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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Prasad
Ramachandran
R
Department of Surgery, University Hospital of South Manchester, Manchester, United Kingdom.
Boland
Gary P
GP
Cramer
Angela
A
Anderson
Elizabeth
E
Knox
W Fiona
WF
Bundred
Nigel J
NJ
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D001707:Biopsy, Needle; D001943:Breast Neoplasms / Q000378:metabolism* / Q000503:physiopathology; D044584:Carcinoma, Ductal / Q000378:metabolism / Q000503:physiopathology; D018275:Carcinoma, Lobular / Q000378:metabolism / Q000503:physiopathology; D018797:Cell Cycle Proteins / Q000378:metabolism; D019938:Cyclin D1 / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27; D015914:Estrogen Replacement Therapy / Q000009:adverse effects*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008875:Middle Aged; D011960:Receptors, Estrogen / Q000378:metabolism; D011980:Receptors, Progesterone / Q000378:metabolism; D012307:Risk Factors; D013375:Substance Withdrawal Syndrome / Q000378:metabolism* / Q000503:physiopathology; D025521:Tumor Suppressor Proteins / Q000378:metabolism
D014408:Biomarkers, Tumor; D018797:Cell Cycle Proteins; D019394:Ki-67 Antigen; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D025521:Tumor Suppressor Proteins; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27