Adjuvant tamoxifen reduces subsequent breast cancer in women with estrogen receptor-positive ductal carcinoma in situ: a study based on NSABP protocol B-24 - PubMed (original) (raw)
Comparative Study
. 2012 Apr 20;30(12):1268-73.
doi: 10.1200/JCO.2010.34.0141. Epub 2012 Mar 5.
Stewart J Anderson, Soonmyung Paik, D Lawrence Wickerham, Iris D Nagtegaal, Sandra M Swain, Elefetherios P Mamounas, Thomas B Julian, Charles E Geyer Jr, Joseph P Costantino, Stephanie R Land, Norman Wolmark
Affiliations
- PMID: 22393101
- PMCID: PMC3341142
- DOI: 10.1200/JCO.2010.34.0141
Comparative Study
Adjuvant tamoxifen reduces subsequent breast cancer in women with estrogen receptor-positive ductal carcinoma in situ: a study based on NSABP protocol B-24
D Craig Allred et al. J Clin Oncol. 2012.
Abstract
Purpose: The NSABP (National Surgical Adjuvant Breast and Bowel Project) B-24 study demonstrated significant benefit with adjuvant tamoxifen in patients with ductal carcinoma in situ (DCIS) after lumpectomy and radiation. Patients were enrolled without knowledge of hormone receptor status. The current study retrospectively evaluated the relationship between receptors and response to tamoxifen.
Patients and methods: Estrogen (ER) and progesterone receptors (PgR) were evaluated in 732 patients with DCIS (41% of original study population). An experienced central laboratory determined receptor status in all patient cases with available paraffin blocks (n = 449) by immunohistochemistry (IHC) using comprehensively validated assays. Results for additional patients (n = 283) determined by various methods (primarily IHC) were available from enrolling institutions. Combined results were evaluated for benefit of tamoxifen by receptor status at 10 years and overall follow-up (median, 14.5 years).
Results: ER was positive in 76% of patients. Patients with ER-positive DCIS treated with tamoxifen (v placebo) showed significant decreases in subsequent breast cancer at 10 years (hazard ratio [HR], 0.49; P < .001) and overall follow-up (HR, 0.60; P = .003), which remained significant in multivariable analysis (overall HR, 0.64; P = .003). Results were similar, but less significant, when subsequent ipsilateral and contralateral, invasive and noninvasive, breast cancers were considered separately. No significant benefit was observed in ER-negative DCIS. PgR and either receptor were positive in 66% and 79% of patients, respectively, and in general, neither was more predictive than ER alone.
Conclusion: Patients in NSABP B-24 with ER-positive DCIS receiving adjuvant tamoxifen after standard therapy showed significant reductions in subsequent breast cancer. The use of adjuvant tamoxifen should be considered for patients with DCIS.
Conflict of interest statement
Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.
Figures
Fig 1.
CONSORT diagram summarizing the random assignment of patients in the clinical trial and distribution of patient cases available for this study. ER, estrogen receptor; PgR, progesterone receptor.
Fig 2.
Representative examples of estrogen receptor (ER) expression in ductal carcinoma in situ (DCIS) determined by immunohistochemistry. (A) Low-grade DCIS, strongly ER positive (Allred score, 5 + 3 = 8/8); (B) high-grade DCIS, ER negative (Allred score, 0/8).
Fig 3.
Kaplan-Meier curves showing probability of any subsequent breast cancer in patients with (A) estrogen receptor (ER) –negative and (B) ER-positive ductal carcinoma in situ (DCIS) treated with adjuvant placebo versus tamoxifen. Tamoxifen benefit (42% reduction in relative risk; P = .001) was restricted to ER-positive DCIS.
Comment in
- Refining the use of endocrine therapy for ductal carcinoma in situ.
Morrow M. Morrow M. J Clin Oncol. 2012 Apr 20;30(12):1249-51. doi: 10.1200/JCO.2011.40.5514. Epub 2012 Mar 5. J Clin Oncol. 2012. PMID: 22393104 No abstract available.
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References
- Bloodgood JC. Comedo carcinoma or comedo-adenoma of the female breast. Am J Cancer. 1934;22:842–853.
- Cheatle GL, Cutler M. Malignant epithelial neoplasia: Carcinoma—The precancerous or potentially carcinomatous state. In: Cheatle GL, Cutler M, editors. Tumours of the Breast. Philadelphia, PA: Lippincott; 1926. pp. 161–332.
- Ernster VL, Barclay J. Increases in ductal carcinoma in situ (DCIS) of the breast in relation to mammography: A dilemma. Natl Cancer Inst Monogr. 1997;22:151–156. - PubMed
- Silverstein MJ. Ductal carcinoma in situ of the breast. Annu Rev Med. 2000;51:17–32. - PubMed
- Weaver DL, Rosenberg RD, Barlow WE, et al. Pathologic findings from the Breast Cancer Surveillance Consortium: Population-based outcomes in women undergoing biopsy after screening mammography. Cancer. 2006;106:732–742. - PubMed
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