Breast Cancer Research and Treatment

, Volume 178, Issue 1, pp 169–176 | Cite as

Multiple foci of microinvasion is associated with an increased risk of invasive local recurrence in women with ductal carcinoma in situ treated with breast-conserving surgery

  • Eileen RakovitchEmail author
  • Rinku Sutradhar
  • Nafisha Lalani
  • Sharon Nofech-Mozes
  • Sumei Gu
  • Mira Goldberg
  • Wedad Hanna
  • Cindy Fong
  • Lawrence Paszat



The impact of Ductal Carcinoma in Situ (DCIS) with multiple foci of microinvasion (MI) (≤ 1 mm) on the risks of local recurrence (LR) and invasive LR is unknown, leading to uncertainty if DCIS with multiple foci of MI requires more aggressive treatment. We report a population-based analysis of the impact of multiple foci of MI, confirmed by pathology review, on the 15-year risks of LR and invasive LR treated with breast-conserving surgery (BCS) ± radiotherapy (RT).


Cohort includes all women diagnosed with DCIS ± MI from 1994 to 2003 treated with BCS ± RT. Cox proportional hazards model was used to evaluate the impact of multiple foci of MI on the risks of LR and invasive LR, adjusting for covariates. The 15-year local and invasive local recurrence-free survival rates were calculated using the Kaplan–Meier method with differences compared by log-rank test.


The cohort includes 2988 women treated by BCS; 2721 had pure DCIS (51% received RT), 267 had DCIS with one or more foci of MI (58% had RT). Median follow-up was 13 years. Median age at diagnosis was 58 years. On multivariable analyses, the presence of multiple foci of MI was associated with an increased risk of invasive LR (HR = 1.59, 95% CI 1.01–2.49, p = 0.04) but not DCIS LR (HR = 0.89, 95% CI 0.46, 1.76, p = 0.7). The 15-year invasive LRFS risks for cases with pure DCIS, with 1 focus or multiple foci of MI were 85.7%, 85.6%, 74.7% following treatment by BCS alone, 87.2%, 89.9%, and 77% for those treated with BCS + RT without boost and 89.2%, 91.3%, and 95% for women treated with BCS + RT and boost.


The presence of multiple foci of MI in DCIS is associated with higher 15-year risks of invasive LR after breast-conserving therapy compared to women with pure DCIS but treatment with whole breast and boost RT can mitigate this risk.


Ductal carcinoma in situ DCIS Microinvasion Radiotherapy Local recurrence 



The authors would like to acknowledge the following pathologists who contributed to the systematic pathology review: A. Tuck, B. Youngson, N. Miller, S. Done, M. Chang, S. Sengupta, P. Jani, L. Elavathil, M. Bonin and Dr. S. Robertson. This study was supported by the ICES, which is funded by an annual grant from the Ontario Ministry of Health and Long-Term Care (MOHLTC). The opinions, results, and conclusions reported in this paper are those of the authors and are independent from the funding sources. No endorsement by ICES or the Ontario MOHLTC is intended or should be inferred. This study was approved by the institutional review board at Sunnybrook Health Sciences Centre, Toronto, Canada. These datasets were linked using unique encoded identifiers and analyzed at the ICES. Parts of this material are based on data and information compiled and provided by Canadian Institute for Health Information (CIHI). However, the analyses, conclusions, opinions, and statements expressed herein are those of the author, and not necessarily those of CIHI. Parts of this material are based on data and information provided by Cancer Care Ontario (CCO). The opinions, results, view, and conclusions reported in this paper are those of the authors and do not necessarily reflect those of CCO. No endorsement by CCO is intended or should be inferred.


This work was supported in part by a grant from the Canadian Cancer Society Research Institute (grant number 18491). Dr. Rakovitch holds the LC Campbell Breast Cancer Research Chair.

Compliance with ethical standards

Conflict of interest

ERakovitch has received research grant funding from Genomic Health Inc. All other authors declare no conflict of interest.

Ethical approval

This study was approved by the Sunnybrook Health Sciences Centre Research Ethics Board. It is an observational analysis, and no procedures or interventions were performed.

Informed consent

This is a population-based retrospective analysis. All personal identifiers for each case in this population cohort were removed. This study was facilitated through ICES which is named as a prescribed entity in Section 45 of PHIPA (Regulation 329/04, Section 18) which allows access and utilization of administrative data for research purposes with a waived requirement for consent.


  1. 1.
    Bianchi S, Vezzosi V (2008) Microinvasive carcinoma of the breast. Pathol Oncol Res 14(2):105–111CrossRefGoogle Scholar
  2. 2.
    Adamovich TL, Simmons RM (2003) Ductal carcinoma in situ with microinvasion. Am J Surg 186(2):112–116CrossRefGoogle Scholar
  3. 3.
    Amin MB, Greene FL, Edge SB, Compton CC, Gershenwald JE, Brookland RK, Meyer L, Gress DM, Byrd DR, Winchester DP (2017) The eighth edition AJCC cancer staging manual: continuing to build a bridge from a population-based to a more “personalized” approach to cancer staging. CA Cancer J Clin 67(2):93–99CrossRefGoogle Scholar
  4. 4.
    Seo YY, Yoo IR, Park SY, Oh JK, Kim SH, Sohn HS (2017) Ductal carcinoma in situ and ductal carcinoma in situ with microinvasion: correlation of FDG uptake with histological and biological prognostic factors. Breast Cancer 24(3):353–361CrossRefGoogle Scholar
  5. 5.
    Wang W, Zhu W, Du F, Luo Y, Xu B (2017) The demographic features, clinicopathological characteristics and cancer-specific outcomes for patients with microinvasive breast cancer: a SEER database analysis. Sci Rep 7:42045CrossRefGoogle Scholar
  6. 6.
    Sue GR, Lannin DR, Killelea B, Chagpar AB (2013) Predictors of microinvasion and its prognostic role in ductal carcinoma in situ. Am J Surg 206(4):478–481CrossRefGoogle Scholar
  7. 7.
    Matsen CB, Hirsch A, Eaton A, Stempel M, Heerdt A, Van Zee KJ, Cody HS 3rd, Morrow M, Plitas G (2014) Extent of microinvasion in ductal carcinoma in situ is not associated with sentinel lymph node metastases. Ann Surg Oncol 21(10):3330–3335CrossRefGoogle Scholar
  8. 8.
    Parikh RR, Haffty BG, Lannin D, Moran MS (2012) Ductal carcinoma in situ with microinvasion: prognostic implications, long-term outcomes, and role of axillary evaluation. Int J Radiat Oncol Biol Phys 82(1):7–13CrossRefGoogle Scholar
  9. 9.
    Margalit DN, Sreedhara M, Chen YH, Catalano PJ, Nguyen PL, Golshan M, Overmoyer BA, Harris JR, Brock JE (2013) Microinvasive breast cancer: ER, PR, and HER-2/neu status and clinical outcomes after breast-conserving therapy or mastectomy. Ann Surg Oncol 20(3):811–818CrossRefGoogle Scholar
  10. 10.
    de Mascarel I, MacGrogan G, Mathoulin-Pelissier S, Soubeyran I, Picot V, Coindre JM (2002) Breast ductal carcinoma in situ with microinvasion: a definition supported by a long-term study of 1248 serially sectioned ductal carcinomas. Cancer 94(8):2134–2142CrossRefGoogle Scholar
  11. 11.
    Rakovitch E, Narod SA, Nofech-Moses S, Hanna W, Thiruchelvam D, Saskin R, Taylor C, Tuck A, Youngson B, Miller N et al (2013) Impact of boost radiation in the treatment of ductal carcinoma in situ: a population-based analysis. Int J Radiat Oncol Biol Phys 86(3):491–497CrossRefGoogle Scholar
  12. 12.
    Rakovitch E, Nofech-Mozes S, Narod S, Hanna W, Thiruchelvam D, Saskin R, Taylor C, Tuck A, Sengupta S, Elavathil L et al (2013) Can we select individuals with low risk ductal carcinoma in situ (DCIS)? A population-based outcomes analysis. Breast Cancer Res Treat 138(2):581–590CrossRefGoogle Scholar
  13. 13.
    Solin LJ, Fowble BL, Yeh IT, Kowalyshyn MJ, Schultz DJ, Weiss MC, Goodman RL (1992) Microinvasive ductal carcinoma of the breast treated with breast-conserving surgery and definitive irradiation. Int J Radiat Oncol Biol Phys 23(5):961–968CrossRefGoogle Scholar
  14. 14.
    In H, Bilimoria KY, Stewart AK, Wroblewski KE, Posner MC, Talamonti MS, Winchester DP (2014) Cancer recurrence: an important but missing variable in national cancer registries. Ann Surg Oncol 21(5):1520–1529CrossRefGoogle Scholar
  15. 15.
    Kim HM, Goodman M, Kim BI, Ward KC (2011) Frequency and determinants of missing data in clinical and prognostic variables recently added to SEER. J Regist Manag 38(3):120–131Google Scholar
  16. 16.
    Maibenco DC, Dombi GW, Kau TY, Severson RK (2006) Significance of micrometastases on the survival of women with T1 breast cancer. Cancer 107(6):1234–1239CrossRefGoogle Scholar
  17. 17.
    Mori M, Tsugawa K, Yamauchi H, Yagata H, Suzuki K, Ohde S, Soejima K, Nakamura S (2013) Pathological assessment of microinvasive carcinoma of the breast. Breast Cancer 20(4):331–335CrossRefGoogle Scholar
  18. 18.
    Yu KD, Wu LM, Liu GY, Wu J, Di GH, Shen ZZ, Shao ZM (2011) Different distribution of breast cancer subtypes in breast ductal carcinoma in situ (DCIS), DCIS with microinvasion, and DCIS with invasion component. Ann Surg Oncol 18(5):1342–1348CrossRefGoogle Scholar
  19. 19.
    Nguyen PL, Taghian AG, Katz MS, Niemierko A, Abi Raad RF, Boon WL, Bellon JR, Wong JS, Smith BL, Harris JR (2008) Breast cancer subtype approximated by estrogen receptor, progesterone receptor, and HER-2 is associated with local and distant recurrence after breast-conserving therapy. J Clin Oncol 26(14):2373–2378CrossRefGoogle Scholar
  20. 20.
    Mamounas EP, Tang G, Fisher B, Paik S, Shak S, Costantino JP, Watson D, Geyer CE Jr, Wickerham DL, Wolmark N (2010) Association between the 21-gene recurrence score assay and risk of locoregional recurrence in node-negative, estrogen receptor-positive breast cancer: results from NSABP B-14 and NSABP B-20. J Clin Oncol 28(10):1677–1683CrossRefGoogle Scholar
  21. 21.
    Voduc KD, Cheang MC, Tyldesley S, Gelmon K, Nielsen TO, Kennecke H (2010) Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol 28(10):1684–1691CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Radiation OncologyTorontoCanada
  2. 2.ICESTorontoCanada
  3. 3.Department of PathologySunnybrook Health Sciences CentreTorontoCanada
  4. 4.Sunnybrook Health Sciences CentreUniversity of TorontoTorontoCanada
  5. 5.Department of OncologyMcMaster UniversityHamiltonCanada
  6. 6.LC Campbell Chair in Breast Cancer ResearchSunnybrook Health Sciences CentreTorontoCanada

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