Pathologic and biologic response to preoperative endocrine therapy in patients with ER-positive ductal carcinoma in situ.
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.Biomarker changes were compared to a cohort of patients who had not received preoperative treatment.


RESULTS
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.


CONCLUSIONS
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.


BACKGROUND
ClinicalTrials.gov NCT00290745.
Chen
Yunn-Yi
YY
Department of Surgery, University of California San Francisco, San Francisco, USA. Yunn-Yi.Chen@ucsf.edu
DeVries
Sandy
S
Anderson
Joseph
J
Lessing
Juan
J
Swain
Rebecca
R
Chin
Koei
K
Shim
Veronica
V
Esserman
Laura J
LJ
Waldman
Frederic M
FM
Hwang
E Shelley
ES
D000328:Adult; D000368:Aged; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D044584:Carcinoma, Ductal; D015331:Cohort Studies; D004965:Estrogen Antagonists / Q000627:therapeutic use*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020249:Hormone Replacement Therapy; D006801:Humans; D000077289:Letrozole; D008875:Middle Aged; D009570:Nitriles / Q000627:therapeutic use; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D013629:Tamoxifen / Q000627:therapeutic use*; D014230:Triazoles / Q000627:therapeutic use
D004965:Estrogen Antagonists; D009570:Nitriles; D011960:Receptors, Estrogen; D014230:Triazoles; D013629:Tamoxifen; D000077289:Letrozole
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