Stop HRT if ER+ Breast Cancer Develops

Short-term biologic response to withdrawal of hormone replacement therapy in patients with invasive breast carcinoma

Ramachandran Prasad, M.B.B.S. 1, Gary P. Boland, B.Sc., M.B., Ch.B. 1, Angela Cramer, B.Sc. 2, Elizabeth Anderson, B.Sc., Ph.D. 2, W. Fiona Knox, M.B., Ch.B. 3, Nigel J. Bundred, M.D. 1 *

1Department of Surgery, University Hospital of South Manchester, Manchester, United Kingdom 2Department of Clinical Research, Christie Hospital NHS Trust, Manchester, United Kingdom 3Department of Pathology, University Hospital of South Manchester, Manchester, United Kingdom

email: Nigel J. Bundred (

*Correspondence to Nigel J. Bundred, Academic Department of Surgery, University Hospital of South Manchester, Southmoor Road, Wythenshawe, Manchester M23 9LT United Kingdom

Fax: (011) 44-161-291-5860

Conference: British Association of Surgical Oncology (BASO), Glasgow, United Kingdom, November 2001

Conference: Society of Academic and Research Surgery (SARS), London, United Kingdom, January 2002

Conference: Association of Surgeons of Great Britain and Ireland (ASGBI), Dublin, Ireland, May 2002



The biologic effect of continuing hormone replacement therapy (HRT) after a diagnosis of breast carcinoma is unclear. The goal of rhe current study was to determine the short-term effect of HRT withdrawal on invasive breast carcinoma using biologic surrogate markers of tumor response.


The study was performed between 1996 and 2000 and comprised 140 women who had been using HRT at the time of breast carcinoma diagnosis by core needle biopsy. The breast tumors were removed a median of 17 days later (range, 2-31 days).

Of these women, 125 women stopped HRT at the time of core needle biopsy and 15 continued to receive HRT until surgery. In addition, 55 women with breast carcinoma from the same time period, who were not receiving HRT at diagnosis, were studied.

Changes in expression of Ki-67 (a measure of epithelial cell proliferation), progesterone receptor (PR), p27KIP-1 (a cyclin-dependent kinase inhibitor), and cyclin D1 (a cell cycle-related protein) were determined by immunohistochemistry on paired sections of the core needle biopsy and surgical specimens from each patient.


In women who stopped HRT, a significant decrease in Ki-67 expression was observed between core needle biopsy and surgery in estrogen receptor (ER)-positive (n = 106; P < 0.001), but not in ER-negative tumors (n = 19; P = 0.58), with an associated reduction in PR (P < 0.001) and cyclin D1 expression (P < 0.001) and an increase in p27KIP-1 (P = 0.03).

These changes in Ki-67 and PR expression occurred irrespective of c-erb-B2 status. No change was observed in any parameter in the other groups of patients.


ER-positive invasive breast carcinomas demonstrated a favorable biologic response to withdrawal of HRT.

Therefore, HRT should be stopped at the time of diagnosis and was subsequently contraindicated.

Cancer 2003;98:2539-46.

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