Objectives: Breast manipulation determines a physiological increase in prolactin (PRL) blood levels, but the clinical and biological impact of surgery-induced changes in PRL secretion still has to be clarified. The postoperative hyperprolactinemia has been related to aggressiveness of the tumor, early disease relapse or metastases, and poor overall survival in node-negative breast cancer patients. Surgery-induced hyperprolactinemia may be associated with a longer disease-free survival in both patients with or without node involvement. Methods: One hundred twenty-seven consecutive node-negative breast cancer patients, who were hospitalized from June 1985 to September 1990, were included in this study. The median follow-up was 12 years. To evaluate PRL secretion, venous blood samples were obtained at day 7th after surgery. In order to exclude the influence of stress and gonadal status, GH and estradiol serum levels were measured in the same blood samples. All endocrine examination were made during the morning, starting at 8.00 a.m. after overnight fasting. Hormonal serum levels were determined by the double antibody radioimmunoassay method. Results: Hyperprolactinemia was significantly more frequent in women younger than 50 years compared with the older ones, while the premenopausal status and T1 stage showed only a borderline significant association with hyperprolactinemia. Patients with normal postsurgical prolactinemia had 5- and 10-year disease-free survival rates of 64 and 56%, respectively, and 5- and 10-year overall survival rates of 84 and 70%, respectively. Patients with postsurgical hyperprolactinemia had 5- and 10-year disease-free survival rates of 89 and 81%, respectively, and 5- and 10-year overall survival rates of 94 and 81%, respectively. The difference in overall survival between the hyperprolactinemic and the normoprolactinemic groups, assessed by the log-rank test, was statistically significant (p = 0.02), and the difference in disease-free survival was highly significant (p = 0.0008). Conclusions: Our study shows that postsurgical hyperprolactinemia is associated with a significantly lower recurrence rate and longer disease-free and overall survival in operable node-negative breast cancer patients. Our data suggest that postoperative hyperprolactinemia could be crucial in the development of recurrence in operable breast cancer. Looking at results, the recurrence rate of node-negative patients who did not show postoperative hyperprolactinemia would be, in theory, similar to that of patients with node-positive disease, suggesting that normal postoperative PRL levels could identify a group of node-negative patients at high risk for recurrence.

Keywords:
Hyperprolactinemia, Breast cancer, node-negative
1.
Clark GM, McGuire WL: Steroid receptors and other prognostic factors in primary breast cancer. Semin Oncol 1988;15:20–25.
2.
Silvestrini R, Dandone MG, Luisi A, et al: Biologic and clinicopathologic factors as indicators of specific relapse types in node-negative breast cancer. J Clin Oncol 1995;13:697–704.
3.
Goffin V, Touraine P, Pitchard C, et al: Should prolactin be considered as a therapeutic target in human breast cancer? Mol Cell Endocrinol 1999;151:79–87.
4.
Vonderhaar BK: Prolactin involvement in breast cancer. Endocr Relat Cancer 1999;6:389–404.
5.
Spady TJ, Harvell DM, Snyder MC, et al: Estrogen-induced tumorigenesis in the Copenhagen rat: Disparate susceptibilities to development of prolactin-producing pituitary tumors and mammary carcinoma. Cancer Lett 1998;13:95–103.
6.
Harvell DM, Strecker TE, Tochacek M, et al: Rat strain-specific actions of 17beta-estradiol in the mammary gland: Correlation between estrogen-induced lobuloalveolar hyperplasia and susceptibility to estrogen-induced mammary cancers. Proc Natl Acad Sci USA 2000;14:2779–2784.
7.
Patel DD, Bhatavdekar JM, Chikhlikar PR, et al: Node negative breast carcinoma: Hyperprolactinemia and/or overexpression of p53 as an independent predictor of poor prognosis compared to newer and established prognosticators. J Surg Oncol 1996;62:86–92.
8.
Lissoni P, Barni S, Ardizzoia A, et al: Prediction of recurrence in operable breast cancer by postoperative changes in prolactin secretion. Oncology 1995;52:439–442.
9.
Boyns AR, Buchan R, Cole EN, et al: Basal prolactin blood levels in three strains of rat with differing incidence of 7,12-dimethylbenz(a)antracene-induced mammary tumors in rats. Eur J Cancer 1973;9:169–171.
10.
Welsch CW, Griber C: Prophylaxis of spontaneously developing mammary carcinoma in C3H/HeJ female mice by suppression of prolactin. Cancer Res 1973;33:2936–2946.
11.
Welsch CW, Nagasawa H: Prolactin and murine mammary tumorigenesis: A review. Cancer Res 1977;37:951–963.
12.
Patel DD, Bhatavdekar JM, Chikhlikar PR, et al: Node negative breast carcinoma: Hyperprolactinemia and/or overexpression of p53 as an independent predictor of poor prognosis compared to newer and established prognosticators. J Surg Oncol 1996;62/2:86–92.
13.
Bhatavdekar JM, Patel DD, Vora HH, et al: Node positive breast cancer: Prognostic significance of the plasma prolactin compared with steroids receptors and clinicopathological features. Oncol Rep 1994;1:841–845.
14.
Martini JF, Piot C, Humeau LM, Struman I, et al: The antiangiogenic factor 16K PRL induces programmed cell death in endothelial cells by caspase activation. Mol Endocrinol 2000;14:1536–1549.
15.
Barni S, Lissoni P, Fumagalli L, et al: Serum levels of insulin-like growth factor-I in operable breast cancer in relation to the main prognostic variables and their perioperative changes in relation to those of prolactin. Tumori 1994;80:212–215.
16.
Gordts SL, Neven P, Van Hooff I, et al: The immunocytochemical versus cytosol measurement of the oestrogen receptor in invasive breast cancer tissue. Eur J Cancer 2000;36(suppl 4):S20–21.
17.
Hanna W, Mobbs BG: Comparative evaluation of ER-ICA and enzyme immunoassay for the quantitation of estrogen receptors in breast cancer. Am J Clin Pathol 1989;91/2:182–186.
18.
Lapidus RG, Nass SJ, Davidson NE: The loss of estrogen and progesterone receptor gene expression in human breast cancer. J Mammary Gland Biol Neoplasia 1998;3/1:85–94.
19.
Leers MP, Nap M: Steroid receptor heterogeneity in relation to DNA index in breast cancer: A multiparameter flow cytometric approach on paraffin-embedded tumor samples. Breast J 2001;7/4:249–259.
20.
Tamoxifen for early breast cancer: An overview of the randomised trials. Early Breast Cancer Trialists’ Collaborative Group. Lancet 1998;351:1451–1467.
21.
Wang DY, Hampson S, Kwa HG, et al: Serum prolactin levels in women with breast cancer and their relationship to survival. Eur J Cancer Clin Oncol 1986;22:487–492.
22.
Fisher B, Redmond C, Fisher ER, et al: Relative worth of estrogen and progesterone receptor and pathologic characteristics of differentiation as indicators of prognosis in node negative breast cancer patients: Findings from National Surgical and Bowel Project (NSABP) Protocol B-06. J Clin Oncol 1988;6:1076–1087.
23.
Arriagada R, Rutqvist LE, Skoog L, et al: Prognostic factors and natural history in lymph node negative breast cancer patients. Breast Cancer Res Treat 1992;21:101–109.
24.
Ravdin PM, Siminoff LA, Davis GJ, et al: Computer program to assist in making decisions about adjuvant therapy for women with early breast cancer. J Clin Oncol 2001;19:980–991.
25.
Loprinzi CL, Thome SD: Understanding the utility of adjuvant systemic therapy for primary breast cancer. J Clin Oncol 2001;19:972–979.
© 2002 S. Karger AG, Basel
2002
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