Ductal Carcinoma in Situ (Stage 0, Tis, N0, M0)
The recommended workup and staging of DCIS includes: history and physical examination; bilateral diagnostic mammography; pathology review; and tumor ER determination.
Genetic counseling is recommended if the patient is considered to be at high risk for hereditary breast cancer as defined by the NCCN Guidelines for Genetic/Familial High-Risk Assessment: Breast and Ovarian.
Although HER2 status is of prognostic significance in invasive cancer, its importance in DCIS has not been elucidated.
To date, studies have either found unclear or weak evidence of HER2 status as a prognostic indicator in DCIS.
The NCCN Panel concluded that knowing the HER2 status of DCIS does not alter the management strategy and routinely should not be determined.
MRI has been prospectively shown to have a sensitivity of up to 98% for high-grade DCIS.
In a prospective, observational study, 193 women with pure DCIS underwent both mammography and MRI imaging preoperatively; 93 (56%) women were diagnosed by mammography and 153 (92%) were diagnosed by MRI (P < .0001).
Of the 89 women with high-grade DCIS, 43 (48%) who were not diagnosed by mammography were diagnosed by MRI alone.
Another study evaluated the role of MRI in determining appropriate candidacy for partial breast irradiation for women with DCIS.
Twenty percent of women with DCIS were identified as ineligible for partial breast irradiation after a bilateral breast MRI.
However, large prospective clinical trials will be necessary to further investigate the clinical role of MRI for diagnosing DCIS and to investigate its effect on recurrence rates or mortality.
The NCCN Panel has included breast MRI as optional during the initial workup of DCIS, noting that the use of MRI has not been shown to increase likelihood of negative margins or decrease conversion to mastectomy with DCIS.
Seemingly pure DCIS on core needle biopsy will be found to be associated with an invasive cancer on surgical excision in about 25% of 47 patients.
For the vast majority of patients with limited disease where negative margins are achieved with the initial excision or with re-excision, lumpectomy or total mastectomy are appropriate treatment options.
Although mastectomy provides maximum local control, the long-term, cause-specific survival with mastectomy appears to be equivalent to that with excision and whole breast irradiation.
Patients with DCIS and evidence of widespread disease (ie, disease in two or more quadrants) on mammography or other imaging, physical examination, or biopsy require a total mastectomy without lymph node dissection.
Many factors impact recurrence risk, including patient age, tumor size, tumor grade, and margin width.
The definition of a negative margin has not been firmly established in DCIS.
There appears to be a consensus that margins greater than 10 mm are accepted as negative (but may be excessive and may compromise cosmetic outcome) and margins less than 1 mm are inadequate, but no uniform consensus exists for margin status between these values.
With pathologic margins between 1 and 10 mm, wider margins are generally associated with lower local recurrence rates.
However, close surgical margins (<1 mm) at the fibroglandular boundary of the breast (chest wall or skin) do not mandate surgical re-excision but can be an indication for higher boost dose radiation to the involved lumpectomy site.
Prospective randomized trials have shown that the addition of whole breast irradiation to a margin-free excision of pure DCIS decreases the rate of in-breast disease recurrence, but does not affect survival or distant metastasis-free survival.
Whole breast irradiation after breast-conserving surgery reduces the relative risk of a local failure by approximately one half.
If whole breast radiation is used, the use of a radiation boost (by photons, brachytherapy, or electron beam) to the tumor bed is recommended to maximize local control, especially in patients 50 years of age or younger.
There is retrospective evidence suggesting that selected patients have a low risk of in-breast recurrence with excision alone without breast irradiation.
For example, in a retrospective review, 10-year disease-free survival (DFS) rates of 186 patients with DCIS treated with lumpectomy alone were 94% for patients with low-risk DCIS and 83% for patients with both intermediate- and high-risk DCIS.
In another retrospective study of 215 patients with DCIS treated with lumpectomy without radiation therapy, endocrine therapy, or chemotherapy, the recurrence rate over 8 years was 0%, 21.5%, and 32.1% in patients with low-, intermediate- or high-risk DCIS, respectively.
A multi-institutional, nonrandomized, prospective study of selected patients with low-risk DCIS treated without radiation has also provided some support for the use of excision without radiation in the treatment of DCIS.
At a median follow-up of 6.2 years, the 5-year risk of ipsilateral breast recurrence was 6.1% (95% confidence interval [CI], 4.1%-8.2%) in the subset of patients with low-/intermediate-grade DCIS and median tumor size of 6 mm.
Margin widths were greater than or equal to 5 mm in 69.2% and 82.9% of patients in the low-/intermediate-risk and high-risk arms, respectively, with margin widths of greater than or equal to 10 mm or no tumor on re-excision observed in 48.5% and 53.3% of patients in the respective groups.
Although an acceptably low ipsilateral recurrence rate was observed in the low-/intermediate-grade arm of the study at 5 years, the 7-year ipsilateral recurrence rate in this group of patients was considerably higher (10.5%; 95% CI, 7.5%-13.6%), suggesting that these events may be delayed but not prevented in this population.
Ipsilateral breast recurrences were approximately equally divided between invasive breast cancer and DCIS in the low-/intermediate-risk group but only about one-third of patients with an in-breast recurrence in the high-risk group had invasive disease.
Another retrospective study reviewed 220 patients with DCIS treated with breast conservation surgery and radiation.
Thirty-six percent received a radiation boost.
At 46 months, none of the 79 patients who received a radiation boost experienced a local recurrence, whereas 8 of 141 patients who did not receive a boost experienced a local recurrence.
Prospective randomized trials have not been carried out to analyze whether wider margins can replace the need for radiation therapy for DCIS.
A retrospective series demonstrated that for margin width of 10 mm, radiation had no additional benefit in reducing the already low local recurrence rate of 4% at the end of 8 years.
Also, if margin width was between 1 mm and less than 10 mm, the addition of radiation therapy led to a non-statistically significant reduction in local recurrence.
However, when margins were less than 1 mm a significant benefit was seen.
A meta-analysis of four large multicentre randomized trials confirmed the results of the individual trials that adding radiation therapy to breast- conserving surgery for DCIS provides a statistically and clinically significant reduction in ipsilateral breast events (HR [hazard ratio], 0.49; 95% CI; 0.41-0.58, P < .0000).
Results from a retrospective study of 445 patients with pure DCIS treated by excision alone indicated that margin width was the most important independent predictor of local recurrence, although the trend for decreasing local recurrence risk with increasing margin width was most apparent with margins less than 1 mm and greater than or equal to 10 mm.
In a meta-analysis of 4660 patients with DCIS treated with breast-conserving surgery and radiation, a surgical margin of less than 2 mm was associated with increased rates of ipsilateral breast tumor recurrence compared with margins of 2 mm, although no significant differences were observed when margins of greater than 2 mm to 5 mm or greater than 5 mm were compared with 2-mm margins.
The results of this study suggest that wide margins (≥2 mm), which can compromise cosmetic outcome, do not provide additional benefit in the population of patients with DCIS receiving radiation therapy following breast-conserving therapy.
A large, retrospective study found that narrow surgical resection margin (≤2 mm) does not increase local recurrence compared to a surgical resection margin of 2 mm.
Further complicating the issue of margin width is the impact of the fibroglandular boundary-the pectoral fascia and the superficial skin where narrower tumor-free margins may provide adequate local control.
The choice of local treatment does not impact overall disease-related survival; therefore, the individual patient’s acceptance of the potential for an increased risk of local recurrence must be considered.
An analysis of specimen margins and specimen radiographs should be performed to ensure that all mammographically detectable DCIS has been excised.
In addition, a post-excision mammogram should be considered where appropriate (eg, the mass and/or microcalcifications are not clearly within the specimen).
Axillary dissection is not recommended for patients with pure DCIS, and axillary nodal involvement in patients with pure DCIS in the breast is rare.
However, a small proportion of women with seemingly pure DCIS on initial biopsy will have invasive breast cancer at the time of the definitive surgical procedure and thus will ultimately require ALN staging.
In patients with seemingly pure DCIS to be treated with mastectomy or with excision in an anatomic location (eg, tail of the breast), which could compromise the performance of a future sentinel lymph node (SLN) procedure, an SLN procedure may be considered.
4个大型多中心随机试验的一项荟萃分析证实了单独试验的结果：对导管内原位癌保乳术增加放疗带来同侧乳腺事件统计学以及临床上明显降低(HR[风险比]，0.49；95% CI；0.41-0.58，P<.0000)。< p="">
NCCN Recommendations for Primary Treatment of DCIS
According to the NCCN Panel, primary treatment options for women with DCIS along with their respective categories of consensus are: lumpectomy plus radiation (category 1); total mastectomy, with or without reconstruction (category 2A); or lumpectomy alone followed by clinical observation (category 2B).
There is no evidence that survival differs between the three treatment options.
Decreased rates of local recurrence following lumpectomy have been observed in randomized trials with the addition of whole breast radiation (category 1).
Although randomized trials evaluating the effectiveness of total mastectomy in DCIS have not been performed, mastectomy is a highly effective strategy to decrease risk of local recurrence (category 2A).
The option of lumpectomy alone should be considered only in cases where the patient and the physician view the individual risks as “low” (category 2B).
According to the NCCN Panel, complete resection should be documented by analysis of margins and specimen radiography.
Post-excision mammography should also be performed whenever uncertainty about adequacy of excision remains.
Clips are used to demarcate the biopsy area because DCIS may be clinically occult and further surgery may be required pending the margin status review by pathology.
Women treated with mastectomy are appropriate candidates for breast reconstruction (see Principles of Breast Reconstruction Following Surgery in the NCCN Guidelines for Breast Cancer).
Contraindications to breast-conserving therapy with radiation therapy are listed in the algorithm (see Special Considerations to Breast-Conserving Therapy Requiring Radiation Therapy in the NCCN Guidelines for Breast Cancer).
Postsurgical Treatment DCIS falls between atypical ductal hyperplasia and invasive ductal carcinoma within the spectrum of breast proliferative abnormalities.
The Breast Cancer Prevention Trial performed by National Surgical Adjuvant Breast and Bowel Project (NSABP) showed a 75% reduction in the occurrence of invasive breast cancer in patients with atypical ductal hyperplasia treated with tamoxifen.
These data also showed that tamoxifen led to a substantial reduction in the risk of developing benign breast disease.
The Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) overview analysis showed that, with 5 years of tamoxifen therapy, women with ER-positive or receptor-unknown invasive tumors had a 39% reduction in the annual odds of recurrence of invasive breast cancer.
Similarly, the NSABP B-24 trial found a benefit from tamoxifen for women with DCIS after treatment with breast conservation surgery and radiation therapy.
In that study, women with DCIS who were treated with breast-conserving therapy were randomized to receive placebo or tamoxifen.
With 13.6 years median follow-up, the women treated with tamoxifen had a 3.4% absolute reduction in ipsilateral in-breast tumor recurrence risk (HR, 0.30; 95% CI, 0.21-0.42; P < .001) and a 3.2% absolute reduction in contralateral breast cancers (HR, 0.68; 95% CI, 0.48-0.95; P = .023).
The women receiving tamoxifen had a 10-year cumulative rate of 4.6% for invasive and 5.6% for noninvasive breast cancers in the ipsilateral breast compared with 7.3% for invasive and 7.2% for noninvasive breast cancers in placebo-treated women.
The cumulative 10-year frequency of invasive and noninvasive breast cancer in the contralateral breast was 6.9% and 4.7% in the placebo and tamoxifen groups, respectively.
No differences in overall survival (OS) were noted.
A retrospective analysis of ER expression in NSABP B-24 suggests that increased levels of ER expression predict for tamoxifen benefit in terms of risk reduction for ipsilateral and contralateral breast cancer development following breast-conserving therapy.
A phase III trial for women with excised DCIS randomized subjects in a 2 x 2 fashion to tamoxifen or not and whole breast radiation therapy or not.
With 12.7 years of median follow-up, the use of tamoxifen decreased all new breast events (HR, 0.71; 95% CI, 0.58-0.88; P = .002).
The use of tamoxifen decreased ipsilateral and contralateral breast events in the subjects not given whole breast radiotherapy (ipsilateral HR, 0.77; 95% CI, 0.59-0.98; contralateral HR, 0.27; 95% CI 0.12-0.59), but not in those receiving whole breast radiotherapy (ipsilateral HR, 0.93; 95% CI, 0.50-1.75; P = .8; contralateral HR, 0.99; 95% CI, 0.39-2.49; P = 1.0).
中位随访13.6年，接受他莫昔芬治疗的女性同侧乳腺内肿瘤复发风险绝对降低3.4%(HR，0.30；95% CI，0.21-0.42；p＜.001)并且对侧乳腺癌绝对降低3.2%(HR，0.68；95% CI，0.48-0.95；P =.023)。
中位随访12.7年，他莫昔芬的使用降低了所有的新发乳腺事件(HR，0.71；95% CI，0.58-0.88；P = .002)。
在未给予全乳放疗的受试者中他莫昔芬的使用降低了同侧及对侧乳腺事件(同侧HR，0.77；95% CI，0.59-0.98；对侧HR，0.27；95% CI0.12-0.59)，在那些接受全乳放疗者中则未降低(同侧HR，0.93；95% CI，0.50-1.75；P =.8；对侧HR，0.99；95% CI，0.39-2.49；P =1.0)。
According to the NCCN Panel, tamoxifen may be considered as a strategy to reduce the risk of ipsilateral breast cancer recurrence in women with ER-positive DCIS treated with breast-conserving therapy (category 1 for those undergoing breast-conserving surgery Followed by radiation therapy; category 2A for those undergoing excision alone).
The benefit of tamoxifen for ER-negative DCIS is not known.
Strategies for reducing the risk of recurrence to the contralateral breast are described in the NCCN Guidelines for Breast Cancer Risk Reduction.
According to the NCCN Panel, follow-up of women with DCIS includes interval history and physical examination every 6 to 12 months for 5 years and then annually, as well as yearly diagnostic mammography.
In patients treated with breast-conserving therapy, the first follow-up mammogram should be performed 6 to 12 months after the completion of breast-conserving radiation therapy (category 2B).
Patients receiving risk reduction agents should be monitored as described in the NCCN Guidelines for Breast Cancer Risk Reduction.
The majority of recurrences of DCIS are in-breast recurrences after breast-conserving therapy, and recurrences mostly occur close to the site of prior disease.
In those women for whom the initial DCIS was treated with excision alone, the treatment for a recurrence of DCIS is similar to that followed previously.
In women whom the initial DCIS was treated with breast-conserving surgery plus radiation therapy, mastectomy is usually necessary to treat DCIS recurrence.
Local recurrences after mastectomy for DCIS should be treated with wide local excision with consideration for chest wall irradiation.
Overall, approximately half of the local recurrences after initial treatment for a pure DCIS are again DCIS, and the others are invasive cancer.
Those with local recurrences that are invasive should receive systemic treatment as appropriate for a newly diagnosed invasive breast cancer.