• B Fisher.
• National Surgical Adjuvant Breast and Bowel Project, 4 Allegheny Center, Pittsburgh, Pennsylvania 15212-5234, USA. bernard.fisher@nsabp.org
• Eur. J. Cancer. 1999 Dec 1; 35 (14): 1963-73.

AbstractThis commentary evaluates progress made in the treatment of breast cancer during the twentieth century. Most of the period from 1900 to 1970 was governed by the 'non-science' of anecdotalism and classical inductivism and was marked by the absence of a scientific gestalt. In keeping with the Halstedian concept that breast cancer was a local disease that spread throughout the body by contiguous extension and could be cured by more expansive surgery, the disease was treated with radical surgery. In 1950, however, a new era of enlightenment began to emerge. The awareness that there was a scientific process in which hypotheses generated from laboratory and clinical investigation could be tested by means of randomised clinical trials was a seminal advance, as were findings from studies that laid the groundwork for the modern era of steroid hormone action, including identification of oestrogen receptors. Expanding knowledge regarding tumour cell kinetics, tumour heterogeneity, and technological advances related to mammography and radiation therapy were also to play a role in making possible the advances in therapy that were subsequently to occur. In the past 30 years, as a result of laboratory and clinical investigation, the Halstedian thesis of cancer surgery was displaced by an alternative hypothesis that was supported by findings from subsequent clinical trials. A new paradigm governed surgery for breast cancer, and lumpectomy followed by radiation therapy became accepted practice. A second paradigm that governed the use of adjuvant systemic therapy arose as a result of laboratory and clinical investigation. Treating patients who were free of identifiable metastatic disease with systemic adjuvant therapy because some of them might develop distant disease in the future was a revolutionary departure from prior treatment strategy and became a new exemplar. Not only did the chemotherapy favourably alter the outcome of breast cancer patients, but the anti-oestrogen tamoxifen benefited patients with all stages of the disease. Tamoxifen also reduced the incidence of contralateral breast cancer, as well as tumour in the ipsilateral breast following lumpectomy. The use of preoperative therapy was also found to enhance breast-conserving surgery in women with large tumours, although its value in other circumstances is still being defined. The observation that, as a result of tamoxifen administration, invasive and non-invasive breast cancers can be prevented in women who are at increased risk for such tumours, and the finding that pathological entities such as atypical hyperplasia, lobular carcinoma in situ (LCIS) and intraductal carcinoma (DCIS) can identify women who should be considered candidates for tamoxifen serve as a fitting capstone to the accomplishments of the twentieth century. Breast cancer prevention has now become a reality. Unfortunately, a variety of circumstances have arisen as the result of advances in the understanding and treatment of breast cancer over the last 30 years that threaten to nullify the progress that has been achieved. This distressing phenomenon may be reviewed as a 'paradox of accomplishment'. The numerous uncertainties, issues and questions that have arisen following the report of each advance in treatment, the surfeit of new information that has not yet been integrated into treatment strategies, the undesirable consequences of enhanced tumour detection, a reversion to Halstedianism and anecdotalism, and the uncertainty of therapeutic decision making resulting from the demonstration of small but statistically significant benefits, particularly in patients with good prognosis, need to be addressed. Inappropriate interpretation of those circumstances threatens to deny women with breast cancer and those at high risk for the disease the opportunity to benefit from treatments that have been proven to be of worth. Perhaps the most important accomplishment of the twentieth century relates to the change in the pro

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