Treatment of cancer of the breast
As has been indicated above, treatment will
largely depend upon clinical stage of the disease at presentation including not
only classical TMN staging but often other tumour characteristics such as
tumour grade. Treatment of early breast cancer will usually involve surgery with
or without radiotherapy. Systemic therapy such as chemotherapy or hormone
therapy is added if there are adverse prognostic factors such as lymph node
invasion indicating a high likelihood of metastatic relapse. At the other end of
the spectrum locally advanced or metastatic disease is usually treated by
systemic therapy to palliate symptoms, with surgery playing a much smaller role.
The
multidisciplinary team approach
As in all branches of medicine good
doctor—patient communication plays a vital role in helping to alleviate
patient anxiety. Participation of the patient in treatment decisions is of
particular importance in breast cancer where there may be uncertainty as to the
best therapeutic option and the desire to treat the patient within the protocol
of a controlled clinical trial. As part of the preoperative and postoperative
management of the patient it is often useful to employ the skills of a trained
breast counsellor and also to have available advice on breast prostheses,
psychological support and physiotherapy, where appropriate. In many specialist
centres the care of breast cancer patients is undertaken as a joint venture
between the surgeon, medical oncologist, radiotherapist and allied health
professionals such as the clinical nurse specialist.
Treatment of
early breast cancer
The aims of treatment are:
1
‘cure’: possible in some patients but recurrence up to 20 years after
initial treatment is nor uncommon;
2.
control of local disease in the breast and axilla;
3.
conservation of local form and function;
4.
prevention or delay of the occurrence of distant metastases.
Local treatment
of early breast cancer
Local control is achieved through surgery
and/or radiotherapy.
Surgery
Surgery still has a central role to play in
the management of breast cancer but there has been a gradual shift towards more
conservative techniques, backed up by clinical trials which have shown equal
efficacy between mastectomy and local excision followed by radiotherapy. This
followed a change in the model of breast cancer spread, which is no longer
thought of as a centrifugal anatomical spread but rather that it is the presence
of micrometastases which predetermines the outcome of the disease.It
was initially hoped that avoiding mastectomy would help to alleviate the
considerable psychological morbidity associated with breast cancer, but recent
studies have shown that over 30 per cent of women develop significant anxiety
and depression following both radical and conservative surgery. After mastectomy
they rend to worry about the effect of the operation on their appearance and
relationships whilst after conservative surgery women may remain fearful of a
recurrence.
Mastectomy
is now only strictly indicated for large tumours (in relation to the size of the
breast), central tumours beneath or involving the nipple, multifocal disease,
local recurrence or for patient preference. The radical Halstead mastectomy
which included excision of the breast, axillary lymph nodes, pectoralis major
and minor muscles is no longer indicated as it causes excessive morbidity with
no survival benefit. Modified radical (‘Patey’) mastectomy is
•
the whole breast;
•
a large portion of skin, the centre of which overlies the tumour, but
always includes the nipple;
•
all of the fat, fascia and lymph nodes of the axilla. The pectoralis
minor muscle is either divided or removed to gain access to the upper two-thirds
of the axilla. The axillary vein and nerves to serratus anterior and latissimus
dorsi should be preserved.
The wound is drained using a wide-bore suction
tube.
Early
mobilisation of the arm is encouraged and physiotherapy helps normal function to
return very quickly — most patients are able to resume light work or housework
within a few weeks.
usually combined with axillary surgery,
usually via a separate incision in the axilla, to either sample the axilla,
remove nodes behind and lateral to pectoralis minor (level II) or perform a full
axillary dissection (level III). A quadrantectomy, axillary dissection and
radiotherapy is known as QUART and has been popularised by Professor Umberto
Veronesi from Milan. Whilst it is recognised that there is a somewhat higher
rate of local recurrence following conservative surgery, even if combined with
radiotherapy, the long-term outlook in terms of survival is unchanged.
The
role of axillary surgery is still debated, but it is accepted that the
presence of metastatic disease within the axillary lymph nodes is still the best
marker for prognosis. However, treatment of the axilla does not affect long-term
survival, suggesting that the axillary nodes act not as a ‘reservoir’ for
disease but as a marker for metastatic potential. An acceptable way to approach
this problem in premenopausal women is to stage the axilla by operation as there
is a good case for giving chemotherapy to lymph node-positive patients. In
postmenopausal patients, tamoxifen is usually given regardless of axillary lymph
node status. If mastectomy is performed it is reasonable to clear the axilla as part
of the operation, but if a wide local excision is planned the surgeon may
choose either operative dissection or postoperative radiotherapy. Axillary
surgery should not be combined with radiotherapy to the axilla because of excess
morbidity. Removal of the internal mammary lymph nodes is unnecessary.
Sentinal
node biopsy is a technique currently under evaluation which may well prove the
way forward in the future in the management of the axilla in patients with
clinically node-negative disease. The sentinal node is localised perioperatively
by the injection of patent blue dye and/or radioisotope-labelled albumin near
the tumour. The marker will pass to the primary node draining the area, be
detected visually or with a hand-held gamma camera, and sent for frozen section
histological analysis. In patients in whom there is no tumour involvement of the
sentinal node, it is hoped that further axillary dissection can be avoided as
skip lesions are thought to occur in less than 3 per cent of patients.
Radiotherapy
Radiotherapy to the chest wall after
mastectomy has been largely abandoned except in cases of extensive local disease
with infiltration of the chest wall. It is conventional to combine
conservative surgery with radiotherapy to the remaining breast tissue. However,
there is currently doubt as to whether all patients undergoing conservative
surgery should receive radiotherapy as most will not develop local recurrence
and thus will be overtreated by adjuvant radiotherapy, which is not without
morbidity and even long-term mortality from inadvertent irradiation to the
myocardium. A UK national clinical trial is currently underway to try to
ascertain whether there is a survival advantage with radiotherapy and to
identify which patients are at highest risk of local relapse, and thus would
benefit most from postoperative breast
irradiation. Currently those thought to be at
highest risk include those with extensive in
situ carcinoma (or of course invasive cancer) at the margins of excision,
patients under 35 years and those with multifocal disease.
Adjuvant
systemic therapy
Over the last 25 years there has been a
revolution in our understanding of the biological nature of carcinoma of the
breast. It is now widely accepted that the outcomes of treatment are
predetermined by the extent of micrometastatic disease at the time of diagnosis.
Variations in the radical extent of local therapy might influence local relapse,
but probably do not alter long-term mortality from the disease. However,
systemic therapy targeted at these putative micrometastases might be expected
to delay relapse and prolong survival. As a result of many international
clinical trials and recent world overview analyses, it can be stated with
extreme statistical confidence that the appropriate use of adjuvant chemotherapy
or hormone therapy will improve relapse-free survival by approximately 30 per
cent, which ultimately translates into an absolute improvement in survival of
the order of 10 per cent at 15 years. Bearing in mind how common the disease is
in Northern Europe and the USA, this translates into figures of major public
health importance.
Who
to treat and with what are still questions for which absolute answers have yet
to found, but the data from an overview of recent trials suggest that lymph
node-positive and poor prognosis node-negative premenopausal women should be
recommended adjuvant combined chemotherapy and that postmenopausal women will
obtain a worthwhile benefit from about 5 years
of tamoxifen, 20 mg daily.
Hormone therapy
Tamoxifen is the most widely used
‘hormonal’ treatment in breast cancer. Its efficacy as an adjuvant therapy
was first reported in 1983 and it has now been shown to reduce the annual rate
of recurrence by 25 per cent, with a 17 per cent reduction in the annual rate of
death. The effect of tamoxifen is favourable in most cases except for oestrogen
receptor ER-negative premenopausal women; postmenopausal women with oestrogen receptor-rich (positive) tumours achieve a greater reduction in the relative
risk of relapse than oestrogen receptor-negative cases. The beneficial effects
of tamoxifen in reducing the risk of tumours in the contralateral breast have
also been observed. Trials studying the optimal duration of treatment are close
to maturity and suggest that 5 years of treatment may be preferable to 2 years.
Other
hormonal agents are being developed which may prove beneficial as adjuvant
therapy, such as the LHRH agonists which induce a reversible ovarian
suppression and thus ire hoped to have the same beneficial effects as surgical
or ~radiation-induced ovarian ablation in premenopausal wo7nen, and the oral
aromatase inhibitors for postmenopausal Nomen.
Chemotherapy
Chemotherapy using a regimen such as a
6-monthly cycle of cyclophosphamide, methotraxate and 5-fluorouracil (CMF) will
achieve a 30 per cent reduction in the risk of relapse over a 10—15-year
period. This treatment has been confined to premenopausal poor prognosis women
(where its effects are likely to be due in part to a chemical castration effect)
but is being increasingly offered to postrnenopausal women with poor prognosis
disease as well. Chemotherapy may be considered in node-negative patients if
other prognostic factors such as tumour grade infer a high risk of recurrence.
The effect of combining hormone and chemotherapy is still under investigation
and is beginning to look promising.
High-dose
chemotherapy with stem cell rescue for patients with heavy lymph node
involvement is still considered experimental and should not be offered outside
controlled trials.
Primary
chemotherapy is being used in many centres for large hut operable tumours that
would traditionally require a mastectomy (and almost certainly postoperative
adjuvant chemotherapy). The aim of this treatment is to shrink the tumour to
enable breast-conserving surgery to be performed. This approach is successful in
up to 80 per cent of cases, but is not associated with improvements in survival
compared with conventionally timed chemotherapy.
Breast
reconstruction
Despite an increasing trend toward
conservative surgery, up to 50 per cent of women still require, or want, a
mastectomy. These women can now he offered immediate or delayed reconstruction
of the breast. Few contraindications to breast reconstruction exist — even
those with a limited life expectancy may benefit from the improved quality of
life, however patients do require counselling before this procedure so that
their expectations of cosmetic outcome are not unrealistic.
The
most common type of reconstruction is using a silicone gel implant under the
pectoralis major muscle.
This
may be combined with prior tissue expansion using an expandable saline
prosthesis first (or a combined device — Fig.
46.37) which creates some ptosis
of the new breast. If the skin at the mastectomy site is poor (for example
following radiotherapy) or if a larger volume of tissue is required, a
musculocutanous flap can be constructed from either the latissimus dorsi muscle
(an LD flap) or the contralateral transversus abdominis muscle (a TRAM flap —
shown in Fig. 46.38). The latter gives an excellent cosmetic result in
experienced hands but is a lengthy procedure and requires careful patient
selection.
Nipple
reconstruction is a relatively simple procedure which can be performed under a
local anaesthetic. Alternatively the patient can be fitted with a prosthetic
nipple. To achieve symmetry, the opposite breast may require a cosmetic
procedure such as reduction or augmentation
External
breast prostheses which fit within the bra may also be recommended and some of
these are illustrated in Fig. 46.39.