Dataset Information

RTOG 9804: a prospective randomized trial for good-risk ductal carcinoma in situ comparing radiotherapy with observation.

ABSTRACT:

Purpose

The Radiation Therapy Oncology Group 9804 study identified good-risk patients with ductal carcinoma in situ (DCIS), a breast cancer diagnosis found frequently in mammographically detected cancers, to test the benefit of radiotherapy (RT) after breast-conserving surgery compared with observation.

Patients and methods

This prospective randomized trial (1998 to 2006) in women with mammographically detected low- or intermediate-grade DCIS, measuring less than 2.5 cm with margins ≥ 3 mm, compared RT with observation after surgery. The study was designed for 1,790 patients but was closed early because of lower than projected accrual. Six hundred thirty-six patients from the United States and Canada were entered; tamoxifen use (62%) was optional. Ipsilateral local failure (LF) was the primary end point; LF and contralateral failure were estimated using cumulative incidence, and overall and disease-free survival were estimated using the Kaplan-Meier method.

Results

Median follow-up time was 7.17 years (range, 0.01 to 11.33 years). Two LFs occurred in the RT arm, and 19 occurred in the observation arm. At 7 years, the LF rate was 0.9% (95% CI, 0.0% to 2.2%) in the RT arm versus 6.7% (95% CI, 3.2% to 9.6%) in the observation arm (hazard ratio, 0.11; 95% CI, 0.03 to 0.47; P < .001). Grade 1 to 2 acute toxicities occurred in 30% and 76% of patients in the observation and RT arms, respectively; grade 3 or 4 toxicities occurred in 4.0% and 4.2% of patients, respectively. Late RT toxicity was grade 1 in 30%, grade 2 in 4.6%, and grade 3 in 0.7% of patients.

Conclusion

In this good-risk subset of patients with DCIS, with a median follow-up of 7 years, the LF rate was low with observation but was decreased significantly with the addition of RT. Longer follow-up is planned because the timeline for LF in this setting seems protracted.

SUBMITTER: McCormick B

PROVIDER: S-EPMC4334775 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:ImportancePatients with ductal carcinoma in situ (DCIS) are treated with radiotherapy to reduce their risk of local invasive recurrence after breast-conserving surgery. However, the association of radiotherapy with breast cancer survival in patients with DCIS has not yet been clearly established.ObjectiveTo determine the extent to which radiotherapy is associated with reduced risk of breast cancer mortality in a large cohort of patients treated for DCIS, using a propensity score-based matching approach.Design, setting, and participantsThis cohort study of women who had first primary DCIS diagnosed between 1998 and 2014 used data from the Surveillance, Epidemiology, and End Results 18 registries database. Information on age and year of diagnosis, ethnicity, income, tumor size, tumor grade, estrogen receptor status, all treatments (surgery and radiation), and outcomes (invasive local recurrence and death from breast cancer) was abstracted for 140 366 women diagnosed with first primary DCIS. Three separate comparisons were performed using 1:1 matching: lumpectomy with radiation vs lumpectomy alone; lumpectomy alone vs mastectomy; and lumpectomy with radiation vs mastectomy.ExposuresUse of radiotherapy and/or extent of surgery.Main outcomes and measuresCrude and adjusted 15-year breast cancer-specific mortality.ResultsOf the 140 366 patients with DCIS in the cohort (109 712 [78.2%] white; mean [SD] age, 58.8 [12.3] years), 35 070 (25.0%) were treated with lumpectomy alone, 65 301 (46.5%) were treated with lumpectomy and radiotherapy, and 39 995 (28.5%) were treated with mastectomy. The actuarial 15-year breast cancer mortality rate was 2.33% for patients treated with lumpectomy alone, 1.74% for patients treated with lumpectomy and radiation, and 2.26% for patients treated with mastectomy. The adjusted hazard ratios for death were 0.77 (95% CI, 0.67-0.88) for lumpectomy and radiotherapy vs lumpectomy alone (29 465 propensity-matched pairs), 0.91 (95% CI, 0.78-1.05) for mastectomy alone vs lumpectomy alone (20 832 propensity-matched pairs), and 0.75 (95% CI, 0.65-0.87) for lumpectomy and radiotherapy vs mastectomy (29 865 propensity-matched pairs).Conclusions and relevanceIn patients with DCIS, treatment with lumpectomy and radiotherapy was associated with a significant reduction in breast cancer mortality compared with either lumpectomy alone or mastectomy alone. This suggests that the survival benefit of radiation is likely not due to local control, but rather to systemic effects.

Project description:Endocrine therapy initiation after ductal carcinoma in situ (DCIS) is highly variable and largely unexplained. National guidelines recommend considering tamoxifen for women with estrogen receptor-positive (ER+) DCIS or who undergo excision alone. We evaluated endocrine therapy use after DCIS over a 15-year period in an integrated health care setting to identify factors related to initiation.Female Group Health Cooperative enrollees ages 18-89 years with a DCIS diagnosis during 1996-2011 were eligible for inclusion. Endocrine therapy was identified through pharmacy records. Tumor and treatment information were from tumor registry reports; demographics and other risk factors were from questionnaires and electronic medical records. Relative risks (RRs) and 95% confidence intervals (CIs) for endocrine therapy initiation were calculated using multivariable generalized linear models.We identified 727 women with a DCIS diagnosis, including 163 (22%) who initiated endocrine therapy (149 tamoxifen, 14 aromatase inhibitor). Younger women were more likely to initiate endocrine therapy (RR 1.69; 95% CI 1.16-2.46 for ages 45-54 vs. 65-74 years). Compared with breast-conserving surgery (BCS) with radiation, women who had BCS alone (RR 0.46; 95% CI 0.25-0.84) or mastectomy (RR 0.54; 95% CI 0.39-0.75) were less likely to use endocrine therapy. ER testing increased from 4% of DCIS cases in 2001 to 71% in 2011; however, endocrine therapy initiation decreased from 58% of ER+ DCIS in 2001-2005 to 37% in 2009-2011.Increasing ER testing since 2001 has not corresponded to parallel increases in endocrine therapy initiation. Age, surgery, and radiation were the primary factors associated with initiation.National guidelines recommend considering tamoxifen for women with ductal carcinoma in situ (DCIS) who are estrogen receptor-positive (ER+) or who undergo excision alone. In this study, the rapid increase in ER testing caused by tamoxifen's approval in 2000 did not lead to increases in endocrine therapy initiation, despite recognition of an increasing number of DCIS tumors as ER+ each year. Contrary to the suggested guidelines, women who had breast-conserving surgery without radiation were less likely to use tamoxifen than those who had radiation. Future Food and Drug Administration approval of new endocrine agents for DCIS (such as aromatase inhibitors) may provide an opportunity to reemphasize benefits by ER and surgery status.