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Rapid response to:


Self reported stress and risk of breast cancer: prospective cohort study

BMJ 2005; 331 doi: (Published 08 September 2005) Cite this as: BMJ 2005;331:548

Rapid Response:

Self-perceived stress and breast cancer risk

Dear Sirs

The finding by Nielsen et al (1) that women with high levels of self-
perceived stress had a lower risk of developing breast cancer, than those
with low levels is very interesting. However the authors’ conclusion lacks
support from their own observations and from other experimental studies.
The authors suggested that the risk reduction observed was most likely
caused by decreased endogenous oestrogen production, due to the effect of
chronic stress on the hypothalamic-pituitary-adrenal axis. They did not
report the hormone receptor status of the tumours in the 251 women who
developed breast cancer during follow-up. If their hypothesis were
correct, then one would expect to observe a reduction in the risk of
developing oestrogen-receptor positive, but not oestrogen-receptor
negative, breast cancer in those women with high stress levels. Most
women who participated in the study were post-menopausal at base-line,
with a mean age of 57 years and, in this population, the main source of
oestrogen production is peripheral tissue aromatase activity rather than
the ovaries as in pre-menopausal women (2.3). The various cytokines known
to be elevated in chronic stress states can influence aromatase activity
(3). Furthermore, the risk reduction was observed mainly in women taking
hormone replacement therapy, whose serum oestrogen levels are determined
mainly by exogenous rather than endogenous sources.

Finally, there is
experimental evidence that chronic stress increases oestrogen and other
steroid levels in serum (4). Therefore, it is difficult to provide a
biological explanation for the observations reported by the authors.
Further prospective studies with an objective stress assessment as base-
line and at regular intervals during follow-up combined with the
measurement of biological factors known to influence the risk of breast
cancer are required.

Professor Kefah Mokbel. MS, FRCS

Professor at Brunel Institute of Cancer Genetics,

Consultant Breast & Endocrine Surgeon.

The Princess Grace Hospital,
42-52 Nottingham Place,
London W1M 3FD


Mr Mohamed Salhab MRCS

Research Fellow, St Georges Hospital,London, SW17 0QT


1. Nielsen et al, Self-reported Stress and Risk of Breast Cancer:
Prospective cohort Study BMJ 2005, 331:548-550

2. Mokbel K. The evolving role of aromatase inhibitors in breast cancer.
Int J Clin Oncol. 2002 ;7(5):279-83. Review.

3. Singh A, Purohit A, Duncan LJ, Mokbel K, Ghilchik MW, Reed MJ. Control
of aromatase activity in breast tumours: the role of the immune system. J
Steroid Biochem Mol Biol. 1997;61(3-6):185-92

4. MacNiven E et al. Chronic stress increases estrogen and other steroids
in inseminated rats. Physiol Behav. 1992; 52(1):159-62.

Competing interests:
None declared

Competing interests: No competing interests

21 September 2005
Kefah Mokbel
Professor at Brunel Institute of Cancer Genetics,Consultant Breast & Endocrine Surgeon.
Mohamed Salhab
The Princess Grace Hospital, 42-52 Nottingham Place, London W1M 3FD