Who Should Not Receive Chemotherapy? Data From American Databases and Trials
Journal of the National Cancer Institute Monographs No.
Who Should Not Receive Chemotherapy? Data From American Databases and Trials
Monica Morrow 0
Helen Krontiras 0
0 Oxford University Press
The demonstration of the effectiveness of chemotherapy in both premenopausal and postmenopausal women, regardless of estrogen receptor (ER) status, raises the question of whether all breast cancer patients should receive chemotherapy. Several patient groups with such a favorable longterm prognosis that they will obtain an extremely small benefit from chemotherapy can be identified. They include patients with lymph node-negative tumors of 1 cm or less in size, those with grade 1 tumors between 1.1 and 2.0 cm in size, and those with tumors of favorable histologic type (tubular and mucinous) up to 3 cm in size. A patient subgroup in which it is not clear that the benefits of chemotherapy routinely exceed the risks is postmenopausal women with ER-positive, lymph node-negative cancers receiving tamoxifen. There is a wide variation in prognosis in this group, and chemotherapy should be reserved for those at high risk of recurrence. Finally, no benefit for chemotherapy in women aged 70 years and older has been identified. The high rate of death from causes other than breast cancer may negate small survival benefits, and after adjustment for quality of life, the duration of treatment exceeds the gain in life expectancy. [J Natl Cancer Inst Monogr 2001;30:109-13]
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The Oxford Overview Analysis (
1
) has clearly demonstrated
that adjuvant systemic chemotherapy reduces the risk of
mortality for women with both lymph node-positive and lymph
node-negative breast cancer and is effective in both
premenopausal and postmenopausal women. In light of the proven
benefit of chemotherapy, it is reasonable to ask whether there are
any groups of breast cancer patients who should not receive this
treatment. Potential patient groups who will not achieve a net
benefit from chemotherapy include women with an extremely
favorable prognosis, where the reduction in mortality from
chemotherapy translates to an absolute survival difference of only
a few percent; patients in whom the potential risks of
chemotherapy outweigh the benefits; and patient subsets for which
chemotherapy has not been proven to have a survival benefit.
This article will discuss breast cancer patient groups who meet
these criteria.
FAVORABLE PROGNOSIS SUBGROUPS
Subsets of lymph node-negative breast cancer patients with a
favorable prognosis have usually been defined on the basis of
tumor size or histologic subtype. The use of screening
mammography has resulted in the increasingly frequent identification
of cancers of 1 cm or less in size. Several large datasets (
2–6
)
confirm that tumors of this size have an extremely favorable
prognosis. The Breast Cancer Detection Demonstration Project
(BCDDP) was one of the earlier studies to report on the
favorable outcome of patients with tumors less than 1 cm in size (
2
).
In the BCDDP, the 880 patients with stage I cancer had an
8-year survival rate of 90%, and for those with tumors less than
1 cm in size, the survival rate was 96%. This favorable prognosis
was observed for both the interval and screen-detected cancers,
where the survival rates at 8 years were 94% and 96%,
respectively (
2
). Eight-year survival rates above 90% were noted
across all age groups for tumors of this size, with women aged
40–44 years having a 99% 8-year survival rate compared with
98% for those aged 50–54 years and 94% for those aged 60–64
years.
More recent studies (
3–6
) have confirmed these favorable
survival rates in large, unselected groups of women. The
National Cancer Data Base (NCDB) (3), a joint project of the
American College of Surgeons Commission on Cancer and
the American Cancer Society, has collected data from 1849
hospitals on 240 031 patients who were diagnosed with breast
cancer from 1985 to 1991. There were 94 106 patients whose cancer
was staged as T1N0, and these women had a 5-year relative
survival rate of 95.3%. When this group was broken down
further into patients with tumors less than 1 cm and those with
tumors between 1 and 2 cm, the relative 5-year survival rates
were 98.4% (n 22 288) and 94.4% (n 71 818), respectively.
Survival data from two different time periods reported by the
Surveillance, Epidemiology, and End Results Program1 (SEER)
are very similar to those of the NCDB. From 1977 through 1982,
57 828 stage I breast cancers were reported (
4
). The 5-year
relative survival rate was 96.3%, ranging from 99.2% for the 269
patients with tumors less than 5 mm in size to 98.3% for those
with tumors 0.5–0.9 cm in size and to 85.8% for patients with
tumors 1.0–1.9 cm in size. These results are confirmed in the
most recent SEER report of patients diagnosed from 1988
through 1994 (
5
). In this time period, 7842 cancers less than
5 mm in size and 11 543 cancers between 5 and 9 mm in size
were reported. Both of t (...truncated)