ABSTRACT
INTRODUCTION: Ductal carcinoma in situ (DCIS) is a noninvasive breast cancer wherein malignant cells are confined within a ductal lobular unit. Although less than half the cases of DCIS will progress to invasive disease, most women are treated aggressively with surgery, radiation, and/or hormone therapy due to the inability to clinically evaluate the extent and location of the disease. Intraductal therapy, in which a drug is administered directly into the mammary duct through the nipple, is a promising approach for treating DCIS, but the feasibility of instilling drug into a diseased duct has not been established. PATIENTS AND METHODS: Four to 6 weeks before their scheduled surgery, 13 women diagnosed with DCIS were subjected to cannulation of the affected duct. After both the absence of perforation and presence of dye in the duct were confirmed by ductogram, pegylated liposomal doxorubicin was instilled. Histopathologic assessment was performed after surgery to assess the treatment effects. RESULTS: Of the 13 women enrolled in the study, 6 had their DCIS duct successfully cannulated without perforation and instilled with the drug. The treatment was well tolerated, and no serious adverse events have been reported. Biomarker studies indicated a general decrease in Ki-67 levels but an increase in annexin-1 and 8-hydroxydeoxyguanosine in the lumen of DCIS-containing ducts, which suggests a local response to pegylated liposomal doxorubicin treatment. CONCLUSIONS: Intraductal therapy offers a nonsurgical strategy to treat DCIS at the site of disease, potentially minimizing the adverse effects of systemic treatment while preventing development of invasive cancer.
Subject(s)
Antibiotics, Antineoplastic/administration & dosage , Breast Neoplasms/drug therapy , Carcinoma, Ductal, Breast/drug therapy , Carcinoma, Intraductal, Noninfiltrating/drug therapy , Doxorubicin/analogs & derivatives , 8-Hydroxy-2'-Deoxyguanosine , Annexin A1/metabolism , Biomarkers, Tumor/metabolism , Breast Neoplasms/pathology , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/pathology , Carcinoma, Ductal, Breast/surgery , Carcinoma, Intraductal, Noninfiltrating/pathology , Carcinoma, Intraductal, Noninfiltrating/surgery , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/metabolism , Doxorubicin/administration & dosage , Feasibility Studies , Female , Follow-Up Studies , Humans , Immunoenzyme Techniques , Ki-67 Antigen/metabolism , Magnetic Resonance Imaging , Neoplasm Staging , Polyethylene Glycols/administration & dosage , Preoperative Care , PrognosisABSTRACT
OBJECTIVE: Our objective was to evaluate the breast cancer risk associated with body burden levels of polychlorinated dibenzo-p-dioxins (PCDDs) and polychlorinated dibenzofurans (PCDFs). METHODS: We conducted a hospital-based case-control study among 79 women diagnosed with invasive breast cancer and 52 controls diagnosed with benign breast conditions. We collected breast adipose tissue and analyzed it for all 17 2,3,7,8-substitituted PCDD/PCDFs. We used unconditional logistic regression to calculate age- and race-adjusted exposure-specific odds ratios (ORs) and 95% confidence intervals (CI) for each individual PCDD/PCDF congener as well as for the summary measures (I-TEQ, Adj-TEQ). RESULTS: Dioxin levels were consistent with reports from other small, contemporary studies of body burdens in the U.S. None of the odds ratios for any of the congeners or summary measures differed significantly from one. Especially for the PCDF congeners, point estimates tended to be below one. One notable exception was octachlorodibenzo-p-dioxin (OCDD), for which the odds ratio for the second and third tertiles appeared modestly elevated (OR = 1.22, 95% CI: 0.47:3.16 and OR = 1.62, 95% CI: 0.64:4.12, respectively), though the test for trend was not significant (p = 0.36). CONCLUSION: Breast cancer risk was not associated with adipose levels of PCDD/PCDFs. More study is suggested among women of color who may have higher body burden levels of these compounds.
