Skip to main content

Advertisement

Log in

Risk prediction for local versus regional/metastatic tumors after initial ductal carcinoma in situ diagnosis treated by lumpectomy

  • Epidemiology
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Among women diagnosed with ductal carcinoma in situ (DCIS), we identified factors associated with local invasive cancer (LIC) and regional/metastatic invasive cancer (RMIC) and provide 10-year risks based on clinically relevant factors. We created a retrospective, population-based cohort of 1492 women with an initial diagnosis of DCIS (1983–1996) treated by lumpectomy alone. Histological and molecular markers (Ki67, ER, PR, COX-2, p16, ERBB2) were collected on DCIS cases with a subsequent tumor (DCIS, LIC, or RMIC) and a subsample of frequency-matched controls without subsequent tumors. Competing risks methods were used to identify factors associated with LIC and RMIC and cumulative incidence methods to estimate 10-year risks for combinations of factors. Median follow-up time was 12.6 years (range 0.5–29.5 years). The overall 10-year risk of LIC (11.9 %) was higher than for RMIC (3.8 %). About half of women with initial DCIS lesions are detected by mammography and p16 negative and have a 10-year risk of LIC of 6.2 % (95 % CI 5.8–6.8 %) and RMIC of 1.2 % (95 % CI 1.1–1.3 %). Premenopausal women whose DCIS lesion was p16 positive or p16 negative and detected by palpation had high 10-year risk of LIC of 23.0 % (95 % CI 19.3–27.4 %). Ten-year risk of RMIC was highest at 22.5 % (95 % CI 13.8–48.1 %) for those positive for p16, COX-2, and ERRB2, and negative for ER, but prevalence of this group is low at 3 %. Ten-year risk of LIC and RMIC is low for the majority diagnosed with DCIS. Combinations of molecular markers and method of detection of initial DCIS lesion can differentiate women at low and high risk of LIC and RMIC.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

CI:

Confidence interval

CIF:

Cumulative incidence function

DCIS:

Ductal carcinoma in situ

IC:

Invasive cancer

LIC:

Local invasive cancer

RMIC:

Regional/metastatic invasive cancer

VNPI:

Van Nuys Prognostic Index

References

  1. Siegel R, Miller K, Jemal A (2015) Cancer statistics, 2015. CA Cancer J Clin 65(1):5–29

    Article  PubMed  Google Scholar 

  2. American Cancer Society (2013) Breast cancer facts & figures (2013-2014) In: American Cancer Society, Inc, Atlanta

  3. Ernster VL, Ballard-Barbash R, Barlow WE, Zheng Y, Weaver DL, Cutter G, Yankaskas BC, Rosenberg R, Carney PA, Kerlikowske K et al (2002) Detection of ductal carcinoma in situ in women undergoing screening mammography. J Natl Cancer Inst 94(20):1546–1554

    Article  PubMed  Google Scholar 

  4. Kerlikowske K (2010) Epidemiology of DCIS. JNCI 2010(41):139–141

    Article  Google Scholar 

  5. Virnig BA, Tuttle TM, Shamliyan T, Kane RL (2010) Ductal carcinoma in situ of the breast: a systematic review of incidence, treatment, and outcomes. JNCI 102(3):170–178

    Article  PubMed  Google Scholar 

  6. Allegra CJ, Aberle DR, Ganschow P, Hahn SM, Lee CN, Millon-Underwood S, Pike MC, Reed SD, Saftlas AF, Scarvalone SA et al (2010) National Institutes of Health State-of-the-Science Conference Statement: diagnosis and management of DCIS September 22–24, 2009. JNCI 102(3):161–169

    Article  PubMed  Google Scholar 

  7. Kerlikowske K, Molinaro A, Cha I, Ljung BM, Ernster VL, Stewart K, Chew K, Moore DH, Waldman F (2003) Characteristics associated with recurrence among women with DCIS treated by lumpectomy. JNCI 95(22):1692–1702

    Article  PubMed  Google Scholar 

  8. Ernster VL, Barclay J, Kerlikowske K, Wilkie H, Ballard-Barbash R (2000) Mortality among women with DCIS of the breast in the population-based SEER program. Arch Intern Med 160(7):953–958

    Article  CAS  PubMed  Google Scholar 

  9. Fisher B, Dignam J, Wolmark N, Mamounas E, Costantino J, Poller W, Fisher ER, Wickerham DL, Deutsch M, Margolese R et al (1998) Lumpectomy and radiation therapy for the treatment of intraductal breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-17. J Clin Oncol 16(2):441–452

    CAS  PubMed  Google Scholar 

  10. Welch HG, Woloshin S, Schwartz LM (2008) The sea of uncertainty surrounding ductal carcinoma in situ—the price of screening mammography. JNCI 100(4):228–229

    Article  PubMed  Google Scholar 

  11. Allred DC (2010) Ductal carcinoma in situ: terminology, classification, and natural history. JNCI Monogr 2010(41):134–138

    Article  Google Scholar 

  12. Sanders ME, Schuyler PA, Dupont WD, Page DL (2005) The natural history of low-grade DCIS of the breast in women treated by biopsy only revealed over 30 years of long-term follow-up. Cancer 103(12):2481–2484

    Article  PubMed  Google Scholar 

  13. Smith BD (2015) When is good enough really good enough? Defining the role of radiation in low-risk DCIS. JCO 33(7):686–691

    Article  Google Scholar 

  14. Ries L, Eisner M, Kosary C, Hankey B, Miller B, Clegg L, Edwards B (2000) SEER cancer statistics review, 1973–1997. In: Bethesda MD (ed) National Cancer Institute

  15. Worni M, Akushevich I, Greenup R, Sarma D, Ryser MD, Myers ER, Hwang ES (2015) Trends in treatment patterns and outcomes for ductal carcinoma in situ. J Natl Cancer Inst 107(12):djv263

    Article  PubMed  Google Scholar 

  16. Owen D, Tyldesley S, Alexander C, Speers C, Truong P, Nichol A, Wai ES (2013) Outcomes in patients treated with mastectomy for ductal carcinoma in situ. Int J Radiat Oncol Biol Phys 85(3):e129–e134

    Article  PubMed  Google Scholar 

  17. Harris JR, Morrow M (2009) Clinical dilemma of DCIS. JCO 27(32):5303–5305

    Article  Google Scholar 

  18. Partridge A, Adloff K, Blood E, Dees EC, Kaelin C, Golshan M, Ligibel J, de Moor JS, Weeks J, Emmons K et al (2008) Risk perceptions and psychosocial outcomes of women with ductal carcinoma in situ: longitudinal results from a cohort study. J Natl Cancer Inst 100(4):243–251

    Article  PubMed  Google Scholar 

  19. Rakovitch E, Franssen E, Kim J, Ackerman I, Pignol J-P, Paszat L, Pritchard K, Ho C, Redelmeier D (2003) A comparison of risk perception and psychological morbidity in women with ductal carcinoma in situ and early invasive breast cancer. Breast Cancer Res Treat 77(3):285–293

    Article  PubMed  Google Scholar 

  20. Silverstein M (2003) The USC/Van Nuys Prognostic Index for DCIS of the breast. Am J Surg 186(4):337–343

    Article  PubMed  Google Scholar 

  21. Kerlikowske K, Molinaro AM, Gauthier ML, Berman HK, Waldman F, Bennington J, Sanchez H, Jimenez C, Stewart K, Chew K et al (2010) Biomarker expression and risk of subsequent tumors after initial DCIS diagnosis. JNCI 102(9):627–637

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Solin LJ, Gray R, Baehner FL, Butler SM, Hughes LL, Yoshizawa C, Cherbavaz DB, Shak S, Page DL, Sledge GW et al (2013) A multigene expression assay to predict local recurrence risk for ductal carcinoma in situ of the breast. JNCI 105(10):701–710

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Tamimi R, Baer H, Marotti J, Galan M, Galaburda L, Fu Y, Deitz A, Connolly J, Schnitt S, Colditz G et al (2008) Comparison of molecular phenotypes of ductal carcinoma in situ and invasive breast cancer. Breast Cancer Res 10(4):R67

    Article  PubMed  PubMed Central  Google Scholar 

  24. Allred D, Harvey J, Berardo M, Clark G (1998) Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol 11(2):155–168

    CAS  PubMed  Google Scholar 

  25. Gauthier ML, Berman HK, Miller C, Kozakeiwicz K, Chew K, Moore D, Rabban J, Chen YY, Kerlikowske K, Tlsty TD (2007) Abrogated response to cellular stress identifies DCIS associated with subsequent tumor events and defines basal-like breast tumors. Cancer Cell 12(5):479–491

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Gray R (2014) cmprsk: Subdistribution analysis of competing risks. In: R package version 2.2, 7 edn

  27. Fine J, Gray R (1999) A proportional hazards model for the subdistribution of a competing risk. JASA 5:190–207

    Google Scholar 

  28. Lostritto K, Strawderman RL, Molinaro AM (2012) A partitioning deletion/substitution/addition algorithm for creating survival risk groups. Biometrics 68(4):1146–1156

    Article  PubMed  Google Scholar 

  29. Molinaro AM, Lostritto K, van der Laan M (2010) partDSA: deletion/substitution/addition algorithm for partitioning the covariate space in prediction. Bioinformatics 26(10):1357–1363

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Pepe MS, Mori M (1993) Kaplan-Meier, marginal or conditional probability curves in summarizing competing risks failure time data? Stat Med 12(8):737–751

    Article  CAS  PubMed  Google Scholar 

  31. Rakovitch E, Nofech-Mozes S, Hanna W, Baehner F, Saskin R, Butler S, Tuck A, Sengupta S, Elavathil L, Jani P et al (2015) A population-based validation study of the DCIS score predicting recurrence risk in individuals treated by breast-conserving surgery alone. Breast Cancer Res Treat 152(2):389–398

    Article  PubMed  PubMed Central  Google Scholar 

  32. Phipps A, Buist DM, Malone K, Barlow W, Porter P, Kerlikowske K, Li C (2011) Family history of breast cancer in first-degree relatives and triple-negative breast cancer risk. Breast Cancer Res Treat 126(3):671–678

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Li C, Beaber E, Tang M-T, Porter P, Daling J, Malone K (2013) Reproductive factors and risk of estrogen receptor positive, triple-negative, and HER2-neu overexpressing breast cancer among women 20–44 years of age. Breast Cancer Res Treat 137(2):579–587

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Esserman L, Shieh Y, Thompson I (2009) Rethinking screening for breast cancer and prostate cancer. JAMA 302(151):1685–1692

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

National Cancer Institute-funded: Research Grant (R01 CA163687) and University of California, San Francisco Breast Cancer SPORE (P50 CA58207); California Breast Cancer Research Program (2RB-0197). Technical support was received from the UCSF Cancer Center (P30 CA82103), UCSF Cancer Center Tissue and Immunohistochemistry Cores, and Northern California Surveillance, Epidemiology, and End Results Program.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Annette M. Molinaro.

Ethics declarations

Conflict of interest

The authors have no conflict of interest.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOCX 35 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Molinaro, A.M., Sison, J.D., Ljung, BM. et al. Risk prediction for local versus regional/metastatic tumors after initial ductal carcinoma in situ diagnosis treated by lumpectomy. Breast Cancer Res Treat 157, 351–361 (2016). https://doi.org/10.1007/s10549-016-3814-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-016-3814-z

Keywords

Navigation