SAN ANTONIOThe mitotic activity index (MAI), a
measure of tumor cell proliferation, has been shown to be an independent
prognostic factor for recurrence-free survival in breast cancer. It is being
used in the Netherlands to select which node-negative patients require adjuvant
chemotherapy, Elsken van der Wall, MD, PhD, said at the 23rd Annual San Antonio
Breast Cancer Symposium.
Dr. van der Wall spoke in place of the scheduled speaker, Paul
J. van Diest, MD, PhD, of the Department of Pathology, Free University
"The mitotic activity index is the best variable with
which to select node-negative breast cancer patients for adjuvant
chemotherapy," Dr. van der Wall said. It has a stronger prognostic
significance in early invasive breast cancer among node-negative patients than
other prognostic factors, including tumor size, she noted.
In the Netherlands, the MAI is being used to select which
premenopausal node-negative patients with early invasive breast cancer are high
risk and thus most likely to benefit from systemic adjuvant chemotherapy.
"Treating all lymph-node-negative patients leads to substantial
over-treatment," Dr. van der Wall said.
A consensus statement from the Dutch Society for Medical
Oncology on Adjuvant Chemotherapy recommends that adjuvant chemotherapy be
given only to high-risk patients, defined as those women who have an MAI equal
to or greater than 10 (in an area of 1.6 mm2) (see box). Low-risk
patients, defined as those with a tumor size of 1 to 3 cm and an MAI less than
10, are not recommended for adjuvant chemotherapy.
Dr. van der Wall presented the results of an 8-year follow-up
of 586 premenopausal node-negative patients from the Multicenter Mammary
Carcinoma Project of the Department of Pathology at the Free University
Hospital. The project was designed to prospectively evaluate the prognostic
value of various features in 3,479 patients with invasive breast cancer.
None of the 586 patients received adjuvant chemotherapy.
Eighty-five patients (14.5%) died of metastatic disease during the follow-up.
The deaths were not evenly distributed among patients with low and high MAI,
Only 19 (6.1%) of 310 patients with a low MAI (less than 10)
died of metastatic disease, compared with 66 (28.3%) of 233 patients with a
high MAI (10 or more). The survival of patients with low MAI was comparably
high in all subgroups, including patients with different tumor diameters and
grades and differences in estrogen-receptor and proges-terone-receptor status.
A number of potential problem areas have been identified with
the MAI, including variations in counting protocol. These concerns have been
addressed in many studies, Dr. van der Wall said. "Many of the studies
were conducted in Europe, particularly Scandinavia, and they have shown that
mitosis counting can be done in a highly reproducible way," she said.
In addition, intratumor heterogeneity is "easily
handled" by a trained pathologist, she said. The ill effects of fixation
delay on mitosis counting accuracy can be avoided so long as fixation is done
within 24 hours.