2012 EDUCATIONAL BOOK - American Society of Clinical Oncology

OVERDIAGNOSIS AND OVERTREATMENT OF BREAST CANCER
Fig 1. The SEER incidence of ductal carcinoma in situ (DCIS), stage I
(localized), stage II (regional), and stage IV (distant) breast cancer
over time. The red line at the bottom represents the incidence of DCIS
in 1980. The large red arrow represents the change in incidence in
DCIS by the year 2002. A concomitant drop in the incidence of
invasive cancer (top red arrow of equal magnitude) has not been
observed.
This evidence has even led to the hypothesis that some
screen-detected invasive breast cancers would likely regress
and be clinically unimportant in the future. 8,10 Some note
that screening of all kinds has led to an epidemic of overdiagnosis.
11 It is difficult to say with absolute certainty that
the increase in cancers detected would never become a
clinical problem, but there is ample evidence that the biology
of screen-detected tumors differs substantially from that of
interval cancers or nonscreening-detected cancers, 12,13 although
some say that the improvement in outcome is explained
by lead-time bias. 14
What is clear is that the lower risk biology associated with
these tumors should safely allow less treatment. In particular,
there are groups of women for whom local therapy, in
particular, can be less, and for whom breast conservation
with adjuvant hormone therapy alone or with intraoperative
radiation therapy is associated with a low risk for local
recurrence and low mortality. 5,7,15 Surveillance Epidemiology
and End Results (SEER) data indicate that as many as
50% of all cancers occur in postmenopausal women and are
KEY POINTS
● SEER data suggest that a meaningful amount of both
invasive and noninvasive breast cancers are likely to
be overdiagnosed and overtreated.
● Further risk stratification is needed in the treatment
of breast cancer to avoid overtreatment.
● Focusing on the prevention of invasive disease may
be one option to reduce the overtreatment of DCIS.
● Learning from experiences in prostate cancer, active
surveillance should be considered for some cases of
DCIS.
● Additional efforts towards the prevention of breast
cancer are greatly needed.
node-negative and low or intermediate grade. 16 Given that
the inclusion of external-beam radiation therapy is considered
a marker of quality care for breast cancer, there is
clearly evidence of overtreatment.
For many years, it has been recognized that there are
various pathologic characteristics and a spectrum of changes
in breast cell morphology, which range from hyperplasia to
atypia to in situ carcinoma. 17,18 Many researchers believed
that each of these changes carried a distinct increase in risk
for future invasive breast cancer. The classic “precursor
pathway,” was accepted and therefore it was assumed that
all low-risk in situ cancers should be treated aggressively to
decrease the risk of a future invasive breast cancer. However,
it has been shown that this is likely not the case, both
in epidemiology studies as well as in cohort studies of
specific “high-risk” lesions.
Considering that evidence suggests overdiagnosis in the
setting of invasive breast cancer, it is reasonable to consider
the possibility of overdiagnosis of DCIS. 9,19 In the context of
DCIS, overdiagnosis may occur if DCIS lesions are precursors
of invasive breast cancer that turn out to be indolent
disease or if the diagnosed DCIS is indolent itself without
the potential to progress to invasive cancer even in the
absence of treatment.
Similar to the situation with invasive breast cancer, SEER
data show a dramatic rise in the incidence of DCIS since the
introduction of screening mammography. However, there is
no corresponding drop in the rate of invasive breast cancer
that could account for successful detection and removal of
DCIS. In contrast, there is an overall increase in the incidence
of invasive breast cancer since the introduction of
screening mammography. After more than 25 years of widespread
efforts to increase rates of screening mammography,
the rate of invasive breast cancer incidence has continued to
increase despite widespread treatment of DCIS, except for a
recently observed leveling in incidence rates. It is possible
that this recent change in breast cancer incidence rates is
due to effective screening programs. However, a number of
epidemiologic studies have shown that this change is directly
associated with the decreased use of hormone replacement
therapy among postmenopausal women. 20-22
These observations raise the question of whether DCIS is
an obligate precursor to invasive breast cancer and would
progress to invasive cancer if left untreated. 23 A recent
modeling analysis explored the relationship between DCIS
progression rates and the assumed increase in the background
rate of invasive breast cancer. 24 The results of this
study demonstrated that different sets of assumptions related
to DCIS and its progression rates could produce
similar projected trends. The study found that, if most DCIS
lesions were destined to progress to invasive breast cancer,
it would then be reasonable to assume that there is a
substantial increase in the baseline rate of invasive breast
cancer over what we have seen. In contrast, if there is only
a modest increase in the baseline rate of invasive breast
cancer after the introduction of screening mammography,
more in line with the observed trends before screening, it
then follows that most DCIS lesions would not have progressed
to invasive breast cancer, even in the absence of
treatment.
Similarly, there is evidence in support of regression for
invasive breast cancer, which may be more relevant for
DCIS than for invasive cancer. 8,11,19 This conclusion has
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