ILLUSTRATIVE CASE SERIES

Ductal Carcinoma in Situ

By Jerome Yates, MD, Hematology/Immunology Unit, National Institute on Aging, NIH. Dr. Yates reports no financial relationships relevant to this field of study.

A 57-year-old, postmenopausal African American schoolteacher was found by annual screening mammogram to have a suspicious irregularity. Follow-up ultrasound did not reveal cystic disease so a repeat "spot" mammogram-assisted biopsy was obtained and a grade 1 invasive ductal carcinoma with tubular elements was found. A lumpectomy was performed confirming these results, but in addition there were elements consistent with non-contiguous ductal carcinoma in situ (DCIS). The carcinoma was 0.7 x 1 cm in size and surgical margins were > 1 cm. A sentinel node biopsy was negative and the tumor was ER+, PR+, and Her2Neu-. Subsequent discussions included the rationale for different treatment options, including bilateral mastectomy with reconstruction, whole breast radiation to the involved breast, and adjuvant chemotherapy and/or anti-estrogen therapy. The most critical issue discussed was the question of bilateral mastectomy or whole breast radiation in light of the DCIS. Subsequent systemic therapy was expected.

Case Discussion

There has been a significant increase in the diagnosis of DCIS since the widespread application of screening mammography. Although this patient demonstrates the coexistence of invasive breast cancer (IBC) and DCIS, population studies have raised questions about the progression of all DCIS to IBC.1 If a large portion of the patients with DCIS progressed to IBC in months to a few years, there would be a major increase in the incidence (new cases) of IBC. The SEER data reflect both an increase in new cases of localized IBC and DCIS since about 1985. Even though the detection and treatment of DCIS has increased dramatically since that time, there has not been a concomitant decrease in IBC, suggesting that either the progression of DCIS occurs in a small number of cases or that the time period for the evolution of IBC from DCIS is much longer than even a period of 5 or 10 years. Mortality from IBC is low among women diagnosed with DCIS with a range of 1% to 2.6% in the 10 years following diagnosis.2 Treatment for DCIS is aggressive: surgery that often is disfiguring, radiation that carries some long-term risks, and the expense and inconvenience of adjuvant hormonal therapy. Just as the need for sub-classifying IBC is driving many laboratories and statisticians to find a molecular signature for indolent, intermediate, and aggressive disease to minimize iatrogenic treatment complications while maximizing treatment for aggressive disease, the same principle holds for the pursuit of a better understanding of the biology of DCIS.

Our understanding of the biology of breast cancer, relevant prognostic variables, and the hazards of overtreatment took us from the Halstead era through the urban ultra-radical mastectomy period and into the subtraction (less surgery) and addition (chemotherapy) phase that we are all familiar with today. Clinical trials conducted by the NSABP, including B-17 and B-24, have provided insight into the importance of radiation and hormonal therapy following breast conserving surgery.3 There is evidence from randomized trials that radiation following breast-conserving therapy for DCIS will reduce the local recurrence by 53% to 70%.4,5 The absolute reduction in the local recurrence from 5 years of tamoxifen administration is in the range of 2%-4% and, considering the vagaries of DCIS progression to IBC, may not be justified or accepted by the patients.

The study of DCIS characteristics as indicators of local recurrence following therapy include comedonecrosis (cell ghosts that attract calcium producing the flecks of density on mammograms), focality, surgical margins, method of detection, and tumor grade and size.6 These clinical indicators will be refined and supplemented with statistical precision and augmented by new molecular predictors of DCIS that will progress to IBC. The stratification of patients in studies of therapeutic approaches will improve our understanding of the merits of treatments. It is hoped this will lead to less aggressive interventions promoting quality-of-life issues in a disease that is being overtreated presently.

After discussions with her physician and her family, this patient elected not to have bilateral mastectomy followed by reconstruction, but instead whole breast radiation followed by mammograms every 6 months for the first 2 years. In light of our current understanding of DCIS, this seems like a rational approach.

References

1. Ozanne EM, et al. Characterizing the impact of 25 years of DCIS treatment. Breast Cancer Res Treat 2011;129:165-173.

2. Kerlikowske K. Epidemiology of ductal carcinoma in situ. J Natl Cancer Inst Monogr 2010;41:139-141.

3. Wapnir IL, 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;103:478-488.

4. Kane R. The impact of surgery, radiation, and systemic treatment on outcomes in patients with ductal carcinoma in situ. J Natl Cancer Inst Monogr 2010;41:130-133.

5. Motwani SB, et al. Ductal carcinoma in situ treated with breast-conserving surgery and radiotherapy: A comparison with ECOG study 5194. Cancer 2011;117:1156-1162.

6. Wang SY, et al. Tumor characteristics as predictors of local recurrence after treatment of ductal carcinoma in situ: a meta-analysis. Breast Cancer Res Treat 2011;127: 1-14.