Endocrine therapy is the oldest form of treatment for metastatic
breast cancer. The availability of numerous new endocrine agents
during the past 10 years has led to significant changes in the use of
this form of therapy. This article identifies appropriate candidates
for endocrine therapy and describes various treatment options for
different subsets of patients with metastatic disease. Overall, Dr.
Pritchard does an excellent job of summarizing this information in
her article. However, a few shortcomings of the article need to be addressed.
Points Requiring Further Comment
The article does not provide a comparison of the two antiestrogens
approved for the treatment of metastatic disease in North America,
ie, tamoxifen (Nolvadex) and toremifene (Fareston). The author fails
to state that both agents have similar antitumor activity. There is
cross-resistance between the two agents, and, thus far, no evidence
suggests the superiority of toremifene over tamoxifen. Also omitted
is the fact that there are no appropriate long-term data on the
efficacy of toremifene in the adjuvant setting.
Exemestane (Aromasin) is a second-generation steroidal aromatase
inhibitor that acts by suicidal inhibition of the aromatase enzyme.
This drug has been evaluated as second-line therapy in postmenopausal
women in a phase III study. All of the patients had received prior
treatment with tamoxifen and, upon disease progression, were included
in the study. The data from this phase III study demonstrate a
similar degree of antitumor activity with exemestane as has been
observed with the other two aromatase inhibitors, anastrozole
(Arimidex) and letrozole (Femara). Of significant interest are data
from limited phase II studies showing that exemestane has antitumor
activity in patients previously treated with aminoglutethimide. No
data currently exist regarding the efficacy of anastrozole or
letrozole following treatment with exemestane. Dr. Pritchard fails to
point out that the appropriate sequence of treatment may be an
Imidozole followed by exemestane. This approach would enhance the
treatment armamentarium for metastatic disease, as exemestane has
significant antitumor activity and a better safety profile than the
pro-gestins, which are currently used as third-line therapy in this
subset of patients.
The article contains a lengthy discussion of combined hormonal
therapy. However, the data are too heterogeneous, and the studies
cited do not have appropriate statistical strength to recommend
combined hormonal therapy in the metastatic setting at present.
Sequential use of these agents is recommended until more convincing
data become available to change this practice.
In the adjuvant setting, ongoing trials are evaluating the role of
combined hormonal therapy. However, results of those studies are not
In postmenopausal patients who are estrogen receptor positive, the
combination of chemotherapy plus tamoxifen is superior to tamoxifen
alone. This point is not clearly made in the article, however.
The article includes a brief discussion of data comparing anastrozole
vs tamoxifen as front-line therapy. (These data became available
after Dr. Prichards Meet the Professor session at
the 1999 American Society of Clinical Oncology (ASCO) meeting, and
were obviously added by the author to update her talk.) These data
suggest the first new treatment option for postmenopausal women in 30
years. In patients with estrogen receptor positive tumors,
anastrozole has antitumor activity that is superior to that of
tamoxifen, and it also has a better safety profile than tamoxifen.
Thus, currently, anastrozole could be considered as initial therapy
for metastatic breast cancer in postmenopausal patients who have an
estrogen receptorpositive tumor. However, detailed reports of
the data are needed before further comments can be made regarding
these two studies.
The availability of a number of new agents and a better understanding
of endocrine treatment have expanded the treatment options for women
with metastatic breast cancer. Endocrine therapies can palliate the
symptoms of patients who have an estrogen-dependent tumor. Sequential
use of endocrine agents can control the disease for an extended
period in this subset of patients.
1. Kaufmann M, Bajetta E, Dirix LY, et al: Survival advantage of
exemestane (EXE, Aromasin) over megestrol acetate (MA) in
postmenopausal women with advanced breast cancer (ABC) refractory to
tamoxifen (TAM): Results of a phase III randomized double-blind study
(abstract). Proc Am Soc Clin Oncol 18:109a, 1999.
2. Bryan TM, Reddel RR: Telomere dynamics and telomerase activity in
vitro immortalized human cells. Eur J Cancer 33:767-773, 1997.
20. Nabholtz JM, Bonneterre J, Buzdar AU, et al: Preliminary results
of two multi-center trials comparing the efficacy and tolerability of
Arimidex (anastrozole) and tamoxifen (TAM) in postmenopausal (PM)
women with advanced breast cancer (ABC) (abstract). Breast Cancer Res
Treat 57:31, 1999.