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Tailored Strategies for DCIS Management

Tailored Strategies for DCIS Management

Few areas in breast disease elicit as much controversy as the management of DCIS. The review by Sanders and Simpson, “Can We Know What to Do When DCIS Is Diagnosed?” nicely highlights those controversies. While the answers to this question may not be cut-and-dried (no surgical pun intended), we endorse the authors' conclusion that there never will be a “one-size-fits-all” algorithm for DCIS treatment, and that treatment should instead be carefully tailored to the individual patient.

The pathologic evaluation of DCIS within a surgical specimen is challenging and is a critical juncture that impacts all subsequent treatment recommendations. Two key factors for determining breast conservation candidacy are extent of disease (“size”) and surgical margin width, which along with tumor grade and presence of necrosis are paramount to making decisions regarding whether re-excision, mastectomy, and/or radiation is necessary. The authors suggest that to assess disease extent, all surgical specimens containing DCIS should be processed with serial sectioning and sequential submission of the entire specimen (so-called “serial sequential sampling”) so that the extent of DCIS can be measured in three dimensions. As surgeons, we strongly endorse this concept, although in practice such extensive processing is labor-intensive and can become impractical for pathologists to perform routinely. Acknowledging these limitations, the College of American Pathologists (CAP) stipulates that any of four different methods for measuring the extent of DCIS may be used: serial sequential sampling, nonsequential sampling, span measurement of DCIS on one slide, and/or measured distance between two affected margins.[1] In practice, the measurement of DCIS extent varies across institutions and is at best an estimate of disease burden.

The definition of a surgically “clear” margin is a hotly debated issue in DCIS management due to its implications for whether radiation therapy is required. The National Surgical Adjuvant Breast and Bowel Project (NSABP) B-17 randomized trial that led to the broad-scale adoption of radiation following breast conservation for DCIS demonstrated that radiation reduced the local recurrence rate from 27% to 12%.[2] Similarly, the randomized European Organisation for Research and Treatment of Cancer (EORTC) 10853 trial also demonstrated the efficacy of radiation in reducing risk of local recurrence; in this trial it was reduced from 14% to 7% at 10-year follow-up.[3] However, both trials were limited in that 40% or more of tumors were not measured pathologically for extent of disease. Furthermore, the surgical margins were often unoriented and unmeasured in these early studies, making comparative assessment of surgical margin width impossible to perform. In these trials, surgical margins were considered to be negative as long as cancer was not present at the resection line (NSABP), or was at least 1 mm from that margin (EORTC)—definitions that would generally be considered inadequate by modern standards. Given this variability, subset analyses could not be conducted to identify select groups of patients for whom radiation therapy might not be necessary.

We tend to disagree with the authors' suggestion that architectural pattern alone (ie, micropapillary DCIS) should steer surgical recommendations away from an attempt at breast conservation. While micropapillary DCIS tends to have a multifocal distribution within the breast (not unlike lobular carcinoma in situ), this is not invariably true. Before recommending mastectomy, we verify with percutaneous sampling that the extent of disease is truly widespread, rather than assuming this to be the case on the basis of histological subtyping. As long as the patient is counseled appropriately about the risk of needing re-excision or possibly mastectomy to attain clear margins (as all breast conservation patients should be), breast conservation should still be offered regardless of the DCIS pathologic subtype.

Silverstein and Lagios have been the most outspoken in advocating against the universal need for post-lumpectomy radiation for DCIS. Their Van Nuys Prognostic Index (which utilizes tumor size, margin width, grade, presence or absence of necrosis, and patient age) purports to predict risk of local failure with excision alone in order to elucidate who may avoid or benefit from radiation therapy.[4,5] Unfortunately, the Van Nuys scale has not been consistently validated by independent groups. In contrast to Sanders and Simpson's suggestion, we generally do not apply the Van Nuys algorithm to predict who may forgo radiation therapy.[6,7] Instead, we take an individualized approach in which we perform the rigorous pathologic (serial sequential sectioning of entire specimen) and radiographic examinations (specimen radiographs and, when needed, post-lumpectomy mammogram to confirm absence of residual calcifications) and then make individualized decisions based on the extent of disease and margin width, as well as consideration of the patient's stated preferences and goals.

Since DCIS does not have significant metastatic potential, we believe there is more room for individualized approaches to care than one might identify for invasive disease, for which mortality risk is a factor.

Silverstein's retrospective series demonstrated that when 10-mm margins were attained, radiation had no benefit in reducing an already low 8-year local failure rate of 4%. If margin width was between 1 mm and < 10 mm, the addition of radiation therapy led to a nonsignificant reduction, and only when margins were < 1 mm did it yield a significant benefit.[8] However, 10-mm margins are viewed by most as excessive, if not unattainable, and can often lead to marked cosmetic deformity, particularly in a modest-sized breast. It is generally accepted that 1 mm is insufficient unless it is present at an anatomic breast boundary (eg, pectoralis fascia) and that local recurrence risk decreases as margin width progressively increases from 1 mm to 10 mm. Having said that, we generally consider ≥ 2- to 3-mm margins to be negative. We do not require wider (5-mm) margins for higher grade DCIS as Sanders and Simpson suggest, because this could lead to an excessive number of re-excision surgeries. In our multidisciplinary approach, our pathologists carefully sample and examine surgical margins, and when we see a narrow margin that is only focally present, our radiation oncologists consider increasing the boost dose to this site.

Prospective trials have been conducted to analyze whether wider margins can replace the need for radiation therapy for DCIS. One prospective trial of 158 patients by Wong et al failed to show that excision to ≥ 1-cm margins alone was adequate for treatment of small (≤ 2.5 cm) low- or intermediate-grade DCIS.[9] The study was closed prematurely because of a high local failure rate of 2.4% per year, or a 5-year projected rate of 12%. The multi-institutional ECOG 5194 trial also prospectively evaluated whether excision alone served as adequate treatment of DCIS, and this study did demonstrate a satisfactorily low 5-year local recurrence rate of only 6.1% among patients with low/intermediate-grade DCIS.[10] Although all cases of low/intermediate-grade DCIS ≤ 2.5 cm were eligible for the study, the median tumor size in this group of 565 patients was only 6 mm, with 76.5% of the tumors less than 10 mm. In addition, although margin width of ≥ 3 mm was accepted as negative, nearly 50% of patients in this group had margins ≥ 1 cm and only 28% had margins < 5 mm. In light of these findings, we generally advise our patients that excision alone is adequate for treatment of low/intermediate-grade DCIS with more minimal disease than the criteria suggested by the ECOG study would accept—those patients with < 1 cm extent of low/intermediate-grade DCIS with at least 5- to 10-mm margins. We do not recommend surgical excision alone for high-grade DCIS, even when it is small (< 1 cm), given the high 5-year recurrence rate of 15% in this subgroup.

Regarding the role of sentinel lymph node biopsy (SLNB) for DCIS, we echo the authors' recommendation that SLNB should be performed when there is pathologic suspicion of invasion (either parenchymal or angiolymphatic) on core biopsy due to the high risk of upstaging to invasive carcinoma in this setting. We also advocate for the use of SLNB in mastectomy for DCIS. However, the role of SLNB in “identifying occult invasion in patients with pure DCIS on lumpectomy” is dubious and yields little useful prognostic information at the cost of a 3% to 7% risk of chronic arm lymphedema. In addition, SLNB can be readily performed subsequent to the initial lumpectomy if upstaging to invasive disease occurs, since high success rates for SLNB have been demonstrated by several groups in this setting.[11,12] In fact, the National Comprehensive Cancer Network 2010 clinical practice guidelines do not recommend SLNB in the setting of lumpectomy for DCIS (regardless of grade); a joint committee of the American College of Surgeons, the American College of Radiology, and the College of American Pathologists reached a similar conclusion.[13]

In summary, we support Sanders and Simpson's conclusion that the management of DCIS needs to be individualized, depending on such factors as histologic grade, the extent of disease, and margin status. However, we would argue that the subset of patients who can be successfully and confidently treated by lumpectomy alone (DCIS < 1 cm, margins > 5 mm, low or intermediate grade) is far smaller than the majority who still benefit from the addition of radiation therapy.

Financial Disclosure: The authors have no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.

References

References

1. Lester SC, Bose S, Chen YY, et al. Protocol for the examination of specimens from patients with invasive carcinoma of the breast. Arch Pathol Lab Med. 2009;133:1515-38.

2. Fisher ER, Dignam J, Tan-Chiu E, et al. Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) eight-year update of Protocol B-17: intraductal carcinoma. Cancer. 1999;86:429-38.

3. Bijker N, Meijnen P, Peterse JL, et al. Breast-conserving treatment with or without radiotherapy in ductal carcinoma-in-situ: ten-year results of European Organisation for Research and Treatment of Cancer randomized phase III trial 10853—a study by the EORTC Breast Cancer Cooperative Group and EORTC Radiotherapy Group. J Clin Oncol. 2006;24:3381-7.

4. Silverstein MJ, Poller D, Craig P, et al. A prognostic index for ductal carcinoma in situ of the breast. Cancer. 1996;77:2267-74.

5. Silverstein MJ. The University of Southern California/Van Nuys prognostic index for ductal carcinoma in situ of the breast. Am J Surg. 2003;186:337-43.

6. MacAusland SG, Hepel JT, Chong FK, et al. An attempt to independently verify the utility of the Van Nuys prognostic index for ductal carcinoma in situ. Cancer. 2007;110:2648-53.

7. Boland GP, Chan KC, Knox WF, et al. Value of the Van Nuys Prognostic Index in prediction of recurrence of ductal carcinoma in situ after breast-conserving surgery. Br J Surg. 2003;90:426-32.

8. Silverstein MJ, Lagios MD, Groshen S, et al. The influence of margin width on local control of ductal carcinoma in situ of the breast. N Engl J Med. 1999;340:1455-61.

9. Wong JS, Kaelin CM, Troyan SL, et al. Prospective study of wide excision alone for ductal carcinoma in situ of the breast. J Clin Oncol. 2006;24:1031-6.

10. Hughes LL, Wang M, Page DL, et al. Local excision alone without irradiation for ductal carcinoma in situ of the breast: a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2009;27:5319-24.

11. Cox CE, Furman BT, Kiluk JV, et al. Use of reoperative sentinel lymph node biopsy in breast cancer patients. J Am Coll Surg. 2008;207:57-61.

12. Port ER, Garcia-Etienne CA, Park J, et al. Reoperative sentinel lymph node biopsy: a new frontier in the management of ipsilateral breast tumor recurrence. Ann Surg Oncol. 2007;14:2209-14.

13. Morrow M, Strom EA, Bassett LW, et al. Standard for management of ductal carcinoma in situ of the breast. CA Cancer J Clin. 2002;52:256-76.

 
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