Management of early breast cancer

Early breast cancer is defined as disease that can be completely extirpated by surgery, that is T1—3, N0-1 tumours. The management of this disease comprises:

♦ Treatment of the breast and axilla

♦ Pathological staging to direct adjuvant therapy

♦ Adjuvant therapy—endocrine, chemotherapy, radiotherapy

Breast surgery

All patients require removal of the primary tumour with either wide local excision or mastectomy. Halsted mastectomy was the operation most extensively applied to breast cancer patients during the first half of the twentieth century, but it has gradually been replaced by a variety of less radical operations.

Total mastectomy and axillary dissection is a less mutilating operation preserving the pectoralis major muscle and its neurovascular bundle. Quadrantectomy, introduced at the beginning of the 1970s, is a breast-conserving operation that removes the primary cancer with a margin of 2.0 cm of normal breast tissue. Lumpectomy is an operation that provides for the removal of the tumour mass with a limited portion of normal tissue (1 cm).

Randomized trials comparing breast-conserving surgery followed by radiotherapy with mastectomy alone have demonstrated similar local control rates and survival. Breast conservation is not always suitable for women with multifocal disease and large tumours in small breasts. Some patients simply prefer mastectomy, not least because of the possible avoidance of radiotherapy. Either treatment should afford a local recurrence rate of <10% after 10 years.

Breast reconstruction can be done either at the time of primary surgery or at a later date—TRAM flap, latissimus dorsi flap, and implants all have a role.

Treatment of the axilla

♦ Clinical assessment is inaccurate

♦ 30% of involved nodes are impalpable

♦ Surgery—axillary node sampling (>4 nodes) (diagnostic)

—axillary clearance levels, I, II, and III (therapeutic); lymphodema and arm pain are complications

—sentinel node biopsy:

—removal of first node which contains secondary deposit —ongoing UK trial —use either blue dye or 99MTc colloid —negative sentinel node avoids clearance

Loco-regional radiotherapy

Breast irradiation has been shown to reduce the risk of local recurrence after breast-conserving surgery from about 30% to <10% at 10 years. Typically, the whole breast is treated with tangential fields to a dose of 50 Gy in 25 fractions (or an equivalent dose-fractionation regimen), with care taken to minimize the volume of lung and heart irradiated. Although a boost of 10-15 Gy is commonly delivered to the tumour bed, using electrons or 192Ir implant, its benefits are unproven.

♦ Older techniques—cardiac side-effects

♦ Modern techniques—safe

—may improve survival

♦ Irradiation of axilla—not required if clearance performed

♦ Radiation to axilla may cause lymphodema and brachial neuropathy

Adjuvant systemic therapy

Breast cancer patients who remain disease-free after local and regional treatment may eventually relapse and die of overt metastases. The current hypothesis ascribes the failure to obtain a cure to occult micro-metastases in distant organs, already present at the time of first surgery. The risk of harbouring occult metastases is low in cases with a small carcinoma and negative nodes and increases with the size of the primary carcinoma and number of axillary metastatic nodes.

There have been many trials among women with operable breast cancer, examining the effects of systemic treatment, either endocrine manoeuvres or chemotherapy or both, on the survival of these patients. The basis of all these therapies is the reduction or eradication of microscopic systemic metastatic disease in women in whom all macroscopic local tumour has been effectively removed. In 1992 the Early Breast Cancer Trialists' Collaborative Group published an overview of 133 randomized trials involving 75 000 women with early breast cancer1-3. This has had major impact, setting standards of care for adjuvant therapy for this disease.

Adjuvant endocrine therapy

♦ 60% of breast cancers are oestrogen receptor positive

♦ Ovarian ablation—improves survival in women under 50 years

—morbidity of vascular disease and osteoporosis

♦ Tamoxifen—improves disease-free and overall survival

—all women, especially post-menopausal —little benefit if ER negative

—5 years is sufficient: better than 2 years; no need for longer

—10% increase in survival for node-positive disease —5% increase in survival for node-negative disease

♦ Side-effects of tamoxifen—menopausal symptoms

—endometrial cancer, 4-fold increase in risk

—decreases contralateral breast cancer risk

Adjuvant chemotherapy

♦ Combination chemotherapy reduces recurrence and mortality

—absolute 10-year survival benefit: 7-11% women <50 years; 2-3% women >50 years

♦ CMF (cyclophosphamide, methotrexate, 5FU) used in most trials

♦ Anthracycline regimes may be better

♦ Used most often in node-positive, large, Grade 3, ER-negative, pre-menopausal tumour patients

♦ Used in some ER-negative, node-positive, post-menopausal patients

Neo-adjuvant therapy

Primary chemotherapy or hormone therapy for operable breast cancer provides early systemic treatment and allows assessment of the response to treatment; by definition this is impossible with adjuvant therapy. Its disadvantages are the delay in definitive local surgery and the risk of over-treatment with chemotherapy in the absence of pathological staging (e.g. post-menopausal, ER-positive, node-negative tumour).

A large randomized trial (NSABP-B18) has shown no difference in survival when pre- and post-operative chemotherapy (doxorubicin and cyclophosphamide) was compared. Pre-operative treatment does downstage the primary tumour and, in some women, facilitates breast-conserving surgery where mastectomy would otherwise be required.

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