Rosen's Breast Pathology, 4e

400

Chapter 11

tamoxifen in the treatment of DCIS showed a nonsignificant reduction in all breast events with the addition of tamoxifen and a RR reduction of 22% after 53 months of follow-up. 414 The NSABP trial on the use of tamoxifen and radio- therapy in DCIS showed benefit, mainly due to reduction in ipsilateral recurrent invasive carcinoma. 415 The 7-year risk of local recurrence in the treated breast after lumpectomy with radiation was reduced from 11.1% without tamoxifen to 7.7% with tamoxifen ( p = 0.02). The risk of all (ipsilateral and contralateral) breast cancer events was reduced from 16.9% to 10.0% ( p = 0.0003). DCIS patients received radio- therapy and were then randomized to tamoxifen (20mg/day) or placebo. After just over 6 years of follow-up, a significant reduction in all new breast cancer events was reported in the tamoxifen group compared with the placebo group. In a re- cent published follow-up study on the NSABP B24 trial with a median follow-up of 14.5 years, 416 it was reported that ad- juvant tamoxifen significantly reduced the ipsilateral, as well as contralateral, risk of DCIS recurrence and/or progression to invasive breast carcinoma by about 50% in patients treated with lumpectomy and radiation, and that the benefit was re- stricted to patients with ER-positive DCIS (defined as those with an Allred score of 3 or more). Using this cutoff, 76% of DCIS were ER positive. Results for PR were comparatively less predictive of benefit. Thus, patients with ER-positive DCIS treated with tamoxifen (vs. placebo) showed signifi- cant decreases in subsequent breast cancer at 10 years (HR, 0.49; p < 0.001) and follow-up (HR, 0.60; p = 0.003), which remained significant in multivariate analysis (HR, 0.64; p = 0.003). Results were similar, but less significant, when sub- sequent ipsilateral and contralateral breast carcinomas were considered. Thus, it is likely that SERM therapy will be rou- tinely established in the treatment of appropriately selected ER-positive breast carcinoma patients. Based on data from the NSABP STAR trial, raloxifen offers less protection than tamoxifen for postmenopausal women. 417 Summary of Treatment Recommendations Patient survival, the appropriate endpoint for most malignant neoplasms, is the measure by which various therapy regimens are assessed. However, survival is of almost no utility in DCIS since the breast cancer–specific survival in DCIS exceeds 95%, regardless of treatment. 418 The low mortality due to DCIS itself is reflected in the 2009 NIH Consensus Statement recommending elimination of the “anxiety-­producing term ‘carcinoma’ from the description of DCIS.” 419 Recurrence of disease in either the in situ or the invasive form, particularly in the ipsilateral, but also in the contralateral, breast is the most commonly assessed data endpoint. In general, approxi- mately one-half of local recurrences in DCIS cases are inva- sive carcinoma. Thus, the primary goal of treatment of DCIS is to reduce the risk of local recurrence. The relatively high morbidity of at least some forms of the disease can be assessed by the wide variety of treatment rec- ommendations that are available to any patient with DCIS. In current practice, DCIS is most commonly diagnosed as a result of the detection of a mammographic abnormality on

Concurrent Proliferative Lesions and Breast Conservation

Adepoju et al. 413 studied the relationship of concurrent atypical duct and lobular hyperplasia and of LCIS to the risk of breast recurrence in women with DCIS treated by breast conservation therapy. Approximately 9.3% of the pa- tients also had microinvasive ductal carcinoma, and about 70% received radiotherapy in addition to surgical excision. Follow-up ranged from 0.3 to 29 years (median, 8.6 years). Eighty patients had concurrent significant proliferative le- sions consisting of atypical duct hyperplasia ( n :54) or atypi- cal lobular hyperplasia (ALH) or LCIS ( n :10). During the course of follow-up, 43 patients (14%) had breast recur- rences, 90% of which were detected by mammography. The risk of local failure was significantly lower in women who had radiotherapy (8.4%) than in those not irradiated (29.5%), and the median time was significantly longer in ra- diated patients (10 vs. 4.9 years). The presence of concurrent atypical duct or lobular hyperplasia or of LCIS did not have a significant effect on recurrence in the breast with DCIS. However, these lesions were associated with a substantially higher frequency of contralateral carcinoma, which oc- curred 4.4 times more often in women who had atypical duct hyperplasia associated with DCIS. The 15-year cumu- lative risk of developing contralateral carcinoma was 19% when atypical duct hyperplasia was present in the ipsilateral breast, and 4.1% when atypical hyperplasia was absent ( p < 0.01). An equally large differential was found for ALH and LCIS coexisting with DCIS (15-year cumulative risk, 22.7% vs. 6.5%), but the difference was not statistically significant. Meta-analysis of Treatment A meta-analysis of published reports compared recurrence rates for patients with DCIS after treatment with one of three modalities. 348 The summary recurrence rates were 1.4% (95% CI, 0.7 to 2.1), 8.9% (95% CI, 6.8 to 11.0), and 22.5% (95% CI, 16.9 to 28.2), respectively, for mastectomy, lumpectomy with radiotherapy, and lumpectomy alone. The proportions of invasive recurrence in each group were 76%, 50%, and 43%. The nearly threefold higher rate of re- currence after lumpectomy without radiotherapy compared with women who were radiated is especially striking in view of the likelihood that excision alone was most often recom- mended for patients with low grade, relatively small lesions with negative margins. The authors observed that “patients with risk factors of presence of necrosis, high-grade cyto- logic features or comedo subtype were found to derive the greatest improvement in local control” from the addition of radiotherapy to conservation surgery. Selective Estrogen Receptor Modulator in DCIS The role of Selective EstrogenReceptorModulators (SERMs), specifically tamoxifen, in managing DCIS has been inves- tigated in the UK/ANZ DCIS trial and also in the NSABP B24 trial. The UK/ANZ Trial comparing radiotherapy and