TY - JOUR
T1 - Pathologic and biologic response to preoperative endocrine therapy in patients with ER-positive ductal carcinoma in situ
AU - Chen, Yunn Yi
AU - DeVries, Sandy
AU - Anderson, Joseph
AU - Lessing, Juan
AU - Swain, Rebecca
AU - Chin, Koei
AU - Shim, Veronica
AU - Esserman, Laura J.
AU - Waldman, Frederic M.
AU - Hwang, E. Shelley
N1 - Funding Information:
We gratefully acknowledge the significant contributions of Sarah Nyante, Chrystal Wa, Laura Johnson, and Kaoru Itakura, for their excellent patient care as well as their dedication to the procurement and archiving of clinical information and pathologic specimens. We thank Amy Heinzerling for her expert preparation of the manuscript. This work was supported by NIH/ K23CA097181 (ESH), the UCSF SPORE Clinical Investigator Research Program (P50 CA58207), and a research grant from Novartis Corporation. This work was presented in part at the 99th Annual USCAP Meeting, Atlanta GA.
PY - 2009/8/18
Y1 - 2009/8/18
N2 - Background: Endocrine 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. Methods: Patients (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. Results: Biomarker changes were compared to a cohort of patients who had not received preoperative treatment. Conclusion: Median 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. Trial Registration: Preoperative 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. ClinicalTrials.gov NCT00290745.
AB - Background: Endocrine 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. Methods: Patients (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. Results: Biomarker changes were compared to a cohort of patients who had not received preoperative treatment. Conclusion: Median 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. Trial Registration: Preoperative 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. ClinicalTrials.gov NCT00290745.
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U2 - 10.1186/1471-2407-9-285
DO - 10.1186/1471-2407-9-285
M3 - Article
C2 - 19689789
AN - SCOPUS:70349864872
SN - 1471-2407
VL - 9
SP - 285
JO - BMC cancer
JF - BMC cancer
M1 - 285
ER -