Elsevier

The Lancet

Volume 365, Issue 9472, 14–20 May 2005, Pages 1727-1741
The Lancet

Seminar
Breast cancer

https://doi.org/10.1016/S0140-6736(05)66546-4Get rights and content

Summary

Breast cancer remains a public-health issue on a global scale. We report new information about the disease from the past 5 years. Early age at first birth, increasing parity, and tamoxifen use are related to long-term lifetime reduction in breast-cancer risk. Ductal carcinomas in situ has been suggested to be renamed ductal intraepithelial neoplasia to emphasise its non-life-threatening nature. An alternative approach, the progenitor/stem cell theory, predicts that only some tumour cells cause cancer progression and that these should be targeted by treatment. Mammography and ultrasonography are still the most effective for women with non-dense and dense breast tissues, respectively. Additionally, MRI, lymphatic mapping, the nipple-sparing mastectomy, partial breast irradiation, neoadjuvant systemic therapy, and adjuvant treatments are promising for subgroups of breast-cancer patients. Although tamoxifen can be offered for endocrine-responsive disease, aromatase inhibitors are increasingly used. Assessment of potential molecular targets is now important in primary diagnosis. Tyrosine-kinase inhibitors and other drugs with anti-angiogenesis properties are currently undergoing preclinical investigations.

Section snippets

Causes of disease

Nowadays, the identification of effective strategies and interventions to prevent breast cancer is still challenging. Although women who have first-degree relatives with a history of the disease are at increased risk, a major pooled analysis has revealed that they are unlikely to ever develop breast cancer, and most who do will be older than 50 years when diagnosed. In countries where breast cancer is common, the lifetime excess incidence of breast cancer is 5·5% for women with one affected

Possibilities of chemoprevention

In the past few years, hormonal intervention using tamoxifen has been shown to reduce the risk of oestrogen-receptor-positive breast cancer.32 Although such findings are good with respect to proof of principle, the degree of side-effects from tamoxifen, some clinically serious and others affecting quality of life, seem to rule out the drug for general use at present.

Our knowledge of breast carcinogenesis remains incomplete. We still have no comprehensive understanding of the mechanisms of

Progression from healthy tissue to invasive carcinoma

Because of the longlasting debate on the preneoplastic potential of benign, proliferative lesions of the breast (ie, florid ductal hyperplasia in fibrocystic disease), a definitive progression model (similar to that for colon adenocarcinoma) has not been determined. Current knowledge on mammary dysplasia is far from reliable. Indeed, cytological or architectural dysplastic changes can be located in various non-malignant breast diseases, such as florid and columnar duct hyperplasia, adenosis,

Diagnosis and staging

The revolution in diagnostic imaging during the past 20 years has greatly changed detection and diagnostic strategies in breast cancer. Moreover, organised screening, education programmes, and improved consciousness of the female population have substantially changed the type of patients seen nowadays compared with those a few decades ago.

Surgery

Once imaging techniques indicate a tumour in the breast, cytological or histological confirmation is vital before further treatment is given. Cytology is effective in solid lesions, especially if sonographically guided.60 But knowledge of the histology of the lesion is the most useful for surgeons, which can be obtained by a core biopsy. A tru-cut biopsy is the simplest method for palpable lesions that are easily reached, whereas a vacuum-assisted needle biopsy can obtain enough material for a

Radiotherapy in breast conservation

In most developed countries, the current standard of care for patients with early-stage breast cancer consists of breast-conserving surgery, followed by 5–6 weeks' postoperative radiotherapy. Women treated with this protocol have similar prognosis to those treated with mastectomy. Although avoidance of breast irradiation was shown to substantially raise local recurrence, the necessity of radiotherapy in breast conservation strategy is still debated.68 Some subgroups of patients could

Systemic treatments

Patients who remain free of disease after adjuvant therapy compared with those needing chronic care to constantly control disease progression is the main difference between adjuvant and the metastatic treatment approaches, respectively. Adjuvant systemic therapy is given to attempt eradication of micrometastatic disease, which could potentially be present in all patients with invasive breast cancer. Its aim is to reduce relapse and increase survival. Postoperative adjuvant therapies cannot be

Systemic treatments for women with overt metastases

Overt metastases usually indicate chronic, incurable disease. Treatments are defined according to efficacy to provide palliation and account for a heterogeneous duration of survival, which could vary from a few weeks to several decades (with an average of a few years). Treatment should increase the total duration of time with no or few disease-related symptoms and with the lowest burdens with respect to side-effects of treatment.145 Although some trials with selected patients have shown, on

Molecular targets and new drugs

The rapid growth in the number of biomolecular markers and development of targeted therapeutic drugs for breast-cancer treatment began more than three decades ago after the discovery of steroid-hormone receptors.150 Increased knowledge of several tyrosine-kinase family receptors has led to the first targeted treatment beyond endocrine therapies, the humanised murine antibody trastuzumab. Assessment of potential molecular targets has therefore become an important part of primary diagnosis to

Conclusions

Although care for patients with breast cancer is genuinely mutlidisciplinary, there is an important general trend to increase targeted interventions within all specialties to obtain efficacious treatment with acute and late toxic effects in organs and tissues kept to a minimum. It is within this context that progress should be viewed; development of tailored adjuvant systemic therapies and better targeted treatments for women with advanced disease. Both approaches will need an improved

Search strategy and selection criteria

We searched the Cochrane Library (data range) and MEDLINE (data range), using the search term “breast cancer”. We mainly selected publications in the past 5 years, but did not exclude older reports that were commonly referenced and highly regarded. We also searched the reference lists of articles identified by this search strategy and selected those we judged as relevant. Several review articles or book chapters were included because they provided comprehensive overviews that were beyond

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