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Endocrine response and resistance in breast cancer: a role for the transcription factor Fos
Author(s) -
Gee Julia M.W.,
Willsher Peter C.,
Kenny Frances S.,
Robertson John F.R.,
Pinder Sarah E.,
Ellis Ian O.,
Nicholson Robert I.
Publication year - 1999
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/(sici)1097-0215(19990219)84:1<54::aid-ijc11>3.0.co;2-x
Subject(s) - endocrine system , transcription factor , breast cancer , medicine , cancer research , oncology , endocrinology , cancer , biology , hormone , genetics , gene
We have previously demonstrated that elevated Fos expression may be important in de novo endocrine resistance in breast cancer. However, changes in Fos expression during endocrine response and subsequently on acquisition of resistance are unknown. This study immunocytochemically monitors Fos protein within sequential biopsies from primary human breast cancer patients obtained pre‐treatment (T1), during tamoxifen therapy (T2, T3) and on disease progression (T5), examining in parallel proliferation [ i.e., MIB1 (Ki67) immunostaining, mitotic activity], cellularity and endocrine response. Significantly diminished Fos, proliferation and cellularity were observed after 6 weeks of therapy in patients exhibiting a better quality and/or duration of response, while modest Fos increases and a maintained proliferation and cellularity were seen in poorer responders. Decreases in Fos, proliferation and cellularity at 6 months similarly hallmarked better responders. We confirmed a significant association between de novo resistance and elevated Fos and proliferation. Additionally, however, these parameters increased at the time of disease relapse over pre‐treatment and “on therapy” values. Our data indicate that tamoxifen response involves a reduction in both tumor cell proliferation and cell survival, potentially entailing diminished Fos protein expression in better‐responding patients. Our data are also supportive of elevated Fos expression being involved in the departure from endocrine control inherent in both primary and acquired resistance. Int. J. Cancer (Pred. Oncol.) 84:54–61, 1999. © 1999 Wiley‐Liss, Inc.