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 more commonly performed and thus is described below. Simple mastectomy involves removal of the breast only with no dissection of the axilla, except for the region of the axillary tail of the breast which usually has attached to it a few nodes low in the anterior group. Because no pathological staging of the axilla is performed with a simple mastectomy, it is often followed by radiotherapy to the axilla.

  Patey’ mastectomy. The breast and associated structures are dissected en bloc (see Fig. 46.36) and the excised mass is composed of:

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. Conservative breast cancer surgery is aimed at removing the tumour plus a rim of at least 1 cm of normal breast tissue. This is commonly referred to as a wide local excision or lumpectomy. A quadrantectomy involves removing the entire segment of the breast which contains the tumour. These are

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 mammoplasty, or mastopexy. A breast reconstructive service can be offered by a suitably trained breast surgeon, a plastic surgeon or ideally a combined oncoplastic approach.

External breast prostheses which fit within the bra may also be recommended and some of these are illustrated in Fig. 46.39.