Irma H. Russo, M.D. and Jose Russo, M.D.

Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, PA.

Every single day during 1997 more than 1,500 American women have been told they suffer some kind of invasive cancer and more than 700 have died as the consequence of advanced stages of the same disease (1). These dismal statistics are still quite conservative, since these figures do not include the number of non-invasive cancers of the skin or the breast that are Daily diagnosed, which also represent a risk of future invasive cancer development (1). An understanding of what is causing all these new malignancies and what is killing women in our society requires specific knowledge on the patterns of incidence, associations with exposure to certain cancer-causing agents, certain genetically determined predisposicions, and all the factors that influence the risk of a woman to develop certain malignancies. The multifaceted aspects of cancer in women requires the contribution of different specialties, such as Surgery, Medical Oncology, Pathology, and Radiotherapy. These, in turn, need to work in conjunction with Epidemiology, Sociobiology and Basic Sciences, among other specialties, for translating specific knowledge inherent to each discipline to the problem of cancer in every individual woman. Since there are multitudes of specialties that require a common pathway of expression, the journal Women and Cancer has been designed for gathering essential information on those factors, encompassing all the types of cancers that affect the health, lifestyle and survival of women.

Every single organ can be the seat of cancer in women, although certain organs, namely the breast, lungs, and colon and rectum are the most frequently affected. Malignancies develop as well in the organs of the genital and endocrine systems, the lymphatic and hematopoietic systems, and the skin. The incidence of cancer that we see in these organs today, however, has dramatically changed as a consequence of socioeconomic and environmental factors. Breast cancer was the leading cause of death in women until 1987, when the first place was taken by lung cancer, as a response to the increased consumption of cigarettes by women. Breast cancer, however, remains the number one cause of death in non-smokers (1). Epidemiological studies are of essential importance for understanding certain trends in cancer incidence. The Vital Statistics of the United States reveal a progressive decrease in mortality caused by cancer of the uterus and of the stomach since 1930, a trend still continuing; while the mortality caused by cancer of the ovary and of the pancreas is slightly increasing over the same period of time. Some associations in these changing trends have become quite clear, such as that between lung cancer and smoking, or the reduction in the significance of cancer of the cervix as a cause of death due to he widespread use of the cervical smear, or Papanicolaou test, as a screening and diagnostic tool, which has resulted in detection of earlier lesions that could be resected when still are in a curable stage. The mortality for gastric cancer has continually decreased in both men and women since 1930, although there is no clearly identified cause for this decrease, except for the interpretation that a combination of factors, and among them improvements in refrigeration and food preservation might have played a protective role. Some increases in cancer incidences can be attributed to specific causes. Cancer in hormone-dependent organs have been found to increase in relation to the use of hormones with the purpose of replacement therapy or contraception, such in the cases of cancer of the endometrium in relation to the use of estrogen-replacement therapy at menopause, although the anti-estrogen Tamoxifen might exert a similar effect. Use of progestogenic contraceptives prior to a first full term pregnancy have been reported to increase the risk of breast cancer, while the use of oral contraceptive has also been associated with a marked decrease in the incidence of ovarian cancer.

Of great concern with regards to the cancer of the breast is the fact that the number of new cases diagnosed in the majority of the Western world countries continues increasing progressively (2-4). The causes of this increase are not known, but they are largely attributed to family history of breast or breast/ovarian cancer (5), prolonged exposure to female hormones, such as occurs in those women with early menarche, late menopause, oral contraceptive or hormone replacement therapy use. Nulliparity or late first full term pregnancy have also been identified as additional sources of risk (6-10). Exposure during childhood and adolescence to certain agents, such as radiations, increases the incidence of this disease (9). The close relationship found between nulliparity and the incidence of breast cancer, while one or more full term pregnancies in a young woman decrease significantly the risk (6,10) indicates that the period of time between menarche and the first pregnancy represents a "window" of critical importance in a woman’s life for determining the future risk of developing breast cancer, even after menopause. The identification of this "window" of risk might constitute a useful tool for the prevention of breast cancer beginning with the protection of this organ from an early age (11). The project of developing this Special Issue on breast Cancer arose as a need after the search for information on this type of cancer was found to be dispersed throughout the literature. This issue proposes to gather state of the art information to be transmitted to physicians, researchers, oncologic nurses, students and all women and men seeking answers on the multiple aspects of this disease. Therefore, the objective of this Special Issue of the Journal Women and Cancer is to condense the major issues of breast cancer as a disease, not only as a pathobiological entity, but also as a socio-epidemiological problem, and to explore new avenues in treatment and in the application of new research tools, such as gene therapy, for the treatment and prevention of the disease.

Leslie Bernstein, Ph.D. Department of Preventive Medicine, University of Southern California School of Medicine, Norris Comprehensive Cancer Center, 1441 Eastlake Avenue, MS 44., Los Angeles, California 90033 USA.

Breast cancer is the most common cancer in women worldwide. Age is an important determinant of risk. Breast cancer incidence rates increase most rapidly during the reproductive years; following menopause, the rate of increase declines or rates plateau, depending on the population studied. Most individual breast cancer risk factors can be understood in light of their effects on the accumulated exposure of a woman’s breast to estrogen and, possibly, to progesterone. Early age at menarche, late age at menopause, nulliparity, late age at first full-term pregnancy, and low parity increase risk, whereas lactation lowers risk. Obesity increases risk in postmenopausal women. Among premenopausal women, participation in physical activities lowers breast cancer risk. Women who have a first degree relative with breast cancer are at increased risk, especially if both a mother and a sister have had breast cancer at an early age. Other factors that may be important determinants of breast cancer risk include certain aspects of diet, alcohol intake, radiation exposure, in utero exposures, and environmental exposures. Currently, there is little practical advice that can be given to women about reducing their breast cancer risk, although recommendations about lactation and participation in physical activity offer possible approaches.

Jose Russo, M.D. and Irma H. Russo, M.D.,Breast Cancer Research Laboratory, Fox Chase Cancer Center, Philadelphia, PA 19111

Janet Rose Osuch, M.D., Michigan State University, Department of Surgery, East Lansing, Michigan 48824

The surgical treatment for breast carcinoma has undergone major changes in the past decade and continues to evolve. Once a disease managed exclusively by surgeons, a multidisciplinary approach involving surgical, radiation and medical oncology is the standard of care in 1997. To understand this shift, it will be helpful to view the surgical treatment of breast cancer within an historical context. In any discussion of surgical treatment, two end points are important: (1) local tumor control and (2) survival. Local recurrences of tumor do little to affect survival from the disease, but are of paramount importance in the quality of life of the patient. Survival is almost always influenced by the systemic recurrence of the disease. The discussion will first address the treatment of invasive cancer (ductal or lobular), with a special section devoted to approaches to in-situ carcinoma. (Women and Cancer, Vol.1S: 22-28,1998)

Henry T. Lynch^*, Jane F. Lynch^*, Joseph Marcus^#, Patrice Watson^{*, *}Department of Preventive Medicine, Creighton University School of Medicine, 2500 California Plaza, Omaha NE 68178^#Department of Pathology, St. Luke’s Hospital, 232 S. Woods Mill Road, Chesterfield MO 63017

The etiologic role of heredity in virtually all forms of cancer has been confirmed during the past decade through rather remarkable discoveries of a succession of cancer predisposing germ-line mutations. These molecular genetic advances apply not only to hereditary forms of cancer but, moreover, they have impacted heavily on our knowledge of so-called "sporadic" forms of cancer. In the case of hereditary breast cancer, particularly the hereditary breast-ovarian cancer (HBOC) syndrome, BRCA1 and BRCA2 germ-line mutations, initially identified by linkage analysis and then cloned, have provided new dimensions to cancer surveillance and management. Specifically, we are now able to signify who is versus whom is not at enormous lifetime susceptibility to cancer at specific targeted anatomic sites and counsel them accordingly. However, translation of this knowledge for effective patient care requires genetic counseling prior to collection of the DNA and at the time of disclosure of results. Unfortunately, there are only a limited number of genetic counselors that have experience with cancer. Hence, physicians in many cases must assume this genetic counseling responsibility as advocated by the American Society of Clinical Oncology. We have discussed not only the pros and cons of DNA based genetic counseling but have also tracked the history in this newly evolving molecular genetic era with particular attention focused upon hereditary forms of breast cancer.

Generosa Grana, MD, UMDNJ Robert Wood Johnson School of Medicine, Cooper Hospital University Medical Center, 3 Cooper Plaza, Suite 215, Camden, New Jersey 18003.

Breast cancer is a heterogeneous disease whose treatment continues to evolve. Because of it’s potential to metastasize even years after adequate local control, the disease should be viewed as one with a potential for systemic spread at diagnosis. Treatment planning for newly diagnosed disease is dependent on the use of established prognostic factors to help assess the cancer’s potential for systemic spread. This information, together with an assessment of toxicity and efficacy of available treatment options will lead to individual treatment recommendations. While adjuvant therapy with chemotherapeutic and/or hormonal agents has been shown to be effective in improving disease-free and overall survival from breast cancer, many

Kathryn Coe, Ph.D., Office of Community and Behavioral Health Promotion, Bureau for Prevention and Health Promotion, Arizona Department of Health Services, 1400 W. Washington, Phoenix, Arizona 85007

The aim of this bicultural epidemiologic study of breast cancer is to develop educational interventions that promote early diagnosis and reduce mortality by building upon a holistic understanding of the biologic and cultural risk factors. While Hispanic women, as a group, experience lower risk than do their Anglo counterparts, there is significant geographical variation in disease distribution among Hispanic women. Lifestyle can explain this geographical variation: Hispanic women who live a westernized lifestyle experience a significantly higher risk of getting breast cancer. Women at lowest risk follow traditional lifestyle patterns involving not only diets low in fat and high in fiber, but daily physical exercise, and a particular reproductive history. These women, who typically live among close kin, marry and begin reproduction soon after puberty and continue, over their life span, a series of pregnancies and breast-feeding. The patterns pointed out in this paper are used to argue that effective educational interventions will inform women of the risk they may incur because of lifestyle choices and will build upon a kinship model of teaching and learning. (Women and Cancer, Vol.1S: 38-43, 1998)