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Clinical response to primary letrozole therapy in elderly patients with early breast cancer : possible role for p53 as a biomarker

Garimella, Veerabhadram; Hussain, Tasadooq; Agarwal, Vijay; Radhakrishna, Selvi; Fox, John N.; Kneeshaw, Peter J.; Long, Ervine D.; Mahapatra, Tapan K.; McManus, Penelope L.; Lind, Michael J.; Drew, Philip J.; Cawkwell, Lynn


Veerabhadram Garimella

Tasadooq Hussain

Vijay Agarwal

Selvi Radhakrishna

John N. Fox

Peter J. Kneeshaw

Ervine D. Long

Tapan K. Mahapatra

Penelope L. McManus

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Professor Michael Lind
Foundation Professor of Oncology/ Head of the Joint Centre for Cancer Studies

Philip J. Drew

Lynn Cawkwell


Primary tamoxifen therapy has been widely used to treat elderly women with ER-positive breast cancer in the past. Aromatase inhibitors may be more beneficial than tamoxifen when used as primary endocrine therapy in elderly patients. We aimed to retrospectively evaluate a series of elderly women with ER-positive breast cancer treated with primary letrozole therapy as sole therapy with a minimum of 5 years follow up. To identify possible predictive biomarkers a pilot immunohistochemical analysis was performed to assess the expression of PR, HER2, EGFR, BCL2 and p53. A total of 45 women, aged more than 70 years with a diagnosis of ER-positive breast cancer that was treated with primary letrozole therapy were identified. A case note review was undertaken to obtain clinical information. Formalin fixed paraffin embedded tumour tissue from diagnostic core biopsies was available for all patients. Immunohistochemical analysis was performed to establish the protein expression status of p53, PR, HER2, EGFR and BCL2. The mean age of the 45 patients was 87 years (range 70–101). Clinical benefit was seen in 60% of the patients. Median progression free survival was 53 months (95% CI – 34–72) and the median time to progression was 43 months (95% CI – 22–64). BCL2 was expressed in 45/45 (100%); PR in 38/45 (84%); EGFR in 13/45 (28%); HER2 in 9/45 (20%) and p53 in 5/45 (11%) of tissue samples. Positive expression of p53 was associated with poor progression free survival (p = 0.03) in this pilot study. This study demonstrates that letrozole as sole treatment appears to be a suitable treatment option for elderly patients with ER-positive breast cancer who are not fit for, or decline, surgery. The analysis of p53 in a larger study is warranted in order to assess its role as a biomarker in this patient group.


Garimella, V., Hussain, T., Agarwal, V., Radhakrishna, S., Fox, J. N., Kneeshaw, P. J., …Cawkwell, L. (2014). Clinical response to primary letrozole therapy in elderly patients with early breast cancer : possible role for p53 as a biomarker. International journal of surgery, 12(8), 821-826.

Journal Article Type Article
Acceptance Date Jun 20, 2014
Online Publication Date Jul 7, 2014
Publication Date 2014-08
Deposit Date Aug 25, 2015
Publicly Available Date Nov 23, 2017
Journal International journal of surgery
Print ISSN 1743-9191
Electronic ISSN 1743-9159
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 12
Issue 8
Pages 821-826
Keywords Aromatase inhibitor; Breast cancer; Elderly; ER; p53
Public URL
Publisher URL
Additional Information Author's accepted manuscript of article published in: International journal of surgery, 2014, v.12, issue 8


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