CHICAGO—Giving tamoxifen concurrently with adjuvant chemotherapy halves
the benefit of the chemohormonal combination compared to giving tamoxifen
after completion of chemotherapy in postmenopausal patients with
node-positive, hormone-receptor positive breast cancer (ASCO abstract 143).
These initial results from North American Breast Intergroup Trial 0100 (INT
0100, SWOG 8814), presented by Kathy S. Albain, MD, are expected to
establish a new standard of care for treating breast cancer in
postmenopausal women.

Based on a median follow-up of 8.5 years, the intergroup data showed that
giving tamoxifen concurrently with chemotherapy reduces both disease-free
survival and overall survival compared to giving chemotherapy followed by
tamoxifen.

"Concurrent chemotamoxifen may result in suboptimal benefit from
this or similar chemotherapy programs, potentially cutting efficacy by as
much as 50%. The results of INT 0100 support a new practice standard of
starting adjuvant tamoxifen after chemotherapy is completed," Dr.
Albain said. She is the trial’s lead investigator as well as director of
breast cancer research and co-director of the Breast Care Center at Loyola University’s Cardinal Bernardin Cancer
Center in Chicago.

Researchers had suspected that tamoxifen might interfere with the effects
of cytotoxic chemotherapy because many currently used antineoplastic agents
are cell-cycle dependent. Tamoxifen freezes tumor cells in the mitotic
pathway, making them less vulnerable to cytotoxic agents.

Objectives and Stratification

Dr. Albain said that the first objective of this trial was to determine
whether adding tamoxifen to anthracycline-based adjuvant therapy with CAF
(oral cyclophosphamide [Cytoxan, Neosar)/doxorubicin
[Adriamycin]/fluorouracil) was superior to tamoxifen alone for treatment of
breast cancer in postmenopausal women with node-positive and
hormone-receptor positive disease. "Last year we reported a significant
disease-free survival and overall survival advantage for the
combination," she said.

The second objective, addressed in this year’s presentation, was to
determine whether CAF followed by tamoxifen (CAF-T) was more effective than
concurrent CAF-tamoxifen therapy (CAFT).