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Imaging Features of Patients Undergoing Active Surveillance for Ductal Carcinoma in Situ

Posted Oct 31, 2017 Updated Apr 10, 2023
By Lars J. Grimm MD MHS , Sujata V. Ghate MD , E. Shelley Hwang MD MPH , Mary Scott Soo MD
13 min read

Rationale and Objectives

The aim of this study was to describe the imaging appearance of patients undergoing active surveillance for ductal carcinoma in situ (DCIS).

Materials and Methods

We retrospectively identified 29 patients undergoing active surveillance for DCIS from 2009 to 2014. Twenty-two patients (group 1) refused surgery or were not surgical candidates. Seven patients (group 2) enrolled in a trial of letrozole and deferred surgical excision for 6–12 months. Pathology and imaging results at the initial biopsy and follow-up were recorded.

Results

In group 1, the median follow-up was 2.7 years (range: 0.6–13.9 years). Fifteen patients (68%) remained stable. Seven patients (32%) underwent additional biopsies with invasive ductal carcinoma diagnosed in two patients after 3.9 and 3.6 years who developed increasing calcifications and new masses. In group 2, one patient (14%) was upstaged to microinvasive ductal carcinoma at surgery. Among the patients in both groups with calcifications ( n = 26), there was no progression to invasive disease among those with stable (50%, 13/26) or decreased (19%, 5/26) calcifications.

Conclusions

Among a DCIS active surveillance cohort, invasive disease progression presented as increasing calcifications and a new mass following more than 3.5 years of stable imaging. In contrast, there was no progression to invasive disease among cases of DCIS with stable or decreasing calcifications. Close imaging is a key follow-up component in active surveillance.

Introduction

Since the widespread adoption of screening mammography, the detection of ductal carcinoma in situ (DCIS) has steadily increased, now representing 20%–30% of all new breast cancer diagnoses . Although DCIS is very common, the natural history of the disease is not well known because complete surgical excision is currently the standard of care . However, there is strong circumstantial evidence that 50%–85% of DCIS cases will never progress to invasive disease , and if DCIS does progress, it is unlikely to shift to a higher nuclear grade . This finding has prompted growing concerns regarding DCIS overdiagnosis and overtreatment with a desire for alternative management strategies .

Active surveillance is a management strategy for low-risk DCIS, which avoids surgical excision, may utilize hormonal therapy to suppress growth, and emphasizes imaging follow-up to detect whether progression to invasive disease occurs . Active surveillance is based on the premise that not all DCIS cases are life threatening and that many patients may die with the disease than from the disease, especially those with competing mortality risks . The safety and effectiveness of active surveillance have been identified as a key research need by the Patient-Centered Outcomes Research Institute and the National Institutes of Health Panel on the Diagnosis and Management of Ductal Carcinoma In Situ . There is only one published manuscript of active surveillance outcomes, which demonstrated feasibility among a well-informed patient population but an increased risk of invasive cancer at surgical excision . There are three active surveillance trials in progress. The LOw Risk DCIS (LORD) trial in Europe compares annual mammography to usual care among women with low-grade DCIS with the primary outcome of ipsilateral invasive cancer . In England, the LOw RISk DCIS (LORIS) trial is comparing annual mammography to usual care among non–high grade DCIS with the primary outcome of ipsilateral invasive cancer-free survival . In the United States, the Comparison of Operative to Monitoring and Endocrine Therapy (COMET) trial is comparing endocrine therapy with biannual mammography vs usual care with ipsilateral invasive cancer diagnosis as the primary outcome .

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Materials and Methods

Case Selection

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Medical Record Review

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Imaging Review

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Results

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Table 1

Patient Demographics and DCIS Characteristics Among Patients Undergoing Active Surveillance Because of Medical Comorbidities or Personal Preference (Group 1) and as Part of a Single-arm Trial of Letrozole for 6–12 Months Followed by Surgical Excision (Group 2)

Group 1

n (%) Group 2

Mean (Range)/ n (%) Total 22 7 Age at diagnosis (y, mean [range]) 61.1 (40.8–88.8) 62.5 (50.8–70.6) Race White or Caucasian 13 (59) 5 (71) Black or African American 3 (14) 2 (29) Unavailable or other 6 (28) 0 (0) Follow-up duration (y, median [range]) 2.7 (0.6–13.9) 0.8 (0.6–0.9) Imaging presentation Calcifications on MG 19 (86) 7 (100) Nonmass enhancement on MRI 2 (9) 0 (0) Focal asymmetry on MG 1 (5) 0 (0) Tumor grade Low 1 (5) 0 (0) Intermediate 11 (50) 3 (43) High 9 (41) 4 (57) Missing 1 (5) 0 (0) ER status Positive 20 (91) 7 (100) Negative 0 (0) 0 (0) Missing 2 (9) 0 (0) PR status Positive 15 (68) 5 (71) Negative 5 (23) 2 (29) Missing 2 (9) 0 (0) Hormonal therapy Letrozole 9 (41) 7 (100) Tamoxifen 7 (32) 0 (0) None 6 (27) 0 (0)

ER, estrogen receptor; MG, mammography; MRI, magnetic resonance imaging; PR, progesterone receptor.

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Figure 1, Flowchart of active surveillance outcomes. Group 1 includes patients who refused surgery or were not surgical candidates. Group 2 includes patients enrolled in a trial that deferred surgery for 6–12 months during treatment with letrozole. DCIS, ductal carcinoma in situ; IDC, invasive ductal carcinoma.

Table 2

Imaging Features and Outcomes of Patients Who Underwent Additional Biopsies During Active Surveillance

Patient Initial DCIS Pathology Initial Imaging Appearance Therapy Change Prompting Biopsy Follow-up Time (y) Biopsy Results Subsequent Plan 1 ER+, PR+, high grade MG: 5.4 cm of pleomorphic, segmental calcifications Letrozole MG: increased calcifications (6.8 cm) and new mass (0.8 cm) 3.9 IDC: ER+, PR+, HER2+, high grade Lumpectomy: 3.0 cm of IDC 2 ER+, PR+, high grade MG: 6.5 cm of pleomorphic, segmental calcifications Letrozole MG: increased calcifications (8.5 cm) and new mass (1.8 cm) 3.6 IDC: ER+, PR+, HER2−, high grade Mastectomy: 3.0 cm of IDC 3.1 † ER+, PR−, intermediate grade MRI: 1.5 cm (largest site) of clumped, multiple regions of NME Tamoxifen MRI: increased size of one site of NME (1.4 cm, previously 0.7 cm) 4.3 “Benign” \* Return to active surveillance 3.2 † MG: increased number of calcifications 5.2 DCIS: ER+, PR+ Return to active surveillance 3.3 † MRI: new site (0.8 cm) of NME 6.8 Flat epithelial atypia Return to active surveillance—12.9 years of follow-up 4.1 † ER+, PR+, intermediate grade MG: 5.6 cm of pleomorphic, linear calcifications Tamoxifen MRI: new mass (0.9 cm) 0.7 Atypical ductal hyperplasia Return to active surveillance 4.2 † MRI: increased size of mass (1.0 cm) in 4.1 2.5 DCIS: ER+, PR+, high grade Return to active surveillance 4.3 † US: new mass (0.7 cm) 3.3 Stromal fibrosis Return to active surveillance—8.5 years of follow-up 5 ER+, PR−, high grade MG: 3.2 cm of linear, segmental calcifications Letrozole US: new mass (1.0 cm) 1.5 Atypical papilloma Return to active surveillance—3.0 years of follow-up 6 ER+, PR−, high grade MRI: 3.7 cm of clumped, regional NME Letrozole MRI: increased NME (4.7 cm)

US: mass (0.9 cm) 0.5 Atypia suspicious for DCIS Return to active surveillance—1.5 years of follow-up 7 ER and PR missing, intermediate grade MG: 8.0 cm of amorphous, regional calcifications None MG: stable calcifications, questionable asymmetry per the referring surgeon 0.3 Atypical ductal and lobular hyperplasia Return to active surveillance—0.4 years of follow-up

DCIS, ductal carcinoma in situ; ER, estrogen receptor; HER2, human epidermal growth factor receptor 2; IDC, invasive ductal carcinoma; MG, mammogram; MRI, magnetic resonance imaging; NME, nonmass enhancement; PR, progesterone receptor; US, ultrasound.

Note: Measurements refer to the long axis.

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Figure 2, Mammogram and ultrasound images of a 69-year-old woman with ER-positive, PR-positive, high-grade DCIS. (a) Initial postbiopsy mammogram reveals 5.4 cm of residual calcifications with a biopsy marking clip and distortion representing postbiopsy changes. (b) Follow-up mammogram 3.9 years later reveals that calcifications have increased to 6.8 cm with the development of a new 8-mm mass posteriorly ( arrow ). (c) Corresponding ultrasound image confirms the presence of a new mass. Subsequent biopsy and lumpectomy revealed 3.0 cm of high-grade, ER-positive, PR-positive, and human epidermal growth factor receptor 2-positive IDC with surrounding DCIS. DCIS, ductal carcinoma in situ; ER, estrogen receptor; IDC, invasive ductal carcinoma; PR, progesterone receptor.

Figure 3, Mammogram images of a 61-year-old woman with ER-positive, PR-positive, high-grade DCIS. (a) Prebiopsy mammogram reveals 5.8 cm of calcifications. The patient was treated with letrozole and underwent surveillance imaging with mammography and MRI was performed. (b) While initially undergoing yearly mammograms and MRI, the patient was lost to follow-up for 2.5 years, when the subsequent mammogram at 3.6 years reveals calcifications have increased to 8.5 cm and a new 1.8-cm mass (arrow). Stereotactic biopsy of the mass and subsequent mastectomy revealed 3.0 cm of high-grade, ER-positive, PR-positive, human epidermal growth factor receptor 2-negative invasive ductal carcinoma with surrounding DCIS and positive lymph nodes. DCIS, ductal carcinoma in situ; ER, estrogen receptor; MRI, magnetic resonance imaging; PR, progesterone receptor.

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Figure 4, MRI images of a 50-year-old woman with ER-positive, PR-positive, intermediate-grade ductal carcinoma in situ that presented as pleomorphic segmental calcifications on mammography (a) and as nonmass enhancement on MRI. (b) The patient was placed on letrozole, and a follow-up MRI performed 6 months later demonstrated a stable nonmass enhancement. Subsequent lumpectomy revealed an ER-positive, PR-negative, human epidermal growth factor receptor 2-negative, low-grade microinvasive ductal carcinoma measuring less than 1 mm. ER, estrogen receptor; MRI, magnetic resonance imaging; PR, progesterone receptor.

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Discussion

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Progression to Invasive Disease

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Underestimation of the Disease

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Changes to Calcifications Over Time

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Limitations

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Conclusions

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Academic Radiology, Volume 24, Issue 11
Journals General Radiology
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