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Preventing overtreatment in DCIS: Where do we stand?

Cristina Germond, PhD | October 18, 2017

While appropriate management of ductal carcinoma in situ (DCIS) is a continued topic of some controversy, strides are being made toward a clearer understanding of what qualifies as “appropriate.”1

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Patient reactions to the perceived threat from DCIS can fuel preference for treatment that is more extensive than necessary to maximize recurrence-free survival.

Snapshot of the controversy

DCIS is a noninvasive cancer of the milk ducts. The introduction of mammographic breast screening in the 1980s was originally intended for early detection of invasive disease, but it ushered in an exponential increase in DCIS detection.2 In the 1970s, the incidence of DCIS was 5.83 per 100,000—by 2011, that incidence had grown to 35.54 per 100,000.3 Data show a 290% increase in DCIS since 1983 among women younger than 50 years of age.4

Currently, DCIS is diagnosed in more than 60,000 patients each year in the US, and it accounts for 20% to 25% of new breast cancer diagnoses annually.5

As diagnosis has increased, so too has treatment. Standard treatment includes surgical excision (lumpectomy or mastectomy) with or without adjuvant radiation or hormone therapy; this regimen provides excellent survival outcomes.6 The catch is that the natural history of untreated DCIS is not well understood.7 DCIS is considered a non-obligate precursor to invasive disease. While there is no question that some cases of DCIS progress to invasive disease, not all cases do.8

Long-term follow-up studies of cases of DCIS that were misclassified as benign and left untreated showed that 20% to 53% of the cases were subsequently diagnosed as invasive cancer during the next 10+ years.9–13

These data emphasize the potential for untreated DCIS to become invasive. They also highlight the significant number of DCIS-diagnosed patients that do not progress to potentially life-threatening disease.

Current standard management approaches can negatively affect long-term health and quality of life, so overdiagnosis and overtreatment of DCIS (ie, diagnosis and treatment of patients whose DCIS would go undetected in the absence of screening) continue to be a topic of great concern.14

Heterogeneous disease

DCIS lesions are diverse in many ways, including nuclear grade, histology, size, and estrogen receptor status. Some of these factors may influence likelihood of progression to invasive cancer.15

For example, consider nuclear grade. Most cases of DCIS are detected as high grade (~50%). High-grade DCIS is more likely to progress to invasive disease if left untreated.16 Even so, some low-to-intermediate grade DCIS will also progress to invasive disease.17 The need for reliable prognostic markers to identify which DCIS will progress to invasive breast cancer is critical.

Addressing overtreatment today

Overtreatment is a recognized risk of DCIS, but it must be considered against the equally real risk of undertreatment until better prognostic markers become available.18 A recent article from experts Monica Morrow, MD, and Steven Katz, MD, MPH, highlights actions clinicians can take now to limit potential overtreatment of DCIS, such as the elimination of primary axillary dissection, the practice of judicial use of sentinel node biopsy with lumpectomy for DCIS, and an improvement in risk communication in patients.19

Patient reactions to the perceived threat from DCIS can fuel preference for treatment that is more extensive than necessary to maximize recurrence-free survival. For example, patient concern regarding recurrence can motivate medically unnecessary contralateral prophylactic mastectomy—these rates have sharply increased in recent years.20

Looking forward

The potential for alternative management strategies, such as surveillance, continue to draw great interest. To this end, ongoing trials in the US (COMET) and UK (LORIS, LORD) are evaluating the safety of active surveillance vs standard surgical management, with or without adjuvant therapy in low-risk DCIS (low-grade or intermediate-grade DCIS with low-grade features).21–23 Definitive answers are expected in 6 to 10 years.

In addition to showing the risk of progression to invasive cancer development over time, the studies will also include patient preference and comfort with observation as a therapy.24

References:

  1. Pilewskie ML. Is low risk DCIS really low risk? Memorial Sloan Kettering Cancer Center website. https://www.mskcc.org/clinical-updates/low-risk-dcis-really-low-risk. Accessed September, 2017.
  2. Francis A, Fallowfield L, Rea D. The LORIS Trial: Addressing overtreatment of ductal carcinoma in situ. Clin Oncol. 2015;27:6-8.
  3. Howlader N, Noone A, Krapcho M, et al. National Cancer Institute. SEER Cancer Statistics Review: 1975-2011. https://seer.cancer.gov/archive/csr/1975_2012/. Accessed September 2017.
  4. Kerlikowske K. Epidemiology of ductal carcinoma In Situ. J Natl Cancer Inst Monogr. 2010;2010(41):139-141.
  5. Pilewskie ML. Is low risk DCIS really low risk? https://www.mskcc.org/clinical-updates/low-risk-dcis-really-low-risk. Accessed September 2017.
  6. National Comprehensive Cancer Network. Breast Cancer. (Version2.2017.) https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. Accessed September 2017.
  7. Pilewskie ML. Is low risk DCIS really low risk? https://www.mskcc.org/clinical-updates/low-risk-dcis-really-low-risk. Accessed September 2017.
  8. Worni M, Akushevich I, Greenup R, et al. Trends in treatment patterns and outcomes for ductal carcinoma in situ. J Natl Cancer Inst. 2015;107(12):djv263.
  9. Collins LC, Tamimi RM, Baer HJ, Connolly JL, Colditz GA, Schnitt SJ. Outcome of patients with ductal carcinoma in situ untreated after diagnostic biopsy: results from the Nurses’ Health Study. 2005;103: 1778-1784.
  10. Allred DC. Ductal carcinoma in situ: terminology, classification, and natural history. J Natl Cancer Inst Monogr. 2010;2010: 134-138.
  11. Eusebi V, Feudale E, Foschini MP, et al. Long-term follow-up of in situ carcinoma of the breast. Seminars in Diagn Path. 1994;11: 223-235.
  12. Erbas B, Provenzano E, Armes J, Gertig D. The natural history of ductal carcinoma in situ of the breast: a review. Breast Cancer Res Treat. 2006;97: 135-144.
  13. Sanders ME, Schuyler PA, Dupont WD, Page DL. The natural history of low-grade ductal carcinoma in situ of the breast in women treated by biopsy only revealed over 30 years of long-term follow-up. 2005;103: 2481-2484.
  14. American Cancer Society. Cancer Facts & Figures 2015. Atlanta: American Cancer Society; 2015.
  15. American Cancer Society. Cancer Facts & Figures 2015. Atlanta: American Cancer Society; 2015.
  16. van Luijt PA, Heijnsdijk EA, Gracheboud J, et al. The distribution of ductal carcinoma in situ (DCIS) grade in 4232 women and its impact on overdiagnosis in breast cancer screening. Breast Cancer Res. 2016;18(1):47.
  17. Collins LC, Tamimi RM, Baer HJ, Connolly JL, Colditz GA, Schnitt SJ. Outcome of patients with ductal carcinoma in situ untreated after diagnostic biopsy: results from the Nurses’ Health Study. 2005;103: 1778-1784.
  18. Sagara Y, Mallory MA, Wong S, et al. Survival benefit of breast surgery for low-grade ductal carcinoma in situ: a Tapopulation-based cohort study. JAMA Surg. 2015;150(8):739-745.
  19. Morrow M, Katz SJ. Addressing overtreatment in DCIS: What should physicians do now? J Natl Cancer Inst. 2015; 107(12): djv290.
  20. Morrow M, Katz SJ. Addressing overtreatment in DCIS: What should physicians do now? J Natl Cancer Inst. 2015; 107(12): djv290.
  21. Francis A, Fallowfield L, Rea D. The LORIS Trial: Addressing overtreatment of ductal carcinoma in situ. Clin Oncol. 2015;27:6-8.
  22. gov. NCT012492607. https://clinicaltrials.gov/ct2/show/NCT02492607. Accessed September 2017.
  23. gov. NCT02926911. https://clinicaltrials.gov/ct2/show/NCT02926911. Accessed September 2017.
  24. Pilewskie ML. Is low risk DCIS really low risk? https://www.mskcc.org/clinical-updates/low-risk-dcis-really-low-risk. Accessed September 2017.

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