The association between guideline adherence, age and overall survival among women with non-metastatic breast cancer: A systematic review

Published:January 31, 2022DOI:


      • Guideline compliance was high for breast cancer treatments in most studies.
      • Studies typically reported improved overall survival with guideline compliant care.
      • Unclear if association between survival and compliance was influenced by age.
      • Interpretation hampered by differences in study design and analysis methods.
      • Consistent study designs are required to improve weak evidence base.



      Conformity with treatment guidelines should benefit patients. Studies have reported variation in adherence to breast cancer (BC) guidelines, particularly among older women. This study investigated (i) whether adherence to treatment guideline recommendations for women with non-metastatic BC improves overall survival (OS), (ii) whether that relationship varies by age.


      MEDLINE and EMBASE were systematically searched for studies on guideline adherence and OS in women with non-metastatic BC, published after January 2000, which examined recommendations on breast surgery, chemotherapy, radiotherapy or endocrine therapy. Study results were summarised using narrative synthesis.


      Sixteen studies met the inclusion criteria. The recommendations for each treatment covered were similar, but studies differed in their definitions of adherence. 5-year OS rates among patients having compliant treatment ranged from 91.3% to 93.2%, while rates among patients having non-compliant treatment ranged from 75.9% to 83.4%. Six studies reported an adjusted hazard ratio (aHR) for non-compliant treatment compared with compliant treatment; all concluded OS was worse among patients whose overall treatment was non-compliant (aHR range: 1.52 [1.30–1.82] to 2.57 [1.96–3.37]), but adjustment for potential confounders was limited. Worse adherence among older women was reported in 12/16 studies, but they did not provide consistent evidence on whether OS was associated with treatment adherence and age.


      Individual studies reported that better adherence to guidelines improved OS among women with non-metastatic BC, but the evidence base has weaknesses including inconsistent definitions of adherence. More precise and consistent research designs, including the evaluation of barriers to adherence across the spectrum of healthcare practice, are required to fully understand guideline compliance, as well as the relationship between compliance and OS following a BC diagnosis.



      aOR (adjusted odds ratio), AI (aromatase inhibitor), ALND (axillary lymph node dissection), AS (axillary surgery), BC (breast cancer), BCS (breast conserving surgery), BrS (Breast surgery), CI (confidence interval), CPGs (clinical practice guidelines), CT (chemotherapy), DCIS (ductal carcinoma in situ), EBC (early breast cancer), ER (estrogen receptor), ET (endocrine therapy), GnRH (gonadotropin releasing hormone), HER2 (human epidermal growth factor receptor 2), HR (hazard ratio), IBC (invasive breast cancer), LABC (locally advanced breast cancer), LCIS (lobular carcinoma in situ), LN (lymph node), Mx (mastectomy), NACT (neoadjuvant chemotherapy), NOS (Newcastle Ottawa Scale), N/A (not applicable), NCCN (National Comprehensive Cancer Network), NR (not reported), OS (overall survival), PMRT (post-mastectomy radiotherapy), PT(s) (patient(s)), RT (radiotherapy), SLNB (sentinel lymph node biopsy), T-mab (trastuzumab)
      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'


      Subscribe to Cancer Treatment Reviews
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • Fitzmaurice Christina
        • et al.
        • Global Burden of Disease Cancer Collaboration
        Global, Regional, and National Cancer Incidence, Mortality, Years of Life Lost, Years Lived With Disability, and Disability-Adjusted Life-Years for 29 Cancer Groups, 1990 to 2017 A Systematic Analysis for the Global Burden of Disease Study.
        JAMA Oncol. 2019;
      1. Cancer Research UK. Breast Cancer Statistics [cited 2020 December]. Available from:

      2. Cancer Research UK. Cancer mortality for common cancers. [cited 2020 August]. Available from:

        • Waks A.G.
        • Winer E.P.
        Breast Cancer Treatment: A Review.
        JAMA. 2019; 321: 288
        • Early Breast Cancer Trialists' Collaborative G
        • Darby S.
        • McGale P.
        • Correa C.
        • Taylor C.
        • Arriagada R.
        • et al.
        Effect of radiotherapy after breast-conserving surgery on 10-year recurrence and 15-year breast cancer death: meta-analysis of individual patient data for 10,801 women in 17 randomised trials.
        Lancet. 2011; 378 (Epub 10/19. PubMed PMID: 22019144): 1707-1716
      3. Long-term outcomes for neoadjuvant versus adjuvant chemotherapy in early breast cancer: meta-analysis of individual patient data from ten randomised trials. Lancet Oncol 2018;19(1):27-39. doi: 10.1016/s1470-2045(17)30777-5. Epub 2017/12/1, PubMed PMID: 29242041; PubMed Central PMCID: PMCPMC5757427.

        • Allemani C.
        • Matsuda T.
        • Di Carlo V.
        • Harewood R.
        • Matz M.
        • Nikšić M.
        • et al.
        Global surveillance of trends in cancer survival 2000-14 (CONCORD-3): analysis of individual records for 37 513 025 patients diagnosed with one of 18 cancers from 322 population-based registries in 71 countries.
        Lancet. 2018; 391 (Epub 2018/02/06, PubMed PMID: 29395269; PubMed Central PMCID: PMCPMC5879496): 1023-1075
        • Miller J.W.
        • Smith J.L.
        • Ryerson A.B.
        • Tucker T.C.
        • Allemani C.
        Disparities in breast cancer survival in the United States (2001-2009): Findings from the CONCORD-2 study: Breast Cancer Survival by Race & Stage.
        Cancer. 2017; 123: 5100-5118
        • Derks M.G.M.
        • Bastiaannet E.
        • Kiderlen M.
        • Hilling D.E.
        • Boelens P.G.
        • Walsh P.M.
        • et al.
        Variation in treatment and survival of older patients with non-metastatic breast cancer in five European countries: a population-based cohort study from the EURECCA Breast Cancer Group.
        Br J Cancer. 2018; 119: 121-129
        • Dodwell D.
        • Jauhari Y.
        • Gathani T.
        • Cromwell D.
        • Gannon M.
        • Clements K.
        • et al.
        Treatment variation in early breast cancer in the UK.
        BMJ (Clin Res Ed). 2020; 371 (Epub 2020/12/03, PubMed PMID: 33262116): m4237
      4. The King's Fund. Variations in health care: The good, the bad and the inexplicable; 2011.

        • Busse R.
        • Klazinga N.
        • Panteli D.
        • Quentin W.
        Improving healthcare quality in Europe: Characteristics, effectiveness and implementation of different strategies.
        European Observatory on Health Systems and Policies. 2019;
        • Wolters R.
        • Regierer A.C.
        • Schwentner L.
        • Geyer V.
        • Possinger K.
        • Kreienberg R.
        • et al.
        A comparison of international breast cancer guidelines – Do the national guidelines differ in treatment recommendations?.
        Eur J Cancer. 2012; 48: 1-11
        • Maes-Carballo M.
        • Gómez-Fandiño Y.
        • Reinoso-Hermida A.
        • Estrada-López C.R.
        • Martín-Díaz M.
        • Khan K.S.
        • et al.
        Quality indicators for breast cancer care: A systematic review.
        The Breast. 2021; 59: 221-231
        • Jeevan R.
        • Cromwell D.A.
        • Trivella M.
        • Lawrence G.
        • Kearins O.
        • Pereira J.
        • et al.
        Reoperation rates after breast conserving surgery for breast cancer among women in England: retrospective study of hospital episode statistics.
        BMJ (Clin Res Ed). 2012; 345 (Epub 2012/07/14 PubMed PMID: 22791786)
      5. National Audit of Breast Cancer in Older Patients (NABCOP) Annual Report. July 2020. Available from [].

        • Purushotham A.
        • Pain S.J.
        • Miles D.
        • Harnett A.
        Variations in treatment and survival in breast cancer.
        Lancet Oncol. 2001; 2 (PubMed PMID: 33134056): 719-725
        • Cardoso F.
        • Gennari A.
        Editorial: Why are guidelines not followed in clinical practice?.
        Breast. 2017; 32 (PubMed PMID: 613969002): 245-246
        • Patrick J.L.
        • Hasse M.E.
        • Feinglass J.
        • Khan S.A.
        Trends in adherence to NCCN guidelines for breast conserving therapy in women with Stage I and II breast cancer: Analysis of the 1998–2008 National Cancer Data Base.
        Surg Oncol. 2017; 26 (PubMed PMID: 29113653): 359-367
        • Niño de Guzmán E.
        • Song Y.
        • Alonso-Coello P.
        • Canelo-Aybar C.
        • Neamtiu L.
        • Parmelli E.
        • et al.
        Healthcare providers’ adherence to breast cancer guidelines in Europe: a systematic literature review.
        Breast Cancer Res Treat. 2020; 181: 499-518
        • Wollschläger D.
        • Meng X.
        • Wöckel A.
        • Janni W.
        • Kreienberg R.
        • Blettner M.
        • et al.
        Comorbidity-dependent adherence to guidelines and survival in breast cancer-Is there a role for guideline adherence in comorbid breast cancer patients? A retrospective cohort study with 2137 patients.
        Breast Journal. 2018; 24: 120-127
        • Hurria A.
        • Levit L.A.
        • Dale W.
        • Mohile S.G.
        • Muss H.B.
        • Fehrenbacher L.
        • et al.
        Improving the Evidence Base for Treating Older Adults With Cancer: American Society of Clinical Oncology Statement.
        JCO. 2015; 33: 3826-3833
        • Page M.J.
        • McKenzie J.E.
        • Bossuyt P.M.
        • Boutron I.
        • Hoffmann T.C.
        • Mulrow C.D.
        • et al.
        The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.
        BMJ (Clin Res Ed). 2021; 372
        • Ricci-Cabello I.
        • Vásquez-Mejía A.
        • Canelo-Aybar C.
        • Niño de Guzman E.
        • Pérez-Bracchiglione J.
        • Rabassa M.
        • et al.
        Adherence to breast cancer guidelines is associated with better survival outcomes: a systematic review and meta-analysis of observational studies in EU countries.
        BMC Health Services Research. 2020; 20
      6. Wells G, Shea B, O'Connell D, Peterson j, Welch V, Losos M, et al. The Newcastle–Ottawa Scale (NOS) for Assessing the Quality of Non-Randomized Studies in Meta-Analysis 2000 [cited]. Available from:

      7. Popay J, Roberts H, Sowden A, Petticrew M, Arai L, Rodgers M, et al. Guidance on the conduct of narrative synthesis in systematic reviews: A product from the ESRC Methods Programme2006.

        • Andreano A.
        • Rebora P.
        • Valsecchi M.G.
        • Russo A.G.
        Adherence to guidelines and breast cancer patients survival: a population-based cohort study analyzed with a causal inference approach.
        Breast Cancer Res Treat. 2017; 164 (PubMed PMID: 615137280): 119-131
        • Cheng S.H.
        • Wang C.J.
        • Lin J.-L.
        • Horng C.-F.
        • Lu M.-C.
        • Asch S.M.
        • et al.
        Adherence to quality indicators and survival in patients with breast cancer.
        Med Care. 2009; 47: 217-225
        • Chéreau E.
        • Coutant C.
        • Gligorov J.
        • Lesieur B.
        • Antoine M.
        • Daraï E.
        • et al.
        Discordance with local guidelines for adjuvant chemotherapy in breast cancer: reasons and effect on survival.
        Clin Breast Cancer. 2011; 11: 46-51
        • Dooley W.
        • Squires R.
        • Bong J.
        • Parker J.
        Do the CMS proposed breast cancer quality measures actually predict improved outcomes?.
        Am J Surg. 2011; 202 (PubMed PMID: 51673300): 787-795
        • Ho P.J.
        • Ow S.G.W.
        • Sim Y.
        • Liu J.
        • Lim S.H.
        • Tan E.Y.
        • et al.
        Impact of deviation from guideline recommended treatment on breast cancer survival in Asia.
        Sci Rep. 2020; 10
        • Hsieh M.C.
        • Zhang L.
        • Wu X.C.
        • Davidson M.B.
        • Loch M.
        • Chen V.W.
        Population-Based Study on Cancer Subtypes, Guideline-Concordant Adjuvant Therapy, and Survival Among Women With Stage I-III Breast Cancer.
        J. 2019; 17 (PubMed PMID: 31200362): 676-686
        • Kantor O.
        • Wang C.-H.
        • Yao K.
        Regional Variation in Performance for Commission on Cancer Breast Quality Measures and Impact on Overall Survival.
        Ann Surg Oncol. 2018; 25: 3069-3075
        • Plavc G.
        • Ratosa I.
        • Zagar T.
        • Zadnik V.
        Explaining variation in quality of breast cancer care and its impact: a nationwide population-based study from Slovenia.
        Breast Cancer Res Treat. 2019; 175 (PubMed PMID: 30847727): 585-594
        • Sun S.X.
        • Hollenbeak C.S.
        • Leung A.M.
        Deviation from the Standard of Care for Early Breast Cancer in the Elderly: What are the Consequences?.
        Ann Surg Oncol. 2015; 22 (PubMed PMID: 25515198): 2492-2499
        • Taubenhansl C.
        • Ortmann O.
        • Gerken M.
        • Inwald E.C.
        • Klinkhammer-Schalke M.
        Guideline-concordant chemotherapy in patients with hormone receptor-positive and node-positive, early breast cancer leads to better overall and metastases-free survival with limited benefit in elderly patients.
        Arch Gynecol Obstet. 2020; 301 (PubMed PMID: 2003715886): 573-583
        • van de Water W.
        • Bastiaannet E.
        • Dekkers O.M.
        • de Craen A.J.
        • Westendorp R.G.
        • Voogd A.C.
        • et al.
        Adherence to treatment guidelines and survival in patients with early-stage breast cancer by age at diagnosis.
        Br J Surg. 2012; 99 (PubMed PMID: 22492310): 813-820
        • Vogsen M.
        • Bille C.
        • Jylling A.M.B.
        • Jensen M.B.
        • Ewertz M.
        Adherence to treatment guidelines and survival in older women with early-stage breast cancer in Denmark 2008–2012.
        Acta Oncol. 2020; 59 (PubMed PMID: 2004876995): 741-747
        • Wimmer T.
        • Ortmann O.
        • Gerken M.
        • Klinkhammer-Schalke M.
        • Koelbl O.
        • Inwald E.C.
        Adherence to guidelines and benefit of adjuvant radiotherapy in patients with invasive breast cancer: results from a large population-based cohort study of a cancer registry.
        Arch Gynecol Obstet. 2019; 299 (PubMed PMID: 30607594): 1131-1140
        • Wockel A.
        • Kurzeder C.
        • Geyer V.
        • Novasphenny I.
        • Wolters R.
        • Wischnewsky M.
        • et al.
        Effects of guideline adherence in primary breast cancer-A 5-year multi-center cohort study of 3976 patients.
        Breast. 2010; 19 (PubMed PMID: 50780921): 120-127
        • Yun Y.H.
        • Park S.M.
        • Noh D.Y.
        • Nam S.J.
        • Ahn S.H.
        • Park B.W.
        • et al.
        Trends in breast cancer treatment in Korea and impact of compliance with consensus recommendations on survival.
        Breast Cancer Res Treat. 2007; 106: 245-253
        • Zhao B.
        • Tsai C.
        • Hunt K.K.
        • Blair S.L.
        Adherence to surgical and oncologic standards improves survival in breast cancer patients.
        J Surg Oncol. 2019; 120 (PubMed PMID: 31172534): 148-159
        • Trapani D.
        • Douillard J.Y.
        • Winer E.P.
        • Burstein H.
        • Carey L.A.
        • Cortes J.
        • et al.
        The Global Landscape of Treatment Standards for Breast Cancer.
        JNCI: Journal of the National Cancer Institute. 2021; 113: 1143-1155
        • Jauhari Y.
        • Gannon M.R.
        • Tsang C.
        • Horgan K.
        • Dodwell D.
        • Clements K.
        • et al.
        Surgery and adjuvant radiotherapy for unilateral ductal carcinoma in situ (DCIS) in women aged over 70 years: A population based cohort study.
        Eur J Surg Oncol. 2019; 45: 1378-1387
      8. All-Party Parliamentary Group on Breast Cancer. Age is just a number. The report of the parliamentary inquiry into older age and breast cancer. [cited 2021 July]. Available from:

        • Wallington M.
        • Saxon E.B.
        • Bomb M.
        • Smittenaar R.
        • Wickenden M.
        • McPhail S.
        • et al.
        30-day mortality after systemic anticancer treatment for breast and lung cancer in England: a population-based, observational study.
        Lancet Oncol. 2016; 17: 1203-1216
        • Battisti N.M.L.
        • Joshi K.
        • Nasser M.S.
        • Ring A.
        Systemic therapy for older patients with early breast cancer.
        Cancer Treat Rev. 2021; 100: 102292
        • Ring A.
        • Battisti N.M.L.
        • Reed M.W.R.
        • Herbert E.
        • Morgan J.L.
        • Bradburn M.
        • et al.
        Bridging The Age Gap: observational cohort study of effects of chemotherapy and trastuzumab on recurrence, survival and quality of life in older women with early breast cancer.
        Br J Cancer. 2021; 125: 209-219
        • Wang T.
        • Mott N.
        • Miller J.
        • Berlin N.L.
        • Hawley S.
        • Jagsi R.
        • et al.
        Patient Perspectives on Treatment Options for Older Women With Hormone Receptor–Positive Breast Cancer: A Qualitative Study.
        JAMA Netw Open. 2020; 3: e2017129
        • Bierbaum M.
        • Rapport F.
        • Arnolda G.
        • Nic Giolla Easpaig B.
        • Lamprell K.
        • Hutchinson K.
        • et al.
        Clinicians’ attitudes and perceived barriers and facilitators to cancer treatment clinical practice guideline adherence: a systematic review of qualitative and quantitative literature.
        Implementation Sci. 2020; 15
        • Mandelblatt J.S.
        • Cai L.
        • Luta G.
        • Kimmick G.
        • Clapp J.
        • Isaacs C.
        • et al.
        Frailty and long-term mortality of older breast cancer patients: CALGB 369901 (Alliance).
        Breast Cancer Res Treat. 2017; 164: 107-117
        • Grimshaw J.
        • Eccles M.
        • Thomas R.
        • MacLennan G.
        • Ramsay C.
        • Fraser C.
        • et al.
        Toward evidence-based quality improvement: Evidence (and its limitations) of the effectiveness of guideline dissemination and implementation strategies 1966–1998.
        J Gen Intern Med. 2006; 21: S14-S20
        • Tomasone J.R.
        • Kauffeldt K.D.
        • Chaudhary R.
        • Brouwers M.C.
        Effectiveness of guideline dissemination and implementation strategies on health care professionals’ behaviour and patient outcomes in the cancer care context: a systematic review.
        Implementation Science. 2020; 15: 41
      9. The Healthcare Quality Improvement Partnership. [cited 2021 July]. Available from:

        • DuMontier C.
        • Loh K.P.
        • Bain P.A.
        • Silliman R.A.
        • Hshieh T.
        • Abel G.A.
        • et al.
        Defining Undertreatment and Overtreatment in Older Adults With Cancer: A Scoping Literature Review.
        JCO. 2020; 38: 2558-2569