Ca 15-3

Clinical Biochemistry 34 (2001) 347–352

Biochemical markers in breast cancer: which ones are clinically useful?
M. J. Duffya,b,c,*
a

Department of Nuclear Medicine, St Vincent’s University Hospital, Dublin, Ireland
b
Department of Surgery, University College Dublin, Dublin, Ireland
c
Conway Institute of Biomolecular and Biomedical Research, University College Dublin, Dublin, Ireland
Received 7November 2000; accepted 21 November 2000

Abstract
Breast cancer is the most common neoplasm affecting women in the Western world with approximately 1 in 11 developing the
malignancy and 1 in 30 dying from the disease. For optimum management of these patients, assay of certain biochemical markers is
necessary. Clinically, the most useful markers in breast cancer are the estrogen and progesteronereceptors that are used to predict response
to hormone therapy. Both American and European Expert Panels have recommended routine determination of these steroid hormone
receptors in all patients with breast cancer. For surveillance of patients with diagnosed breast cancer, both CA 15–3 and BR 27.29 can be
used. Serial determinations of these markers have the potential to preclinically detectrecurrent disease and monitor the treatment of
advanced disease. However, the benefit of this monitoring on patient outcome or quality of life is not clear. New or potentially new markers
for breast cancer include BRCA1 and BRCA2 for selecting patients at high risk of developing breast cancer, urokinase plasminogen
activator and PA1–1 for assessing prognosis and HER-2 for predicting response to thetherapeutic antibody, Herceptin. © 2001 The
Canadian Society of Clinical Chemists. All rights reserved.
Keywords: Breast cancer; Tumor markers; Estrogen receptor; CA 15–3; BR 27.29; HER-2; Urokinase; PAI-1

1. Introduction
Breast cancer is by far the most frequent cancer in
women, worldwide and ranks third overall when both sexes
are considered together [1]. It is the most common cancer in
women in alldeveloped countries (except Japan), as well as
in North Africa, South America, Southeastern and Western
Asia [1]. Worldwide, approximately 1 million new cases of
breast cancer were reported in 1997 [2]. While the incidence
of breast cancer appears to be increasing, mortality rates are
now declining, in at least some Western countries [3]. This
decrease in mortality is most likely due to both theincreased
use of screening for early disease and the widespread administration of systemic adjuvant therapies.
The optimum management of patients with breast cancer
requires a multidisciplinary approach including the use of
certain tumor markers. The aim of this paper is to review the
use of biochemical markers in the detection and management of patients with breast cancer. The application of
*Department of Nuclear Medicine, St Vincent’s University Hospital,
Dublin 4, Ireland. Tel.: 353-1-2094378; fax: 353-1-2696018.
E-mail address: Michael.J.Duffy@ucd.ie (M.J. Duffy).

markers will be discussed under the following headings:
risk assessment, determining prognosis, selecting appropriate therapy and monitoring patients with diagnosed disease.

2. Risk assessment
Approximately, 5 to 10% ofbreast cancers are caused by
the inheritance of a germline mutation in a cancer predisposing gene. Numerically, the most important of these
genes are BRCA1 and BRCA2 [4]. The BRCA1 gene is
located on the long arm of chromosome 17 (17q21) and
encodes a protein containing 1863 amino acids [5]. The
BRCA1 protein appears to have multiple functions, being
involved in regulating transcription, inhibitingcellular proliferation and repairing DNA [6]. Over 100 different mutations in the BRCA1 gene have now been described [4].
Most of these mutations gives rise to a truncated protein due
either to a frameshift or nonsense mutation.
BRCA2 is a larger gene than BRAC1 and codes for a
protein of 3418 amino acids [7]. The BRCA2 protein appears to have similar functions to that of BRCA1 and like...