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Association of DCIS size and margin status with risk of developing breast cancer post-treatment: multinational, pooled cohort study.

Publication ,  Journal Article
Schmitz, RSJM; van den Belt-Dusebout, AW; Clements, K; Ren, Y; Cresta, C; Timbres, J; Liu, Y-H; Byng, D; Lynch, T; Menegaz, BA; Collyar, D ...
Published in: BMJ
October 30, 2023

OBJECTIVE: To examine the association between size and margin status of ductal carcinoma in situ (DCIS) and risk of developing ipsilateral invasive breast cancer and ipsilateral DCIS after treatment, and stage and subtype of ipsilateral invasive breast cancer. DESIGN: Multinational, pooled cohort study. SETTING: Four large international cohorts. PARTICIPANTS: Patient level data on 47 695 women with a diagnosis of pure, primary DCIS between 1999 and 2017 in the Netherlands, UK, and US who underwent surgery, either breast conserving or mastectomy, often followed by radiotherapy or endocrine treatment, or both. MAIN OUTCOME MEASURES: The main outcomes were 10 year cumulative incidence of ipsilateral invasive breast cancer and ipsilateral DCIS estimated in relation to DCIS size and margin status, and adjusted hazard ratios and 95% confidence intervals, estimated using multivariable Cox proportional hazards analyses with multiple imputed data RESULTS: The 10 year cumulative incidence of ipsilateral invasive breast cancer was 3.2%. In women who underwent breast conserving surgery with or without radiotherapy, only adjusted risks for ipsilateral DCIS were significantly increased for larger DCIS (20-49 mm) compared with DCIS <20 mm (hazard ratio 1.38, 95% confidence interval 1.11 to 1.72). Risks for both ipsilateral invasive breast cancer and ipsilateral DCIS were significantly higher with involved compared with clear margins (invasive breast cancer 1.40, 1.07 to 1.83; DCIS 1.39, 1.04 to 1.87). Use of adjuvant endocrine treatment was not significantly associated with a lower risk of ipsilateral invasive breast cancer compared to treatment with breast conserving surgery only (0.86, 0.62 to 1.21). In women who received breast conserving treatment with or without radiotherapy, higher DCIS grade was not significantly associated with ipsilateral invasive breast cancer, only with a higher risk of ipsilateral DCIS (grade 1: 1.42, 1.08 to 1.87; grade 3: 2.17, 1.66 to 2.83). Higher age at diagnosis was associated with lower risk (per year) of ipsilateral DCIS (0.98, 0.97 to 0.99) but not ipsilateral invasive breast cancer (1.00, 0.99 to 1.00). Women with large DCIS (≥50 mm) more often developed stage III and IV ipsilateral invasive breast cancer compared to women with DCIS <20 mm. No such association was found between involved margins and higher stage of ipsilateral invasive breast cancer. Associations between larger DCIS and hormone receptor negative and human epidermal growth factor receptor 2 positive ipsilateral invasive breast cancer and involved margins and hormone receptor negative ipsilateral invasive breast cancer were found. CONCLUSIONS: The association of DCIS size and margin status with ipsilateral invasive breast cancer and ipsilateral DCIS was small. When these two factors were added to other known risk factors in multivariable models, clinicopathological risk factors alone were found to be limited in discriminating between low and high risk DCIS.

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Published In

BMJ

DOI

EISSN

1756-1833

Publication Date

October 30, 2023

Volume

383

Start / End Page

e076022

Location

England

Related Subject Headings

  • Risk Factors
  • Neoplasm Recurrence, Local
  • Mastectomy, Segmental
  • Mastectomy
  • Humans
  • Hormones
  • General & Internal Medicine
  • Female
  • Cohort Studies
  • Carcinoma, Intraductal, Noninfiltrating
 

Citation

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Schmitz, R. S. J. M., van den Belt-Dusebout, A. W., Clements, K., Ren, Y., Cresta, C., Timbres, J., … Grand Challenge PRECISION consortium, . (2023). Association of DCIS size and margin status with risk of developing breast cancer post-treatment: multinational, pooled cohort study. BMJ, 383, e076022. https://doi.org/10.1136/bmj-2023-076022
Schmitz, Renée S. J. M., Alexandra W. van den Belt-Dusebout, Karen Clements, Yi Ren, Chiara Cresta, Jasmine Timbres, Yat-Hee Liu, et al. “Association of DCIS size and margin status with risk of developing breast cancer post-treatment: multinational, pooled cohort study.BMJ 383 (October 30, 2023): e076022. https://doi.org/10.1136/bmj-2023-076022.
Schmitz RSJM, 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 Oct 30;383:e076022.
Schmitz, Renée S. J. M., et al. “Association of DCIS size and margin status with risk of developing breast cancer post-treatment: multinational, pooled cohort study.BMJ, vol. 383, Oct. 2023, p. e076022. Pubmed, doi:10.1136/bmj-2023-076022.
Schmitz RSJM, van den Belt-Dusebout AW, Clements K, Ren Y, Cresta C, Timbres J, Liu Y-H, Byng D, Lynch T, Menegaz BA, Collyar D, Hyslop T, Thomas S, Love JK, Schaapveld M, Bhattacharjee P, Ryser MD, Sawyer E, Hwang ES, Thompson A, Wesseling J, Lips EH, Schmidt MK, Grand Challenge PRECISION consortium. Association of DCIS size and margin status with risk of developing breast cancer post-treatment: multinational, pooled cohort study. BMJ. 2023 Oct 30;383:e076022.

Published In

BMJ

DOI

EISSN

1756-1833

Publication Date

October 30, 2023

Volume

383

Start / End Page

e076022

Location

England

Related Subject Headings

  • Risk Factors
  • Neoplasm Recurrence, Local
  • Mastectomy, Segmental
  • Mastectomy
  • Humans
  • Hormones
  • General & Internal Medicine
  • Female
  • Cohort Studies
  • Carcinoma, Intraductal, Noninfiltrating