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Epidemiology

Invasive recurrence after breast conserving treatment of ductal carcinoma in situ of the breast in the Netherlands: time trends and the association with tumour grade

British Journal of Cancer volume 131, pages 852–859 (2024)Cite this article

Subjects

Abstract

Background

The first aim of this study was to examine trends in the risk of ipsilateral invasive breast cancer (iIBC) after breast-conserving surgery (BCS) of ductal carcinoma in situ (DCIS). A second aim was to analyse the association between DCIS grade and the risk of iIBC following BCS.

Patients and methods

In this population-based, retrospective cohort study, the Netherlands Cancer Registry collected information on 25,719 women with DCIS diagnosed in the period 1989–2021 who underwent BCS. Of these 19,034 received adjuvant radiotherapy (RT). Kaplan–Meier analyses and Cox regression models were used.

Results

A total of 1135 patients experienced iIBC. Ten-year cumulative incidence rates of iIBC for patients diagnosed in the periods 1989–1998, 1999–2008 and 2009–2021 undergoing BCS without RT, were 12.6%, 9.0% and 5.0% (P < 0.001), respectively. For those undergoing BCS with RT these figures were 5.7%, 3.7% and 2.2%, respectively (P < 0.001). In the multivariable analyses, DCIS grade was not associated with the risk of iIBC.

Conclusion

Since 1989 the risk of iIBC has decreased substantially and has become even lower than the risk of invasive contralateral breast cancer. No significant association of DCIS grade with iIBC was found, stressing the need for more powerful prognostic factors to guide the treatment of DCIS.

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Fig. 1: DCIS grade.
Fig. 2: Adjuvant radiotherapy.
Fig. 3: Cumulative incidence of ipsilateral invasive breast cancer for patients with DCIS according to period of diagnosis.
Fig. 4: Cumulative incidence of ipsilateral invasive breast cancer for patients with DCIS according to DCIS grade.

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Data availability

All data supporting the findings in this study are presented in the manuscript and the supplementary information, and additional raw data can be made available via the NCR upon request and after approval of a study proposal.

References

  1. Maxwell AJ, Hilton B, Clements K, Dodwell D, Dulson-Cox J, Kearins O, et al. Unresected screen-detected ductal carcinoma in situ: Outcomes of 311 women in the Forget-Me-Not 2 study. Breast. 2022;61:145–55.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Ryser MD, Weaver DL, Zhao F, Worni M, Grimm LJ, Gulati R, et al. Cancer Outcomes in DCIS Patients Without Locoregional Treatment. J Natl Cancer Inst. 2019;111:952–60.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Ernster VL, Ballard-Barbash R, Barlow WE, Zheng Y, Weaver DL, Cutter G, et al. Detection of Ductal Carcinoma In Situ in Women Undergoing Screening Mammography. JNCI: J Natl Cancer Inst. 2002;94:1546–54.

    Article  PubMed  Google Scholar 

  4. Bleyer A, Welch HG. Effect of Three Decades of Screening Mammography on Breast-Cancer Incidence. N. Engl J Med. 2012;367:1998–2005.

    Article  CAS  PubMed  Google Scholar 

  5. IKNL. NKR Cijfers. Available from: https://iknl.nl/kankersoorten/borstkanker/registratie/incidentie. Accessed on: 07-05-2024

  6. van Seijen M, Lips EH, Thompson AM, Nik-Zainal S, Futreal A, Hwang ES, et al. Ductal carcinoma in situ: to treat or not to treat, that is the question. Br J Cancer. 2019;121:285–92.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Cardoso F, Kyriakides S, Ohno S, Penault-Llorca F, Poortmans P, Rubio IT, et al. Early breast cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2019;30:1194–220.

    Article  CAS  PubMed  Google Scholar 

  8. Correa C, McGale P, Taylor C, Wang Y, Clarke M, Davies C, et al. Overview of the randomized trials of radiotherapy in ductal carcinoma in situ of the breast. J Natl Cancer Inst Monogr 2010;2010:162–77.

    Article  CAS  PubMed  Google Scholar 

  9. Schmitz R, van den Belt-Dusebout AW, Clements K, Ren Y, Cresta C, Timbres J, et al. Association of DCIS size and margin status with risk of developing breast cancer post-treatment: multinational, pooled cohort study. Bmj. 2023;383:e076022.

    Article  PubMed  PubMed Central  Google Scholar 

  10. Tang P, Wang X, Schiffhauer L, Wang J, Bourne P, Yang Q, et al. Relationship between nuclear grade of ductal carcinoma in situ and cell origin markers. Ann Clin Lab Sci. 2006;36:16–22.

    PubMed  Google Scholar 

  11. van Dooijeweert C, van Diest PJ, Willems SM, Kuijpers CCHJ, Overbeek LIH, Deckers IAG. Significant inter- and intra-laboratory variation in grading of ductal carcinoma in situ of the breast: a nationwide study of 4901 patients in the Netherlands. Breast Cancer Res Treat. 2019;174:479–88.

    Article  PubMed  Google Scholar 

  12. Thompson AM, Clements K, Cheung S, Pinder SE, Lawrence G, Sawyer E, et al. Management and 5-year outcomes in 9938 women with screen-detected ductal carcinoma in situ: the UK Sloane Project. Eur J Cancer. 2018;101:210–9.

    Article  PubMed  Google Scholar 

  13. Collins LC, Achacoso N, Haque R, Nekhlyudov L, Fletcher SW, Quesenberry CP Jr, et al. Risk factors for non-invasive and invasive local recurrence in patients with ductal carcinoma in situ. Breast Cancer Res Treat. 2013;139:453–60.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Elshof LE, Schaapveld M, Schmidt MK, Rutgers EJ, van Leeuwen FE, Wesseling J. Subsequent risk of ipsilateral and contralateral invasive breast cancer after treatment for ductal carcinoma in situ: incidence and the effect of radiotherapy in a population-based cohort of 10,090 women. Breast Cancer Res Treat. 2016;159:553–63.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Chua BH, Link EK, Kunkler IH, Whelan TJ, Westenberg AH, Gruber G, et al. Radiation doses and fractionation schedules in non-low-risk ductal carcinoma in situ in the breast (BIG 3-07/TROG 07.01): a randomised, factorial, multicentre, open-label, phase 3 study. Lancet. 2022;400:431–40.

    Article  PubMed  Google Scholar 

  16. Luiten JD, Luiten EJT, van der Sangen MJC, Vreuls W, Duijm LEM, Tjan-Heijnen VCG, et al. Patterns of treatment and outcome of ductal carcinoma in situ in the Netherlands. Breast Cancer Res Treat. 2021;187:245–54.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Mohamed AA, Luo Y, Peng H, Jankowitz RC, Wu S. Understanding Clinical Mammographic Breast Density Assessment: a Deep Learning Perspective. J Digit Imaging. 2018;31:387–92.

    Article  PubMed  Google Scholar 

  18. Bonnett M, Wallis T, Rossmann M, Pernick NL, Carolin KA, Segel M, et al. Histologic and Radiographic Analysis of Ductal Carcinoma In Situ Diagnosed Using Stereotactic Incisional Core Breast Biopsy. Mod Pathol. 2002;15:95–101.

    Article  PubMed  Google Scholar 

  19. Dahlstrom JE, Sutton S, Jain S Histologic-Radiologic Correlation of Mammographically Detected Microcalcification in Stereotactic Core Biopsies. The American Journal of Surgical Pathology. 1998;22.

  20. Wetstein SC, Stathonikos N, Pluim JPW, Heng YJ, ter Hoeve ND, Vreuls CPH, et al. Deep learning-based grading of ductal carcinoma in situ in breast histopathology images. Lab Investig. 2021;101:525–33.

    Article  CAS  PubMed  Google Scholar 

  21. Whelan TJ, Pignol J-P, Levine MN, Julian JA, MacKenzie R, Parpia S, et al. Long-Term Results of Hypofractionated Radiation Therapy for Breast Cancer. N. Engl J Med. 2010;362:513–20.

    Article  CAS  PubMed  Google Scholar 

  22. Haviland JS, Owen JR, Dewar JA, Agrawal RK, Barrett J, Barrett-Lee PJ, et al. The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. Lancet Oncol. 2013;14:1086–94.

    Article  PubMed  Google Scholar 

  23. Murray Brunt A, Haviland JS, Wheatley DA, Sydenham MA, Alhasso A, Bloomfield DJ, et al. Hypofractionated breast radiotherapy for 1 week versus 3 weeks (FAST-Forward): 5-year efficacy and late normal tissue effects results from a multicentre, non-inferiority, randomised, phase 3 trial. Lancet. 2020;395:1613–26.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Correa C, Harris EE, Leonardi MC, Smith BD, Taghian AG, Thompson AM, et al. Accelerated Partial Breast Irradiation: Executive summary for the update of an ASTRO Evidence-Based Consensus Statement. Practical Radiat Oncol. 2017;7:73–9.

    Article  Google Scholar 

  25. Specialisten FM Breast Cancer - Radiotherapy 2017.

  26. Team R. RStudio Team. RStudio: Integrated Development Environment for R [Internet]. 2015.

  27. Rakovitch E, Nofech-Mozes S, Narod SA, Hanna W, Thiruchelvam D, Saskin R, et al. Can we select individuals with low risk ductal carcinoma in situ (DCIS)? A population-based outcomes analysis. Breast Cancer Res Treat. 2013;138:581–90.

    Article  PubMed  Google Scholar 

  28. Miller ME, Muhsen S, Olcese C, Patil S, Morrow M, Van Zee KJ. Contralateral Breast Cancer Risk in Women with Ductal Carcinoma In Situ: Is it High Enough to Justify Bilateral Mastectomy? Ann Surg Oncol. 2017;24:2889–97.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Wapnir IL, Dignam JJ, Fisher B, Mamounas EP, Anderson SJ, Julian TB, et al. Long-term outcomes of invasive ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and B-24 randomized clinical trials for DCIS. J Natl Cancer Inst. 2011;103:478–88.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Donker M, Litière S, Werutsky G, Julien JP, Fentiman IS, Agresti R, et al. Breast-conserving treatment with or without radiotherapy in ductal carcinoma In Situ: 15-year recurrence rates and outcome after a recurrence, from the EORTC 10853 randomized phase III trial. J Clin Oncol. 2013;31:4054–9.

    Article  PubMed  Google Scholar 

  31. Shaaban AM, Hilton B, Clements K, Provenzano E, Cheung S, Wallis MG, et al. Pathological features of 11,337 patients with primary ductal carcinoma in situ (DCIS) and subsequent events: results from the UK Sloane Project. Br J Cancer. 2021;124:1009–17.

    Article  CAS  PubMed  Google Scholar 

  32. Keymeulen K, Geurts SME, Lobbes MBI, Heuts EM, Duijm LEM, Kooreman LFS, et al. Population-based study of the effect of preoperative breast MRI on the surgical management of ductal carcinoma in situ. Br J Surg. 2019;106:1488–94.

    Article  CAS  PubMed  Google Scholar 

  33. Anderson C, Winn AN, Dusetzina SB, Nichols HB. Endocrine Therapy Initiation among Older Women with Ductal Carcinoma In Situ. J Cancer Epidemiol. 2017;2017:6091709.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Chaudhry A, Theodora K, Speers C, Olson RA. Prescribing Practices of Endocrine Therapy for Ductal Carcinoma In Situ in British Columbia. Int J Radiat Oncol, Biol, Phys. 2017;99:E39.

    Article  Google Scholar 

  35. Laws A, Punglia RS. Endocrine Therapy for Primary and Secondary Prevention After Diagnosis of High-Risk Breast Lesions or Preinvasive Breast Cancer. J Clin Oncol. 2023;41:3092–9.

    Article  CAS  PubMed  Google Scholar 

  36. Lazzeroni M, Puntoni M, Guerrieri-Gonzaga A, Serrano D, Boni L, Buttiron Webber T, et al. Randomized Placebo Controlled Trial of Low-Dose Tamoxifen to Prevent Recurrence in Breast Noninvasive Neoplasia: A 10-Year Follow-Up of TAM-01 Study. J Clin Oncol. 2023;41:3116–21.

    Article  CAS  PubMed  Google Scholar 

  37. van Seijen M, Jóźwiak K, Pinder SE, Hall A, Krishnamurthy S, Thomas JS, et al. Variability in grading of ductal carcinoma in situ among an international group of pathologists. J Pathol Clin Res. 2021;7:233–42.

    Article  PubMed  PubMed Central  Google Scholar 

  38. Groen EJ, Elshof LE, Visser LL, Rutgers EJT, Winter-Warnars HAO, Lips EH, et al. Finding the balance between over- and under-treatment of ductal carcinoma in situ (DCIS). Breast. 2017;31:274–83.

    Article  PubMed  Google Scholar 

  39. Kanbayashi C, Thompson AM, Hwang E-SS, Partridge AH, Rea DW, Wesseling J, et al. The international collaboration of active surveillance trials for low-risk DCIS (LORIS, LORD, COMET, LORETTA). J Clin Oncol. 2019;37:TPS603–TPS.

    Article  Google Scholar 

  40. Elshof LE, Tryfonidis K, Slaets L, van Leeuwen-Stok AE, Skinner VP, Dif N, et al. Feasibility of a prospective, randomised, open-label, international multicentre, phase III, non-inferiority trial to assess the safety of active surveillance for low risk ductal carcinoma in situ; The LORD study. Eur J Cancer. 2015;51:1497–510.

    Article  PubMed  Google Scholar 

  41. Hwang ES, Hyslop T, Lynch T, Frank E, Pinto D, Basila D, et al. The COMET (Comparison of Operative versus Monitoring and Endocrine Therapy) trial: a phase III randomised controlled clinical trial for low-risk ductal carcinoma in situ (DCIS). BMJ Open. 2019;9:e026797.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Francis A, Thomas J, Fallowfield L, Wallis M, Bartlett JMS, Brookes C, et al. Addressing overtreatment of screen detected DCIS; the LORIS trial. Eur J Cancer. 2015;51:2296–303.

    Article  PubMed  Google Scholar 

  43. Paszat L, Sutradhar R, Zhou L, Nofech-Mozes S, Rakovitch E. Including the Ductal Carcinoma-In-Situ (DCIS) Score in the Development of a Multivariable Prediction Model for Recurrence After Excision of DCIS. Clin Breast Cancer. 2019;19:35–46.

    Article  PubMed  Google Scholar 

  44. Weinmann S, Leo MC, Francisco M, Jenkins CL, Barry T. Leesman G, et al. Validation of a ductal carcinoma in situ biomarker profile for risk of recurrence after breast-conserving surgery with and without radio therapy. Clin Cancer Res. 2020;26:4054–63.

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Acknowledgements

We thank the NCR for providing the data and their data managers for collecting the data. We thank Anita Botterweck, data analyst at Netherlands Comprehensive Cancer Organisation (IKNL), for the data selection and for providing the dataset.

Author information

Authors and Affiliations

  1. Department of Epidemiology, Maastricht University, Maastricht, Netherlands

    Rebecca L. O’Leary & Adri C. Voogd

  2. Department of Radiology, Canisius Wilhelmina Hospital, Nijmegen, Netherlands

    Lucien E. M. Duijm

  3. Department of Radiation Oncology (Maastro), GROW-School for Oncology and Reproduction, Maastricht University Medical Centre, Maastricht, Netherlands

    Liesbeth J. Boersma

  4. Department of Radiation Oncology, Catharina Hospital, Eindhoven, Netherlands

    Maurice J. C. van der Sangen

  5. Department of Research and Development, Netherlands Comprehensive Cancer Organisation (IKNL), Utrecht, Netherlands

    Linda de Munck & Adri C. Voogd

  6. Division of Molecular Pathology, the Netherlands Cancer Institute, Amsterdam, Netherlands

    Jelle Wesseling

  7. Department of Pathology, the Netherlands Cancer Institute – Antoni van Leeuwenhoek, Amsterdam, Netherlands

    Jelle Wesseling

  8. Department of Pathology, Leiden University Medical Center, Leiden, Netherlands

    Jelle Wesseling

  9. Department of Surgery, Catharina Hospital, Eindhoven, Netherlands

    Robert-Jan Schipper

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Contributions

Study design: ACV. Performed the research and collected data: RLOL, LEMD, LJB, RJS and ACV. Analysed the data: RLOL. Manuscript drafting: RLOL, LEMD, LJB, RJS and ACV. Provided discussion, critical feedback and manuscript editing: LEMD, LJB, MJCS, RJS, LM and JW.

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Correspondence to Adri C. Voogd.

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O’Leary, R.L., Duijm, L.E.M., Boersma, L.J. et al. Invasive recurrence after breast conserving treatment of ductal carcinoma in situ of the breast in the Netherlands: time trends and the association with tumour grade. Br J Cancer 131, 852–859 (2024). https://doi.org/10.1038/s41416-024-02785-6

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  • DOI: https://doi.org/10.1038/s41416-024-02785-6

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