Ductal Carcinoma In Situ of the Breast

Ductal carcinoma in situ (DCIS) of the breast is a potentially invasive neoplasm. Risk factors include high estrogen states such as use of oral contraceptive (OC) pills, nulliparity, advanced age at first birth, and also family history and genetic mutations. The incidence of this usually clinically silent condition has risen in the past few decades due to widespread screening and diagnostic mammography, with final diagnosis confirmed by biopsy. At present, treatment options include total or simple mastectomy or lumpectomy with radiation. Adjuvant therapy includes antiestrogens like tamoxifen and human epidermal growth factor receptor 2 (HER2) suppression therapy. With the latest advances in chemotherapy and better understanding on the pathogenesis of the lesion, it is anticipated that more effective modalities of treatment may soon be available.     

The Diagnosis and Treatment of Ductal Carcinoma In Situ of the Breast

Abstract: Ductal carcinoma in situ of the breast is the most favorable presentation of breast cancer; therefore appropriate local treatment is imperative. Intraductal carcinoma is being diagnosed more frequently with the increasing use of screening mammography. A number of pathologic features have been identified which are useful for classification and for prognostic information. In addition, the molecular pathology and its relationship to tumor behavior and prognosis is becoming more well understood. The role of axillary dissection has been examined in a number of series and is generally agreed to be unnecessary for this presentation of breast cancer, allowing many women to avoid the sequela of axillary surgery. This review discusses the use of breast conservation treatment and the evolving indications for excision alone in the treatment of ductal carcinoma in situ. The outcomes for breast conservation therapy from both randomized trials and institutional series have confirmed excellent survival rates. Salvage therapy for local recurrence is frequently successful, resulting in nearly equivalent survivals in women undergoing breast conservation therapy compared to mastectomy. In addition, intriguing but preliminary results from both breast cancer prevention studies and trials looking at the use of tamoxifen for intraductal cancer suggest a local control benefit in women using the drug.     

Targeted Intraoperative Radiotherapy for the Management of Ductal Carcinoma In Situ of the Breast

Multiple long‐term studies have demonstrated a propensity for breast cancer recurrences to develop near the site of the original breast cancer. Recognition of this local recurrence pattern laid the foundation for the development of accelerated partial breast irradiation (APBI) approaches designed to limit the radiation treatment field to the site of the malignancy. However, there is a paucity of data regarding the efficacy of APBI in general, and intraoperative radiotherapy (IORT), in particular, for the management of ductal carcinoma in situ (DCIS). As a result, use of APBI, remains controversial. A prospective nonrandomized trial was designed to determine if patients with pure DCIS considered eligible for concurrent IORT based on preoperative mammography and contrast‐enhanced magnetic resonance imaging (CE‐MRI) could be successfully treated using IORT with minimal need for additional therapy due to inadequate surgical margins or excessive tumor size. Between November 2007 and June 2014, 35 women underwent bilateral digital mammography and bilateral breast CE‐MRI prior to selection for IORT. Patients were deemed eligible for IORT if their lesion was ≤4 cm in maximal diameter on both digital mammography and CE‐MRI, pure DCIS on minimally invasive breast biopsy or wide local excision, and considered resectable with clear surgical margins using breast‐conserving surgery (BCS). Postoperatively, the DCIS lesion size determined by imaging was compared with lesion size and surgical margin status obtained from the surgical pathology specimen. Thirty‐five patients completed IORT. Median patient age was 57 years (range 42–79 years) and median histologic lesion size was 15.6 mm (2–40 mm). No invasive cancer was identified. In more than half of the patients in our study (57.1%), MRI failed to detect a corresponding lesion. Nonetheless, 30 patients met criteria for negative margins (i.e., margins ≥2 mm) whereas five patients had positive margins (<2 mm). Two of the five patients with positive margins underwent mastectomy due to extensive imaging‐occult DCIS. Three of the five patients with positive margins underwent successful re‐excision at a subsequent operation prior to subsequent whole breast irradiation. A total of 14.3% (5/35) of patients required some form of additional therapy. At 36 months median follow‐up (range of 2–83 months, average 42 months), only two patients experienced local recurrences of cancer (DCIS only), yielding a 5.7% local recurrence rate. No deaths or distant recurrences were observed. Imaging‐occult DCIS is a challenge for IORT, as it is for all forms of breast‐conserving therapy. Nonetheless, 91.4% of patients with DCIS were successfully managed with BCS and IORT alone, with relatively few patients requiring additional therapy.     

Clinical Outcome after Selective Treatment of Patients Diagnosed with Ductal Carcinoma In Situ of the Breast

Background The effect of treatment of patients diagnosed with ductal carcinoma in situ (DCIS) of the breast was evaluated, and factors associated with local recurrence were assessed. Methods The study involved 504 patients treated by means of wide local excision alone (WLE) (n = 91), wide local excision and radiotherapy (WLE+RT) (n = 119), or mastectomy (n = 294) at the Netherlands Cancer Institute between 1986 and 2005. Clinical, pathological, and follow-up data were evaluated. Results The median time to follow-up was 6.7 years. The 8-year overall local recurrence rate was 12% after breast-conserving treatment (BCT) [15.6% after WLE and 8.8% after WLE+RT (P = 0.161)] and 0.9% after mastectomy (P < 0.0001). In total, 18 (66.7%) invasive local recurrences and 9 (33.3%) DCIS local recurrences occurred. The 8-year distant metastasis rate was 4% after BCT [4.3% after WLE and 4.2% after WLE+RT (P = 0.983)] and 0.9% after mastectomy (P = 0.048). Median tumor extent was 10, 15, and 35 mm for patients treated with WLE, WLE+RT, and mastectomy, respectively. Margins were involved in 6.4% of all patients. Factors associated with local recurrence were age younger than 40 years (HR 8.66), surgical margin involvement (HR 5.75), WLE (HR 26.77), and WLE+RT (HR 7.42). Conclusion BCT of DCIS bears the risk of residual disease progressing into invasive local recurrence and distant metastasis. A re-excision or mastectomy is therefore desired in all patients with unclear margins. Mastectomy treatment is associated with optimal local control and might be considered for patients younger than 40 years who are at high risk of local recurrence.     

Ductal Carcinoma In Situ with Microinvasion

Abstract: The natural history of patients with ductal carcinoma in situ (DCIS) and microinvasion is poorly defined and the clinical management of these patients, with particular reference to management of the axilla, has been controversial. Studies addressing this lesion have used highly varied and sometimes arbitrary criteria for the evaluation of microinvasion. At the Armed Forces Institute of Pathology, we have defined microinvasion as a single focus of invasive carcinoma ≤ 2 mm or up to three foci of invasion, each ≤ 1 mm in greatest dimension. Such minuscule invasive carcinomas are apparently rare, accounting for considerably less than 1% of cases of breast carcinoma reviewed in consultation at our institution. To determine the frequency of axillary lymph node metastases associated with this lesion, we retrospectively reviewed 38 cases of DCIS with microinvasion (n= 29) or probable microinvasion (n= 9), all treated with mastectomy and axillary node dissection between 1980 and 1996. The foci of microinvasion ranged from 0.25 to 1.75 mm (mean 0.6 mm) in greatest dimension and were present adjacent to DCIS in 95.3% of cases. The extent of DCIS did not correlate with the number of foci of microinvasion. Axillary node dissections yielded a mean of 19.3 lymph nodes (range 7-38) and all lymph nodes were negative for metastatic tumor. None of 33 patients, followed for a mean of 7.5 years (range 1.0-14.4 years), developed local recurrence or metastasis. While the cases of microinvasive carcinoma evaluated in this study were not associated with axillary node metastases and appear to have an excellent prognosis, further study is indicated to determine the appropriate management and long-term prognosis of patients with this lesion.     

Apoptosis in Ductal Carcinoma in Situ of the Breast

Abstract: Programmed cell death (apoptosis) may play a role in tumor development and progression. The importance of apoptosis dysregulations in ductal carcinoma in situ (DCIS) and its relationships with p53 mutations and expression of bcl-2 has received little attention in the literature. In a series of 58 DCIS patients, we evaluated the number of apoptotic cells by the TUNEL technique in subgroups of DCIS and correlated it with immunohistochemical expression of hormone receptors, c- erb B-2, p53, bcl-2, and Ki-67 (MIB-1) and DNA content measured by image cytometry. High apoptotic index (greater than 3%) was related to high tumor grade, negative hormone receptors, c- erb B-2 overexpression, aneuploidy and lack of bcl-2 immunohistochemical stain. Apoptosis was not related to p53 or proliferative index. The findings are similar to those found in infiltrating breast cancer.     

Characterization and Treatment of Local Recurrence Following Breast Conservation for Ductal Carcinoma In Situ

Purpose

The optimal treatment strategy for ductal carcinoma in situ (DCIS) continues to evolve and should consider the consequences of initial treatment on the likelihood, type, and treatment of recurrences.

Methods

We conducted a retrospective cohort study using two data sources of patients who experienced a recurrence (DCIS or invasive cancer) following breast-conserving surgery (BCS) for index DCIS: patients with an index DCIS diagnosed from 1997 to 2008 at the academic institutions of the National Comprehensive Cancer Network (NCCN; N = 88) and patients with an index DCIS diagnosed from 1990 to 2001 at community-based integrated healthcare delivery sites of the Health Maintenance Organization Cancer Research Network (CRN) (N = 182).

Results

Just under half of local recurrences in both cohorts were invasive cancer. While 40 % of patients in both cohorts underwent mastectomy alone at recurrence, treatment of the remaining patients varied. In the earlier CRN cohort, most other patients underwent repeat BCS (39 %) with only 18 % receiving mastectomy with reconstruction, whereas only 16 % had repeat BCS and 44 % had mastectomy with reconstruction in the NCCN cohort. Compared with patients not treated with radiation, those who received radiation for index DCIS were less likely to undergo repeat BCS (NCCN: 6.6 vs. 37 %, p = 0.001; CRN: 20 vs. 48 %, p = 0.0004) and more likely to experience surgical complications after treatment of recurrence (NCCN: 15 vs. 4 %, p = 0.17; CRN: 40 vs. 25 %, p = 0.09).

Conclusion

We found that treatment of recurrences after BCS and subsequent complications may be affected by the use of radiotherapy for the index DCIS. Initial treatment of DCIS may have long-term implications that should be considered.     

Effect of MRI on the Management of Ductal Carcinoma In Situ of the Breast

Introduction

The accuracy of breast magnetic resonance imaging (MRI) for detection of ductal carcinoma in situ (DCIS) has prompted recommendations for its routine preoperative use, but its clinical benefit is debated. We reviewed our experience with MRI in DCIS patients to assess the utility of MRI for surgical planning.

Methods

DCIS patients (2008–2010) were identified through a prospectively maintained database and grouped into MRI and no-MRI groups. The rates of additional biopsies, altered surgical management, and reoperation were compared. Additionally, DCIS size ascertained by mammography, MRI, and final pathology was compared.

Results:

Of 352 DCIS patients, 217 received MRI and 135 did not. The type of initial operation and number of reoperations were similar between the two groups, but successful breast conservation was more frequent in the no-MRI group (p = 0.06). The additional biopsy rate was 38 % in the MRI group versus 7 % in the no-MRI group; ≥2 additional biopsies were performed in 18 % of the MRI group and 2 % of the no-MRI group (p < 0.0001). These yielded a cancer diagnosis in 26 % of MRI and 33 % of no-MRI patients (p = 0.73). MRI was not superior to mammogram in detecting size of DCIS lesions preoperatively; 52 % of mammograms were accurate (within 1 cm) compared with 41 % of MRIs.

Conclusions

DCIS patients who undergo preoperative breast MRI are far more likely to undergo additional biopsies. Unless these can be demonstrated to lead to improved long-term outcomes, the utility of routine preoperative MRI in DCIS patients remains questionable.     

Ductal Carcinoma In Situ of the Breast: The Van Nuys Experience by Treatment

Abstract: Ductal carcinoma in situ (DCIS) represents a broad biologic spectrum of disease with a wide range of treatment approaches. A lack of clear and universally accepted treatment criteria has resulted in a diverse range of confusing clinical recommendations, distressing to both patients and clinicians. Data is presented on 543 patients treated at The Breast Center in Van Nuys, California: 228 by mastectomy, 185 by excision plus radiation therapy, and 130 by excision alone. The local recurrence-free survival at 5 years was 98% for mastectomy patients, 87% for those who received excision plus radiation therapy, and 79% for those treated with excision alone. The difference between each of the recurrence-free survival curves was statistically significant. Margin width was an important predictor of which breast preservation patients were most likely to benefit from postexcisional radiation therapy. There was no benefit from the addition of radiation therapy for patients with margin widths of 10 mm in every direction. The benefit was intermediate for patients with margin widths of 1–9 mm. Patients with margin widths less than 1 mm received the most benefit from postoperative radiation therapy. Radiation therapy is not without side effects and it should not be routinely added to every breast preservation patient's therapeutic plan. Careful consideration must be given to its risks versus its potential benefits. Numerous prognostic factors, such as nuclear grade, the presence of comedo-type necrosis, tumor size, and margin width can all be used to aid in the treatment decision-making process.     

An Overview of the History and Epidemiology of Ductal Carcinoma In Situ of the Breast

Abstract: Since the first pathologic studies of breast cancer were undertaken in the nineteenth century, an intraepithelial stage has been recognized in the transition from normal tissue to invasive cancer. In 1932 this was labeled in situ breast carcinoma, but was rarely diagnosed and considered only a clinical oddity. With the establishment of screening mammography over the past 20 years, both the ductal and lobular types of in situ breast carcinoma have been increasingly diagnosed. The lobular variant, lobular carcinoma in situ (LCIS), is now considered a marker of risk for subsequent invasive cancer, and is managed expectantly without surgical ablation. The ductal form, ductal carcinoma in situ (DCIS), is considered a true premalignant lesion, which should be treated largely in the same way as invasive breast carcinoma. An understanding of the epidemiology and biologic implications of DCIS is necessary for a rational approach to treatment.     

Factors Affecting Successful Breast Conservation for Ductal Carcinoma in Situ

Background Successful breast-conserving therapy in DCIS is restricted by high rates of residual disease resulting in the need for radiotherapy and/or re-excision. This study identifies patients with DCIS who are most at risk of compromised margins and of residual disease. Methods All patients undergoing breast-conserving surgery for DCIS over a 6-year period were included. Method of diagnosis, mammographic size, pathological size, DCIS-margin distance and residual disease on re-excision were analysed. Results One hundred and thirty-five patients underwent initial breast-conserving surgery for DCIS. The compromised margin rate was 72%, and the rate of residual disease on re-operation was 54%. On univariate analysis, underestimation of pathological size by mammography by >1 cm occurred in 40% of those with compromised margins undergoing a therapeutic operation compared to only 14% of those with clear margins (P = 0.02). However, on multivariate analysis only pathological size (P < 0.0001, OR = 1.0,95% CI 1.037–1.128) and lack of a preoperative diagnosis by core biopsy (P < 0.0001, OR = 5.3,95% CI 1.859–15.08) were predictive of compromised margins. The presence of residual disease on re-excision was associated with increasing pathological size (P < 0.0001, OR = 1.085,95% CI 1.038–1.134) and decreasing DCIS-margin distance (P = 0.03, OR = 6.694,95% CI 1.84–37.855). Twenty-nine percent (n = 13/45) of lesions ≤3 cm compared to 84% (n = 27/32) of lesions >3 cm had residual disease on re-operation (P < 0.0001). Residual disease was present in 62% (n = 34/55), 64% (n = 7/11) and 17% (n = 2/12) of patients with DCIS-margin distances ≤1, 1–2 and 2–5 mm, respectively. Conclusion Considerable underestimation of DCIS extent by mammography occurs in a high proportion of patients with compromised margins in breast conservation. Patients at particularly high risk of residual disease on re-excision are those with lesions >3 cm and those with DCIS-margin distances of ≤ 2mm.     

Local Recurrence After Mastectomy for Ductal Carcinoma In Situ

Abstract: Local recurrence after mastectomy for invasive cancer generally carries a poor prognosis. Local recurrence after mastectomy for ductal carcinoma in situ (DCIS) is rare and its impact on survival is unknown. Sixty-eight patients were treated with mastectomy for DCIS at the Fox Chase Cancer Center between 1985 and 1996, and only one of these developed a chest wall recurrence. An additional five patients treated with mastectomy at other institutions and referred to Fox Chase after local recurrence were also identified. These six patients had only DCIS as their primary pathology. Four of the six patients were premenopausal (median age 42 years). The median interval to local recurrence was 5.0 years (2.8–9.3 years). The median follow-up from initial diagnosis was 10.5 years (4.3–26.7 years) and 5.2 years (1.4–17.6 years) from recurrence. All of the recurrences were invasive and treatment included wide local excision with radiotherapy in all of the patients followed by adjuvant chemotherapy for the premenopausal patients. None of the patients had metastatic disease at presentation. The disease-free survival from initial recurrence was 83% and 63% at 5 and 10 years, respectively. The 5- and 10-year survival following local recurrence was 80%. One patient died 3.6 years after recurrence with metastatic disease, while a second patient developed metastatic disease 11.8 years after her initial recurrence. The remaining four patients are alive (NED), ranging from 1.4 to 10.7 years following their local recurrence. Local recurrence following mastectomy for DCIS is rare, usually invasive, and may have a long interval to failure. Salvage using conventional multimodality therapy appears to result in long-term survival.