What is stage zero DCIS (Ductal Carcinoma In Situ) and its treatment options?

What is Stage Zero DCIS (Ductal Carcinoma In Situ)?

Stage zero DCIS is a non-invasive breast neoplasia where abnormal epithelial cells proliferate within the breast ducts but remain confined by the basement membrane, representing an early, localized stage between atypical ductal hyperplasia and invasive ductal carcinoma. 1, 2

Definition and Biology

• DCIS sits on the spectrum of breast proliferative abnormalities as a pre-invasive condition where neoplastic cells have not breached the ductal basement membrane 1, 2
• The disease is biologically and morphologically heterogeneous, meaning not all DCIS lesions behave the same way 3, 4
• Approximately 25-60% of DCIS lesions will progress to invasive ductal carcinoma if left completely untreated 1, 5
• However, when appropriately treated, DCIS has an excellent prognosis with 10-year overall survival rates of 97.2-98.6% 1, 2

Clinical Presentation

• DCIS most commonly presents as mammographically detected microcalcifications in 90-98% of cases, typically pleomorphic and arranged in linear or segmental patterns 3, 1, 2
• About 10% present as uncalcified masses on mammography 1, 2
• Before widespread mammography screening, DCIS accounted for only 2-3% of breast cancers, but now represents approximately 20-25% of all screen-detected breast cancers in the United States 1, 2
• This translates to approximately 55,720-62,280 new cases diagnosed annually 1, 2

Diagnosis

• Definitive diagnosis requires pathologic evaluation of tissue specimen because imaging alone cannot determine whether the basement membrane has been invaded 1, 2
• A critical pitfall is underestimating occult invasive disease: 25.9% of cases diagnosed as pure DCIS on core biopsy are upstaged to invasive cancer at surgical excision 2

Treatment Options

The NCCN guidelines provide three primary treatment pathways: lumpectomy with whole-breast radiation, total mastectomy with or without sentinel node biopsy, and lumpectomy alone without radiation. 1

Surgical Approaches

• Breast-conserving surgery (BCS) without lymph node sampling is the current NCCN guideline recommendation 3
• There is no difference in overall survival between mastectomy and BCS for DCIS 2
• Total mastectomy provides maximum local control with approximately 1% chest wall recurrence risk but represents potential overtreatment for many patients 1
• Axillary lymph node dissection is not routinely recommended because the cumulative incidence of axillary node metastasis in patients diagnosed preoperatively with DCIS is low (0-14%) 2

Radiation Therapy

• Lumpectomy with whole-breast radiation reduces local recurrence risk by approximately 50-70% compared to lumpectomy alone 1, 2
• Randomized trials demonstrate that radiotherapy after BCS reduces ipsilateral breast tumor recurrence rates significantly 2
• The annualized recurrence rate for DCIS varies from 2-4.6% for surgery alone versus 1.4-2.5% for surgery with radiation therapy 3

Adjuvant Endocrine Therapy

• Tamoxifen 20 mg daily for 5 years is FDA-approved for DCIS following breast surgery and radiation to reduce the risk of invasive breast cancer 6
• In the NSABP B-24 trial, tamoxifen reduced invasive breast cancer incidence by 43% (relative risk 0.57,95% CI: 0.39-0.84, p=0.004) 6
• Tamoxifen specifically reduced ipsilateral invasive cancer from 10.6 per 1,000 women per year to 5.9 per 1,000 women per year 6
• The benefit is primarily seen in estrogen receptor-positive DCIS 1
• Tamoxifen also provides risk reduction in the contralateral breast 2, 6

Recurrence Patterns

• Following breast-conservation therapy, approximately 50% of recurrences manifest as invasive cancer and 50% as DCIS 1, 2, 4
• The mean time to recurrence is approximately 4.5 years, though recurrences can occur even after 5 years 3
• 75-80% of recurrences present mammographically as microcalcifications, often with similar morphology to the initial DCIS 3
• 90% of local recurrences involve the lumpectomy quadrant 3

Risk Factors for Progression

• Larger DCIS lesion size increases progression risk 1, 2
• Younger age at diagnosis is associated with higher risk 1, 2
• HER2 overexpression correlates with increased progression risk 1, 2
• Nuclear grade, presence of comedo necrosis, and margin involvement are commonly used predictors, though these remain imperfect 1, 4

Surveillance After Treatment

• Regular mammography is the primary surveillance modality, as 85-91% of recurrences are detected solely by mammography 3
• The annual risk of developing invasive recurrence is estimated at 0.86% (ipsilateral 0.53%, contralateral 0.30%) 3
• Long-term follow-up is essential as recurrences can occur beyond 5 years 3

Staging Workup

Routine staging with CT, PET, or bone scans is NOT recommended for DCIS. 3

• ASCO Choosing Wisely guidelines specifically advise against routine performance of PET, CT, and radionuclide bone scans in DCIS because unnecessary imaging leads to harm through radiation exposure, misdiagnosis, unnecessary invasive procedures, and overtreatment 3
• DCIS is considered low risk for metastasis, and there is no evidence demonstrating treatment benefit from staging imaging in asymptomatic individuals 3