Abstract
BackgroundEndocrine therapy is commonly recommended in the adjuvant setting for patients as treatment for ductal carcinoma in situ (DCIS). However, it is unknown whether a neoadjuvant (preoperative) anti-estrogen approach to DCIS results in any biological change. This study was undertaken to investigate the pathologic and biomarker changes in DCIS following neoadjuvant endocrine therapy compared to a group of patients who did not undergo preoperative anti-estrogenic treatment to determine whether such treatment results in detectable histologic alterations.MethodsPatients (n = 23) diagnosed with ER-positive pure DCIS by stereotactic core biopsy were enrolled in a trial of neoadjuvant anti-estrogen therapy followed by definitive excision. Patients on hormone replacement therapy, with palpable masses, or with histologic or clinical suspicion of invasion were excluded. Premenopausal women were treated with tamoxifen and postmenopausal women were treated with letrozole. Pathologic markers of proliferation, inflammation, and apoptosis were evaluated at baseline and at three months.Biomarker changes were compared to a cohort of patients who had not received preoperative treatment.ResultsMedian age of the cohort was 53 years (range 38–78); 14 were premenopausal. Following treatment, predominant morphologic changes included increased multinucleated histiocytes and degenerated cells, decreased duct extension, and prominent periductal fibrosis. Two postmenopausal patients had ADH only with no residual DCIS at excision. Postmenopausal women on letrozole had significant reduction of PR, and Ki67 as well as increase in CD68-positive cells. For premenopausal women on tamoxifen treatment, the only significant change was increase in CD68. No change in cleaved caspase 3 was found. Two patients had invasive cancer at surgery.ConclusionPreoperative therapy for DCIS is associated with significant pathologic alterations. These changes may be clinically significant. Further work is needed to identify which women may be the best candidates for such treatment for DCIS, and whether best responders may safely avoid surgical intervention.Trial RegistrationClinicalTrials.gov NCT00290745
Highlights
Endocrine therapy is commonly recommended in the adjuvant setting for patients as treatment for ductal carcinoma in situ (DCIS)
Our aim was to determine whether a 3-month course of preoperative endocrine therapy for DCIS could result in measurable histologic and immunohistochemical changes when compared to baseline assessments made on initial diagnostic core biopsy
Treated Cases Patients treated at the University of California San Francisco Comprehensive Cancer Center between 2003 and 2007 were offered participation in an investigator-initiated clinical trial studying the effect of preoperative endocrine therapy in DCIS
Summary
Endocrine therapy is commonly recommended in the adjuvant setting for patients as treatment for ductal carcinoma in situ (DCIS). It is unknown whether a neoadjuvant (preoperative) anti-estrogen approach to DCIS results in any biological change. This study was undertaken to investigate the pathologic and biomarker changes in DCIS following neoadjuvant endocrine therapy compared to a group of patients who did not undergo preoperative antiestrogenic treatment to determine whether such treatment results in detectable histologic alterations. Ductal carcinoma in situ (DCIS) was diagnosed in over 60,000 women in the United States in 2008[1]. The incidence of DCIS has risen almost 5-fold over the last 15 years, and represents 25–30% of all mammographically detected breast cancers[2,3]. As mammographic screening has become more sensitive and widespread, more clinically occult preinvasive disease continues to be detected
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