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Benefit of adjuvant chemotherapy in patients with lobular breast cancer: A systematic review of the literature and metanalysis

  • D. Trapani
    Affiliations
    Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy
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  • S. Gandini
    Affiliations
    Department of Experimental Oncology, IEO, European Institute of Oncology IRCSS, Milan, Italy
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  • Author Footnotes
    1 Contributed equally.
    C. Corti
    Footnotes
    1 Contributed equally.
    Affiliations
    Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy

    Departement of Hematology and Oncology (DIPO), University of Milan, Milan, Italy
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  • Author Footnotes
    1 Contributed equally.
    E. Crimini
    Footnotes
    1 Contributed equally.
    Affiliations
    Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy

    Departement of Hematology and Oncology (DIPO), University of Milan, Milan, Italy
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  • F. Bellerba
    Affiliations
    Department of Experimental Oncology, IEO, European Institute of Oncology IRCSS, Milan, Italy
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  • I. Minchella
    Affiliations
    Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy
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  • C. Criscitiello
    Affiliations
    Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy

    Departement of Hematology and Oncology (DIPO), University of Milan, Milan, Italy
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  • P. Tarantino
    Affiliations
    Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy

    Departement of Hematology and Oncology (DIPO), University of Milan, Milan, Italy
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  • G. Curigliano
    Correspondence
    Corresponding author at: European Institute of Oncology (IEO), IRCCS, Early Drug Development for Innovative Therapies, Via Ripamonti 435, 20141 Milan, Italy. University of Milan, Department of Oncology and Hematology (DIPO), Via Festa Del Perdono 1, 20122 Milan, Italy.
    Affiliations
    Division of New Drugs and Early Drug Development, European Institute of Oncology IRCCS, Milan, Italy

    Departement of Hematology and Oncology (DIPO), University of Milan, Milan, Italy
    Search for articles by this author
  • Author Footnotes
    1 Contributed equally.
Published:April 08, 2021DOI:https://doi.org/10.1016/j.ctrv.2021.102205

      Highlights

      • We explored the role of adjuvant chemotherapy in the treatment of patients with localized lobular breast cancer (ILC)?
      • In this systematic review of the literature and metanalysis, a role of the adjuvant chemotherapy in the setting of ILC was not confirmed. The analysis on 38,387 patients across 8 studies did not show an additional benefit of chemotherapy (Hazard Ratio for Overall Survival: 0.99; 95%CI 0.86–1.14). However, all the investigations were retrospective, and subgroup analyses in high-risk patients showed some signals of possible adjunctive benefits.
      • Prospective investigations of adjuvant therapies in high-risk patients with ILC are highly warranted. The current decision- making is largely based on evidence from non-randomized clinical investigations, prompting controlled clinical studies.

      Abstract

      The role of adjuvant chemotherapy (aCT) for patients with localized lobular breast cancer (ILC) is still controversial. It is unclear what is the magnitude of benefit of the CT in this setting. In this systematic review of the literature and metanalysis, we aimed to estimate the benefit of aCT in addition to the standard treatments in the early ILC setting. We identified the records by searching Medline, CENTRAL, Web of Science, SCOPUS, and Google Scholar, and the meeting proceeding of the principal oncology meetings of the last 10 years, with no language or time restriction. A research strategy was developed with mapped and MeSH terms. Studies on the clinical use of aCT reporting survival outcomes in the ILC setting were double-screened and tabulated. PRISMA methodology was used for data extraction and synthesis. We extracted information on the study design and setting, eligible population and population size, histology variants, menopausal status, treatment regimens, follow-up duration. Hazard ratios (HR) and 95% confidence interval (CI) were extracted and transformed into logHR and corresponding standard error to obtain the Summary HR (SHR). Heterogeneity (I2 statistics) and publication bias (Macaskill test) were tested; a random effect models provided by SAS Proc Mixed was used for data analysis. Sensitivity analysis was conducted to examine the impact of inclusion criteria on the summary results.
      Disease-free (DFS), overall (OS) and cancer-specific survival (BCSS) were the primary endpoints of the investigation. The systematic review and metanalysis included 38,387 patients across 8 clinical studies. aCT was not associated with an improvement of OS (SHR 0.99; 95%CI 0.86–1.14), with low heterogeneity (I2 = 28%) and no publication bias (p = 0.43). Sensitivity analysis resulted in unchanged conclusions. We did not perform a metanalysis of the DFS estimates, as only reported in 3 studies. The value of aCT in improving DFS was unconfirmed, consistently with the OS results. Our research did not confirm a certain role of aCT for patients with ILC. Research gaps were identified, warranting the development of prospective, controlled ad hoc investigations.

      Abbreviations:

      BCI (breast cancer Index), BCSS (breast cancer specific survival), CI (95% confidence interval), DFS (disease- free survival), ER (estrogen receptor), HER2 (human epidermal growth factor receptor 2), HR (Hazard Ratio), IBCSG (International breast cancer Study Group), IHC (immunohistochemistry), LVI (Lymphovascular Invasion), OS (overall survival), pCR (pathological complete response), PEPI (preoperative endocrine prognostic index), PET (positron-emission tomography), PgR (progesterone receptor), PICO (Population, Intervention, Comparison, and quantitative Outcomes), RS (Recurrence Score), SEER (Surveillance, Epidemiology, and End Results program), SHR (Summary HR)

      Keywords

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      References

        • Martinez V.
        • Azzopardi J.G.
        Invasive lobular carcinoma of the breast: incidence and variants.
        Histopathology. 1979; 3: 467-488
        • Weigelt B.
        • Geyer F.C.
        • Natrajan R.
        • Lopez-Garcia M.A.
        • Ahmad A.S.
        • Savage K.
        • et al.
        The molecular underpinning of lobular histological growth pattern: a genome-wide transcriptomic analysis of invasive lobular carcinomas and grade- and molecular subtype-matched invasive ductal carcinomas of no special type.
        J Pathol. 2010; 220: 45-57https://doi.org/10.1002/path.2629
        • Di Costanzo D.
        • Rosen P.P.
        • Gareen I.
        • Franklin S.
        • Lesser M.
        Prognosis in infiltrating lobular carcinoma. An analysis of “classical” and variant tumors.
        Am J Surg Pathol. 1990; 14 (PMID: 2153007): 12-23https://doi.org/10.1097/00000478-199001000-00002
      1. Tan PH, Ellis I, Allison K, Brogi E, Fox SB, Lakhani S, Lazar AJ, Morris EA, Sahin A, Salgado R, Sapino A, Sasano H, Schnitt S, Sotiriou C, van Diest P, White VA, Lokuhetty D, Cree IA; WHO Classification of Tumours Editorial Board. The 2019 World Health Organization classification of tumours of the breast. Histopathology. 2020 Aug;77(2):181-185. doi: 10.1111/his.14091. Epub 2020 Jul 29. PMID: 32056259.

      2. Curtis C, Shah SP, Chin SF, Turashvili G, Rueda OM, Dunning MJ, Speed D, Lynch AG, Samarajiwa S, Yuan Y, Gräf S, Ha G, Haffari G, Bashashati A, Russell R, McKinney S; METABRIC Group, Langerød A, Green A, Provenzano E, Wishart G, Pinder S, Watson P, Markowetz F, Murphy L, Ellis I, Purushotham A, Børresen-Dale AL, Brenton JD, Tavaré S, Caldas C, Aparicio S. The genomic and transcriptomic architecture of 2000 breast tumours reveals novel subgroups. Nature. 2012 Apr 18;486(7403):346-52. doi: 10.1038/nature10983. PMID: 22522925; PMCID: PMC3440846.

      3. Ciriello G, Gatza ML, Beck AH, Wilkerson MD, Rhie SK, Pastore A, Zhang H, McLellan M, Yau C, Kandoth C, Bowlby R, Shen H, Hayat S, Fieldhouse R, Lester SC, Tse GM, Factor RE, Collins LC, Allison KH, Chen YY, Jensen K, Johnson NB, Oesterreich S, Mills GB, Cherniack AD, Robertson G, Benz C, Sander C, Laird PW, Hoadley KA, King TA; TCGA Research Network, Perou CM. Comprehensive Molecular Portraits of Invasive Lobular BC. Cell. 2015 Oct 8;163(2):506-19. doi: 10.1016/j.cell.2015.09.033. PMID: 26451490; PMCID: PMC4603750.

        • McCart Reed A.E.
        • Kutasovic J.R.
        • Lakhani S.R.
        • Simpson P.T.
        Invasive lobular carcinoma of the breast: morphology, biomarkers and 'omics.
        BC Res. 2015; 17: 12https://doi.org/10.1186/s13058-015-0519-x
        • Christgen M.
        • Bartels S.
        • van Luttikhuizen J.L.
        • et al.
        E-cadherin to P-cadherin switching in lobular BC with tubular elements.
        Mod Pathol. 2020; 33: 2483-2498https://doi.org/10.1038/s41379-020-0591-3
        • Silva L.D.
        • Parry S.
        • Reid L.
        • Keith P.
        • Waddell N.
        • Kossai M.
        • et al.
        Aberrant expression of E-cadherin in lobular carcinomas of the breast.
        Am J Surg Pathol. 2008; 32: 773-783https://doi.org/10.1097/PAS.0b013e318158d6c5
        • Johnson K.
        • Sarma D.
        • Hwang E.S.
        Lobular BC series: imaging. BC Res. 2015; 17: 94https://doi.org/10.1186/s13058-015-0605-0. PMID: 26163296; PMCID: PMC4499185
      4. Beniey M. Peritoneal Metastases from BC: A Scoping Review. Cureus.2019;11(8):e5367. Published 2019 Aug doi:10.7759/cureus.5367.

      5. Inoue M, Nakagomi H, Nakada H, Furuya K, Ikegame K, Watanabe H, et al. Specific sites of metastases in invasive lobular carcinoma: a retrospective cohort study of metastatic BC. BC. 2017 Sep;24(5):667–672. doi: 10.1007/s12282-017-0753-4. Epub 2017 Jan 20. PMID: 28108967.

        • Gauthier H.
        • Guilhaume M.N.
        • Bidard F.C.
        • Pierga J.Y.
        • Girre V.
        • Cottu P.H.
        • et al.
        Survival of BC patients with meningeal carcinomatosis.
        Ann Oncol. 2010; 21 (Epub 2010 Apr 29 PMID: 20430906): 2183-2187https://doi.org/10.1093/annonc/mdq232
        • Rakha E.A.
        • El-Sayed M.E.
        • Powe D.G.
        • Green A.R.
        • Habashy H.
        • Grainge M.J.
        • et al.
        Invasive lobular carcinoma of the breast: response to hormonal therapy and outcomes.
        Eur J Can. 2008; 44: 73-83https://doi.org/10.1016/j.ejca.2007.10.009
      6. Pestalozzi BC, Zahrieh D, Mallon E, Gusterson BA, Price KN, Gelber RD, Holmberg SB, Lindtner J, Snyder R, Thürlimann B, Murray E, Viale G, Castiglione-Gertsch M, Coates AS, Goldhirsch A; International BC Study Group. Distinct clinical and prognostic features of infiltrating lobular carcinoma of the breast: combined results of 15 International BC Study Group clinical trials. J Clin Oncol. 2008 Jun 20;26(18):3006-14. doi: 10.1200/JCO.2007.14.9336. Epub 2008 May 5. PMID: 18458044.

        • Zhao H.
        The prognosis of invasive ductal carcinoma, lobular carcinoma and mixed ductal and lobular carcinoma according to molecular subtypes of the breast.
        BC. 2021; 28: 187-195https://doi.org/10.1007/s12282-020-01146-4
      7. Delpech Y, Coutant C, Hsu L, Barranger E, Iwamoto T, Barcenas CH, Hortobagyi GN, Rouzier R, Esteva FJ, Pusztai L. Clinical benefit from neoadjuvant chemotherapy in oestrogen receptor-positive invasive ductal and lobular carcinomas. Br J Cancer. 2013 Feb 5;108(2):285–91. doi: 10.1038/bjc.2012.557. Epub 2013 Jan 8. PMID: 23299541; PMCID: PMC3566807.

        • Cristofanilli M.
        • Gonzalez-Angulo A.
        • Sneige N.
        • Kau S.-W.
        • Broglio K.
        • Theriault R.L.
        • et al.
        Invasive lobular carcinoma classic type: response to primary chemotherapy and survival outcomes.
        J Clin Oncol. 2005; 23: 41-48https://doi.org/10.1200/JCO.2005.03.111
      8. Higgins JPT, Green S. Cochrane Handbook for Systematic Reviews of Interventions, Version 5.1.0. The Cochrane Collaboration; 2013.

      9. Moher D, Liberati A, Tetzlaff J, Altman DG; PRISMA Group. Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement. PLoS Med. 2009 Jul 21;6(7):e1000097. doi: 10.1371/journal.pmed.1000097. Epub 2009 Jul 21. PMID: 19621072; PMCID: PMC2707599.

        • Peterson J.
        • Welch V.
        • Losos M.
        • Tugwell P.
        The Newcastle-Ottawa scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses.
        Ottawa: Ottawa Hospital Research Institute. 2011; (Available at: http://www.ohri.ca/programs/clinical_epidemiology/oxford.asp (last access 3 Dec 2020))
        • van Houwelingen H.C.
        • Arends L.R.
        • Stijnen T.
        Advanced methods in meta-analysis: multivariate approach and meta-regression.
        Stat Med. 2002; 21: 589-624
        • Macaskill P.
        • Walter S.D.
        • Irwig L.
        A comparison of methods to detect publication bias in meta-analysis.
        Stat Med. 2001; 20: 641-654https://doi.org/10.1002/(ISSN)1097-025810.1002/sim.v20:410.1002/sim.698
        • de Nonneville A.
        • Jauffret C.
        • Gonçalves A.
        • Classe J.-M.
        • Cohen M.
        • Reyal F.
        • et al.
        Adjuvant chemotherapy in lobular carcinoma of the breast: a clinicopathological score identifies high-risk patient with survival benefit.
        BC Res Treat. 2019; 175: 379-387https://doi.org/10.1007/s10549-019-05160-9
        • Iorfida M.
        • Maiorano E.
        • Orvieto E.
        • Maisonneuve P.
        • Bottiglieri L.
        • Rotmensz N.
        • et al.
        Invasive lobular BC: subtypes and outcome.
        BC Res Treat. 2012 Jun; 133 (Epub 2012 Mar 8 PMID: 22399188): 713-723https://doi.org/10.1007/s10549-012-2002-z
      10. Metzger-Filho O, Ferreira AR, Jeselsohn R, Barry WT, Dillon DA, Brock JE, Vaz-Luis I, Hughes ME, Winer EP, Lin NU. Mixed Invasive Ductal and Lobular Carcinoma of the Breast: Prognosis and the Importance of Histologic Grade. Oncologist. 2019 Jul;24(7):e441-e449. doi: 10.1634/theoncologist.2018-0363. Epub 2018 Dec 5. PMID: 30518616; PMCID: PMC6656459.

        • Chen X.H.
        • Zhang W.W.
        • Wang J.
        • Sun J.Y.
        • Li F.Y.
        • He Z.Y.
        • et al.
        21-gene recurrence score and adjuvant chemotherapy decisions in patients with invasive lobular BC.
        Biomark Med. 2019; 13 (Epub 2018 Dec 19 PMID: 30565472): 83-93https://doi.org/10.2217/bmm-2018-0396
      11. Truin W, Voogd AC, Vreugdenhil G, van der Heiden-van der Loo M, Siesling S, Roumen RM. Effect of adjuvant chemotherapy in postmenopausal patients with invasive ductal versus lobular BC. Ann Oncol. 2012 Nov;23(11):2859-2865. doi: 10.1093/annonc/mds180. Epub 2012 Jun 27. PMID: 22745216.

        • Hu G.
        • Hu G.
        • Zhang C.
        • Lin X.
        • Shan M.
        • Yu Y.
        • et al.
        Adjuvant chemotherapy could not bring survival benefit to HR-positive, HER2-negative, pT1b-c/N0-1/M0 invasive lobular carcinoma of the breast: a propensity score matching study based on SEER database.
        BMC Can. 2020; 20https://doi.org/10.1186/s12885-020-6614-0
        • Kizy S.
        • Huang J.L.
        • Marmor S.
        • Tuttle T.M.
        • Hui J.Y.C.
        Impact of the 21-gene recurrence score on outcome in patients with invasive lobular carcinoma of the breast.
        BC Res Treat. 2017; 165 (Epub 2017 Jun 24 PMID: 28647915): 757-763https://doi.org/10.1007/s10549-017-4355-9
        • Marmor S.
        • Hui J.Y.C.
        • Huang J.L.
        • Kizy S.
        • Beckwith H.
        • Blaes A.H.
        • et al.
        Relative effectiveness of adjuvant chemotherapy for invasive lobular compared with invasive ductal carcinoma of the breast.
        Cancer. 2017; 123: 3015-3021https://doi.org/10.1002/cncr.v123.1610.1002/cncr.30699
      12. Cortazar P, Zhang L, Untch M, Mehta K, Costantino JP, Wolmark N, Bonnefoi H, Cameron D, Gianni L, Valagussa P, Swain SM, Prowell T, Loibl S, Wickerham DL, Bogaerts J, Baselga J, Perou C, Blumenthal G, Blohmer J, Mamounas EP, Bergh J, Semiglazov V, Justice R, Eidtmann H, Paik S, Piccart M, Sridhara R, Fasching PA, Slaets L, Tang S, Gerber B, Geyer CE Jr, Pazdur R, Ditsch N, Rastogi P, Eiermann W, von Minckwitz G. Pathological complete response and long-term clinical benefit in BC: the CTNeoBC pooled analysis. Lancet. 2014 Jul 12;384(9938):164-72. doi: 10.1016/S0140-6736(13)62422-8. Epub 2014 Feb 14. Erratum in: Lancet. 2019 Mar 9;393(10175):986. PMID: 24529560.

      13. Burstein HJ, Curigliano G, Loibl S, Dubsky P, Gnant M, Poortmans P, Colleoni M, Denkert C, Piccart-Gebhart M, Regan M, Senn HJ, Winer EP, Thurlimann B; Members of the St. Gallen International Consensus Panel on the Primary Therapy of Early BC 2019. Estimating the benefits of therapy for early-stage BC: the St. Gallen International Consensus Guidelines for the primary therapy of early BC 2019. Ann Oncol. 2019 Oct 1;30(10):1541-1557. doi: 10.1093/annonc/mdz235. PMID: 31373601.

      14. Cardoso F, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rubio IT, Zackrisson S, Senkus E; ESMO Guidelines Committee. Electronic address: [email protected] Early BC: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up†. Ann Oncol. 2019 Aug 1;30(8):1194-1220. doi: 10.1093/annonc/mdz173. Erratum in: Ann Oncol. 2019 Oct 1;30(10):1674. Erratum in: Ann Oncol. 2019 Oct;30(10):1674. Erratum in: Ann Oncol. 2020 Sep 7;: PMID: 31161190.

      15. National Comprehensive Cancer Network (NCCN, 2020). Clinical practice guidelines in oncology, management of BC. Version 6.2020. Available at: https://www.nccn.org/ (last access 3 Dec 2020).

        • Trapani D.
        • Curigliano G.
        How to treat lobular cancer in the adjuvant setting?.
        Curr Opin Oncol. 2020; 32 (PMID: 32826487): 561-567https://doi.org/10.1097/CCO.0000000000000674
        • Jacobs C.
        • Ibrahim M.F.
        • Clemons M.
        • Hutton B.
        • Simos D.
        • Caudrelier J.M.
        • et al.
        Treatment choices for patients with invasive lobular BC: a doctor survey.
        J Eval Clin Pract. 2015; 21 (Epub 2015 Jun 9 PMID: 26059404): 740-748https://doi.org/10.1111/jep.12379
      16. Buus R, Sestak I, Kronenwett R, Ferree S, Schnabel CA, Baehner FL, Mallon EA, Cuzick J, Dowsett M. Molecular Drivers of Oncotype DX, Prosigna, EndoPredict, and the BC Index: A TransATAC Study. J Clin Oncol. 2020 Oct 27:JCO2000853. doi: 10.1200/JCO.20.00853. Epub ahead of print. PMID: 33108242.

      17. Sparano JA, Gray RJ, Ravdin PM, Makower DF, Pritchard KI, Albain KS, Hayes DF, Geyer CE Jr, Dees EC, Goetz MP, Olson JA Jr, Lively T, Badve SS, Saphner TJ, Wagner LI, Whelan TJ, Ellis MJ, Paik S, Wood WC, Keane MM, Gomez Moreno HL, Reddy PS, Goggins TF, Mayer IA, Brufsky AM, Toppmeyer DL, Kaklamani VG, Berenberg JL, Abrams J, Sledge GW Jr. Clinical and Genomic Risk to Guide the Use of Adjuvant Therapy for BC. N Engl J Med. 2019 Jun 20;380(25):2395-2405. doi: 10.1056/NEJMoa1904819. Epub 2019 Jun 3. PMID: 31157962; PMCID: PMC6709671.

      18. Kalinsky K, et al. Tamoxifen Citrate, Letrozole, Anastrozole, or Exemestane With or Without Chemotherapy in Treating Patients With Invasive Breast Cancer (RxPONDER/ NCT01272037). Presented at SABCS 2020, abstract # GS3-00.

        • Singh K.
        • He X.
        • Kalife E.T.
        • Ehdaivand S.
        • Wang Y.
        • Sung C.J.
        Relationship of histologic grade and histologic subtype with oncotype Dx recurrence score; retrospective review of 863 BC oncotype Dx results.
        BC Res Treat. 2018; 168 (Epub 2017 Dec 11 PMID: 29230662): 29-34https://doi.org/10.1007/s10549-017-4619-4
        • Felts J.L.
        • Zhu J.
        • Han B.
        • Smith S.J.
        • Truica C.I.
        An Analysis of Oncotype DX Recurrence Scores and Clinicopathologic Characteristics in Invasive Lobular BC.
        Breast J. 2017; 23 (Epub 2017 Jan 18 PMID: 28097781): 677-686https://doi.org/10.1111/tbj.12751
        • Metzger O.
        • Cardoso F.
        • Poncet C.
        • Desmedt C.
        • Linn S.
        • Wesseling J.
        • et al.
        Clinical Utility of MammaPrint testing in Invasive Lobular Carcinoma: Results from the MINDACT phase III trial.
        ORAL-007. 12th European BC Conference. 2020; 138: S5-S6
      19. Cardoso F, van't Veer LJ, Bogaerts J, Slaets L, Viale G, Delaloge S, Pierga JY, Brain E, Causeret S, DeLorenzi M, Glas AM, Golfinopoulos V, Goulioti T, Knox S, Matos E, Meulemans B, Neijenhuis PA, Nitz U, Passalacqua R, Ravdin P, Rubio IT, Saghatchian M, Smilde TJ, Sotiriou C, Stork L, Straehle C, Thomas G, Thompson AM, van der Hoeven JM, Vuylsteke P, Bernards R, Tryfonidis K, Rutgers E, Piccart M; MINDACT Investigators. 70-Gene Signature as an Aid to Treatment Decisions in Early-Stage BC. N Engl J Med. 2016 Aug 25;375(8):717-29. doi: 10.1056/NEJMoa1602253. PMID: 27557300.

        • Nunes R.
        • Salganik M.
        • Liu J.
        • Schnabel C.A.
        • Richardson A.L.
        Likelihood of late relapse assessed by the BC Index (BCI) in LN-invasive lobular compared to invasive ductal carcinoma.
        J Clin Oncol. 2017; (Journal of Clinical Oncology 35, no. 15_suppl)https://doi.org/10.1200/JCO.2017.35.15_suppl.e12025
        • Zhang Y.
        • Schnabel C.A.
        • Schroeder B.E.
        • Jerevall P.L.
        • Jankowitz R.C.
        • Fornander T.
        • et al.
        BC index identifies early-stage estrogen receptor-positive BC patients at risk for early- and late-distant recurrence.
        Clin Cancer Res. 2013; 19 (Epub 2013 Jun 11 PMID: 23757354): 4196-4205https://doi.org/10.1158/1078-0432.CCR-13-0804
        • Bartlett J.M.S.
        • Sgroi D.C.
        • Treuner K.
        • Zhang Y.
        • Ahmed I.
        • Piper T.
        • et al.
        BC Index and prediction of benefit from extended endocrine therapy in BC patients treated in the Adjuvant Tamoxifen-To Offer More? (aTTom) trial.
        Ann Oncol. 2019; 30: 1776-1783https://doi.org/10.1093/annonc/mdz289. PMID: 31504126; PMCID: PMC6927322
      20. Ellis MJ, Tao Y, Luo J, A'Hern R, Evans DB, Bhatnagar AS, Chaudri Ross HA, von Kameke A, Miller WR, Smith I, Eiermann W, Dowsett M. Outcome prediction for estrogen receptor-positive BC based on postneoadjuvant endocrine therapy tumor characteristics. J Natl Cancer Inst. 2008 Oct 1;100(19):1380-8. doi: 10.1093/jnci/djn309. Epub 2008 Sep 23. PMID: 18812550; PMCID: PMC2556704.

        • Smith I.
        • Robertson J.
        • Kilburn L.
        • Wilcox M.
        • Evans A.
        • Holcombe C.
        • et al.
        Long-term outcome and prognostic value of Ki67 after perioperative endocrine therapy in postmenopausal women with hormone-sensitive early BC (POETIC): an open-label, multicentre, parallel-group, randomised, phase 3 trial.
        Lancet Oncol. 2020; 21: 1443-1454https://doi.org/10.1016/S1470-2045(20)30458-7. PMID: 33152284; PMCID: PMC7606901
        • Prat A.
        • Saura C.
        • Pascual T.
        • Hernando C.
        • Muñoz M.
        • Paré L.
        • et al.
        Ribociclib plus letrozole versus chemotherapy for postmenopausal women with hormone receptor-positive, HER2-negative, luminal B BC (CORALLEEN): an open-label, multicentre, randomised, phase 2 trial.
        Lancet Oncol. 2020; 21 (Epub 2019 Dec 11 PMID: 31838010): 33-43https://doi.org/10.1016/S1470-2045(19)30786-7
        • Gao J.J.
        • Cheng J.
        • Bloomquist E.
        • Sanchez J.
        • Wedam S.B.
        • Singh H.
        • et al.
        CDK4/6 inhibitor treatment for patients with hormone receptor-positive, HER2-negative, advanced or metastatic BC: a US Food and Drug Administration pooled analysis.
        Lancet Oncol. 2020; 21 (Epub 2019 Dec 16 PMID: 31859246): 250-260https://doi.org/10.1016/S1470-2045(19)30804-6
      21. Johnston SRD, Harbeck N, Hegg R, Toi M, Martin M, Shao ZM, Zhang QY, Martinez Rodriguez JL, Campone M, Hamilton E, Sohn J, Guarneri V, Okada M, Boyle F, Neven P, Cortés J, Huober J, Wardley A, Tolaney SM, Cicin I, Smith IC, Frenzel M, Headley D, Wei R, San Antonio B, Hulstijn M, Cox J, O'Shaughnessy J, Rastogi P; monarchE Committee Members and Investigators. Abemaciclib Combined With Endocrine Therapy for the Adjuvant Treatment of HR+, HER2-, Node-Positive, High-Risk, Early BC (monarchE). J Clin Oncol. 2020 Dec 1;38(34):3987-3998. doi: 10.1200/JCO.20.02514. Epub 2020 Sep 20. PMID: 32954927.

        • Wolff A.C.
        CDK4/6 Inhibition in Early-Stage BC: The New Standard?.
        J Clin Oncol. 2020; 38 (Epub 2020 Sep 20 PMID: 32954928): 3977-3979https://doi.org/10.1200/JCO.20.02688
        • Mayer E.
        • Gnant M.I.
        • De Michele A.
        • Martin M.
        • Burstein H.
        • Prat A.
        • et al.
        LBA12 - PALLAS: A randomized phase III trial of adjuvant palbociclib with endocrine therapy versus endocrine therapy alone for HR+/HER2- early BC (ESMO Meeting 2020).
        Ann Oncol. 2020; 31: S1142-S1215https://doi.org/10.1016/annonc/annonc325
      22. O'Shaughnessy J, et al. Abemaciclib Combined with Endocrine Therapy for the Adjuvant Treatment of HR+, HER2-, Node-Positive, High-Risk, Early BC (monarchE), updated results. Presented at: 2020 Virtual San Antonio BC Symposium; December 8-11, 2020. Abstract GS1-01.

      23. Loibl S, Marmé F, Martin M, et al. Phase III study of palbociclib combined with endocrine therapy (ET) in patients with hormone-receptor-positive (HR+), HER2-negative primary BC and with high relapse risk after neoadjuvant chemotherapy (NACT): First results from PENELOPE-B. Presented at: 2020 Virtual San Antonio BC Symposium; December 8-11, 2020. Abstract GS1-02.