Breast cancer is the most common malignancy among women worldwide, and a quarter of all breast cancers are diagnosed in premenopausal women. Adjuvant chemotherapy is well established as the therapy of choice for hormone receptor-negative breast cancers. Historically, ovarian ablation substantially inhibited the progression of hormone-responsive breast cancer. Current adjuvant treatment options for premenopausal patients with hormone receptor-positive breast cancer include endocrine therapy and chemotherapy. Pharmacologic ovarian suppression alone has limited efficacy in the adjuvant setting, but it offers good clinical outcomes when combined with tamoxifen or chemotherapy. In recent years, aromatase inhibitors (AIs) have become the endocrine therapy of choice in postmenopausal women with hormone-responsive breast cancer, but their efficacy in the premenopausal setting is yet to be established. However, in a large, phase III randomized study (Austrian Breast and Colorectal Cancer Study Group Trial 12) that matured earlier this year, the combination of ovarian suppression and AI, anastrozole, did not show superior efficacy compared with ovarian suppression plus tamoxifen, but was associated with fewer serious adverse effects in premenopausal women with early stage hormone-responsive breast cancer. Data from ongoing and future trials will help to further define the role of ovarian suppression and AIs in the adjuvant setting for premenopausal breast cancer.

Many older women today with early-stage breast cancer have estimated survivals exceeding 5–10 years at the time of diagnosis and should be considered for systemic adjuvant chemotherapy. When available and if eligible, such patients should be offered clinical trials participation. Given the median age for onset of breast cancer, trials should also be developed to specifically investigate the disease in this age group. Oncologists caring for elders need to educate their colleagues as well as their patients concerning the pitfalls of age bias and the potential hazard of under-treatment and poorer outcomes.

The international standard regimen of radiotherapy for women with early breast cancer following mastectomy or local tumour excision involves the delivery of daily doses (fractions) of 2.0 Gy to a total dose of 50 Gy. Recent randomised clinical trials suggest that there is most unlikely to be any disadvantages in terms of local tumour control or late adverse effects, and obvious advantages in terms of convenience, for schedules treating to a lower total dose using a smaller number of larger fractions. Fifteen or 16 fractions of 2.67 Gy are being adopted in some countries, and future research will test the limits of this approach, termed accelerated hypofractionation.

Bisphosphonates offer a potentially effective adjuvant therapy to reduce recurrence of bone metastases in breast cancer patients. Clinical trials are at the early stage, but initial results have shown promise. There are three published adjuvant trials of oral clodronate, and one trial each of pamidronate and zoledronic acid. Observed complications so far include osteonecrosis of the jaw or maxilla because bisphosphonates inhibit bone turnover, as well as renal toxicity. Thus, care needs to be taken with dosage and duration of treatment and patients carefully managed.

Endocrine adjuvant therapy for breast cancer has been associated with a decrease in bone mineral density (BMD) and bone loss. For aromatase inhibitors, this bone loss is likely to be the most significant limitation to their long-term use. Treatments traditionally used to counteract his effect include exercise and supplementation with calcium and vitamin D. A newer treatment is the use of bisphosphonates, a class of drugs that reduce osteoclast activity. Clinical trials currently underway to examine the effect of bisphosphonate treatment on breast cancer patients have shown improvement in bone strength. Additional benefits of bisphosphonates, currently under study, give this class of drugs an important role to play in the treatment of cancer treatment-induced bone loss.

Breast cancer is one of the leading causes of cancer mortality in women in developed countries even though most women with the disease die of other causes. Postoperative adjuvant chemotherapy with anthracycline-based regimens has been proven to decrease the risk of relapse and cancer-related mortality in women with early stage breast cancer contributing to the improving survival seen with this disease. The taxanes have been effective additions to several adjuvant regimens based on recent prospective randomized studies. In the quest to further improve outcomes with adjuvant chemotherapy, dose and schedule modifications based on kinetic models have been compared with standard regimens. In this paper we review of several key trials testing a specific modification called ‘dose-dense’ chemotherapy.

Bone metastases frequently occur in advanced breast cancer patients and once incorporated into bone have profound effects on bone physiology. Bisphosphonates are potent inhibitors of osteoclastic function and are becoming increasingly important for the management of patients with breast cancer. They affect the ability of cancer cells to accelerate bone turnover and as a result control pain and reduce the risk of pathological fracture.

Furthermore ongoing clinical trials are investigating the role of bisphosphonates as an adjuvant therapy in high-risk breast cancer patients with an aim to prevent bone metastasis.

This article reviews the mechanisms of bone metastasis and will discuss present and future developments for the monitoring and treatment of metastatic bone disease.

Endocrine therapy is now established as the treatment option of choice for postmenopausal women with hormone receptor-positive advanced breast cancer. The benefit of the third-generation aromatase inhibitors (AIs) in this setting has prompted their evaluation in the treatment of early breast cancer. This article reviews the current clinical status of AIs as adjuvant therapy for early-stage breast cancer in postmenopausal women, focusing on the largest adjuvant breast cancer study till date to provide data, the ‘Arimidex’, Tamoxifen, Alone or in Combination (ATAC) trial.

The early and clinically occult spread of viable tumour cells throughout the body is increasingly considered as a hallmark of cancer progression, because recent data suggest that these cells are precursors of subsequent distant relapse. Using monoclonal antibodies to epithelial cytokeratins or tumour-associated cell-membrane glycoproteins, individual carcinoma cells can be detected in cytological bone marrow preparations at frequencies of 10-5 to 10-6. Prospective clinical studies have shown that the presence of these immunostained micrometastatic cells in bone marrow, as a frequent site of overt metastases, is prognostically relevant with regard to relapse-free period and overall survival. This screening approach might therefore be used to improve tumour staging and to guide stratification of patients for adjuvant therapy in clinical trials. Another promising clinical application is the use of these micrometastatic cells to monitor response to adjuvant therapies, which at present can be assessed only retrospectively after an extended period of clinical follow-up. This review summarises current data on the clinical significance of occult metastatic breast cancer cells in bone marrow.