACT with the same chemotherapy given postoperatively. Primary outcomes were tumour response, extent of local therapy, local and distant recurrence, breast cancer death, and overall mortality. Analyses by intention-to-treat used standard regression (for response and frequency of breast-conserving therapy) and log-rank methods (for recurrence and mortality).

Findings: Patients entered the trials from 1983 to 2002 and median follow-up was 9 years (IQR 5-14), with the last follow-up in 2013. Most chemotherapy was anthracycline based (3838 [81%] of 4756 women). More than two thirds (1349 [69%] of 1947) of women allocated NACT had a complete or partial clinical response. Patients allocated NACT had an increased frequency of breast-conserving therapy (1504 [65%] of 2320 treated with NACT vs 1135 [49%] of 2318 treated with adjuvant chemotherapy). NACT was associated with more frequent local recurrence than was adjuvant chemotherapy: the 15 year local recurrence was 21·4% for NACT versus 15·9% for adjuvant chemotherapy (5·5% increase [95% CI 2·4-8·6]; rate ratio 1·37 [95% CI 1·17-1·61]; p=0·0001). No significant difference between NACT and adjuvant chemotherapy was noted for distant recurrence (15 year risk 38·2% for NACT vs 38·0% for adjuvant chemotherapy; rate ratio 1·02 [95% CI 0·92-1·14]; p=0·66), breast cancer mortality (34·4% vs 33·7%; 1·06 [0·95-1·18]; p=0·31), or death from any cause (40·9% vs 41·2%; 1·04 [0·94-1·15]; p=0·45).

Interpretation: Tumours downsized by NACT might have higher local recurrence after breast-conserving therapy than might tumours of the same dimensions in women who have not received NACT. Strategies to mitigate the increased local recurrence after breast-conserving therapy in tumours downsized by NACT should be considered-eg, careful tumour localisation, detailed pathological assessment, and appropriate radiotherapy.

Funding: Cancer Research UK, British Heart Foundation, UK Medical Research Council, and UK Department of Health.

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Monica Morrow, Atif J Khan.
J Clin Oncol, 2020 May 23; 38(20). PMID: 32442069    Free PMC article.
Multidisciplinary Management of Breast Cancer With Extensive Regional Nodal Involvement.
Benjamin D Smith, Matthew P Goetz, Judy C Boughey.
J Clin Oncol, 2020 May 23; 38(20). PMID: 32442073    Free PMC article.
Current State of the Art in the Adjuvant Systemic Treatment of Premenopausal Patients With Early Breast Cancer.
Francesca Parisi, Maria Grazia Razeti, +7 authors, Matteo Lambertini.
Clin Med Insights Oncol, 2020 Jul 11; 14. PMID: 32647477    Free PMC article.
The Diagnostic Performance of Minimally Invasive Biopsy in Predicting Breast Pathological Complete Response After Neoadjuvant Systemic Therapy in Breast Cancer: A Meta-Analysis.
Yan Li, Yidong Zhou, +4 authors, Qiang Sun.
Front Oncol, 2020 Jul 18; 10. PMID: 32676452    Free PMC article.
Systematic Review.
Dynamic Risk Profiling Using Serial Tumor Biomarkers for Personalized Outcome Prediction.
David M Kurtz, Mohammad S Esfahani, +20 authors, Ash A Alizadeh.
Cell, 2019 Jul 10; 178(3). PMID: 31280963    Free PMC article.
Reduced symptom burden with the support of an interactive app during neoadjuvant chemotherapy for breast cancer - A randomized controlled trial.
Maria Fjell, Ann Langius-Eklöf, +2 authors, Kay Sundberg.
Breast, 2020 Apr 05; 51. PMID: 32247251    Free PMC article.
Sentinel Node Biopsy After Neoadjuvant Systemic Therapy for Breast Cancer: The Method Matters.
Harry D Bear, Kandace P McGuire.
Ann Surg Oncol, 2019 Apr 26; 26(8). PMID: 31020504    Free PMC article.
AGO Recommendations for the Diagnosis and Treatment of Patients with Early Breast Cancer: Update 2019.
Nina Ditsch, Michael Untch, +42 authors, Achim Wöckel.
Breast Care (Basel), 2019 Sep 29; 14(4). PMID: 31558897    Free PMC article.
Multiparametric MRI-based radiomics analysis for the prediction of breast tumor regression patterns after neoadjuvant chemotherapy.
Xiaosheng Zhuang, Chi Chen, +10 authors, Kun Wang.
Transl Oncol, 2020 Aug 08; 13(11). PMID: 32759037    Free PMC article.
Hyperpolarized 13C MRI of Tumor Metabolism Demonstrates Early Metabolic Response to Neoadjuvant Chemotherapy in Breast Cancer.
Ramona Woitek, Mary A McLean, +27 authors, Ferdia A Gallagher.
Radiol Imaging Cancer, 2020 Aug 18; 2(4). PMID: 32803167    Free PMC article.
Early stage triple negative breast cancer: Management and future directions.
Lubna N Chaudhary.
Semin Oncol, 2020 Jun 09; 47(4). PMID: 32507668    Free PMC article.
Engagement in an Interactive App for Symptom Self-Management during Treatment in Patients With Breast or Prostate Cancer: Mixed Methods Study.
Marie-Therése Crafoord, Maria Fjell, +2 authors, Ann Langius-Eklöf.
J Med Internet Res, 2020 Jul 15; 22(8). PMID: 32663140    Free PMC article.
Management of the Axilla after Neoadjuvant Systemic Therapy.
Trista J Stankowski-Drengler, Heather B Neuman.
Curr Treat Options Oncol, 2020 May 29; 21(7). PMID: 32462230    Free PMC article.
Breast Cancer Outcomes of Neoadjuvant Versus Adjuvant Chemotherapy by Receptor Subtype: A Scoping Review.
Trista J Stankowski-Drengler, Devon Livingston-Rosanoff, +3 authors, Heather B Neuman.
J Surg Res, 2020 May 19; 254. PMID: 32422430    Free PMC article.
Gene signature-based prediction of triple-negative breast cancer patient response to Neoadjuvant chemotherapy.
Yanding Zhao, Evelien Schaafsma, Chao Cheng.
Cancer Med, 2020 Jul 22;. PMID: 32692484    Free PMC article.
Machine Learning-Based Radiomics Nomogram Using Magnetic Resonance Images for Prediction of Neoadjuvant Chemotherapy Efficacy in Breast Cancer Patients.
Shujun Chen, Zhenyu Shu, +5 authors, Feng Shao.
Front Oncol, 2020 Sep 15; 10. PMID: 32923392    Free PMC article.
Standard-dose epirubicin increases the pathological complete response rate in neoadjuvant chemotherapy for breast cancer: a multicenter retrospective study.
Ben-Jie Shan, Xia-Bo Shen, +8 authors, Yue-Yin Pan.
Gland Surg, 2020 Sep 22; 9(4). PMID: 32953611    Free PMC article.
Neoadjuvant Chemotherapy without Radiation in Colorectal Cancer.
Jyotsna Bhudia, Rob Glynne-Jones, Thomas Smith, Marcia Hall.
Clin Colon Rectal Surg, 2020 Sep 25; 33(5). PMID: 32968364    Free PMC article.
Poly-ADP-Ribosylation of Estrogen Receptor-Alpha by PARP1 Mediates Antiestrogen Resistance in Human Breast Cancer Cells.
Nicholas Pulliam, Jessica Tang, +6 authors, Kenneth P Nephew.
Cancers (Basel), 2019 Jan 10; 11(1). PMID: 30621214    Free PMC article.
Primary systemic therapy in HER2-positive operable breast cancer using trastuzumab and chemotherapy: efficacy data, cardiotoxicity and long-term follow-up in 142 patients diagnosed from 2005 to 2016 at a single institution.
Silvia Antolín, Benigno Acea, +7 authors, Lourdes Calvo.
Breast Cancer (Dove Med Press), 2019 Jan 16; 11. PMID: 30643452    Free PMC article.
Paradigm shift in the local treatment of breast cancer: mastectomy to breast conservation surgery.
Kowsi Murugappan, Apoorva Saboo, Lu Kuo, Owen Ung.
Gland Surg, 2019 Jan 29; 7(6). PMID: 30687624    Free PMC article.
Primary medical therapy and breast conservation treatment: the medical oncology perspective.
Nan Soon Wong.
Gland Surg, 2019 Jan 29; 7(6). PMID: 30687629    Free PMC article.
Impact of clinical and pathological factors on local recurrence after breast-conserving treatment: CT-based localization for a tumor bed boost yielded better local control when compared with a surgical scar.
Lize Wang, Jinfeng Li, +4 authors, Tao Ouyang.
J Cancer, 2019 Feb 06; 10(3). PMID: 30719169    Free PMC article.
Neoadjuvant Therapy for Breast Cancer as a Model for Translational Research.
Cigdem Selli, Andrew H Sims.
Breast Cancer (Auckl), 2019 Mar 01; 13. PMID: 30814840    Free PMC article.
Post-neoadjuvant treatment and the management of residual disease in breast cancer: state of the art and perspectives.
Rafael Caparica, Matteo Lambertini, +3 authors, Martine Piccart.
Ther Adv Med Oncol, 2019 Mar 06; 11. PMID: 30833989    Free PMC article.
Neoadjuvant Therapy Should Be the Standard of Care for Every Node Positive Breast Cancer Patient.
Omar Hamdy.
J Breast Cancer, 2019 Apr 04; 22(1). PMID: 30941242    Free PMC article.
Insulin-like growth factor-1, metabolic abnormalities, and pathological complete remission rate in HER2-positive breast cancer patients receiving neoadjuvant therapy.
Yi-Wei Tong, Gen Wang, +7 authors, Kun-Wei Shen.
Onco Targets Ther, 2019 Jun 14; 12. PMID: 31190894    Free PMC article.
Mechanisms behind prometastatic changes induced by neoadjuvant chemotherapy in the breast cancer microenvironment.
Vladimir M Perelmuter, Liubov A Tashireva, +4 authors, Nadezhda V Cherdyntseva.
Breast Cancer (Dove Med Press), 2019 Jul 17; 11. PMID: 31308736    Free PMC article.
Monitoring the response to neoadjuvant chemotherapy in patients with breast cancer using ultrasound scattering coefficient: A preliminary report.
Katarzyna Dobruch-Sobczak, Hanna Piotrzkowska-Wróblewska, +6 authors, Jerzy Litniewski.
J Ultrason, 2019 Jul 30; 19(77). PMID: 31355579    Free PMC article.
Breast Edema Following Breast-Conserving Surgery and Radiotherapy: Patient-Reported Prevalence, Determinants, and Effect on Health-Related Quality of Life.
Danny A Young-Afat, Madelijn L Gregorowitsch, +9 authors, Helena M Verkooijen.
JNCI Cancer Spectr, 2019 Jul 31; 3(2). PMID: 31360894    Free PMC article.
Do early HER2-overexpression breast cancer patients benefit from undergoing neoadjuvant trastuzumab and mastectomy? A meta-analysis.
Lin He, Qian Wu, +3 authors, Yuhua Song.
Cancer Manag Res, 2019 Sep 12; 11. PMID: 31507328    Free PMC article.
Clinical and pathological factors predictive of response to neoadjuvant chemotherapy in breast cancer: A single center experience.
Salvatore Del Prete, Michele Caraglia, +11 authors, Raffaele Addeo.
Oncol Lett, 2019 Sep 14; 18(4). PMID: 31516598    Free PMC article.
Impact of Delayed Neoadjuvant Systemic Chemotherapy on Overall Survival Among Patients with Breast Cancer.
Debora de Melo Gagliato, Xiudong Lei, +4 authors, Mariana Chavez-MacGregor.
Oncologist, 2020 May 21;. PMID: 32431013    Free PMC article.
Does the Sequence of Anthracycline and Taxane Matter? The NeoSAMBA Trial.
José Bines, Isabele A Small, +9 authors, Martin Bonamino.
Oncologist, 2020 Jun 02;. PMID: 32476183    Free PMC article.
Is insulin resistance a predictor for complete response in breast cancer patients who underwent neoadjuvant treatment?
Ozkan Alan, Tugba Akin Telli, +13 authors, Perran Fulden Yumuk.
World J Surg Oncol, 2020 Sep 11; 18(1). PMID: 32907593    Free PMC article.
Do we still need breast cancer screening in the era of targeted therapies and precision medicine?
Rubina Manuela Trimboli, Paolo Giorgi Rossi, +4 authors, Francesco Sardanelli.
Insights Imaging, 2020 Sep 26; 11(1). PMID: 32975658    Free PMC article.
Update on breast cancer diagnosis and management: new topics for primary care.
Julie Cox, Amir Bhatti, Yitka Graham, Daniela Lee.
Br J Gen Pract, 2020 Oct 03; 70(699). PMID: 33004378    Free PMC article.
Does Use of Neoadjuvant Chemotherapy Affect the Decision to Pursue Fertility Preservation Options in Young Women with Breast Cancer?
Angelena Crown, Shirin Muhsen, +4 authors, Mary L Gemignani.
Ann Surg Oncol, 2020 Aug 09; 27(12). PMID: 32767225    Free PMC article.
Long-term Oncologic Outcomes of Immediate Breast Reconstruction vs Conventional Mastectomy Alone for Breast Cancer in the Setting of Neoadjuvant Chemotherapy.
Zhen-Yu Wu, Hee-Jeong Kim, +11 authors, BeomSeok Ko.
JAMA Surg, 2020 Oct 15;. PMID: 33052412    Free PMC article.
Early Prediction of Tumor Response to Neoadjuvant Chemotherapy and Clinical Outcome in Breast Cancer Using a Novel FDG-PET Parameter for Cancer Stem Cell Metabolism.
Chanwoo Kim, Sang-Ah Han, +2 authors, Deog Yoon Kim.
J Pers Med, 2020 Sep 23; 10(3). PMID: 32957507    Free PMC article.
A Perspective on Therapeutic Pan-Resistance in Metastatic Cancer.
Dimitrios Korentzelos, Amanda M Clark, Alan Wells.
Int J Mol Sci, 2020 Oct 08; 21(19). PMID: 33022920    Free PMC article.
Chinese breast cancer surgery: clinical practice and research.
Ling Xin, Jia-Yi Li, Zhi-Gang Yu, Yin-Hua Liu.
Chin Med J (Engl), 2020 Aug 10; 133(19). PMID: 32769500    Free PMC article.
Neoadjuvant chemotherapy: practice and thinking for Chinese patients with early breast cancer.
Xue-Fei Wang, Song-Jie Shen, +4 authors, Qiang Sun.
Chin Med J (Engl), 2020 Aug 10; 133(19). PMID: 32769502    Free PMC article.
Pathological Complete Response with Neoadjuvant Trastuzumab Combined with Chemotherapy in HER2 Positive Breast Cancer: A Single Institution Retrospective Analysis from Vietnam.
Huyen Thi Phung, Hoa Thi Nguyen, +3 authors, Chu Van Nguyen.
Breast Cancer (Dove Med Press), 2020 Oct 30; 12. PMID: 33116813    Free PMC article.
Early response and pathological complete remission in Breast Cancer with different molecular subtypes: a retrospective single center analysis.
Jin Hong, Jiayi Wu, +6 authors, Kunwei Shen.
J Cancer, 2020 Oct 31; 11(23). PMID: 33123282    Free PMC article.
FZR1 as a novel biomarker for breast cancer neoadjuvant chemotherapy prediction.
Shuo Liu, Haobin Wang, +7 authors, Shijing Yue.
Cell Death Dis, 2020 Sep 27; 11(9). PMID: 32978372    Free PMC article.
Quantitative ultrasound radiomics using texture derivatives in prediction of treatment response to neo-adjuvant chemotherapy for locally advanced breast cancer.
Archya Dasgupta, Stephen Brade, +14 authors, Gregory J Czarnota.
Oncotarget, 2020 Nov 05; 11(42). PMID: 33144919    Free PMC article.
Tumor mutation burden and JARID2 gene alteration are associated with short disease-free survival in locally advanced triple-negative breast cancer.
Xiangmei Zhang, Jingping Li, +4 authors, Baoen Shan.
Ann Transl Med, 2020 Nov 05; 8(17). PMID: 33145271    Free PMC article.
Landmark trials in the medical oncology management of early stage breast cancer.
Whitney Hensing, Cesar A Santa-Maria, Lindsay L Peterson, Jennifer Y Sheng.
Semin Oncol, 2020 Sep 17; 47(5). PMID: 32933761    Free PMC article.