Skip to main content

Advertisement

SpringerLink
Log in

Risk of Contralateral Breast Cancer in Women with Ductal Carcinoma In Situ Associated with Synchronous Ipsilateral Lobular Carcinoma In Situ

  • Breast Oncology
  • Published:
Annals of Surgical Oncology Aims and scope Submit manuscript

Abstract

Background

Lobular carcinoma in situ (LCIS) is a risk factor for breast cancer, but the effect of LCIS found in association with ductal carcinoma in situ (DCIS) is unknown. In this study, we compared contralateral breast cancer (CBC) and ipsilateral breast tumor recurrence (IBTR) rates among women with DCIS with or without synchronous ipsilateral LCIS treated with breast-conserving surgery (BCS).

Methods

DCIS patients undergoing BCS from 2000 to 2011 with a contralateral breast at risk were stratified by the presence or absence of synchronous ipsilateral LCIS with the index DCIS (DCIS + LCIS vs. DCIS). Those with contralateral, bilateral, or prior ipsilateral LCIS were excluded. Associations of patient, tumor, and treatment factors with CBC and IBTR were evaluated.

Results

Of 1888 patients identified, 1475 (78%) had DCIS and 413 (22%) had DCIS + LCIS. At median follow-up of 7.2 (range 0–17) years, 307 patients had a subsequent first breast event; 207 IBTR and 100 CBC. The 10-year cumulative incidence of IBTR was similar in both groups: 15.0% vs. 14.2% (log-rank, p = 0.8) for DCIS + LCIS vs. DCIS, respectively. The 10-year cumulative incidence of CBC was greater in the DCIS + LCIS group: 10.9% vs. 6.1% for DCIS (log-rank, p < 0.001). After adjustment for other factors, CBC risk remained higher in DCIS + LCIS compared with DCIS (hazard ratio 2.06, 95% confidence interval 1.36–3.11, p = 0.001); there was no significant difference in IBTR risk.

Conclusions

Compared with DCIS alone, DCIS + LCIS is associated with similar IBTR risk but double the risk of CBC. This finding should inform treatment decisions, in particular regarding endocrine therapy for risk reduction.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Haagensen CD, Lane N, Lattes R, Bodian C. Lobular neoplasia (so-called lobular carcinoma in situ) of the breast. Cancer. 1978;42(2):737–69.

    Article  CAS  Google Scholar 

  2. King TA, Pilewskie M, Muhsen S, et al. Lobular carcinoma in situ: a 29-year longitudinal experience evaluating clinicopathologic features and breast cancer risk. J Clin Oncol. 2015;33(33):3945–52.

    Article  Google Scholar 

  3. Page DL, Dupont WD, Rogers LW, Rados MS. Atypical hyperplastic lesions of the female breast. A long-term follow-up study. Cancer. 1985;55(11):2698–708.

    CAS  PubMed  Google Scholar 

  4. Page DL, Kidd TE, Jr., Dupont WD, Simpson JF, Rogers LW. Lobular neoplasia of the breast: higher risk for subsequent invasive cancer predicted by more extensive disease. Hum Pathol. 1991;22(12):1232–9.

    Article  CAS  Google Scholar 

  5. Rosen PP, Kosloff C, Lieberman PH, Adair F, Braun DW, Jr. Lobular carcinoma in situ of the breast. Detailed analysis of 99 patients with average follow-up of 24 years. Am J Surg Pathol. 1978;2(3):225–51.

  6. Wong SM, King T, Boileau JF, Barry WT, Golshan M. Population-based analysis of breast cancer incidence and survival outcomes in women diagnosed with lobular carcinoma in situ. Ann Surg Oncol. 2017;24(9):2509–17.

    Article  Google Scholar 

  7. Chuba PJ, Hamre MR, Yap J, et al. Bilateral risk for subsequent breast cancer after lobular carcinoma-in situ: analysis of surveillance, epidemiology, and end results data. J Clin Oncol. 2005;23(24):5534–41.

    Article  Google Scholar 

  8. Adepoju LJ, Symmans WF, Babiera GV, et al. Impact of concurrent proliferative high-risk lesions on the risk of ipsilateral breast carcinoma recurrence and contralateral breast carcinoma development in patients with ductal carcinoma in situ treated with breast-conserving therapy. Cancer. 2006;106(1):42–50.

    Article  Google Scholar 

  9. Ciocca RM, Li T, Freedman GM, Morrow M. Presence of lobular carcinoma in situ does not increase local recurrence in patients treated with breast-conserving therapy. Ann Surg Oncol. 2008;15(8):2263–71.

    Article  Google Scholar 

  10. Griem KL, Hartsell WF, Recine DC, et al. What is the significance of a lobular carcinoma in situ (LCIS) component in women treated with breast conserving therapy (SCT) for early stage breast cancer? Int J Radiat Oncol Biol Phys. 1993;27 (supplement):269–70.

    Article  Google Scholar 

  11. Jolly S, Kestin LL, Goldstein NS, Vicini FA. The impact of lobular carcinoma in situ in association with invasive breast cancer on the rate of local recurrence in patients with early-stage breast cancer treated with breast-conserving therapy. Int J Radiat Oncol Biol Phys. 2006;66(2):365–71.

    Article  Google Scholar 

  12. Moran M, Haffty BG. Lobular carcinoma in situ as a component of breast cancer: the long-term outcome in patients treated with breast-conservation therapy. Int J Radiat Oncol Biol Phys. 1998;40(2):353–8.

    Article  CAS  Google Scholar 

  13. Ottesen GL, Graversen HP, Blichert-Toft M, Christensen IJ, Andersen JA. Carcinoma in situ of the female breast. 10 year follow-up results of a prospective nationwide study. Breast Cancer Res Treat. 2000;62(3):197–210.

  14. Sasson AR, Fowble B, Hanlon AL, et al. Lobular carcinoma in situ increases the risk of local recurrence in selected patients with stages I and II breast carcinoma treated with conservative surgery and radiation. Cancer. 2001;91(10):1862–9.

    Article  CAS  Google Scholar 

  15. Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365(9472):1687–717.

  16. Gao X, Fisher SG, Emami B. Risk of second primary cancer in the contralateral breast in women treated for early-stage breast cancer: a population-based study. Int J Radiat Oncol Biol Phys. 2003;56(4):1038–45.

    Article  Google Scholar 

  17. Nichols HB, Berrington de Gonzalez A, Lacey JV, Jr., Rosenberg PS, Anderson WF. Declining incidence of contralateral breast cancer in the United States from 1975 to 2006. J Clin Oncol. 2011;29(12):1564–9.

  18. Reiner AS, John EM, Brooks JD, et al. Risk of asynchronous contralateral breast cancer in noncarriers of BRCA1 and BRCA2 mutations with a family history of breast cancer: a report from the Women’s Environmental Cancer and Radiation Epidemiology Study. J Clin Oncol. 2013;31(4):433–9.

    Article  Google Scholar 

  19. Reiner AS, Sisti J, John EM, et al. Breast cancer family history and contralateral breast cancer risk in young women: an update from the women’s environmental cancer and radiation epidemiology study. J Clin Oncol. 2018;36(15):1513–20.

    Article  CAS  Google Scholar 

  20. 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(10):2889–97.

    Article  Google Scholar 

  21. Muhsen S, Barrio AV, Miller M, et al. Outcomes for women with minimal-volume ductal carcinoma in situ completely excised at core biopsy. Ann Surg Oncol. 2017;24(13):3888–95.

    Article  Google Scholar 

  22. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2016. CA Cancer J Clin. 2016;66(1):7–30.

    Article  Google Scholar 

  23. Rudloff U, Brogi E, Brockway JP, et al. Concurrent lobular neoplasia increases the risk of ipsilateral breast cancer recurrence in patients with ductal carcinoma in situ treated with breast-conserving therapy. Cancer. 2009;115(6):1203–14.

    Article  Google Scholar 

  24. Bijker N, Meijnen P, Peterse JL, et al. Breast-conserving treatment with or without radiotherapy in ductal carcinoma-in situ: ten-year results of European Organisation for Research and Treatment of Cancer randomized phase III trial 10853–a study by the EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group. J Clin Oncol. 2006;24(21):3381–7.

    Article  Google Scholar 

  25. Collins LC, Achacoso N, Haque R, et al. Risk factors for non-invasive and invasive local recurrence in patients with ductal carcinoma in situ. Breast Cancer Res Treat. 2013;139(2):453–60.

    Article  Google Scholar 

  26. Cronin PA, Olcese C, Patil S, Morrow M, Van Zee KJ. Impact of age on risk of recurrence of ductal carcinoma in situ: outcomes of 2996 women treated with breast-conserving surgery over 30 years. Ann Surg Oncol. 2016;23(9):2816–24.

    Article  Google Scholar 

  27. Fisher B, Dignam J, Wolmark N, et al. Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial. Lancet. 1999;353(9169):1993–2000.

    Article  CAS  Google Scholar 

  28. Ringberg A, Nordgren H, Thorstensson S, et al. Histopathological risk factors for ipsilateral breast events after breast conserving treatment for ductal carcinoma in situ of the breast–results from the Swedish randomised trial. Eur J Cancer. 2007;43(2):291–8.

    Article  CAS  Google Scholar 

  29. Van Zee KJ, Liberman L, Samli B, et al. Long term follow-up of women with ductal carcinoma in situ treated with breast-conserving surgery: the effect of age. Cancer. 1999;86(9):1757–67.

    Article  Google Scholar 

  30. Allred DC, Anderson SJ, Paik S, et al. Adjuvant tamoxifen reduces subsequent breast cancer in women with estrogen receptor-positive ductal carcinoma in situ: a study based on NSABP protocol B-24. J Clin Oncol. 2012;30(12):1268–73.

    Article  CAS  Google Scholar 

  31. Cuzick J, Sestak I, Pinder SE, et al. Effect of tamoxifen and radiotherapy in women with locally excised ductal carcinoma in situ: long-term results from the UK/ANZ DCIS trial. Lancet Oncol. 2011;12(1):21–9.

    Article  CAS  Google Scholar 

  32. Donker M, Litiere S, Werutsky G, 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(32):4054–9.

    Article  Google Scholar 

  33. Wapnir IL, Dignam JJ, Fisher B, 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(6):478–88.

    Article  Google Scholar 

  34. Warnberg F, Garmo H, Emdin S, et al. Effect of radiotherapy after breast-conserving surgery for ductal carcinoma in situ: 20 years follow-up in the randomized SweDCIS Trial. J Clin Oncol. 2014;32(32):3613–8.

    Article  Google Scholar 

  35. Claus EB, Stowe M, Carter D, Holford T. The risk of a contralateral breast cancer among women diagnosed with ductal and lobular breast carcinoma in situ: data from the Connecticut Tumor Registry. Breast. 2003;12(6):451–6.

    Article  Google Scholar 

  36. Innos K, Horn-Ross PL. Risk of second primary breast cancers among women with ductal carcinoma in situ of the breast. Breast Cancer Res Treat. 2008;111(3):531–40.

    Article  Google Scholar 

  37. Flanagan MR, Rendi MH, Gadi VK, Calhoun KE, Gow KW, Javid SH. Adjuvant endocrine therapy in patients with ductal carcinoma in situ: a population-based retrospective analysis from 2005 to 2012 in the National Cancer Data Base. Ann Surg Oncol. 2015;22(10):3264–72.

    Article  Google Scholar 

  38. Karavites LC, Kane AK, Zaveri S, et al. Tamoxifen acceptance and adherence among patients with ductal carcinoma in situ (DCIS) treated in a multidisciplinary setting. Cancer Prev Res (Phila). 2017;10(7):389–97.

    Article  CAS  Google Scholar 

  39. Livaudais JC, Hwang ES, Karliner L, et al. Adjuvant hormonal therapy use among women with ductal carcinoma in situ. J Womens Health (Larchmt). 2012;21(1):35–42.

    Article  Google Scholar 

  40. Narod SA, Iqbal J, Giannakeas V, Sopik V, Sun P. Breast cancer mortality after a diagnosis of ductal carcinoma in situ. JAMA Oncol. 2015;1(7):888–96.

    Article  Google Scholar 

  41. Nichols HB, Bowles EJ, Islam J, et al. Tamoxifen initiation after ductal carcinoma in situ. Oncologist. 2016;21(2):134–40.

    Article  CAS  Google Scholar 

  42. McCormick B, Winter K, Hudis C, et al. RTOG 9804: a prospective randomized trial for good-risk ductal carcinoma in situ comparing radiotherapy with observation. J Clin Oncol. 2015;33(7):709–15.

    Article  CAS  Google Scholar 

  43. Pilewskie M, Stempel M, Rosenfeld H, Eaton A, Van Zee KJ, Morrow M. Do LORIS Trial eligibility criteria identify a ductal carcinoma in situ patient population at low risk of upgrade to invasive carcinoma? Ann Surg Oncol. 2016;23(11):3487–93.

    Article  Google Scholar 

Download references

Acknowledgment

The preparation of this study was funded in part by NIH/NCI Cancer Center Support Grant No. P30 CA008748 to Memorial Sloan Kettering Cancer Center. This study was presented in poster format at the 41st Annual San Antonio Breast Cancer Symposium, December 4–8, 2018, San Antonio, TX.

Author information

Author notes

  1. Megan E. Miller MD

    Present address: Department of Surgery, University Hospitals, Case Western Reserve University School of Medicine, Cleveland, OH, USA

  2. Shirin Muhsen MD

    Present address: Clemenceau Medical Center/Johns Hopkins International, Beirut, Lebanon

  3. Megan E. Miller and Shirin Muhsen have contributed equally to this work.

Authors and Affiliations

  1. Breast Service, Department of Surgery, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Megan E. Miller MD, Shirin Muhsen MD, Cristina Olcese BS, Kimberly J. Van Zee MS, MD, FACS & Melissa Pilewskie MD, FACS

  2. Biostatistics Service, Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Emily C. Zabor DrPH & Jessica Flynn BS

  3. Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA

    Dilip Giri MD

Authors
  1. Megan E. Miller MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shirin Muhsen MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Emily C. Zabor DrPH
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jessica Flynn BS
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Cristina Olcese BS
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dilip Giri MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Kimberly J. Van Zee MS, MD, FACS
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Melissa Pilewskie MD, FACS
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Melissa Pilewskie MD, FACS.

Ethics declarations

Disclosures

Dr. Kimberly J. Van Zee has served on the Advisory Board of Genomic Health.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Miller, M.E., Muhsen, S., Zabor, E.C. et al. Risk of Contralateral Breast Cancer in Women with Ductal Carcinoma In Situ Associated with Synchronous Ipsilateral Lobular Carcinoma In Situ. Ann Surg Oncol 26, 4317–4325 (2019). https://doi.org/10.1245/s10434-019-07796-9

Download citation

  • Received:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1245/s10434-019-07796-9

Search

Navigation