Carcinoma of
the breast
Breast cancer is the commonest cause of death in middle-aged women in
Western countries. In 1985, 719 000 new cases were diagnosed world-wide. In
England and Wales one in 12 women will develop the disease during their
lifetime.
Aetiological
factors
I. Geographical. It occurs commonly
in the Western world accounting for 3—5 per
cent of deaths, yet is a rare tumour in Japan. In developing countries it
accounts for 1—3 per cent of deaths.
2. Age. Carcinoma of the breast is
extremely rare below the age of 20, but thereafter the incidence steadily rises
so that by the age of 90 nearly 20 per cent of women are affected (Fig.
46.27).
By age 25
1 in 19608
By age 60
1 in 24
By age 30
1 in 2525
By age 65 1
in 17
By age 35
1 in 622
By age
70 1 in 14
By age 40
1 in 217
By age
75
1 in 11
By age 45
1 in 93
By age 80
l in 10
By age 50
l in 50
By age 85 l
in 9
By age 55
1 in 33
Ever
1in 8
1987—1988 Cancer incidence rates,
NCI, USA.
3.
Gender. Less than I per cent of patients with breast cancer are male.
4.
Genetic. It occurs more commonly in women with a family history of breast
cancer than in the general population. Breast cancer related to a specific
mutation accounts for about 5 per cent of breast cancers, yet has far-reaching repercussions in
terms of counselling and attempted prevention in these women. This will be
discussed more fully in a subsequent section.
5. Diet. Because breast cancer so commonly affects women in the
‘developed’ world, dietary factors may play a part in its causation. There
is some evidence that there is a link between diets low in phyto-oestrogens. A
high intake of alcohol is associated with an increased risk of developing breast
cancer.
6.
Endocrine. Breast cancer is commoner in nulliparous women and
breastfeeding in particular appears to be protective. Also protective is having
a first child at an early age, especially if associated with late menarche and
early menopause. It is known that in postmenopausal women, breast cancer is more
common in the obese. This is thought to he because of an increased conversion of
steroid hormones to oestradiol in the body fat. The role of exogenous hormones,
in particular the oral contraceptive pill and hormone replacement therapy, in
the development of breast cancer is more controversial, but it can be said with
some authority that for most women the benefits of these treatments will far
outweigh the small putative risk.
The increase in the likelihood of developing
breast cancer associated with the above risk factors is usually quantified in
terms of the relative risk (RR). Thus a RR of 2.0 means that the individual has
twice the chance of developing breast cancer as the average for the population,
whilst a RR of 0.5 indicates a risk reduction of 50 per cent.
Pathology
Breast cancer may arise from the epithelium of
the duct system anywhere from the nipple end of major lactiferous ducts to the
terminal duct unit which is in the breast lobule. It may be entirely in
situ — an increasingly common phenomenon with the advent of breast cancer screening — or may be invasive cancer. The degree of differentiation of
the tumour is usually described by three grades — well differentiated,
moderately or poorly differentiated. Ductal carcinoma is the most common
variant, but lobular carcinoma occurs in up to 10 per cent of cases, although
this may be mixed. Rarer histological variants, usually carrying a better
prognosis, include colloid carcinoma whose cells produce abundant mucin,
medullary carcinoma with solid sheets of large cells often associated with a
marked lymphocytic reaction and tubular carcinoma. Invasive lobular carcinoma is
commonly multi-focal and/or bilateral.
Inflammatory
carcinoma is a fortunately rare, highly aggressive cancer which presents as a
painful, swollen breast, which is warm with cutaneous oedema. This is due to
blockage of the subdermal lymphatics with carcinoma cells. Inflammatory cancer
usually involves at least one-third of the breast and may mimic a breast
abscess. A biopsy will confirm the diagnosis and show undifferentiated carcinoma
cells.
In situ carcinoma is preinvasive cancer which has not breached the epithelial
basement membrane. This was
previously a rare, usually asymptomatic
finding in breast biopsy specimens but is becoming increasingly common owing to
the advent of mammographic screening — it accounts for 20 per cent of cancers
detected by screening. In situ carcinoma
may be ductal (DCIS) or lobular (LCIS), the latter often multifocal and
bilateral. Both are markers for the later development of invasive cancer which
will go on to develop in at least 20 pet cent of cases. Although mastectomy is
curative, this is overtreatment in many cases and the best treatment for in
situ carcinoma is the subject of a number of clinical trials.
Paget’s
disease of the nipple
Pager’s disease of the nipple (Fig.
46.28a
and b) is a superficial manifestation of an underlying breast carcinoma. It
presents as an eczema-like condition of the nipple and areola which persists in
spite of local treatment. The nipple is eroded slowly and eventually disappears.
If left, the underlying carcinoma will sooner or later become clinically
evident. Thus nipple eczema should be biopsied if there is any doubt about its
cause. Microscopically Pager’s disease is characterised by the presence of
large, ovoid cells with abundant, clear, pale-staining cytoplasm in the
Malpighian layer of the epidermis.
The spread of
mammary carcinoma
1.
Local spread. The tumour increases in size and invades other portions of
the breast. It tends to involve the skin and to penetrate the pectoral muscles,
and even the chest wall.
2.
Lymphatic metastasis occurs primarily to the axillary lymph nodes and to
the internal mammary chain of lymph nodes. The site of the tumour within the
breast does not dictate which nodes will be involved, e.g. medial tumours
spread just as readily to the axillary nodes as do lateral tumours. The
involvement of lymph nodes is not necessarily a chronological event in the
evolution of the carcinoma, but rather a marker for the metastatic potential of
that tumour. In advanced disease there may be involvement of supraclavicular
nodes and of any contralateral lymph nodes.
3.
Spread by the bloodstream. It is by this route that skeletal metastases
occur (in order of frequency) in the lumbar vertebrae, femur, thoracic
vertebrae, rib and skull; they are generally osteolytic. Metastases may also
occur in the liver, lung and brain, and occasionally the adrenal glands and
ovaries.
Clinical
presentation
While any portion of the breast, including the
axillary tail, may be involved, breast cancer commences most frequently in the
upper, outer quadrant (Figs 46.29 and 46.30). Most breast cancers will present
as a hard lump, which may be
Phenomena
resulting from lymphatic obstruction in Staging of breast cancer
advanced breast
cancer
Peau d’orange is due to cutaneous lymphatic
oedema. Where the infiltrated skin is tethered by the sweat ducts it cannot
swell, leading to an appearance like orange skin. Occasionally the same
phenomenon is seen over a chronic abscess.
Late
oedema of the arm is a troublesome complication of breast cancer treatment
fortunately seen less often now that radical axillary dissection and
radiotherapy are rarely combined. It does however occasionally still occur after
either modality of treatment alone and appears anytime from months to years
after treatment. There is usually no precipitating cause but recurrent tumour
should be excluded as neoplastic infiltration of the axilla can cause arm
swelling due to both lymphatic and venous blockage. This neoplastic infiltration
is often painful due to nerve involvement.
An
oedematous limb is susceptible to bacterial infections following quite minor
trauma, and these require vigorous antibiotic treatment. Treatment of late
oedema is difficult but limb elevation, elastic arm stockings and pneumatic
compression devices can be useful.
Cancer-en-cuirasse4.
The skin of the chest is infiltrated with carcinoma and has been likened to a
coat.
It
may be associated with a grossly swollen arm. This usually occurs in cases with
local recurrence after mastectomy, and occasionally is seen to follow the
distribution of irradiation to the chest wall. The condition may respond to
palliative systemic treatment but prognosis in terms of survival is poor.
Lymphangiosarcoma
(Fig. 46.34) is a rare complication of lymphoedema with an onset many years
following the original treatment. It takes the form of multiple subcutaneous
nodules in the upper limb and must be distinguished from recurrent carcinoma of
the breast. The prognosis is poor but some cases respond to cytotoxic therapy or
irradiation. Interscapulothoracic (forequarter) amputation is sometimes
indicated.
There are two traditional systems of
classification for breast carcinoma which predominantly rely on clinical staging
of the disease. These are the Manchester system and the International Union
Against Cancer TNM (tumour, nodes, metastases) staging system. These are
illustrated in Table 46.6.
The
TNM system was an attempt to allow a common language amongst oncologists
world-wide, thus allowing accurate information exchange and evaluation of
studies of treatment, as well as providing prognostic information to aid in the
planning of treatment for the individual patient. However, this refinement of
taxonomy in fact contributes little to any of these activities.
Further
subdivisions in the TNM system now mean that there are seven T-stages, four
N-stages and three M-stages, allowing for 180 possible combinations.
Pathological lymph node staging depends on both the number of lymph nodes
removed, thus the extent of surgery, and how assiduous the pathologist is in
looking for deposits of tumour within the nodes. ‘M’ staging depends on what
investigations have been performed — thus will vary between centres.
Consequently staging is observer biased.
Although
prognosis broadly correlates with stage, other factors also influence prognosis
and should be assessed, for example the Nottingham Prognostic Index includes nor
only tumour size and lymph node status but tumour grade.
Conventional
staging will indicate broadly which treatment is required but again other
factors may be equally important. For example, surgical treatment of a small
stage I, or II (T1 or T2) breast tumour usually requires
only wide local excision rather than mastectomy — but the latter may have to
be performed if the breast is very small, the tumour central or multifocal, or
for patient preference. Equally the use of adjuvant systemic therapy is decided
on not only tumour size and lymph node status but also biological measures such
as oestrogen receptor status, patient age and menopausal status, and in the case
of tamoxifen this can be recommended irrespective of clinicopathological
variables.
Thus
as we gain more knowledge of the biological variables which affect prognosis
it becomes increasingly clear that it is these factors (discussed in more detail
below) rather than anatomical mapping which influence outcome and
Prognosis of
breast cancer
The best indicators of likely prognosis in breast cancer are still tumours size and lymph node status (Fig. 46.35). However, it is realised that some large tumours will remain confined to the breast for decades whereas some very small tumours are incurable at diagnosis. Hence the prognosis of a cancer depends not on its chronological age but on its invasive and metastatic potential. In an attempt to define which tumours will behave aggressively, and thus require early systemic treatment, a host of prognostic factors has been described. These include histological grade of the tumour, hormone receptor status, measures of tumours proliferation such as 5-phase fraction and thymidine-labelling index, growth factor analysis and oncogene or oncogene product measurements. Many others are under investigation but have proved of little practical value in patient management.