Invasive breast carcinoma - IARC

lesions {1707}, suggesting that both are
'neoplastic' and at a similar stage of
genetic evolution.
The most direct evidence for a precursor
role of LN comes from mutational analysis
of the E-cadherin gene {259,260}. In
one study {261}, 27 of 48 (56%) invasive
lobular carcinomas had mutation in the
E-cadherin gene, while none of 50 breast
cancers of other types showed any alteration.
It was subsequently demonstrated
that truncating mutations identified in
invasive lobular carcinoma were also
present in the adjacent LN, providing
direct proof that LN was a precursor
lesion {3034}.
Prognosis and predictive factors
The relative risk (RR) for subsequent
development of invasive carc i n o m a
among patients with LN ranges from 6.9
to about 12 times that expected in
women without LN {87,88,1100}.
Amongst 1174 women in 18 separate retrospective
studies, diagnosed as having
LN and treated by biopsy alone, 181
(15.4%) eventually developed invasive
c a rcinoma {88,1096,1100,2150,2428,
2438}. Of these, 102 (8.7%) developed in
the ipsilateral breast, and 79 (6.7%) in
the contralateral breast, demonstrating
an almost equal risk for either breast.
However, in a prospective study of 100
cases of LN with 10 years of follow-up,
11 of 13 invasive recurrences were ipsilateral
{2127}.
With extended follow-up, the risk of
development of invasive cancer continues
to increase to 35% for those women
who survive 35 years after their initial
diagnosis of LN. Furthermore, the RR
increases substantially from 4.9 (95% CI:
3.7–6.4) after one biopsy with LN to 16.1
(95% CI:6.9–31.8) after a second biopsy
with LN {298}.
Early studies suggested that among LN
lesions, there are no clinical or pathological
features associated with incre a s e d
risk of subsequent invasive carc i n o m a
{2150,2438}. However, a more re c e n t
study using the three tiered grading system,
but with a comparatively short follow-up
of 5 years, found that LIN 3 and, to
a lesser extent LIN 2, were associated
with an increased risk {869}, but LIN 1
was not. In another study, 86% of invasive
carcinomas associated with LIN 3
w e re lobular in type, in contrast to 47% of
those associated with LIN 2 and only 11%
of those associated with LIN 1 {338}.
Fig. 1.78 Lobular neoplasia. Loosely cohesive neoplastic cells are proliferating in this lobule, but they have
not distended the acini.
A
C
Fig. 1.79 Lobular neoplasia. A Necrotic type with massive distention of the acini. B Note the loosely cohesive
cells and the necrosis. C Lobular neoplasia, pleomorphic type. Even though there is not a significant distention
of the involved TDLU, the neoplastic cells are highly pleomorphic and loosely cohesive. This is the
intraepithelial counterpart of pleomorphic invasive lobular carcinoma. D LN involving sclerosing adenosis.
The lobulated configuration of the sclerosing adenosis is apparent at low magnification. The ductules in
part of the lesion are filled and expanded by proliferation of a monotonous neoplastic cell population. This
setting may be confused with invasive carcinoma, particularly when the sections are suboptimal.
Management of LN has evolved with
increased understanding of the disease
{1082}. The current consensus is that LN
constitutes a risk factor and a non obligate
precursor for subsequent development
of invasive carcinoma in either
breast, of either ductal or lobular type,
but only in a minority of women after
B
D
long-term follow-up. The current recommended
management for LN is, therefore,
life long follow-up with or without
tamoxifen treatment. Re-excision should
be considered in cases of massive acinar
distension, and when pleomorphic,
signet ring or necrotic variants are identified
at or close to the margin.
62 Tumours of the breast