xviii
Introduction
invasive carcinoma and 3 (8%) had DCIS.
42
The other re-
port described the detection of invasive carcinoma in 1 of
28 (3.8%) women and DCIS in 4 (14.3%) others during a
median follow-up of 38 months.
43
The consequences of short follow-up and clinical moni-
toring in the foregoing prospective studies are significant.
In every instance, subsequent DCIS was detected more
frequently than invasive carcinoma. Had the patients not
been monitored closely it is highly likely that many of those
subsequently found to have DCIS would have developed
invasive carcinoma in later years. In fact, it is troubling that
the frequency of invasive carcinoma was so high (3.6% to
6.8%) after a median follow-up of only 5 years or less in pa-
tients known to have DCIS. This suggests that at least some
of these women may have harbored invasive carcinoma
when DCIS was first detected, and/or that progression from
DCIS to invasion can occur rapidly. In any case, none of the
preceding prospective studies can be cited as evidence in fa-
vor of the proposal to eliminate the word “carcinoma” from
DCIS, or in support of a “treatment” plan based on clinical
follow-up alone that underestimates the potential of DCIS
to give rise to invasive carcinoma.
In view of the foregoing evidence, and other data pre-
sented in Chapter 11, there is an urgent need to better
understand the factors involved in the biology of untreated
DCIS, especially the low-grade variants of the disease. This
will certainly involve intensive molecular studies, including
gene expression profiling of DCIS and invasive ductal car-
cinoma lesions, but it is important not to overlook the role
that the “host” environment might play in modulating the
evolution of DCIS. As noted above, the same issue pertains
to LCIS, and despite more than a decade of investigation,
there is still no reliable guide to predicting the likelihood
that invasive carcinoma will appear in a particular patient
with classical LCIS.
Deleting the word “carcinoma” from
DCIS will not solve the fundamental problem. Understating
the risk associated with failing to adequately treat low-grade
DCIS is likely to create a false sense of security, and might
cause significant harm
.
Does Invasive Ductal Carcinoma,
NOS, Have a Future?
The 2012 World Health Organization (WHO) publication
on the classification of mammary carcinoma replaces the
term “invasive ductal carcinoma, NOS,” with “invasive car-
cinoma of no special type” because the word “ductal” in this
context “…perpetuates the traditional but incorrect concept
that these tumors are derived exclusively from mammary
ductal epithelium in distinction to lobular carcinomas,
which were deemed to have arisen from within lobules, for
which there is also no evidence.”
44
The muddled thinking
of the authors of the WHO book who made these asser-
tions is manifested by the fact that they retained terms such
as DCIS, atypical ductal hyperplasia, and invasive lobular
diagnostic biopsy sample in some cases. In others, however,
it is possible that persistent DCIS remained dormant, either
failing to develop the capacity to invade and metastasize or
actually regressing, possibly to extinction.
Data from two studies involving a total of 38 women
with low-grade micropapillary, papillary, and cribriform
DCIS are particularly relevant to this issue.
35,36
Previously
overlooked DCIS in these cases was found in the course of
reviewing breast biopsies that had been diagnosed originally
as benign, a circumstance that attests to the low-grade nature
of most of the lesions. With follow-up averaging 21.6 years
35
and 30 years,
36
respectively, invasive carcinoma was found
in 16 (48%) of the combined total of 38 patients. In the
latter study,
36
the frequency of subsequent carcinoma was
9.1 times expected, with a 95% CI of 4.73 to 17.5. A third,
more recent review of biopsies classified as benign found
13 instances of previously unrecognized DCIS (4 low grade,
6 intermediate grade, and 3 high grade).
37
In the course of
follow-up, subsequent ipsilateral invasive carcinoma was
diagnosed in 6 of the 13 (46%) patients after intervals of 4 to
18 years. In this study, the odds ratio of developing invasive
carcinoma in women with DCIS when compared to women
with nonproliferative breast disease was 13.5, with a 95%
CI of 3.7 to 49.7.
A number of prospective studies of patients with DCIS
who had no treatment after a biopsy are also available. The
studies differ from the foregoing retrospective studies in two
important respects: (1) because the patients were known to
have DCIS and were monitored clinically after the initial
biopsy, new abnormalities were promptly investigated; and
(2) reported clinical follow-up rarely exceeded 5 years.
Two studies described selected patients with clinically
occult DCIS that was detected by mammography. In one,
70 patients were followed for a median of 47 months after
biopsy-proven DCIS was diagnosed.
38
Among the DCIS le-
sions, 51% had a comedo (high grade) component and 29%
were predominantly comedo-DCIS. During the course of
follow-up, invasive carcinomas were detected in 3 (4.3%)
patients, and 8 (11.4%) were found to have further evidence
of DCIS. Another report describing a selected group of
untreated DCIS patients included 59 women.
39
During a
median follow-up of 37 months, invasive carcinoma was
detected in 4 (6.8%) and additional DCIS in 6 (10.9%).
There are two noteworthy population-based studies of
women with DCIS who had no treatment after a diagnostic
biopsy. One series consisted of 112 patients with a median
follow-up of 53 months during which 5 (4.4%) invasive car-
cinomas and 19 (17%) instances of DCIS were detected.
40
A
smaller study of 21 patients described the finding of invasive
carcinoma in 3 (14.3%) patients during a median follow-up
of 7 years.
41
Finally, two prospective studies of women with untreated
DCIS detected by mammography screening can be cited.
In one report, 38 women with predominantly low-grade
cribriform DCIS were followed for a median period of 60
months, during which time 2 (5%) were found to have
