Breast cancer—have we been chasing the wrong target?

Invasive breast cancer has been a major therapeutic target of surgeons over the last two centuries. It was obvious that, if left alone, these hard breast tumors would spread and kill patients. We now have a much better understanding of the process of breast carcinogenesis. From this, we are beginning to develop effective strategies for preventing breast cancer in high-risk women. With these new understandings comes the question, ‘‘Should we be screening women for the same thing surgeons were over 100 years ago? ’’ Shouldn’t our attention be focussed on screening for those premalignant events that we can pre-empt from progression? To answer these questions, we must look back at our history of treatment of breast cancer—the successes and many failures of our past. We also must take stock of what we currently know and what we still need to find out about this disease. For nearly two millennia, melancholy was thought to be the etiology of cancer because of Galen’s Carinogenica Melancholia. St. John’s wort and other herbal treatments made little difference in the mortality from this disease. With the advent of the microscope and more scientific approaches to disease, Billroth and others developed lumpectomy and axillary dissection as a more reasonable approach to this disease. Unfortunately, without attention to microscopic margins and the biology of breast cancer, these initial attempts at surgical local control of breast cancer failed on average 85% of the time within 3 years, according to all clinical series published from 1850–1894. Gross at the University of Pennsylvania introduced the idea of mastectomy in the 1880s but still without attention to the biology of breast cancer and pathologic margins. Halsted [1] then designed and reported the first successful local therapy for breast cancer—requiring en bloc resection with careful attention to pathologic margins in 1894. Even current breast conservation, until the last decade, has included within the radiation port all the tissue that would have been removed in the old Halsted radical mastectomy. Only recently, and in the very best prognosis patients, have less than whole breast radiation approaches been adopted for modern breast conservation with lumpectomy. In spite of all these changes in our local therapy and the addition of systemic adjuvant therapy, it is very humbling to note that Halsted’s 5-year clinical disease free survival for pathologically node negative breast cancer was 85%. Most of our modern series fail to show results that good for palpable lesions similar to those he was treating. What is the moral of the story of our therapeutic successes and failures in breast cancer? Halsted, in an editorial to accompany his original radical mastectomy study, said that the real hope in breast cancer was simply earlier diagnosis and extirpation of the invasive focus of disease. From 1930 until 1997 there was no lasting improvement in the age-adjusted death rate from breast cancer in the U.S. [2]. In the last several years, for the first time, this age-adjusted death rate for breast cancer has fallen, and this is associated primarily with rapid decreases in the average size of breast cancer at diagnosis [3]. It becomes apparent that our therapeutic approaches are far more successful before invasion or shortly after invasion begins—exactly what Halsted had predicted over 100 years ago. We currently theorize that all breast cancers go through stages of hyperplasia, atypical hyperplasia, and in situ carcinoma before invasive cancers develop. We also recognize that this process happens most of the time slowly over many years. In spite of this, we continue to focus our efforts to detect breast cancers at the stage of