The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Seema A Khan - One of the best experts on this subject based on the ideXlab platform.
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REVIEW Breast-tissue sampling for risk assessment and prevention
2015Co-Authors: Carol J Fabian, Bruce F Kimler, Matthew S Mayo, Seema A KhanAbstract:Breast tissue and duct fluid provide a rich source of biomarkers to both aid in the assessment of short-term risk of developing breast cancer and predict and assess responses to prevention interventions. There are three methods currently being utilized to sample breast tissue in asymptomatic women for risk assessment: nipple-aspirate fluid (NAF), random periareolar fine-needle aspiration (RPFNA) and Ductal Lavage. Prospective single-institution trials have shown that the presence of atypical cells in NAF fluid or RPFNA specimens is associated with an increased risk of breast cancer. Furthermore, RPFNA-detected atypia has been observed to further stratify risk based on the commonly used Gail risk-assessment model. A prospective trial evaluating risk prediction on the basis of atypical cells in Ductal-Lavage fluid is ongoing. The ability of other established non-genetic biomarkers (mammo-graphic breast density; serum levels of bioavailable estradiol, testosterone, insulin-like growth factor-1 and its insulin like growth factor binding protein-3) to stratify risk based on the Gail model is as yet incompletely defined. Modulation of breast intra-epithelial neoplasia (i.e. hyperplasia with or without atypia) with or without associated breast-tissue molecular markers, such as proliferation, is currently being used to evaluate response in Phase II chemoprevention trials. RPFNA has been the metho
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ARTICLES Ductal Lavage Findings in Women With Known Breast Cancer Undergoing Mastectomy
2014Co-Authors: Seema A Khan, Elizabeth L. Wiley, Norma Rodriguez, Carol Baird, Rathi Ramakrishnan, Ritu Nayar, Michele Bryk, Kevin B. Bethke, Valerie L. Staradub, Judith WolfmanAbstract:Background: Ductal Lavage has the potential to detect cancer by sampling breast epithelium in asymptomatic high-risk women. To assess the utility of Ductal Lavage as a cancer diagnostic test, we investigated the association between duc-tal Lavage cytologic findings and histologic findings in women with known breast cancer undergoing mastectomy. Methods: Ductal Lavage was performed in the operating room before mastectomy on 44 breasts from 32 women with known can-cer and on eight breasts from seven women undergoing prophylactic mastectomy, two with occult malignancy. If the Ductal Lavage sample from one or more ducts contained enough epithelial cells for a cytologic diagnosis, Lavaged ducts were injected with a mixture of colored dye, gelatin, and a radiographic contrast compound after mastectomy, and breast tissue was radiographed and sectioned. Histologi
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Ductal Lavage for Detection of Cellular Atypia in Women at High Risk for Breast Cancer
2013Co-Authors: William C Dooley, Seema A Khan, Henry Mark Kuerer, Brittmarie Ljung, Umberto Veronesi, Massimiliano Cazzaniga, Richard M Elledge, David T Hung, Joyce A. O’shaughnessy, Rogsbert F PhillipsAbstract:Background: Breast cancer originates in breast epithelium and is associated with progressive molecular and morphologic changes.Women with atypical breast Ductal epithelial cells have an increased relative risk of breast cancer.In this study, Ductal Lavage, a new procedure for collecting Ductal cells with a microcatheter, was compared with nipple aspiration with regard to safety, tolerability, and the ability to detect abnormal breast epithelial cells. Methods: Women at high risk for breast cancer who had nonsuspicious mammograms and clinical breast examinations underwent nipple aspiration followed by Lavage of fluid-yielding ducts.All statistical tests were two-sided. Results: The 507 women enrolled included 291 (57%) with a history of breast cancer and 199 (39%) with a 5-year Gail risk for breast cancer of 1.7 % or more. Nipple aspirate fluid (NAF) samples wer
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Breast Ductal Lavage for Assessment of Breast Cancer Biomarkers
Hormones and Cancer, 2010Co-Authors: Robert T Chatterton, Michele Bryk, Noah P Parker, Mito Habe-evans, Denise M. Scholtens, Seema A KhanAbstract:Lavage of the Ductal systems of the breast provides fluid (Ductal Lavage fluid, DLF) containing hormones and products of hormone actions that may represent more accurately the composition of the breast than samples collected from blood or urine. The present study was undertaken to assess the presence of potential cancer biomarkers, their variation among individuals at high risk for breast cancer, and differences associated with menopause and tamoxifen treatment. Seventy seven tamoxifen-eligible subjects with a 5-year breast cancer risk estimate (Gail > 1.6%; N = 53) or recently diagnosed breast cancer ( N = 24) were offered tamoxifen therapy; those not accepting tamoxifen were under observation only. After 6 months, all subjects underwent Ductal Lavage (DL) in an unaffected breast. Estradiol (E2), estrone sulfate, androstenedione, dehydroepiandrosterone (DHEA), DHEA sulfate, progesterone, cathepsin D, and epidermal growth factor (EGF) were measured in Ductal Lavage fluid (DLF) by immunoassays. Data were expressed as the mass of analyte per milligram of protein in DLF and normalized by natural log transformation. With the exception of DHEA, none of the analytes measured were significantly lower in postmenopausal women than in premenopausal women. The mean log_e concentration difference in estradiol was 10.9%. Tamoxifen treatment for 6 months did not result in a significantly greater concentration of E2 or in any of the other analytes in DLF of pre- or postmenopausal women. The between-duct variance of the concentration of free steroids within the same breast averaged 51% less than that between subjects, and was similar to that of non-diffusible proteins. The maintenance of estradiol concentrations in the breast after menopause demonstrates the importance of local biosynthesis. The fact that DLF E2 does not reflect the high serum concentrations of E2 during tamoxifen treatment indicates that breast concentrations of estradiol may be under feedback control. Unlike studies of low risk populations, progesterone concentrations were not significantly less in postmenopausal than in premenopausal women. The similarity in variance of free steroids and protein analytes between ducts of a breast indicates little transfer of steroids between lobules.
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relation of hormones in Ductal Lavage fluid to age tamoxifen treatment and breast cancer risk
BMC Proceedings, 2009Co-Authors: Robert T Chatterton, Michael J Avram, Irene Helenowski, Michelle Bryk, Seema A KhanAbstract:Breast Ductal Lavage provides a source of both cells and fluid from the breast in a non-invasive manner. The fluid contains freely diffusible steroid hormones and other factors that may be secreted or released from the epithelial cells that line the alveoli and ducts of the breast as well as from myoepithelial cells, stomal cells, and immune cells that populate the breast. The purpose of the present study was to determine how perturbations of the system are reflected in Ductal Lavage fluid (DLF). We examined changes associated with menopausal status, tamoxifen treatment, and Gail model breast cancer risk scores.
Massimiliano Cazzaniga - One of the best experts on this subject based on the ideXlab platform.
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abstract p3 10 02 presence of atypia in Ductal Lavage and risk of subsequent breast cancer in a prospective study
Cancer Research, 2018Co-Authors: A De Censi, Massimiliano Cazzaniga, Chiara Casadio, Laura Chiapparini, Sara Gandini, Aliana Guerrierigonzaga, Debora Macis, Paolo Veronesi, B BonanniAbstract:Background: Atypical hyperplasia is considered a nearly obligate precursor of breast cancer and is associated with a higher risk of developing breast cancer (BC). Attempts to improve early detection of breast cancer and to provide individualized breast cancer risk assessment would greatly benefit from sampling cellular material from the target tissue. Ductal Lavage (DL) is a minimally invasive technique which provides adequate material to detect atypical cells in mammary ducts. However, long term data of the association between atypia from Ductal Lavage and BC risk are lacking. We studied the prevalence of atypia in DL in different risk categories and its ability to predict BC development in women at risk. Methods: From March 2000 to July 2012 we performed DL in a consecutive series of 348 women with median age of 45 years (range 19-74) at increased BC risk based on the following characteristics: 5 yrs Gail model > 1.66% or > 10% probability of BRCA mutation (n = 155), history of contralateral BC (CBC, n = 161), presence of a BRCA pathogenic variant (n = 32). We analyzed the presence of atypical cells in the baseline specimen of Ductal Lavage and in repeated Lavage and observed their evolution during follow-up. Results: The procedure was safe and well tolerated in most women, with pain and disconfort preventing the procedure in 5.4% of subjects. Overall, 126 (36%) women had atypia at baseline, with a prevalence of 32%, 39%, and 41% in the Gail, CBC and BRCA groups, respectively (p = 0.38). The overall prevalence of atypia considering all visits was 44% (range 36-51). After a median follow up of 6 years, cumulative BC events were 8% in women without atypia versus 14% in those with atypia (log-rank p = 0.08). In the highest risk groups (CBC and BRCA pathogenic variants), the number of BC events was 16 (21%) in women with atypia versus 11 (10%) in women without atypia (p = 0.02 after adjustment for age). Conclusions: Our findings suggest that cytologic atypia in the fluid obtained by DL predicts subsequent BC in women at increased risk, providing individual risk assessment. The reversal of atypia in DL should be evaluated as a surrogate biomarker of BC therapeutic prevention. Supported by: Associazione Italiana per la Ricerca sul Cancro (AIRC), Lega Italina per la Lotta contro i Tumori (LILT), AVON Foundation for Women. Citation Format: De Censi A, Cazzaniga M, Gandini S, Casadio C, Chiapparini L, Guerrieri-Gonzaga A, Macis D, Veronesi P, Bonanni B. Presence of atypia in Ductal Lavage and risk of subsequent breast cancer in a prospective study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-10-02.
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association of atypia in Ductal Lavage and breast cancer risk
Journal of Clinical Oncology, 2017Co-Authors: A De Censi, Massimiliano Cazzaniga, Chiara Casadio, Laura Chiapparini, Sara Gandini, Aliana Guerrierigonzaga, Debora Macis, Paolo Veronesi, Bernardo BonanniAbstract:e13040Background: Atypical hyperplasia is considered a nearly obligate precursor of breast cancer and is associated with a higher risk of developing breast cancer (BC). Attempts to improve early de...
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Ductal Lavage for Detection of Cellular Atypia in Women at High Risk for Breast Cancer
2013Co-Authors: William C Dooley, Seema A Khan, Henry Mark Kuerer, Brittmarie Ljung, Umberto Veronesi, Massimiliano Cazzaniga, Richard M Elledge, David T Hung, Joyce A. O’shaughnessy, Rogsbert F PhillipsAbstract:Background: Breast cancer originates in breast epithelium and is associated with progressive molecular and morphologic changes.Women with atypical breast Ductal epithelial cells have an increased relative risk of breast cancer.In this study, Ductal Lavage, a new procedure for collecting Ductal cells with a microcatheter, was compared with nipple aspiration with regard to safety, tolerability, and the ability to detect abnormal breast epithelial cells. Methods: Women at high risk for breast cancer who had nonsuspicious mammograms and clinical breast examinations underwent nipple aspiration followed by Lavage of fluid-yielding ducts.All statistical tests were two-sided. Results: The 507 women enrolled included 291 (57%) with a history of breast cancer and 199 (39%) with a 5-year Gail risk for breast cancer of 1.7 % or more. Nipple aspirate fluid (NAF) samples wer
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breast Ductal Lavage for biomarker assessment in high risk women rationale design and methodology of a randomized phase ii clinical trial with nimesulide simvastatin and placebo
BMC Cancer, 2012Co-Authors: Matteo Lazzeroni, Massimiliano Cazzaniga, Chiara Casadio, Aliana Guerrierigonzaga, Davide Serrano, Serena Mora, C Jemos, Maria Pizzamiglio, Laura Cortesi, Davide RadiceAbstract:Background Despite positive results from large phase III clinical trials proved that it is possible to prevent estrogen-responsive breast cancers with selective estrogen receptor modulators and aromatase inhibitors, no significant results have been reached so far to prevent hormone non-responsive tumors. The Ductal Lavage (DL) procedure offers a minimally invasive method to obtain breast epithelial cells from the Ductal system for cytopathologic analysis. Several studies with long-term follow-up have shown that women with atypical hyperplasia have an elevated risk of developing breast cancer. The objective of the proposed trial is to assess the efficacy and safety of a daily administration of nimesulide or simvastatin in women at higher risk for breast cancer, focused particularly on hormone non-responsive tumor risk. The primary endpoint is the change in prevalence of atypical cells and cell proliferation (measured by Ki67) in DL or fine needle aspirate samples, after 12 months of treatment and 12 months after treatment cessation.
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breast Ductal Lavage for biomarker assessment in high risk women rationale design and methodology of a randomized phase ii clinical trial with nimesulide simvastatin and placebo
BMC Cancer, 2012Co-Authors: Matteo Lazzeroni, Massimiliano Cazzaniga, Chiara Casadio, Aliana Guerrierigonzaga, Davide Serrano, Serena Mora, C Jemos, Maria Pizzamiglio, Laura Cortesi, Davide RadiceAbstract:Despite positive results from large phase III clinical trials proved that it is possible to prevent estrogen-responsive breast cancers with selective estrogen receptor modulators and aromatase inhibitors, no significant results have been reached so far to prevent hormone non-responsive tumors. The Ductal Lavage (DL) procedure offers a minimally invasive method to obtain breast epithelial cells from the Ductal system for cytopathologic analysis. Several studies with long-term follow-up have shown that women with atypical hyperplasia have an elevated risk of developing breast cancer. The objective of the proposed trial is to assess the efficacy and safety of a daily administration of nimesulide or simvastatin in women at higher risk for breast cancer, focused particularly on hormone non-responsive tumor risk. The primary endpoint is the change in prevalence of atypical cells and cell proliferation (measured by Ki67) in DL or fine needle aspirate samples, after 12 months of treatment and 12 months after treatment cessation. From 2005 to 2011, 150 women with a history of estrogen receptor negative Ductal intraepithelial neoplasia or lobular intraepithelial neoplasia or atypical hyperplasia, or unaffected subjects carrying a mutation of BRCA1 or with a probability of mutation >10% (according to BRCAPRO) were randomized to receive nimesulide 100mg/day versus simvastatin 20mg/day versus placebo for one year followed by a second year of follow-up. This is the first randomized placebo controlled trial to evaluate the role of DL to study surrogate endpoints biomarkers and the effects of these drugs on breast carcinogenesis. In 2007 the European Medicines Agency limited the use of systemic formulations of nimesulide to 15 days. According to the European Institute of Oncology Ethics Committee communication, we are now performing an even more careful monitoring of the study participants. Preliminary results showed that DL is a feasible procedure, the treatment is well tolerated and the safety blood tests do not show any significant liver toxicity. There is an urgent need to confirm in the clinical setting the potential efficacy of other compounds in contrasting hormone non-responsive breast cancer. This paper is focused on the methodology and operational aspects of the clinical trial. (ClinicalTrials.gov Identifier: NCT01500577)
Carol J Fabian - One of the best experts on this subject based on the ideXlab platform.
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REVIEW Breast-tissue sampling for risk assessment and prevention
2015Co-Authors: Carol J Fabian, Bruce F Kimler, Matthew S Mayo, Seema A KhanAbstract:Breast tissue and duct fluid provide a rich source of biomarkers to both aid in the assessment of short-term risk of developing breast cancer and predict and assess responses to prevention interventions. There are three methods currently being utilized to sample breast tissue in asymptomatic women for risk assessment: nipple-aspirate fluid (NAF), random periareolar fine-needle aspiration (RPFNA) and Ductal Lavage. Prospective single-institution trials have shown that the presence of atypical cells in NAF fluid or RPFNA specimens is associated with an increased risk of breast cancer. Furthermore, RPFNA-detected atypia has been observed to further stratify risk based on the commonly used Gail risk-assessment model. A prospective trial evaluating risk prediction on the basis of atypical cells in Ductal-Lavage fluid is ongoing. The ability of other established non-genetic biomarkers (mammo-graphic breast density; serum levels of bioavailable estradiol, testosterone, insulin-like growth factor-1 and its insulin like growth factor binding protein-3) to stratify risk based on the Gail model is as yet incompletely defined. Modulation of breast intra-epithelial neoplasia (i.e. hyperplasia with or without atypia) with or without associated breast-tissue molecular markers, such as proliferation, is currently being used to evaluate response in Phase II chemoprevention trials. RPFNA has been the metho
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assessment of rna in human breast tissue sampled by random periareolar fine needle aspiration and Ductal Lavage and processed as fixed or frozen specimens
Reproductive Biology, 2013Co-Authors: Teresa A Phillips, Carol J Fabian, Bruce F Kimler, Brian K PetroffAbstract:Abstract Ductal Lavage (DL) and random periareolar fine needle aspiration (RPFNA) have both been proposed as minimally invasive techniques to sample breast tissue during breast cancer prevention trials. Laser capture microdissection (LCM), linear RNA amplification and quantitative real-time polymerase chain reaction (qPCR) theoretically overcome the limitations of small specimen size obtained with DL and RPFNA. In order to test the yield, relative stability and amplifiability of RNA from fixed and archived RPFNA and DL specimens, breast tissue was sampled from individual high risk women ( n = 9) by both DL and RPFNA. RPFNA samples showed good RNA/cDNA yield and amplification while only 2 of 9 of the paired DL specimens had cDNA of adequate quality for subsequent PCR. One and two rounds of linear amplification provided approximately a 200- and 20,000-fold enrichment of RNA, respectively. PCR analysis consistently detected ER and COX-1 mRNA in the majority of RPFNA samples examined while pS2, PCNA, VEGF and survivin expression varied with subject. RNA yield and/or stability was greater for fixed and archived RPFNA than DL specimens of breast tissue. In a subsequent study examining an expanded biomarker gene panel in fixed vs. frozen RPFNA samples, mRNA profiles and ranked relative mRNA abundance were similar ( r = 0.89) for frozen and fixed RPFNA specimens. In summary, frozen RPFNA samples may be optimal for RNA endpoints in human breast cancer prevention trials but fixed RPFNA specimens allow similar analyses with greater convenience.
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is there a future for Ductal Lavage
Clinical Cancer Research, 2007Co-Authors: Carol J FabianAbstract:Non–lesion-directed minimally invasive breast tissue sampling is currently used in the research setting both for risk stratification and for acquisition of material for response biomarkers in phase II chemoprevention trials. Prospective data linking morphology to eventual development of cancer are
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comparison of cytomorphology in specimens obtained by random periareolar fine needle aspiration and Ductal Lavage from women at high risk for development of breast cancer
Breast Cancer Research and Treatment, 2006Co-Authors: Carola M Zalles, Bruce F Kimler, Marie Simonsen, Julie L Clark, Trina Metheny, Carol J FabianAbstract:Ductal Lavage (DL) and random periareolar fine needle aspiration (RPFNA) are both being used to harvest epithelial cells for risk assessment as well as response evaluation in chemoprevention trials. The magnitude of increase in relative risk has been defined in a prospective study for RPFNA but not for DL atypia. We attempted both procedures in 26 women at high risk for development of breast cancer. Median age was 43 (range 32–57); 15 women were premenopausal, with 6 of the postmenopausal women on HRT. Collection of nipple aspirate fluid (NAF) was attempted and, if successful, was followed by DL; RPFNA was then performed on all women. Both procedures were attempted the same day (follicular phase of menstrual cycle if premenopausal) in 24 subjects and within three months for two subjects. Twenty-three subjects produced NAF, 17 of the 23 (74%) had a successful duct cannulation as part of the DL procedure, with 16 yielding sufficient ((10) Ductal cells for morphologic assessment. Twenty-five of 26 (96%) subjects had a successful RPFNA procedure with adequate cellularity for morphology. There was concordance between DL and RPFNA specimens for traditional cytologic category assessment in 10/16 (63%), Masood index score in 13/16 (82%), and Consensus Panel assessment in 12/16 (75%) of specimens. We conclude that same day DL and RPFNA is feasible, with 62% and 96% of high-risk women having a successful procedure with evaluable cytomorphology. RPFNA was more likely to yield an evaluable specimen, but if a cellular DL specimen was obtained, morphology was generally similar.
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breast tissue sampling for risk assessment and prevention
Endocrine-related Cancer, 2005Co-Authors: Carol J Fabian, Bruce F Kimler, Matthew S Mayo, Seema A KhanAbstract:Breast tissue and duct fluid provide a rich source of biomarkers to both aid in the assessment of shortterm risk of developing breast cancer and predict and assess responses to prevention interventions. There are three methods currently being utilized to sample breast tissue in asymptomatic women for risk assessment: nipple-aspirate fluid (NAF), random periareolar fine-needle aspiration (RPFNA) and Ductal Lavage. Prospective single-institution trials have shown that the presence of atypical cells in NAF fluid or RPFNA specimens is associated with an increased risk of breast cancer. Furthermore, RPFNA-detected atypia has been observed to further stratify risk based on the commonly used Gail risk-assessment model. A prospective trial evaluating risk prediction on the basis of atypical cells in Ductal-Lavage fluid is ongoing. The ability of other established non-genetic biomarkers (mammographic breast density; serum levels of bioavailable estradiol, testosterone, insulin-like growth factor1 and its insulin like growth factor binding protein-3) to stratify risk based on the Gail model is as yet incompletely defined. Modulation of breast intra-epithelial neoplasia (i.e. hyperplasia with or without atypia) with or without associated breast-tissue molecular markers, such as proliferation, is currently being used to evaluate response in Phase II chemoprevention trials. RPFNA has been the method most frequently used for Phase II studies of 6‐12months duration. However, Ductal Lavage, RPFNA and random and directed core needle biopsies are all being utilized in ongoing multi-institutional Phase II studies. The strengths and weaknesses of each method are reviewed.
Chiara Casadio - One of the best experts on this subject based on the ideXlab platform.
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abstract p3 10 02 presence of atypia in Ductal Lavage and risk of subsequent breast cancer in a prospective study
Cancer Research, 2018Co-Authors: A De Censi, Massimiliano Cazzaniga, Chiara Casadio, Laura Chiapparini, Sara Gandini, Aliana Guerrierigonzaga, Debora Macis, Paolo Veronesi, B BonanniAbstract:Background: Atypical hyperplasia is considered a nearly obligate precursor of breast cancer and is associated with a higher risk of developing breast cancer (BC). Attempts to improve early detection of breast cancer and to provide individualized breast cancer risk assessment would greatly benefit from sampling cellular material from the target tissue. Ductal Lavage (DL) is a minimally invasive technique which provides adequate material to detect atypical cells in mammary ducts. However, long term data of the association between atypia from Ductal Lavage and BC risk are lacking. We studied the prevalence of atypia in DL in different risk categories and its ability to predict BC development in women at risk. Methods: From March 2000 to July 2012 we performed DL in a consecutive series of 348 women with median age of 45 years (range 19-74) at increased BC risk based on the following characteristics: 5 yrs Gail model > 1.66% or > 10% probability of BRCA mutation (n = 155), history of contralateral BC (CBC, n = 161), presence of a BRCA pathogenic variant (n = 32). We analyzed the presence of atypical cells in the baseline specimen of Ductal Lavage and in repeated Lavage and observed their evolution during follow-up. Results: The procedure was safe and well tolerated in most women, with pain and disconfort preventing the procedure in 5.4% of subjects. Overall, 126 (36%) women had atypia at baseline, with a prevalence of 32%, 39%, and 41% in the Gail, CBC and BRCA groups, respectively (p = 0.38). The overall prevalence of atypia considering all visits was 44% (range 36-51). After a median follow up of 6 years, cumulative BC events were 8% in women without atypia versus 14% in those with atypia (log-rank p = 0.08). In the highest risk groups (CBC and BRCA pathogenic variants), the number of BC events was 16 (21%) in women with atypia versus 11 (10%) in women without atypia (p = 0.02 after adjustment for age). Conclusions: Our findings suggest that cytologic atypia in the fluid obtained by DL predicts subsequent BC in women at increased risk, providing individual risk assessment. The reversal of atypia in DL should be evaluated as a surrogate biomarker of BC therapeutic prevention. Supported by: Associazione Italiana per la Ricerca sul Cancro (AIRC), Lega Italina per la Lotta contro i Tumori (LILT), AVON Foundation for Women. Citation Format: De Censi A, Cazzaniga M, Gandini S, Casadio C, Chiapparini L, Guerrieri-Gonzaga A, Macis D, Veronesi P, Bonanni B. Presence of atypia in Ductal Lavage and risk of subsequent breast cancer in a prospective study [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P3-10-02.
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association of atypia in Ductal Lavage and breast cancer risk
Journal of Clinical Oncology, 2017Co-Authors: A De Censi, Massimiliano Cazzaniga, Chiara Casadio, Laura Chiapparini, Sara Gandini, Aliana Guerrierigonzaga, Debora Macis, Paolo Veronesi, Bernardo BonanniAbstract:e13040Background: Atypical hyperplasia is considered a nearly obligate precursor of breast cancer and is associated with a higher risk of developing breast cancer (BC). Attempts to improve early de...
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breast Ductal Lavage for biomarker assessment in high risk women rationale design and methodology of a randomized phase ii clinical trial with nimesulide simvastatin and placebo
BMC Cancer, 2012Co-Authors: Matteo Lazzeroni, Massimiliano Cazzaniga, Chiara Casadio, Aliana Guerrierigonzaga, Davide Serrano, Serena Mora, C Jemos, Maria Pizzamiglio, Laura Cortesi, Davide RadiceAbstract:Background Despite positive results from large phase III clinical trials proved that it is possible to prevent estrogen-responsive breast cancers with selective estrogen receptor modulators and aromatase inhibitors, no significant results have been reached so far to prevent hormone non-responsive tumors. The Ductal Lavage (DL) procedure offers a minimally invasive method to obtain breast epithelial cells from the Ductal system for cytopathologic analysis. Several studies with long-term follow-up have shown that women with atypical hyperplasia have an elevated risk of developing breast cancer. The objective of the proposed trial is to assess the efficacy and safety of a daily administration of nimesulide or simvastatin in women at higher risk for breast cancer, focused particularly on hormone non-responsive tumor risk. The primary endpoint is the change in prevalence of atypical cells and cell proliferation (measured by Ki67) in DL or fine needle aspirate samples, after 12 months of treatment and 12 months after treatment cessation.
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breast Ductal Lavage for biomarker assessment in high risk women rationale design and methodology of a randomized phase ii clinical trial with nimesulide simvastatin and placebo
BMC Cancer, 2012Co-Authors: Matteo Lazzeroni, Massimiliano Cazzaniga, Chiara Casadio, Aliana Guerrierigonzaga, Davide Serrano, Serena Mora, C Jemos, Maria Pizzamiglio, Laura Cortesi, Davide RadiceAbstract:Despite positive results from large phase III clinical trials proved that it is possible to prevent estrogen-responsive breast cancers with selective estrogen receptor modulators and aromatase inhibitors, no significant results have been reached so far to prevent hormone non-responsive tumors. The Ductal Lavage (DL) procedure offers a minimally invasive method to obtain breast epithelial cells from the Ductal system for cytopathologic analysis. Several studies with long-term follow-up have shown that women with atypical hyperplasia have an elevated risk of developing breast cancer. The objective of the proposed trial is to assess the efficacy and safety of a daily administration of nimesulide or simvastatin in women at higher risk for breast cancer, focused particularly on hormone non-responsive tumor risk. The primary endpoint is the change in prevalence of atypical cells and cell proliferation (measured by Ki67) in DL or fine needle aspirate samples, after 12 months of treatment and 12 months after treatment cessation. From 2005 to 2011, 150 women with a history of estrogen receptor negative Ductal intraepithelial neoplasia or lobular intraepithelial neoplasia or atypical hyperplasia, or unaffected subjects carrying a mutation of BRCA1 or with a probability of mutation >10% (according to BRCAPRO) were randomized to receive nimesulide 100mg/day versus simvastatin 20mg/day versus placebo for one year followed by a second year of follow-up. This is the first randomized placebo controlled trial to evaluate the role of DL to study surrogate endpoints biomarkers and the effects of these drugs on breast carcinogenesis. In 2007 the European Medicines Agency limited the use of systemic formulations of nimesulide to 15 days. According to the European Institute of Oncology Ethics Committee communication, we are now performing an even more careful monitoring of the study participants. Preliminary results showed that DL is a feasible procedure, the treatment is well tolerated and the safety blood tests do not show any significant liver toxicity. There is an urgent need to confirm in the clinical setting the potential efficacy of other compounds in contrasting hormone non-responsive breast cancer. This paper is focused on the methodology and operational aspects of the clinical trial. (ClinicalTrials.gov Identifier: NCT01500577)
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breast Ductal Lavage dl and p16 immunocytochemistry
Journal of Clinical Oncology, 2011Co-Authors: Chiara Casadio, Laura Chiapparini, S Di Vincenzo, Bernardo Bonanni, Massimiliano CazzanigaAbstract:1587 Background: The low sensitivity in detecting high-grade atypical cells makes cytologic evaluation of DL specimens a low-yield tool for assessing risk or identifying intraepithelial neoplasia. ...
Ritu Nayar - One of the best experts on this subject based on the ideXlab platform.
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ARTICLES Ductal Lavage Findings in Women With Known Breast Cancer Undergoing Mastectomy
2014Co-Authors: Seema A Khan, Elizabeth L. Wiley, Norma Rodriguez, Carol Baird, Rathi Ramakrishnan, Ritu Nayar, Michele Bryk, Kevin B. Bethke, Valerie L. Staradub, Judith WolfmanAbstract:Background: Ductal Lavage has the potential to detect cancer by sampling breast epithelium in asymptomatic high-risk women. To assess the utility of Ductal Lavage as a cancer diagnostic test, we investigated the association between duc-tal Lavage cytologic findings and histologic findings in women with known breast cancer undergoing mastectomy. Methods: Ductal Lavage was performed in the operating room before mastectomy on 44 breasts from 32 women with known can-cer and on eight breasts from seven women undergoing prophylactic mastectomy, two with occult malignancy. If the Ductal Lavage sample from one or more ducts contained enough epithelial cells for a cytologic diagnosis, Lavaged ducts were injected with a mixture of colored dye, gelatin, and a radiographic contrast compound after mastectomy, and breast tissue was radiographed and sectioned. Histologi
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Ductal Lavage is an inefficient method of biomarker measurement in high risk women
Cancer Prevention Research, 2009Co-Authors: Seema A Khan, Ritu Nayar, Michele Bryk, Nanjiang Hou, Heather A Lankes, Deepa B Patil, David Ivancic, Shahla Masood, Alfred RademakerAbstract:Effective methods of serial epithelial sampling to measure breast-specific biomarkers will aid the rapid evaluation of new preventive interventions. We report here a proof- of-principle phase 2 study to assess the utility of Ductal Lavage (DL) to measure biomar- kers of tamoxifen action. We enrolled women with a 5-year breast cancer risk estimate >1.6% or the unaffected breast of women with T1a orT 1b breast cancer. After entry DL, participants chose tamoxifen or observation and underwent repeat DL 6 months later. Samples were processed for cytology and immunohistochemistry for estrogen receptor α, Ki-67, and cyclooxygenase-2. Of 182 women recruited, 115 (63%) underwent entry and repeat DL; 85 (47%) had sufficient cells for analysis from ≥ 1d uct at bo th time points; in 78 (43%), cells were sufficient from ≥1 matched ducts. Forty-six women chose observation and 39 chose tamoxifen. We observed greater reductions in the tamoxifen group than in the observation group for Ki-67 (adjusted P = 0.03) and estrogen receptor α (adjusted P = 0.07), but not in cyclooxygenase-2 (adjusted P = 0.4) labeling. Cytologic findings showed a trend toward improvement in the tamoxifen group compared with the observation group. Interobserver variability for cytologic diagnosis between two observers showed good agreement (κ = 0.44). Using DL, we observed the expected changes in tamoxifen-related biomarkers; however, poor reproducibility of biomarkers in the obser- vation group, the 53% attrition rate of subjects from recruitment to biomarker analyses, and the expense of DL are significant barriers to the use of this procedure for biomarker assessment over time.
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reproducibility of Ductal Lavage cytology and cellularity over a six month interval in high risk women
Breast Cancer Research and Treatment, 2008Co-Authors: Deepa B Patil, Ritu Nayar, Nanjiang Hou, Alfred Rademaker, Michelle Bryk, Heather A Lankes, Shahla Masood, Seema A KhanAbstract:Background Ductal Lavage (DL) allows repeat sampling of breast epithelium for serial observation in a chemoprevention setting; however, the reproducibility of duct cannulation, cell yield and cytology has not been addressed. Methods We conducted a Phase 2 trial, wherein high risk women chose tamoxifen treatment or observation following an entry DL procedure. We present data from the non-intervention arm of our study to assess the reproducibility of cannulation, cell yield, and cytologic diagnosis from DL of the same duct at two time-points. Inter-observer variability was assessed by a blinded review of Papanicoloau-stained slides by two cytopathologists. Results Sixty-five women had a successful Lavage of 187 ducts at baseline and chose observation; 63/65 (97%) had a successful Lavage 6 months later. Successful recannulation of the same duct was accomplished in 63 women (97%) and162 ducts (87%). Total epithelial cell yields ≥100 were obtained from 57/65 women (88%) and 129/187 ducts (69%) at baseline, and 46/63 women (73%) and 80/162 ducts (49%) at both time-points. Cytologic diagnosis was reproducible in 27/63 (43%) women and 77/162 (48%) ducts. Inter-observer variability for cytologic diagnosis between two observers showed good agreement (κ = 0.62). Conclusions Recannulation and Lavage of the same duct after a 6 month interval can be achieved with high frequency; however, reproducibility of cell yield and cytologic findings from the same duct is sub-optimal, leading to significant attrition of evaluable subjects. The utility of DL for the serial monitoring of breast epithelium is therefore limited.
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endocrine biomarkers in Ductal Lavage samples from women at high risk for breast cancer
Cancer Epidemiology Biomarkers & Prevention, 2005Co-Authors: Deepa Bhandare, Ritu Nayar, Michele Bryk, Nanjiang Hou, Rachel H Cohn, Nazar Golewale, Noah P Parker, Robert T Chatterton, Alfred Rademaker, Seema A KhanAbstract:Background: Ductal Lavage is a method of minimal epithelial sampling of the breast, with potential utility for repeat sampling and biomarker analysis in chemoprevention studies. We report here the baseline findings from a study designed to assess the utility of Ductal Lavage in this setting. Methods: Tamoxifen-eligible, high-risk women underwent Ductal Lavage; epithelial cell number (ECN) and morphology were assessed on Papanicolaou-stained slides. Additional slides were immunostained for estrogen receptor (ER) α, Ki-67, and cyclooxygenase-2, and the labeling index (LI) was established by counting negative and positive cells. The Ductal Lavage supernatant (DLS) was assayed for estradiol, several of its precursors, progesterone, cathepsin D, interleukin-6, and epidermal growth factor (EGF). Results: One hundred sixty-eight women have entered the study (mean age, 51 years; mean 5-year Gail score, 2.8). Ductal Lavage was accomplished in 145 (86.3%) women. Data were analyzed by duct and by woman (averaging data across all ducts). Mild atypia was seen in 43 of 145 (29.6%), whereas severe atypia was seen in 2 (1.4%) of women. We observed significant positive correlations between ECN and cytologic atypia, ER LI, cyclooxygenase-2 LI, and Ki-67 LI. EGF levels in supernatant were significantly associated with estrogenic precursors, ER LI and ECN. A factor representing the DLS hormone and protein variables explained 36% of the variance; total ECN was highest when factor score and ER LI were high and was lowest when both were low ( P for interaction = 0.001). Conclusions: Biomarker analyses in epithelial cells and DLS are feasible. The significant associations of EGF with other markers suggest a possible role in increasing epithelial cell mass.
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Ductal Lavage findings in women with known breast cancer undergoing mastectomy
Journal of the National Cancer Institute, 2004Co-Authors: Seema A Khan, Elizabeth L. Wiley, Norma Rodriguez, Carol Baird, Rathi Ramakrishnan, Ritu Nayar, Michele Bryk, Kevin B. Bethke, Valerie L. Staradub, Judith WolfmanAbstract:Background: Ductal Lavage has the potential to detect cancer by sampling breast epithelium in asymptomatic high-risk women. To assess the utility of Ductal Lavage as a cancer diagnostic test, we investigated the association between Ductal Lavage cytologic findings and histologic findings in women with known breast cancer undergoing mastectomy. Methods: Ductal Lavage was performed in the operating room before mastectomy on 44 breasts from 32 women with known cancer and on eight breasts from seven women undergoing prophylactic mastectomy, two with occult malignancy. If the Ductal Lavage sample from one or more ducts contained enough epithelial cells for a cytologic diagnosis, Lavaged ducts were injected with a mixture of colored dye, gelatin, and a radiographic contrast compound after mastectomy, and breast tissue was radiographed and sectioned. Histologic findings in ducts with and without dye were recorded. Associations between cytologic results and histologic results were examined by univariate and multivariable analyses. Results: At least one duct was Lavaged in 36 breasts (mean = 1.4 ducts per breast); all histologic and cytologic procedures were completed in 28 breasts and in 39 ducts. Markedly atypical or malignant cytology was found in five cancer-containing breasts. In 39 ducts with complete cytologic and histologic data and when marked atypia or malignant cells defined a positive cytologic test, sensitivity was 43% (95% confidence interval [CI] = 23% to 72%), specificity was 96% (95% CI = 86% to 100%), and accuracy was 77% (95% CI = 63% to 89%). When mild or marked atypia or malignant cells defined a positive cytologic test, sensitivity was 79% (95% CI = 57% to 96%), specificity was 64% (95% CI = 46% to 83%), and accuracy was 69% (95% CI = 55% to 83%). When all 31 cytologically evaluable breasts were analyzed, sensitivity was 17% (95% CI = 7% to 35%), specificity was 100% (95% CI = 5% to 100%), and accuracy was 19% (95% CI = 9% to 38%). Conclusion: In breasts with cancer, Ductal Lavage appears to have low sensitivity and high specificity for cancer detection, possibly because cancer-containing ducts fail to yield fluid or have benign or mildly atypical cytology.
