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The Evolution of Paradigms for the Management of Breast Cancer: a Personal Perspective1

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The Evolution of Paradigms for the Management of Breast Cancer: a Personal Perspective1 (CANCER RESEARCH 52, 2371-2383, May I, 1992] Perspectivesin CancerResearch The Evolution of Paradigms for the Management of Breast Cancer: A Personal Perspective1 Bernard Fisher2 National Surgical Adjuvant Breast and Bowel Project Headquarters, Pittsburgh, Pennsylvania 15261 Introduction will develop the disease in her lifetime (1). Surveillance, Epi demiology, and End Results program (SEER) data indicate Although female breast cancer remains a major public health that, as age increases, so does the incidence of breast cancer problem, notable improvements have occurred in its treatment. (2). Whereas, for women 50-54 years of age the incidence is For most of this century, women with primary breast cancer 212 per 100,000, it increases progressively over the next 25 have been treated by radical mastectomy or some variation of years to 435 per 100,000 for women 80 to 84 years old. As that procedure. In recent years lumpectomy has become the ominous as they may seem, these statistics do not begin to recommended operation for most patients. Before the mid- portray the magnitude of the problem. The 75,000 or more 1970s, postoperative adjuvant systemic therapy was not used; women with invasive breast cancer clinically and/or mammo- now it is a major component of treatment strategies. How have graphically diagnosed each year represent only the tip of an these drastic changes come about? Are they the result of anec iceberg. Those women comprise only one cohort of the female dotal recitations of personal experiences or the outcome of population whose breasts contain a spectrum of aberrations, more abstruse circumstances? How are future changes apt to among which are the detected cancers (Fig. 1). occur? Are we to believe that science has little or nothing to do At the top of the spectrum (Fig. 1/4) are women whose breasts with the process? contain invasive and noninvasive cancers of sufficient size to be Science will continue to determine how breast cancer is detected clinically. In that same category are women with perceived and managed in the future. Clinical practice must be palpable benign lesions considered to carry no added risk, as based on a rational foundation that underlies our comprehen well as those whose breasts contain lesions that put them at sion of the disease; this understanding relates to the "science" increased risk for invasive cancer, e.g., atypical ductal or lobular of the time in which we practice. The science of breast cancer hyperplasia, and florid or solid papillary hyperplasia. Near this in 1992 is different from that of 1892, and the science of breast end of the spectrum (Fig. \B) are women with abnormal breasts cancer in the next decade will differ from that of today. As the harboring lesions similar to those above that can be detected burgeoning science of molecular biology unfolds, it is unrealistic only by mammography. Among those with "normal" breasts in to expect that operative procedures and systemic therapy mo the middle of the spectrum (Fig. 1C) are women with the dalities now used to treat breast cancer will remain static, any previously described lesions that are nondetectable but, if ma more than it could have been assumed that surgery would lignant, are likely to eventually become clinically or mammo- remain unchanged during the past century, given the changes graphically identifiable. Near the bottom of the schema (Fig. in our understanding of the disease during that time. ID) are women, considered normal, who may have breast tissue The increased use of mammography and recent advances in that has undergone biological alteration, a term used to encom basic tumor biology (particularly as they relate to cancer etiol pass molecular-biologic, genetic, and biochemical factors that ogy) have resulted in an expanded perception of the breast may play a seminal role in the etiology of invasive breast cancer. cancer problem. This essay will describe how breast cancer If modern concepts of carcinogenesis as they relate to the therapy has evolved and will continue to advance as a conse process of initiation and promotion are applicable to breast quence of transitions from paradigm to paradigm. It will also cancer, there is reason to believe that there are women within present several scientific developments that have the potential the so-called normal population who have "biological breast for creating new paradigms for breast cancer management in cancers." These lesions have not yet become what we recognize the not too distant future. How adequately past, present, and under the microscope as cancers (phenotypic), but they have future paradigms relate to the currently expanding view of the undergone molecular-biologic changes that will result in tumors disease is also considered. that may, at some future time, be diagnosed by current clinical An Expanded Perception of the Breast Cancer Problem. In and mammographie methods. It is here that a single normal 1969, 66,000 new cases of breast cancer were diagnosed and cell is "emancipated" from host controls and that—as a result 29,000 women died from the disease. By 1975 there were 88,000 of its altered growth regulation—the resulting neoplastic stem new cases and 33,000 deaths, with 1 in 14 women at risk for cell gives rise to a clone of tumor cells. These phenomena and developing the disease. During the 1990s, more than 1.7 million those that follow depend upon a series of complex events women (about 175,000 per year) in the United States will be involving alterations in cellular oncogenes, tumor suppressor newly diagnosed with invasive breast cancer, and about 30% of genes, gene products, and growth factors that can augment or them will ultimately die from it; approximately 1 in 9 women inhibit cell proliferation, and related activities (3-5). As neo plastic growth progresses, new mutations occur and new clones, Received 12/3/91 ; accepted 2/27/92. ' The laboratory and clinical investigations referred to in this publication were which have a growth advantage over their predecessors, appear. supported by USPHS grants from the National Cancer Institute and by grants At some point, genetic alterations may occur which give rise to from the American Cancer Society. 2To whom requests for reprints should be addressed, at National Surgical cells that have acquired competence for establishing métastases. Adjuvant Breast and Bowel Project Headquarters. Room 914, Scaife Hall, 3550 Early in the onset of a tumor, angiogenesis, an event necessary Terrace Street. Pittsburgh. PA 15261. for tumor progression, takes place. (6) At the bottom of the 2371 Downloaded from cancerres.aacrjournals.org on October 2, 2021. © 1992 American Association for Cancer Research. EVOLUTION OF PARADIGMS FOR THE MANAGEMENT OF BREAST CANCER breast cancer, I became familiar with the work of Thomas Kühn,a theoretical physicist, philosopher, and historian of science, who described the developmental pathways of physical sciences as transitions from paradigm to paradigm which occur as a result of scientific revolutions (7, 8). Kühnandothers who have discussed the evolutionary process of science have not given meaningful consideration to how radical changes take place in biology and medicine (9, 10). Some theorists, in fact, contend that Kuhnian revolutions do not occur at all in these •¿Â®Â°oOx^0®® sciences (11). Others dispute that perspective (12). It is my 2 contention that Kuhn's interpretation of the nature of scientific en9en l1BIOLOGICALCHANGES-".S 00 LU< •¿CD O®"•"O •¿Â»0O -JCE .'. revolution is directly relevant to medicine and that his descrip ~jm QQ*Éu°- tion of the pathway of paradigmatic change can be used to -(GENEGENOTYPIC ALTERATION, illustrate how the treatment of breast cancer has evolved to its •¿.F®*ô •¿*•' "• DNAetc.)"NO"CHANGES(AT DAMAGE, ujz present state. (I hasten to point out that, although retrospec 9"gzc tively relating progress in medical science to a particular schema FORBREASTRISK CANCER)C is legitimate, following the steps comprising that pathway does not necessarily guarantee success in obtaining new knowledge.) Fig. 1. Spectrum of changes in women with normal and abnormal breasts. •¿, invasive cancers; O, in situ cancers (DCIS, LCIS); ®,hyperplasia, atypical hyperplasia, sclerosing adenosis; •¿,biologicalcancers; x, fibroadenomas, simple cysts, adenosis, duct ectasia. Developmental Pathways of Science The Transition from Paradigm to Paradigm According to spectrum (Fig. IE) are women who may have no phenotypically Kühn.Atsome time in history, according to Kühn,ascientific expressed lesions and no biological changes in their breasts. community acknowledges the existence of scientific achieve These women, despite putatively normal breasts, are at risk for ments so unprecedented that they attract an increasing number of adherents away from the model that governs the community's developing breast cancer even though they may have no defin able risk factors. Although the spectrum depicts a change that activity (Fig. 2). For a time, the new science serves as a foun dation for the practice of these "converts." The model governing could exist in the breast of a particular woman at a particular time, it fails to convey the dynamics of the change that occurs their activity is called a paradigm, a term used to encompass "all of the beliefs, values, and techniques shared by members of over time. It does not indicate how the stepwise progression of a [scientific] community" (7). Although a paradigm is accepted a lesion that travels from one end of the spectrum to the other is instigated or show how much time elapses between the first because it seems better than its competitors, it seldom explains change that gives rise to a cancer and the presence of a cancer all of the enigmas that confront it. Consequently, it provides a that can be detected.
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