This excellent and practical article
by Dr. Ravdin is worthwhile
reading for every physician involved
in the long-term care of women
with a previous diagnosis of breast
cancer. Dr. Ravdin clearly outlines
the theoretical rationale underlying the
increased risk of osteopenia and osteoporosis
in women with a history of
breast cancer. The fact that such women
commonly undergo premature
menopause either deliberately, as part
of treatment for breast cancer, or as a
secondary effect of chemotherapy, and
that estrogen-replacement therapy
with or without progesterone(Drug information on progesterone) remains
contraindicated for fear of increasing
the risk of recurrence, clearly contributes
to the increased possibility of
developing osteopenia or osteoporosis.
New data supporting the role of
aromatase inhibitors in adjuvant therapy[1-4] will undoubtedly lead to the
increased use of these agents in the
adjuvant therapy of breast cancer, with
the probability of increasing the risk
of decreased bone density.
Underestimate of Risk
It seems clear from the adjuvant
studies of aromatase inhibitors cited
above that there may well be an increased
incidence of osteopenia, osteoporosis,
and/or fractures associated
with even the short-term use of these
agents in adjuvant therapy. The Arimidex, Tamoxifen(Drug information on tamoxifen) Alone or in Combination
(ATAC) trial reports an increased
incidence of fracture, while the Canadian-
led MA.17 study and the Intergroup Exemestane(Drug information on exemestane) Study (IES) report
marginally increased self-reported or
physician-elicited incidences of osteoporosis
and/or fracture. Since osteoporosis
develops gradually over
several years and fractures may be asymptomatic-
or, if symptomatic, are
often seen only 5 to 10 years or more
into the natural history of this disease-
reports from studies with a median follow-
up of 3 to 5 years likely represent
an underestimate of the risk of fracture
in women receiving this therapy.
Thus, Dr. Ravdin's succinct summary
of a practical approach to such
patients is both timely and useful. In
truth, however, there is little evidence
demonstrating that the use of approaches
that are effective in osteoporosis
in general are equally
effective in women with a prior diagnosis
of breast cancer. Theoretically,
it would seem that these approaches
should work in a similar fashion, but
few studies have been conducted in
these women up to the present time.
Ongoing Trials
Currently, several ongoing trials
are exploring the role of zoledronic
acid (Zometa) in women receiving anastrozole(Drug information on anastrozole) (Arimidex), and of other
bisphosphonates in women receiving
exemestane (Aromasin). Specific results
of such trials are not as yet available.
Hopefully, these powerful
bisphosphonates will work as well in
such women as they have been shown
to do in osteoporotic and osteopenic
women without a history of breast
cancer.
In the meantime, Dr. Ravdin's article
will provide a scientifically based
and practical approach to the management
of this situation in postmenopausal
women with the diagnosis of
breast cancer.
