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Other Guidelines
The management of lobular carcinoma in situ (LCIS). Is LCIS
the same as ductal carcinoma in situ (DCIS)?
Risks associated with LCIS
It is generally stated in the literature that the diagnosis of
LCIS is most frequent in women aged 40 to 50 years, a decade earlier than DCIS.
However, it is apparent from recent literature that the incidence in
post-menopausal women is increasing
[24]. Calculating the true incidence of LCIS has always proved
difficult as there are no specific clinical abnormalities, in particular,
absence of a palpable lump, and, because most (but not all) LCIS is not
associated with microcalcifications, it is often undetectable by mammography
[25] [26].
When examining a pathologic specimen, there is no macroscopic features
characteristic of LCIS to guide tissue sampling. The diagnosis of LCIS is
therefore often made as an incidental, microscopic finding in breast biopsy
performed for other indications. For these reasons, the true incidence of LCIS
in the general population is unknown, and many asymptomatic women presumably go
undiagnosed. In studies, the incidence of LCIS in otherwise benign breast
biopsy is documented as between 0.5% and 3.8%
[3] [27].
Characteristically, LCIS is both multifocal and bilateral in a
large percentage of cases. Over 50% of patients diagnosed with LCIS show
multiple foci in the ipsilateral breast, and roughly 30% of patients have
further LCIS in the contralateral breast
[28] [29] [30].
Such multifocality in a clinically non-detectable lesion is one of the reasons
why planning subsequent management has proven problematic and contentious.
LCIS has generally been considered a risk indicator, conferring an
increased rate of development of invasive carcinoma of about 1-2% per year,
with a lifetime risk of 30-40%
[3] [31]
[32]. There is a suggestion that the risk for invasive carcinoma is
greater for PLCIS than classic LCIS
[11].
Page et al.[7] [27]
documented that the relative risk for development of subsequent breast cancer
was different in women diagnosed with ALH compared with LCIS. Patients
diagnosed with ALH have a fourfold to fivefold higher risk than the general
population (i.e. women, of comparable age, who have had a breast biopsy
performed with no atypical proliferative disease diagnosed)
[7] [33].
This relative risk appears doubled to 8 to 10x for LCIS
[27]. Thus, although LN is a helpful term for collectively describing
this group of lesions, specific classification into ALH and LCIS may still be
justified or preferable in terms of risk stratification and management
decisions.
In a meta-analysis of nine separate studies evaluating the outcome
of a new diagnosis of LCIS, 228 patients were identified. Of these, a
proportion underwent either unilateral or bilateral mastectomy. On follow-up,
15% of 172 patients (who did not undergo unilateral mastectomy as primary
treatment) had invasive carcinoma in the ipsilateral breast and 9.3% of 204
patients had invasive carcinoma in the contralateral breast
[34]. The development of contralateral breast cancer is three times
more likely in patients diagnosed with LCIS than in those without LCIS
[35]. The risk for development of breast cancer is therefore bilateral
[28], and it used to be a common belief that this risk was equal for
both breasts. However, more recent studies demonstrate carcinoma is three times
more likely to develop in the ipsilateral compared with the contralateral
breast
[7] [36]
[37], supporting the view that ALH and LCIS act both as precursor
lesions and as risk indicators.
The time to the development of invasive cancer in an individual
patient after a diagnosis of LCIS is difficult to predict. Page et al.[27]
documented that in two thirds ofwomen in whom invasive cancer developed, it did
so within 15 years of biopsy. In a separate study, in over 50% of patients
inwhomcancer developed, it did so between 15 and 30 years after biopsy, with an
average interval of 20.4 years
[29]. This extended time span may have significant implications for
planning patient follow-up.
Both invasive ductal carcinoma (IDC) and ILC occur with LCIS, a
fact that some have used to suggest that LCIS is not a true precursor lesion.
However, the incidence of ILC occurring with LCIS is significantly greater than
without
[38]. The coexistence of DCIS and LCIS may explain the IDC component
observed, whereby DCIS and not LCIS is the likely precursor lesion
[39]
[40]. Evidence for the role of LCIS as a precursor for ILC is supported
by the epidemiologic data outlined previously, the morphologic similarity
between cells of ALH/LCIS and lobular carcinoma, and the development of tumours
in regions localised to ALH/LCIS. Work on molecular aspects of lobular lesions,
in particular, that focusing on the marker E-cadherin, adds to this view
[41] (see below).
It has been suggested for more than 50 years that LCIS and ILC
show an association with a positive family history of breast cancer. To date,
the predisposition gene(s) have not been identified and the current literature
does not support a significant role for germline mutations in BRCA1, BRCA2 or
E-Cadherin in its pathogenesis
[42]
[43]
[44].
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