Rosen's Breast Pathology, 4e

401

Ductal Carcinoma In Situ

in women with ER-positive DCIS. 423 In the randomized NSABP B24 trial, the 7-year risk of breast recurrence was 7.7% with lumpectomy and radiation plus tamoxifen and 11.1% after lumpectomy and radiation alone. 387 From the foregoing review, it is clear that, as a group, pa- tients with DCIS benefit from the addition of radiotherapy to breast-conserving surgery because the breast recurrence rate is reduced by about 50%. Radiotherapy is usually indicated for any of the following circumstances: high-grade DCIS, when margins are close (variously described as 10 mm or less), and for patients younger than 50 years. Tamoxifen may be added for hormone receptor–positive DCIS. Omitting ra- diotherapy is a consideration for women older than 50 years with a widely clear margin (variously defined as more than 10 mm) and low-grade histology without necrosis. This type of DCIS is very likely to be hormone receptor positive and, therefore, amenable to adjuvant tamoxifen treatment. How- ever, this approach is not without risk as described by Wong et al., 378 who reported an in-breast recurrence rate of 2.4% per patient-year of follow-up and a projected 5-year breast recurrence rate of 12%. Mammography is an essential component of the clinical follow-up of women treated by breast-conserving surgery with or without radiotherapy and/or tamoxifen. 248 In one se- ries of 162 women, 33 (20%) developed recurrent ipsilateral carcinoma 6 to 168 months (median, 26) after primary ther- apy. 424 Review of mammograms from 20 patients with re- current carcinoma revealed that 17 (85%) of the recurrences were detected solely on the basis of calcifications, which had a pattern similar to that of calcifications seen prior to the ini- tial excision in 82% of cases. DCIS alone was present in 65% of recurrences, whereas 35% also had invasive carcinoma. Particular attention should be paid to the mammographic follow-up of the contralateral breast in women with atypical hyperplasia or LCIS coexisting with DCIS. The role of rou- tine MRI screening in the follow-up of women with DCIS, treated by breast conservation, remains to be determined. Some patients may choose mastectomy, even if they are candidates for breast conservation. Mastectomy is prefer- able for the patient with such widespread DCIS that negative margins cannot be achieved with a cosmetically acceptable surgical procedure. Many but not all of these patients have dispersed calcifications on mammography. Lumpectomy with or without radiation will suffice for most women with DCIS limited to a single focus on the basis of pathologic and clinical findings, if the margins of excision are negative, if the lesion is not comedo type with necrosis and high nuclear grade, and if the lesion is small (variously defined as less than 1.0 cm or less than 2.5 cm). Radiation after lumpectomy is recommended regardless of size if the DCIS has high nuclear grade, necrosis, or is distinctively of the comedocarcinoma type, and if the margins are indeterminate or are involved. The assessment of margins is only a guide to and not a pre- cise measurement of the completeness of excision for DCIS. This was demonstrated by Silverstein et al., 425 who compared the findings in reexcision specimens from patients who had positive and who had negative margins in their initial exci- sional biopsy specimens. Although the chance of finding

routine screening in asymptomatic women. In such a situ- ation, most patients have relatively limited disease and are eligible for breast conservation (i.e., maximal preservation of disease-free breast). The common breast conservation treatment options include lumpectomy alone, lumpectomy followed by radiation, or mastectomy. An SERM, such as tamoxifen, is the main systemic treatment option. Typically, most patients with DCIS do not require a mastectomy, and the majority of patients in the United States and elsewhere choose breast conservation. 420 Treatment recommendations for DCIS are made on the basis of clinical and pathologic findings in consultation with the patient. Important considerations include the manner of clinical presentation (e.g., palpable, incidental, or mammo- graphic), extent by mammography, size measured grossly or microscopically when possible, margin status of the lumpec- tomy, and histologic features of the DCIS such as nuclear grade, growth pattern (e.g., cribriform, comedo, solid, or papillary), and the presence or absence of necrosis. The issue is complicated by the many different combinations of these and other features that can occur in a given case. Numerous studies cited indicate that margin status and the biologic characteristics of DCIS represented histologi- cally by nuclear grade and the presence or absence of necrosis are the most important predictors of local recurrence in the breast after breast conservation with or without radiotherapy. Tumor size correlates well with the extent of the lesion and thus influences margin status. For example, Cheng et al. 421 reported positive lumpectomy margins in 15%, 28%, and 69% of patients with DCIS lesions measured as less than 1.0 cm, 1.0 to 2.4 cm, and 2.5 cm or larger, respectively. Biologic characteristics, at least partially reflected in the histologic ap- pearance of DCIS, have a complex influence on the success of treatment by affecting the rate of growth (and to some extent the time to detection of clinical recurrences) and radiosen- sitivity of residual DCIS after lumpectomy. Consequently, it is possible for patients with comparable amounts of incom- pletely excised residual high-grade (comedo) and low-grade (cribriform) DCIS who receive the same treatment to have similar absolute risks for breast recurrence, but they may differ in time to clinical detection of recurrence, especially of invasive lesions, and in responsiveness to radiotherapy or antiestrogens. Follow-up for more than 10 years of large uni- formly treated patient groups with diverse types of DCIS will be needed to reliably assess the interplay of these factors. Retrospective and prospective randomized studies re- viewed in detail in this chapter have demonstrated that ra- diotherapy after excisional surgery reduces the chance of recurrence in the breast by about 50%. The degree to which a reduced frequency of breast recurrence contributes to over- all survival remains to be determined for patients with DCIS. The possibility that there could be a survival advantage con- ferred by reducing breast recurrences is suggested by a meta- analysis of randomized studies of radiotherapy and breast conservation in women with invasive breast carcinoma that detected this beneficial effect. 422 The addition of a selective ER modulator such as tamoxi- fen to breast conservation therapy reduces breast recurrences