Cover -- Half-title -- Title -- Copyright -- Contents -- Contributors -- 1 History of breast cancer therapy -- History of surgery for breast cancer -- Introduction -- The empiric period -- The pessimistic period -- The optimistic period -- The realistic period -- The rise and fall of endocrine surgery for metastatic disease -- Introduction of radiation therapy for breast cancer -- History -- Influence of radiotherapy on local control and survival -- Timing of radiotherapy -- Theoretical considerations in the spread of breast cancer -- Evolution of conservative surgery for breast cancer -- Surgery of the breast -- Axillary surgery -- Sentinel node biopsy in the management of the axilla -- Timing of surgery -- Reconstructive surgery -- Need for systemic therapy in early breast cancer -- Conclusion -- REFERENCES -- 2 Chemoprevention of breast cancer -- Introduction -- Chemoprevention as a strategy in breast cancer -- Rationale for tamoxifen chemoprevention trials -- The Royal Marsden Tamoxifen Prevention Trial -- The NSABP-P1 trial -- The Italian Tamoxifen Prevention Study -- Overview of the reported tamoxifen breast cancer prevention trials -- Compliance and statistical power -- The differences between the trials in terms of risk of breast cancer among the participants -- The use of HRT -- Adverse effects of tamoxifen in the breast cancer prevention trials -- Menopausal symptoms and anxiety -- Vascular events -- Endometrial cancer -- Ocular effects -- Cardiovascular disease -- Bone density and fractures -- Risk-benefit calculation -- Evolving chemoprevention -- Raloxifene -- Nutriceuticals - breast cancer prevention with phyto-oestrogens -- Fenretinide breast cancer prevention -- Conclusion and future directions -- REFERENCES -- 3 Familial breast cancer -- Introduction -- BRCA1 -- BRCA2 -- Other genes associated with increased risk of breast cancer.

Referral, assessment and clinical management of women for familial breast cancer -- Referral -- Assessment -- Clinical management -- Conclusion -- REFERENCES -- 4 Hormone replacement therapy and breast cancer -- Introduction -- The incidence of oestrogen deficiency symptoms in women with breast cancer -- Alternatives to HRT for the management of postmenopausal oestrogen deficiency -- Is serum oestradiol an important indicator of the risk of developing breast cancer recurrence? -- Indirect evidence that HRT may not have an adverse effect in breast cancer survivors -- HRT, breast density and mammography -- HRT and its effect on tumour biology and breast cancer mortality -- HRT and breast cancer risk in women at high risk of developing breast cancer -- Familial breast cancer -- Benign breast disease -- Observational studies of HRT in breast cancer survivors -- Potential antagonism between tamoxifen and HRT -- Is a randomized trial of HRT in breast cancer survivors feasible? -- Conclusion -- REFERENCES -- 5 Screening for breast cancer -- Introduction -- Why screen? -- The principles of screening and their application to breast cancer -- Evaluation of screening benefit -- Bias in survival evaluation -- Lead time bias -- Length bias -- Randomized controlled trials -- What is the evidence that screening works in different age groups? -- Screening in women aged 50-64 years of age -- Screening in women over the age of 65 -- Screening women aged 40-49 years -- Screening for women under 40 years old -- Organization aspects of screening - the UK model -- Sensitivity and specificity of screening - the performance of the UK NHSBSP -- Benefits and adverse effects of breast screening -- Future developments -- Challenges facing screening programmes - resources -- Best practice for screening programmes, two views, two readers and extension of age.

Digital technology and computer aided detection -- Nonoperative diagnosis -- 'Family history' screening of younger women -- Ultrasound for screening -- Magnetic resonance imaging -- Conclusion -- REFERENCES -- 6 The management of in situ breast cancer -- Introduction -- Epidemiology -- Pathology of DCIS -- Classification of DCIS -- Natural history of DCIS -- Molecular biology of DCIS -- Interphase cytogenetics -- Oncogenes and steroid receptors -- Diagnosis of DCIS -- Treatment of DCIS -- Historical perspective -- Breast-conserving surgery -- Role of radiotherapy -- Role of adjuvant medical therapy -- Role of axillary surgery -- Follow-up -- Future studies -- Conclusion -- REFERENCES -- 7 Adjuvant systemic therapy -- The rationale for systemic adjuvant therapy -- Adjuvant chemotherapy -- Node-negative patients -- The place of anthracyclines -- Poor risk patients and dose intensification -- High-dose adjuvant chemotherapy -- Toxicity -- Adjuvant endocrine therapy -- Ovarian ablation -- Adjuvant tamoxifen -- Duration of tamoxifen -- Side-effects of tamoxifen -- Adjuvant aromatase inhibitors -- Combined chemotherapy and endocrine therapy -- Premenopausal women with node-positive, receptor-positive breast cancer -- Postmenopausal women with node-positive, receptor-positive breast cancer -- Tamoxifen and chemotherapy for node-negative, receptor-positive breast cancer -- Concurrent versus sequential chemohormonal therapy -- Future prospects -- REFERENCES -- 8 Adjuvant radiotherapy in the management of breast cancer -- Introduction -- Radiotherapy and breast conservation -- Risk factors for recurrence following breast-conserving surgery -- Natural history of and risk factors for local recurrence -- The importance of local recurrence -- The balance between optimal local control and cosmesis -- Margin status and local recurrence risk.

The effect of radiotherapy dose escalation -- The influence of systemic therapy on local recurrence following breast conservation -- The effect of re-excision -- Postmastectomy radiotherapy -- Optimizing breast conservation with adjuvant radiotherapy -- Variation in UK radiotherapy practices for women with breast cancer: the START study -- Sequencing of chemotherapy and radiotherapy -- Radiotherapy and postmastectomy breast reconstruction -- Radiotherapy and implant reconstruction -- Dose distribution -- Radiotherapy and TRAM flap reconstruction -- Conclusion -- Summary -- REFERENCES -- 9 Predictors of response and resistance to medical therapy -- 9a Cell kinetic parameters and response to therapy -- Introduction -- DNA flow cytometry -- Predictors of response to therapy -- Adjuvant chemotherapy for node-negative breast cancer -- Prediction of response to neoadjuvant chemotherapy -- Adjuvant chemotherapy for node-positive breast cancer -- Hormonal therapy -- Tumour p53 status as a possible predictor of response to therapy -- Potential predictors of response in clinical trials -- Conclusion -- REFERENCES -- 9b Predictors of response and resistance to medical therapy: endocrine therapy -- Introduction -- Oestrogen receptor (ER) -- Structure and function of the oestrogen receptor -- Measurement of ER -- ER as a predictor of hormone response -- Oestrogen-regulated proteins predictive of hormone response -- Progesterone receptor (PR) -- Oestrogen-inducible protein (pS2) -- Heat shock protein 27(HSP27) -- Markers of lack of response to endocrine therapy -- Epidermal growth factor receptor (EGFR) and c-erbB-2 (HER-2/neu) -- Urokinase -- Transforming growth factor Alpha -- Prolactin -- Prostate-specific antigen (PSA) -- Mechanisms of endocrine resistance -- Oestrogen receptor mechanisms -- Absence of oestrogen receptor -- Exon variants and deletions.

Mutations of the hormone binding domain -- Tumour cell elimination of antioestrogens -- Clonal selection -- Acquisition of steroidogenic metabolic pathways -- Constitutive production of mitogens -- Messenger system interactions -- Effects of oncogenes on cell cycle control -- Alteration of secreted proteins -- The use of steroid receptors in clinical trials -- Conclusion -- REFERENCES -- 9c Predictors of response and resistance to medical therapy: chemotherapy -- Introduction -- Laboratory studies - potential mechanisms for drug resistance -- Proximal mechanisms -- Drug-specific targets -- Distal response: apoptosis regulatory oncogenes -- Bcl-2 -- Gene p53 -- Extrachromosomal DNA and drug resistance -- Clinical studies - predictive markers of chemotherapy response/resistance -- HER-2/neu -- Changes in cell proliferation and apoptosis -- Bcl-2 -- p53 -- Opportunities for therapy -- Modulation of chemoresistance -- Targeted therapy -- Conclusion -- REFERENCES -- 10 Primary medical therapy in breast cancer -- Introduction -- Primary medical therapy in locally advanced breast cancer -- Primary chemotherapy in operable primary breast cancer -- Primary medical therapy in patients with small tumours -- Chemotherapy regimens used in primary medical therapy -- Duration of primary medical therapy -- Type of surgery -- The timing of radiotherapy -- Local recurrence rates after combined modality treatment -- The use of adjuvant therapy after surgery/radiotherapy -- Endocrine therapy as primary medical therapy -- Prognostic factors in primary medical therapy -- Impact of primary medical therapy on survival -- Conclusion -- REFERENCES -- 11 Medical therapy of advanced disease -- Introduction -- Principles of treatment -- Endocrine versus cytotoxic treatment? -- Selective oestrogen receptor modulators (SERMS) -- Ovarian suppression -- Aromatase inhibitors.

Progestins.