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Abstract P2-06-19: Transferrin Receptor (CD71) identifies poor response to Tamoxifen in oestrogen receptor positive breast cancer patients [Abstract]

Nicholson, Robert Ian, Habashy, H., Gee, Julia Margaret Wendy, Finlay, Pauline, Farrow, Lynne, Jasani, Bharat, Barrett-Lee, Peter, Robertson, J. and Ellis, Ieuan 2011. Abstract P2-06-19: Transferrin Receptor (CD71) identifies poor response to Tamoxifen in oestrogen receptor positive breast cancer patients [Abstract]. Cancer Research 70 (24 Sup) , P2-P6. 10.1158/0008-5472.SABCS10-P2-06-19

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Abstract

Background: CD71 is involved in the cellular uptake of iron and is expressed on cells with high proliferation. Interestingly, we have Interestingly, we shown that its expression is associated with elevated tumour proliferation, shortened breast cancer specific survival and worsened outlook in ER+ adjuvant tamoxifen treated early breast cancer patients (Habashy et al, 2010). Here we extend our studies of the relationship between CD71 and tamoxifen outcome by study of an exploratory series of patients where endocrine response was directly assessable. Material and Methods: CD71 (clone 10F11 antibody; Abcam, Cambridge, UK) and proliferation (MIB1) immunohistochemistry were performed as described in Habashy et al (2010) on 87 formalin fixed paraffin-embedded breast cancers. These were obtained from patients within the Nottingham Tenovus Multiple Antibody Study who had received systemic tamoxifen therapy for locally advanced primary carcinoma or metastatic disease or for recurrence after surgery alone. All had lesions assessable for response quality at 6 months, with survival and duration of antihormone response measured from initiation of antihormone to death or progression on therapy respectively. 48 tumours were classified as ER+ and 39 ER-. Results: Within this tamoxifen treated series, 68/87 patients were deemed positive for CD71 (plasma membrane and cytoplasmic), showing HScore values >=5. In the ER+ subgroup, a greater clinical response rate to tamoxifen was seen in CD71 — tumours (10 CR/PR, 3 S and 2 P) versus their CD71+ counterparts (CR/PR, 11 S and 16 P, p=0.015). CD71 positivity was associated with a significantly shortened time to progression and death (Kaplan Meier Test, p=0.026 and p=0.005 respectively). Examination of the proliferation marker MIB1 in ER+ tumours revealed a positive association with CD71 expression (Spearman's Test, p=0.01). In ER-patients, comprising predominantly progressive disease on tamoxifen therapy, CD71 status showed no impact on either time to progression of the disease or death. Discussion: The present study extends our novel findings relating CD71 expression to loss of response to tamoxifen in ER+ breast cancer and reveals CD71 associates with increased tumour cell proliferation in clinical disease. Whether CD71 plays a causative role in the direction of these events and can be targeted to improve endocrine response requires to be ascertained.

Item Type: Article
Date Type: Publication
Status: Published
Schools: Pharmacy
Medicine
Subjects: R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Publisher: American Association for Cancer Research
ISSN: 0008-5472
Last Modified: 10 Oct 2017 14:28
URI: http://orca-mwe.cf.ac.uk/id/eprint/32435

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