Response and resistance to the endocrine prevention of breast cancer.

2.50
Hdl Handle:
http://hdl.handle.net/10541/65699
Title:
Response and resistance to the endocrine prevention of breast cancer.
Authors:
Howell, Anthony ( 0000-0002-3879-5991 ) ; Bundred, Nigel J; Cuzick, Jack; Allred, D Craig; Clarke, Robert B
Abstract:
The data from observational studies and clinical trials indicates that it is possible to prevent BC for prolonged periods using various endocrine manipulations. Ovarian suppression is thought to give lifelong protection and recent data indicate that the effectiveness of Tam continues after cessation of treatment at 5-8 years. It is clear from three randomised trials that SERMs prevent ERalpha+ tumors only in women at increased risk and at population risk of BC entered into these trials. The data from the Ral trials also suggests that this agent appears less effective than Tam in preventing DCIS. This is surprising since a large proportion of DCIS is ERalpha+. Equally surprising is the effectiveness of oophorectomy and Tam in mutation carriers, particularly BRCA1, which is associated with ERalpha+ tumors. The fact that ERT can be given without apparently abrogating the effect of oophorectomy and also to naturally postmenopausal women without increasing BC risk suggests that cyclical estrogen or estrogen + progestin are important for BC initiation and/or progression. The question arises whether the information we have concerning the responsiveness of ERalpha+ cells in TDLU, premalignant lesions, and invasive cancers give an indication of the targets for endocrine prevention. Data summarised in Table 1 indicate that TDLU are responsive to estrogen, ED, and SERMs/SERDs in premenopausal women and there may be the targets for the preventative effect of early oophorectomy particularly in BRCA1 carriers where we have demonstrated endocrine responsiveness of TDLU, which at this heterozygote stage are ERalpha+. The decline in numbers of atypical lobules in breasts without invasive cancer suggests that these are targets for the 'preventive' effect of the menopause, as suggested by Wellings. The data also suggest that ERalpha+ DCIS is responsive to estrogen and ED supporting premalignant lesions is a target as does the data from the NSABP P1 trial indicating a marked preventive effect of Tam in women previously diagnosed with atypical ductal hyperplasia and a preventative effect on CIS.
Affiliation:
CRC Department Medical Oncology, University of Manchester Christie Hospital and Holt Radium Inst., Manchester, UK.
Citation:
Response and resistance to the endocrine prevention of breast cancer. 2008, 617:201-11 Adv. Exp. Med. Biol.
Journal:
Advances in Experimental Medicine and Biology
Issue Date:
2008
URI:
http://hdl.handle.net/10541/65699
DOI:
10.1007/978-0-387-69080-3_19
PubMed ID:
18497044
Type:
Article
Language:
en
ISSN:
0065-2598
Appears in Collections:
All Christie Publications ; Medical Oncology; Surgery

Full metadata record

DC FieldValue Language
dc.contributor.authorHowell, Anthony-
dc.contributor.authorBundred, Nigel J-
dc.contributor.authorCuzick, Jack-
dc.contributor.authorAllred, D Craig-
dc.contributor.authorClarke, Robert B-
dc.date.accessioned2009-04-21T16:43:46Z-
dc.date.available2009-04-21T16:43:46Z-
dc.date.issued2008-
dc.identifier.citationResponse and resistance to the endocrine prevention of breast cancer. 2008, 617:201-11 Adv. Exp. Med. Biol.en
dc.identifier.issn0065-2598-
dc.identifier.pmid18497044-
dc.identifier.doi10.1007/978-0-387-69080-3_19-
dc.identifier.urihttp://hdl.handle.net/10541/65699-
dc.description.abstractThe data from observational studies and clinical trials indicates that it is possible to prevent BC for prolonged periods using various endocrine manipulations. Ovarian suppression is thought to give lifelong protection and recent data indicate that the effectiveness of Tam continues after cessation of treatment at 5-8 years. It is clear from three randomised trials that SERMs prevent ERalpha+ tumors only in women at increased risk and at population risk of BC entered into these trials. The data from the Ral trials also suggests that this agent appears less effective than Tam in preventing DCIS. This is surprising since a large proportion of DCIS is ERalpha+. Equally surprising is the effectiveness of oophorectomy and Tam in mutation carriers, particularly BRCA1, which is associated with ERalpha+ tumors. The fact that ERT can be given without apparently abrogating the effect of oophorectomy and also to naturally postmenopausal women without increasing BC risk suggests that cyclical estrogen or estrogen + progestin are important for BC initiation and/or progression. The question arises whether the information we have concerning the responsiveness of ERalpha+ cells in TDLU, premalignant lesions, and invasive cancers give an indication of the targets for endocrine prevention. Data summarised in Table 1 indicate that TDLU are responsive to estrogen, ED, and SERMs/SERDs in premenopausal women and there may be the targets for the preventative effect of early oophorectomy particularly in BRCA1 carriers where we have demonstrated endocrine responsiveness of TDLU, which at this heterozygote stage are ERalpha+. The decline in numbers of atypical lobules in breasts without invasive cancer suggests that these are targets for the 'preventive' effect of the menopause, as suggested by Wellings. The data also suggest that ERalpha+ DCIS is responsive to estrogen and ED supporting premalignant lesions is a target as does the data from the NSABP P1 trial indicating a marked preventive effect of Tam in women previously diagnosed with atypical ductal hyperplasia and a preventative effect on CIS.en
dc.language.isoenen
dc.subjectBreast Canceren
dc.subjectEndocrine Preventionen
dc.subjectDrug Responseen
dc.subjectHRT-
dc.subject.meshBreast Neoplasms-
dc.subject.meshDrug Resistance, Neoplasm-
dc.subject.meshFemale-
dc.subject.meshHormone Replacement Therapy-
dc.subject.meshHumans-
dc.titleResponse and resistance to the endocrine prevention of breast cancer.en
dc.typeArticleen
dc.contributor.departmentCRC Department Medical Oncology, University of Manchester Christie Hospital and Holt Radium Inst., Manchester, UK.en
dc.identifier.journalAdvances in Experimental Medicine and Biologyen

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