Abstract:
The prevalence of breast cancer (BC) continues to increase and is the leading cause
of cancer deaths in many countries. Numerous in vitro and in vivo studies have
demonstrated that 2‐methoxyestradiol (2‐ME) has antiproliferative and antiangiogenic
effects in BC, thereby inhibiting tumour growth and metastasis. We compared
the effect of 2‐ME in early‐ and late‐stage BC using a transgenic mouse model—
FVB/N‐Tg(MMTV‐PyVT)—of spontaneously development of aggressive mammary
carcinoma with lung metastasis. Mice received 100 mg/kg 2‐ME treatment
immediately when palpable mammary tumours were identified (early‐stage BC;
Experimental group 1) and 28 days after palpable mammary tumours were detected
(late‐stage BC; Experimental group 2). 2‐ME was administered via oral gavage three
times a week for 28 days after initiation of treatment, whereas control mice received
the vehicle containing 10% dimethyl sulfoxide and 90% sunflower oil for the same
duration as the treatment group. Mammary tumours were measured weekly over the
28 days and at termination, blood, mammary and lung tissue were collected for
analysis. Mice with a tumour volume threshold of 4000mm3 were killed before the
treatment regime was completed. 2‐ME treatment of early‐stage BC led to lower
levels of mammary tumour necrosis, whereas tumour mass and volume were
increased. Additionally, necrotic lesions and anti‐inflammatory CD163‐expressing
cells were more frequent in pulmonary metastatic tumours in this group. In contrast,
2‐ME treatment of late‐stage BC inhibited tumour growth over the 28‐day period
and resulted in increased CD3+ cell number and tumour necrosis. Furthermore,
2‐ME treatment slowed down pulmonary metastasis but did not increase survival
of late‐stage BC mice. Besides late‐stage tumour necrosis, none of the other results
were statistically significant. This study demonstrates that 2‐ME treatment has an
antitumour effect on late‐stage BC, however, with no increase in survival rate,
whereas the treatment failed to demonstrate any benefit in early‐stage BC.
