. 2020 Sep;11(1).
doi: 10.1186/s13244-020-00905-3.

Do we still need breast cancer screening in the era of targeted therapies and precision medicine?

Rubina Manuela Trimboli 1 Paolo Giorgi Rossi 2 Nicolò Matteo Luca Battisti 3 Andrea Cozzi 4 Veronica Magni 5 Moreno Zanardo 4 Francesco Sardanelli 4 
  • PMID: 32975658
  •     72 References
  •     1 citations


Breast cancer (BC) is the most common female cancer and the second cause of death among women worldwide. The 5-year relative survival rate recently improved up to 90% due to increased population coverage and women's attendance to organised mammography screening as well as to advances in therapies, especially systemic treatments. Screening attendance is associated with a mortality reduction of at least 30% and a 40% lower risk of advanced disease. The stage at diagnosis remains the strongest predictor of recurrences. Systemic treatments evolved dramatically over the last 20 years: aromatase inhibitors improved the treatment of early-stage luminal BC; targeted monoclonal antibodies changed the natural history of anti-human epidermal growth factor receptor 2-positive (HER2) disease; immunotherapy is currently investigated in patients with triple-negative BC; gene expression profiling is now used with the aim of personalising systemic treatments. In the era of precision medicine, it is a challenging task to define the relative contribution of early diagnosis by screening mammography and systemic treatments in determining BC survival. Estimated contributions before 2000 were 46% for screening and 54% for treatment advances and after 2000, 37% and 63%, respectively. A model showed that the 10-year recurrence rate would be 30% and 25% using respectively chemotherapy or novel treatments in the absence of screening, but would drop to 19% and 15% respectively if associated with mammography screening. Early detection per se has not a curative intent and systemic treatment has limited benefit on advanced stages. Both screening mammography and systemic therapies continue to positively contribute to BC prognosis.

Keywords: Breast neoplasms; Cancer screening; Mammography; Precision medicine; Prognosis.

Seven-Year Follow-Up Analysis of Adjuvant Paclitaxel and Trastuzumab Trial for Node-Negative, Human Epidermal Growth Factor Receptor 2-Positive Breast Cancer.
Sara M Tolaney, Hao Guo, +23 authors, Eric P Winer.
J Clin Oncol, 2019 Apr 03; 37(22). PMID: 30939096    Free PMC article.
Highly Cited.
1-Phenylalanine mustard (L-PAM) in the management of primary breast cancer. A report of early findings.
B Fisher, P Carbone, +9 authors, E R Fisher.
N Engl J Med, 1975 Jan 16; 292(3). PMID: 1105174
Highly Cited.
Extended adjuvant aromatase inhibition after sequential endocrine therapy (DATA): a randomised, phase 3 trial.
Vivianne C G Tjan-Heijnen, Irene E G van Hellemond, +14 authors, Dutch Breast Cancer Research Group (BOOG) for the DATA Investigators.
Lancet Oncol, 2017 Oct 17; 18(11). PMID: 29031778
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).
Lancet Oncol, 2017 Dec 16; 19(1). PMID: 29242041    Free PMC article.
Highly Cited. Review.
Mammography screening reduces rates of advanced and fatal breast cancers: Results in 549,091 women.
Stephen W Duffy, László Tabár, +31 authors, Tony Hsiu-Hsi Chen.
Cancer, 2020 May 12; 126(13). PMID: 32390151    Free PMC article.
Mammography: an update of the EUSOBI recommendations on information for women.
Francesco Sardanelli, Eva M Fallenberg, +5 authors, European Society of Breast Imaging (EUSOBI), with language review by Europa Donna–The European Breast Cancer Coalition.
Insights Imaging, 2016 Nov 18; 8(1). PMID: 27854006    Free PMC article.
AI shows promise for breast cancer screening.
Etta D Pisano.
Nature, 2020 Jan 03; 577(7788). PMID: 31894156
Contrast-enhanced Mammography: Current Applications and Future Directions.
Kimeya F Ghaderi, Jordana Phillips, +2 authors, Tejas S Mehta.
Radiographics, 2019 Nov 08; 39(7). PMID: 31697627
Influence of tumour stage at breast cancer detection on survival in modern times: population based study in 173,797 patients.
Sepideh Saadatmand, Reini Bretveld, Sabine Siesling, Madeleine M A Tilanus-Linthorst.
BMJ, 2015 Oct 08; 351. PMID: 26442924    Free PMC article.
Highly Cited.
Can We Use Survival Data from Cancer Registries to Learn about Disease Recurrence? The Case of Breast Cancer.
Angela B Mariotto, Zhaohui Zou, +3 authors, Ruth Etzioni.
Cancer Epidemiol Biomarkers Prev, 2018 Oct 20; 27(11). PMID: 30337342
Optimal Duration of Extended Adjuvant Endocrine Therapy for Early Breast Cancer; Results of the IDEAL Trial (BOOG 2006-05).
Erik J Blok, Judith R Kroep, +10 authors, IDEAL Study Group.
J Natl Cancer Inst, 2017 Sep 20; 110(1). PMID: 28922787
Survival of cancer patients in Italy.
Vincenzo Coviello, Carlotta Buzzoni, +8 authors, AIRTUM Working Group.
Epidemiol Prev, 2017 Jun 21; 41(2 Suppl 1). PMID: 28629213
Technique, protocols and adverse reactions for contrast-enhanced spectral mammography (CESM): a systematic review.
Moreno Zanardo, Andrea Cozzi, +5 authors, Francesco Sardanelli.
Insights Imaging, 2019 Aug 04; 10(1). PMID: 31376021    Free PMC article.
Diagnostic performance of digital versus film mammography for breast-cancer screening.
Etta D Pisano, Constantine Gatsonis, +10 authors, Digital Mammographic Imaging Screening Trial (DMIST) Investigators Group.
N Engl J Med, 2005 Sep 20; 353(17). PMID: 16169887
Highly Cited.
Combination chemotherapy as an adjuvant treatment in operable breast cancer.
G Bonadonna, E Brusamolino, +8 authors, U Veronesi.
N Engl J Med, 1976 Feb 19; 294(8). PMID: 1246307
Highly Cited.
The emerging role of contrast-enhanced mammography.
Andrea Cozzi, Simone Schiaffino, Francesco Sardanelli.
Quant Imaging Med Surg, 2020 Jan 14; 9(12). PMID: 31929976    Free PMC article.
Position paper on screening for breast cancer by the European Society of Breast Imaging (EUSOBI) and 30 national breast radiology bodies from Austria, Belgium, Bosnia and Herzegovina, Bulgaria, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Iceland, Ireland, Italy, Israel, Lithuania, Moldova, The Netherlands, Norway, Poland, Portugal, Romania, Serbia, Slovakia, Spain, Sweden, Switzerland and Turkey.
Francesco Sardanelli, Hildegunn S Aase, +48 authors, Gabor Forrai.
Eur Radiol, 2016 Nov 04; 27(7). PMID: 27807699    Free PMC article.
West German Study Group Phase III PlanB Trial: First Prospective Outcome Data for the 21-Gene Recurrence Score Assay and Concordance of Prognostic Markers by Central and Local Pathology Assessment.
Oleg Gluz, Ulrike A Nitz, +18 authors, Nadia Harbeck.
J Clin Oncol, 2016 Mar 02; 34(20). PMID: 26926676
Highly Cited.
Digital breast tomosynthesis for breast cancer detection: a diagnostic test accuracy systematic review and meta-analysis.
Mostafa Alabousi, Nanxi Zha, +7 authors, Abdullah Alabousi.
Eur Radiol, 2020 Jan 05; 30(4). PMID: 31900699
Systematic Review.
Status of implementation and organization of cancer screening in The European Union Member States-Summary results from the second European screening report.
Partha Basu, Antonio Ponti, +11 authors, Rengaswamy Sankaranarayanan.
Int J Cancer, 2017 Sep 25; 142(1). PMID: 28940326
Highly Cited.
Impact of artificial intelligence on radiology: a EuroAIM survey among members of the European Society of Radiology.
European Society of Radiology (ESR).
Insights Imaging, 2019 Nov 02; 10(1). PMID: 31673823    Free PMC article.
Benefit from exemestane as extended adjuvant therapy after 5 years of adjuvant tamoxifen: intention-to-treat analysis of the National Surgical Adjuvant Breast And Bowel Project B-33 trial.
Eleftherios P Mamounas, Jong-Hyeon Jeong, +17 authors, Norman Wolmark.
J Clin Oncol, 2008 Mar 12; 26(12). PMID: 18332472
Radiomics and liquid biopsy in oncology: the holons of systems medicine.
Emanuele Neri, Marzia Del Re, +4 authors, Romano Danesi.
Insights Imaging, 2018 Nov 16; 9(6). PMID: 30430428    Free PMC article.
Effectiveness of Breast Cancer Screening: Systematic Review and Meta-analysis to Update the 2009 U.S. Preventive Services Task Force Recommendation.
Heidi D Nelson, Rochelle Fu, +3 authors, Linda Humphrey.
Ann Intern Med, 2016 Jan 13; 164(4). PMID: 26756588
Highly Cited. Systematic Review.
Breast Cancer Screening and Diagnosis: A Synopsis of the European Breast Guidelines.
Holger J Schünemann, Donata Lerda, +21 authors, European Commission Initiative on Breast Cancer (ECIBC) Contributor Group.
Ann Intern Med, 2019 Nov 26; 172(1). PMID: 31766052
The EndoPredict score provides prognostic information on late distant metastases in ER+/HER2- breast cancer patients.
P Dubsky, J C Brase, +18 authors, Austrian Breast and Colorectal Cancer Study Group (ABCSG).
Br J Cancer, 2013 Oct 26; 109(12). PMID: 24157828    Free PMC article.
Highly Cited.
Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer.
Soonmyung Paik, Gong Tang, +11 authors, Norman Wolmark.
J Clin Oncol, 2006 May 25; 24(23). PMID: 16720680
Highly Cited.
Trastuzumab containing regimens for early breast cancer.
Lorenzo Moja, Ludovica Tagliabue, +4 authors, Roberto D'Amico.
Cochrane Database Syst Rev, 2012 Apr 20; (4). PMID: 22513938    Free PMC article.
Highly Cited. Systematic Review.
CMF revisited in the 21st century.
E Munzone, G Curigliano, +2 authors, A Goldhirsch.
Ann Oncol, 2011 Jul 01; 23(2). PMID: 21715566
70-Gene Signature as an Aid to Treatment Decisions in Early-Stage Breast Cancer.
Fatima Cardoso, Laura J van't Veer, +32 authors, MINDACT Investigators.
N Engl J Med, 2016 Aug 25; 375(8). PMID: 27557300
Highly Cited.
Estimating the benefits of therapy for early-stage breast cancer: the St. Gallen International Consensus Guidelines for the primary therapy of early breast cancer 2019.
H J Burstein, G Curigliano, +11 authors, Members of the St. Gallen International Consensus Panel on the Primary Therapy of Early Breast Cancer 2019.
Ann Oncol, 2019 Aug 03; 30(10). PMID: 31373601
Highly Cited.
Supplemental MRI Screening for Women with Extremely Dense Breast Tissue.
Marije F Bakker, Stéphanie V de Lange, +18 authors, DENSE Trial Study Group.
N Engl J Med, 2019 Nov 28; 381(22). PMID: 31774954
Use of letrozole after aromatase inhibitor-based therapy in postmenopausal breast cancer (NRG Oncology/NSABP B-42): a randomised, double-blind, placebo-controlled, phase 3 trial.
Eleftherios P Mamounas, Hanna Bandos, +17 authors, Norman Wolmark.
Lancet Oncol, 2018 Dec 05; 20(1). PMID: 30509771    Free PMC article.
Cancer statistics, 2019.
Rebecca L Siegel, Kimberly D Miller, Ahmedin Jemal.
CA Cancer J Clin, 2019 Jan 09; 69(1). PMID: 30620402
Highly Cited.
Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA).
A Schneeweiss, S Chia, +10 authors, J Cortés.
Ann Oncol, 2013 May 25; 24(9). PMID: 23704196
Highly Cited.
Adjuvant Chemotherapy Guided by a 21-Gene Expression Assay in Breast Cancer.
Joseph A Sparano, Robert J Gray, +27 authors, George W Sledge.
N Engl J Med, 2018 Jun 05; 379(2). PMID: 29860917    Free PMC article.
Highly Cited.
Trends in radiology and experimental research.
Francesco Sardanelli.
Eur Radiol Exp, 2017 Jan 01; 1(1). PMID: 29708170    Free PMC article.
Cancer treatment and survivorship statistics, 2019.
Kimberly D Miller, Leticia Nogueira, +6 authors, Rebecca L Siegel.
CA Cancer J Clin, 2019 Jun 12; 69(5). PMID: 31184787
Highly Cited.
HER2-positive breast cancer.
Sibylle Loibl, Luca Gianni.
Lancet, 2016 Dec 13; 389(10087). PMID: 27939064
Highly Cited. Review.
Neratinib after trastuzumab-based adjuvant therapy in HER2-positive breast cancer (ExteNET): 5-year analysis of a randomised, double-blind, placebo-controlled, phase 3 trial.
Miguel Martin, Frankie A Holmes, +32 authors, ExteNET Study Group.
Lancet Oncol, 2017 Nov 18; 18(12). PMID: 29146401
Highly Cited.
Can mass x-ray surveys be used in detection of early cancer of the breast?
J Am Med Assoc, 1956 Jul 14; 161(11). PMID: 13331765
Harms of Breast Cancer Screening: Systematic Review to Update the 2009 U.S. Preventive Services Task Force Recommendation.
Heidi D Nelson, Miranda Pappas, +3 authors, Linda Humphrey.
Ann Intern Med, 2016 Jan 13; 164(4). PMID: 26756737
Highly Cited. Systematic Review.
20-Year Risks of Breast-Cancer Recurrence after Stopping Endocrine Therapy at 5 Years.
Hongchao Pan, Richard Gray, +9 authors, EBCTCG.
N Engl J Med, 2017 Nov 09; 377(19). PMID: 29117498    Free PMC article.
Highly Cited.
Advanced breast cancer rates in the epoch of service screening: The 400,000 women cohort study from Italy.
Donella Puliti, Lauro Bucchi, +19 authors, IMPACT COHORT Working Group.
Eur J Cancer, 2017 Feb 22; 75. PMID: 28222306
Adjuvant Pertuzumab and Trastuzumab in Early HER2-Positive Breast Cancer.
Gunter von Minckwitz, Marion Procter, +16 authors, APHINITY Steering Committee and Investigators.
N Engl J Med, 2017 Jun 06; 377(2). PMID: 28581356    Free PMC article.
Highly Cited.
Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial.
Christina Davies, Hongchao Pan, +36 authors, Adjuvant Tamoxifen: Longer Against Shorter (ATLAS) Collaborative Group.
Lancet, 2012 Dec 12; 381(9869). PMID: 23219286    Free PMC article.
Highly Cited.
5-year analysis of neoadjuvant pertuzumab and trastuzumab in patients with locally advanced, inflammatory, or early-stage HER2-positive breast cancer (NeoSphere): a multicentre, open-label, phase 2 randomised trial.
Luca Gianni, Tadeusz Pienkowski, +17 authors, Pinuccia Valagussa.
Lancet Oncol, 2016 May 18; 17(6). PMID: 27179402
Highly Cited.
International evaluation of an AI system for breast cancer screening.
Scott Mayer McKinney, Marcin Sieniek, +28 authors, Shravya Shetty.
Nature, 2020 Jan 03; 577(7788). PMID: 31894144
Neoadjuvant therapy for breast cancer.
Lucia Mangone, Pamela Mancuso, +8 authors, Paolo Giorgi Rossi.
Tumori, 2019 Sep 10; 105(6). PMID: 31496430
De-escalating and escalating treatments for early-stage breast cancer: the St. Gallen International Expert Consensus Conference on the Primary Therapy of Early Breast Cancer 2017.
G Curigliano, H J Burstein, +52 authors, B Xu.
Ann Oncol, 2017 Aug 26; 28(8). PMID: 28838210    Free PMC article.
Highly Cited.
Extending Aromatase-Inhibitor Adjuvant Therapy to 10 Years.
Paul E Goss, James N Ingle, +17 authors, Wendy R Parulekar.
N Engl J Med, 2016 Jun 07; 375(3). PMID: 27264120    Free PMC article.
Highly Cited.
Comparison of PAM50 risk of recurrence score with oncotype DX and IHC4 for predicting risk of distant recurrence after endocrine therapy.
Mitch Dowsett, Ivana Sestak, +7 authors, Jack Cuzick.
J Clin Oncol, 2013 Jul 03; 31(22). PMID: 23816962
Highly Cited.
Randomized trial of letrozole following tamoxifen as extended adjuvant therapy in receptor-positive breast cancer: updated findings from NCIC CTG MA.17.
Paul E Goss, James N Ingle, +15 authors, Joseph L Pater.
J Natl Cancer Inst, 2005 Sep 08; 97(17). PMID: 16145047
Highly Cited.
Liquid Biopsy for Cancer: Review and Implications for the Radiologist.
Jacob J Underwood, Rehan S Quadri, +4 authors, Patrick D Sutphin.
Radiology, 2019 Nov 21; 294(1). PMID: 31746691
Mastectomy rates are decreasing in the era of service screening: a population-based study in Italy (1997-2001).
M Zorzi, D Puliti, +13 authors, IMPACT Working Group.
Br J Cancer, 2006 Oct 18; 95(9). PMID: 17043685    Free PMC article.
Changes in chemotherapy usage and outcome of early breast cancer patients in the last decade.
A Hennigs, F Riedel, +9 authors, A Schneeweiss.
Breast Cancer Res Treat, 2016 Nov 03; 160(3). PMID: 27744486    Free PMC article.
Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis.
Patricia Cortazar, Lijun Zhang, +34 authors, Gunter von Minckwitz.
Lancet, 2014 Feb 18; 384(9938). PMID: 24529560
Highly Cited. Review.
Predicting distant recurrence in receptor-positive breast cancer patients with limited clinicopathological risk: using the PAM50 Risk of Recurrence score in 1478 postmenopausal patients of the ABCSG-8 trial treated with adjuvant endocrine therapy alone.
M Gnant, M Filipits, +22 authors, Austrian Breast and Colorectal Cancer Study Group.
Ann Oncol, 2013 Dec 19; 25(2). PMID: 24347518
Highly Cited.
Recommendations on screening for breast cancer in women aged 40-74 years who are not at increased risk for breast cancer.
Scott Klarenbach, Nicki Sims-Jones, +8 authors, Canadian Task Force on Preventive Health Care.
CMAJ, 2018 Dec 12; 190(49). PMID: 30530611    Free PMC article.
Highly Cited.
Association of Screening and Treatment With Breast Cancer Mortality by Molecular Subtype in US Women, 2000-2012.
Sylvia K Plevritis, Diego Munoz, +20 authors, Jeanne S Mandelblatt.
JAMA, 2018 Jan 11; 319(2). PMID: 29318276    Free PMC article.
Highly Cited.
Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries.
Freddie Bray, Jacques Ferlay, +3 authors, Ahmedin Jemal.
CA Cancer J Clin, 2018 Sep 13; 68(6). PMID: 30207593
Highly Cited.
Association of Digital Breast Tomosynthesis vs Digital Mammography With Cancer Detection and Recall Rates by Age and Breast Density.
Emily F Conant, William E Barlow, +13 authors, Population-based Research Optimizing Screening Through Personalized Regimen (PROSPR) Consortium.
JAMA Oncol, 2019 Mar 01; 5(5). PMID: 30816931    Free PMC article.
Highly Cited.
Pembrolizumab for Early Triple-Negative Breast Cancer.
Peter Schmid, Javier Cortes, +19 authors, KEYNOTE-522 Investigators.
N Engl J Med, 2020 Feb 27; 382(9). PMID: 32101663
Effect of implementing digital breast tomosynthesis (DBT) instead of mammography on population screening outcomes including interval cancer rates: Results of the Trento DBT pilot evaluation.
Daniela Bernardi, Maria A Gentilini, +6 authors, Nehmat Houssami.
Breast, 2019 Oct 15; 50. PMID: 31607526    Free PMC article.
Effect of screening and adjuvant therapy on mortality from breast cancer.
Donald A Berry, Kathleen A Cronin, +8 authors, Cancer Intervention and Surveillance Modeling Network (CISNET) Collaborators.
N Engl J Med, 2005 Oct 28; 353(17). PMID: 16251534
Highly Cited.
Molecular classification of breast cancer: implications for selection of adjuvant chemotherapy.
Fabrice Andre, Lajos Pusztai.
Nat Clin Pract Oncol, 2006 Nov 03; 3(11). PMID: 17080180
Breast cancer deaths averted over 3 decades.
R Edward Hendrick, Jay A Baker, Mark A Helvie.
Cancer, 2019 Feb 12; 125(9). PMID: 30740647
Prediction of late disease recurrence and extended adjuvant letrozole benefit by the HOXB13/IL17BR biomarker.
Dennis C Sgroi, Erin Carney, +16 authors, Paul E Goss.
J Natl Cancer Inst, 2013 Jul 03; 105(14). PMID: 23812955    Free PMC article.
Interval and Consecutive Round Breast Cancer after Digital Breast Tomosynthesis and Synthetic 2D Mammography versus Standard 2D Digital Mammography in BreastScreen Norway.
Tone Hovda, Åsne S Holen, +7 authors, Solveig Hofvind.
Radiology, 2019 Dec 11; 294(2). PMID: 31821118
Tailoring Adjuvant Endocrine Therapy for Premenopausal Breast Cancer.
Prudence A Francis, Olivia Pagani, +34 authors, SOFT and TEXT Investigators and the International Breast Cancer Study Group.
N Engl J Med, 2018 Jun 05; 379(2). PMID: 29863451    Free PMC article.
Highly Cited.
Long-term Pooled Safety Analysis of Palbociclib in Combination With Endocrine Therapy for HR+/HER2- Advanced Breast Cancer.
Véronique Diéras, Hope S Rugo, +11 authors, Richard S Finn.
J Natl Cancer Inst, 2018 Jul 23; 111(4). PMID: 30032196    Free PMC article.
A new molecular predictor of distant recurrence in ER-positive, HER2-negative breast cancer adds independent information to conventional clinical risk factors.
Martin Filipits, Margaretha Rudas, +25 authors, EP Investigators.
Clin Cancer Res, 2011 Aug 03; 17(18). PMID: 21807638
Highly Cited.
Breast Cancer Screening Practice and Associated Factors Among Women Aged 20-70 Years in Urban Settings of SNNPR, Ethiopia.
Abiyu Ayalew Assefa, Geleta Abera, Medhin Geta.
Breast Cancer (Dove Med Press), 2021 Jan 16; 13. PMID: 33447077    Free PMC article.