Breast Cancer Control Challenge or Chimera

Arthur I. Holleb, MD*

HE TITLE OF THIS KEYNOTE lecture “Breast Cancer T Control: Challenge or Chimera,” is adapted from Dr. Charles Cameron’s James Ewing Lecture of 1973.’ Cameron noted that, “If the title seems cute or contrived, it is not, if you agree that chimera can mean an impossible or foolish fancy.” I leave it to the reader to decide whether or not breast cancer control is a rational pursuit or chi- merical.

Have we had a surfeit of conferences on breast cancer in recent years? Probably not. The topic remains timely, with foci including ways to motivate the public to engage in self-help programs and deal with psychosocial prob- lems; technological advances in detection, diagnosis, and prognostication; improved clinical management and re- habilitation; changed philosophies regarding the biological behavior of breast cancer, and finally consideration of the possibility of the health-oriented consumer actively par- ticipating in, and perhaps ultimately determining, her own treatment.

The facts of breast cancer remain grim. At present, one of every ten newborn American girls is destined to get breast cancer during her life. In 1989, there were approx- imately 142,000 new cases and 43,000 deaths from breast cancer. These numbers are too large to comprehend but they break down into one newly diagnosed breast cancer every 4 minutes and one death from breast cancer every 12 minutes in the US.

Breast cancer has been known since the days of the ancient Egyptians. Hieroglyphic transliteration of a por- tion of the Edwin Smith papyrus, circa 1600 to 1500 BC, probably contains the first mention of a breast tumor in history.

Galen attributed breast cancer to an imbalance of hu- mors and an excess of black bile. He treated the disease by modifications of the diet designed to diminish mel- ancholia. Today we modify the diet to reduce total fat intake as a possible preventive measure.

Presented at the American Cancer Society National Conference on Breast Cancer, Chicago Westin Hotel, Chicago, Illinois, July 19-2 1, 1989.

* Consultant, Medical Affairs Department of the American Cancer Society.

Address for reprints: Arthur I. Holleb, MD, 3 Highridge Road, Larch- mont, NY 10538.

Accepted for publication January 28, 1989.

Historically, mastectomy was sometimes reserved for women accused of deviation. Descriptions and paintings of these primitive and brutal operations are found in the legend of the martyrdom of Saint Agatha, the Patron Saint of the breast, wet nurses, and bell founders. “In art she is sometimes depicted as carrying her breasts on a salver. These were mistaken for loaves of bread and thus arose the custom of blessing bread on Saint Agatha’s Day. In Scandinavian countries it is believed that cruel Governor Quintianus had Saint Agatha brushed to death. Therefore, on February 5th, Saint Agatha’s Day, it is traditional for girls to abstain from brushing their hair.”’

During the Renaissance, Galen’s concepts were ques- tioned by Vesalius as a result of a growing understanding of surgical pathology. Approaches to the cure of breast cancer by Pare, De Chauliac, Scultetus, Petit, Velpeau, Moore, Pancoast, Gross, Volkmann, Billroth, and Hei- denhain, among others, all led to Halsted and Meyer’s refinement into the classical radical mastectomy, a pro- cedure based on Handley’s concept that breast cancers spread in a direct and continuous way. This operation, which became so firmly entrenched in the surgical man- agement of breast cancer, however, did not appear over- night in the late 1880s.

Precedence for the modern radical mastectomy is uni- versally bestowed on William Stewart Halsted and rightly so. He was not, however, the first to remove the pectoralis major muscle. As early as 1570, Cabrol did this and dusted the wound with vitriol. As Lewison’ noted, “It was Halsted who conceived of its routine removal as an integral part of the complete operation. In fact, it was in the complete- ness of his method that Halsted achieved a success which set a new standard in the development of surgery and established a paragon of surgical precision which had no precedent in the history of cancer treatment. Its composite character and cosmopolitan development were inevi- table.”

Thereafter, breast cancer history is well known: the use of postoperative radiation therapy; Haagensen’s grave prognostic signs and consistent support of the Halsted Radical Mastectomy, along with Dr. Frank Adair, the Chief of the Breast Service at Memorial Hospital, who performed as many as seven radical mastectomies in one day; the supraradical excision of the internal mammary

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chain in continuity with the Halsted Radical; simple mas- tectomy with or without postoperative radiation therapy; the reversal toward lumpectomy, tylectomy, partial mas- tectomy, segmental resection, and the clinical trials of quadrantectomy in Milan; the reports of in situ breast cancer; adjuvant chemotherapy; estrogen and progester- one receptors; a resurgence of the biological determinism concept that insisted delay in diagnosis and the method of treatment made no difference, a therapeutic nihilism suggesting that all breast cancers result in death; and finally the newer diagnostic techniques of low-dose mammog- raphy, thermography, ultrasound and diaphanography, computed tomography scans, and nuclear magnetic res- onance (NMR) which became magnetic resonance im- aging.

In the 1970s the American Cancer Society and the Na- tional Cancer Institute initiated the nationwide Breast Cancer Detection Demonstration Projects (BCDDP) based on the pioneering 1960s Health Insurance Plan of New York (HIP) study. The BCDDP was nearly demol- ished by some epidemiologists who created headlines screaming “unnecessary mastectomies” and the induction of more breast cancer through mammography than mammography could find. While all these things were going on, clinical trials of limited surgery in the National Surgical Adjuvant Breast Project (NSABP) were being pursued and resulted in markedly changed patterns of surgical treatment for breast cancer here and abroad. The most recent reports are now evaluating preoperative che- motherapy and preoperative radiation therapy before consideration of other procedures and treatments.

Let me point out that 45 years ago, when I started my internship, the Halsted Radical Mastectomy was unques- tioned. A failure to cure was usually attributed to a wom- an’s delay or to a family physician who did not get the woman to a surgeon quickly enough. The management of breast cancer was so straightforward that only one or two authors could write an entire textbook. Major books were written by Gross in 1880, Deaver and MacFarlane in 1917, and Geschickter in 1943. Later, Haagensen, Lewison, and others added to the literature.

When I first chose a career in surgical oncology, with a primary focus on breast cancer, my colleagues advised me to go into obstetrics instead, which produced bouncing babies, happy parents, and doting grandparents; or into dermatology with no night calls and the fine prospect that almost all of your patients survived. I suppose that those of us, like many of you here today, who chose a career in oncology, did so at that time because the challenge was enormous and the weapons scarce.

Penicillin and sulfa drugs were relatively recent, nitro- gen mustard was the best we had in chemotherapy, ra- diation therapy was a moonlighting occupation of many diagnostic radiologists, radical surgery was risky at best,

and lung cancer was an uncommon disease. The practice of clinical oncology was in its infancy.

Forty-five years ago, the typical breast cancer was the size of a ping pong ball when first seen, and most had already spread to the axillary lymph nodes. The Halsted Radical Mastectomy was the procedure of choice because of the locally advanced stage of the disease. Now we are treating breast cancers too small to be palpated by the most experienced examiner in this room, and breast pres- ervation procedures are commonplace. Still, if a mastec- tomy must be done, reconstruction is readily available using modern technology. Also, well-designed postoper- ative chemotherapy offers the promise of increasing sur- vival rates further. We have learned how better to identify those women who are at higher risk for breast cancer, whereas in the past we had no knowledge of cancer fam- ilies or genetic predisposition.

Estrogen and progesterone receptors now give us clues about the best ways to treat recurrent breast cancer. Other considerations are genetic factors, nutrition, precursors of breast cancer, screening of large populations, breast cancer in the poor, growth factors, DNA flow cytometry, and thymidine labeling index, as well as other exciting new developments and approaches.

Until recently the psychosocial sphere of breast cancer was barely considered, and rehabilitation was virtually nonexistent. Today, special help comes from programs of the American Cancer Society: Reach to Recovery, Can- surmount, I Can Cope, clergy programs, and others. To- day coping is extremely important because more patients are surviving than ever before, and when cure is not pos- sible, productive life is being extended.

Let me take you back in time once more. In 1969, at least three very important events took place: the moon landing; the first episode of Sesame Street; and the first National Conference on Breast Cancer was held by the American Cancer Society in Washington, D. C. In Richard Nixon’s State of the Union Message in January 197 1, he proclaimed that, “The time has come when the same kind of concentrated effort that split the atom and took man to the moon should be turned toward conquering this dread disease. Let us make a total commitment to achieve this goal.” Two days before Christmas, Nixon signed the bill making into law The National Cancer Act of 197 1, a most controversial piece of legislation.

The first National Conference on Breast Cancer in 1969 was jointly sponsored by the American Cancer Society (ACS), the U. S. Public Health Service, and the American College of Radi~logy.~ Sidney Farber was the ACS Pres- ident, and Wendell Scott chaired the meeting. “Scottie,” as he liked to be called, chaired the College of Radiology’s Mammography Committee. This conference was one of the earliest cooperative efforts between a voluntary health agency and the federal government.

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Let me share some of the highlights with you. On the opening day reference was made to the National Cancer Act of 1937, which established the National Cancer In- stitute and a pattern for federal support of biomedical research. The other institutes of the present National In- stitute of Health structure stem directly from that legis- lative act.

In 1969, it was said that the years ahead were rich with promise, and today some refer to the 1980s as “the golden years of cancer research.” Scottie was convinced that we could control breast cancer the way we controlled cancer of the cervix.

That conference is indelibly etched in my mind. Dr. Roald Grant labeled breast cancer “the foremost cancer of women,” most fatal, most feared, most biopsies, most news articles, most controversial, most radically treated, most operations, most radiation therapy, most chemo- therapy, and the most prolific in sheer quantity of neo- plastic tissue produced by human beings. Dr. William Ross of the Department of Health, Education, and Wel- fare’s Cancer Control Program pointed out that, despite new knowledge, we had failed to change significantly the mortality rate of breast cancer. I checked the current data with Larry Garfinkel, Vice President for Epidemiology and Statistics of the American Cancer Society. He told me that, “between 1979 and 1986 the incidence rate of breast cancer increased by 24%, the same for premeno- pausal and postmenopausal women, and that overall mortality rates for breast cancer have been stable. Women under age 50 have had a decline in mortality of 0.8% per year since 1973 whereas women over age 50 have had an average increase in mortality annually of 0.4% during the same period (personal communication, 1989).”

As you can see, we still have a long way to go. At that first National Conference on Breast Cancer, Dr.

Sidney Cutler proposed a 15-year risk period for evalu- ating survival to replace the formerly used 5-year period. Dr. Rick Raventos urged adoption of the relatively new TNM system rather than the vivid prose seen in office records and on hospital charts.

Dr. Michael Shimkin was there to say that breast cancer was the prototype of all neoplasia, including our frustra- tions about cure.

Dr. Roy Hertz described our ignorance about the pos- sible effects of oral contraceptives on the initiation of breast cancer. The same issue is being raised today.

Dr. Jonathan Rhoads was among the first to say, “if you would do a biopsy, then do it!.” One cannot always rely on a normal mammogram. Dr. Rhoads was always at least 20 years ahead of his time.

Dr. Philip Strax and Sam Shapiro confirmed the need for clinical examinations at a time shortly after their pi- oneering HIP study of mammographic screening. Dr. Robert Egan extolled the virtues of this technology.

Dr. Abe Lilienfeld advised controlled clinical trials of thermography, expressing his concern over its use in screening.

Dr. J. Gershon-Cohen evaluated xeroradiography, mammography, thermography, and mammometry. Mammometry measured skin surface temperature by af- fixing small skin contact thermometics. This technique was discontinued almost as quickly as it was begun.

Dr. Richard S. Handley described the surgeon’s point of view about the biology of breast cancer. He said he awaited the day when a new Pasteur, who would not be a surgeon, would arise and revolutionize current concepts and methods.

Dr. Ernst Wynder, also ahead of his time, said, “with the exception of women with previous breast cancer and those with breast cancer in the immediate family, no par- ticular group of women appears to require more surveil- lance than the average woman.” He also pointed out the possible importance of fat intake in various countries of the world.

Dr. Leon Dmochowski implicated viruses as possible etiologic factors, and Dr. A1 Segaloff discussed biological determinants as outcome predictors.

Dr. Bernard Fisher pleaded for adjunctive systemic therapy and greater participation in the clinical trials of the National Surgical Adjuvant Breast Project.

Dr. R. J. Handley said it was just as erroneous to say that the larger the operation, the greater the hope for cure as it was to say no form of treatment made any difference.

Dr. Harvey Butcher made a strong pitch in favor of the Halsted Radical Mastectomy and Dr. George Crile, Jr. proposed limited surgery. As a matter of fact, Crile said, if normal nodes are removed, the incidence of metastases will increase. This is also true when normal nodes are irradiated.

Dr. William Powers described the uncertainty of the value of preoperative and postoperative radiation therapy, and Dr. George Rosemund, for the first time at a national meeting, described the American Cancer Society’s Reach to Recovery Program, which was adapted from Mrs. Terese Lasser in that same year, 1969.

Dr. Jerome Urban described his routine biopsy of the opposite breast; Dr. Benjamin Byrd discussed palliative mastectomy; Dr. Richard Wilson evaluated adrenalec- tomy and hypophysectomy; Dr. Phillip Rubin described the value of bone scans; and Dr. B. J. Kennedy discussed hormone therapy.

Finally, Herbert Seidman, an ACS epidemiologist, gave a brilliant statistical update on the 1969 information available covering virtually every aspect of breast cancer. It is a classic in its field.

These were the giants on whose shoulders we stand today. That is the past. How about the future?

I predict that the more we educate people about breast

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cancer, the more it will come out of the closet. Less and less will there be a cry of anger and resentment against the heavens or fate: the “why me,” the “why has God done this to me?’ syndrome. The sense of shame and self- blame when breast cancer strikes will decrease, and breast cancer will be looked on as an illness like any other, not a social disgrace or stigma.

I anticipate treatments designed so that patients can live with dignity and respect, not merely exist. More often, we are giving the breast cancer patient what I like to call an “ego prosthesis.”

1 anticipate greater and more open communication among patients, families, and physicians; more truth tell- ing; fewer charades and conspiracies of silence.

Informed consent will be identified as essential to every morally defensible patient-physician encounter. And, to be valid, consent will have to preserve the moral agency of the patient and safeguard her value system. This area of communication will become more personalized to avoid manipulation or deception.

I anticipate a greater role for oncology nurses and on- cology social workers in all aspects of cancer education and management. Their impact will be considerable.

In dealing with advanced breast cancer we will avoid the mistake of predicting a patient’s life span. We still hear proclamations of “6 months to live,” or of that magic gestational period, “9 months.” Although we doctors like to think we walk hand in hand with God, we do not. Our estimates of life’s duration are too often proved wrong. Many patients who were given a short-term prognosis have outlived their doctors by many years.

As in the past, the basic scientist will continue to help the clinician manage the cancer patient at the bedside.

Now my crystal ball becomes clouded, for who can tell in advance what serendipitous event may occur in a re- search laboratory of clinical institution, whose mind will be there to make the most of it, and what remarkably happy events may occur. I am reminded of the old Chinese proverb that states, “predictions are particularly difficult, especially in regard to the future.”

There have been other American Cancer Society con- ferences on breast cancer since 1969, each with its own star attractions and giants, all leading to today’s meeting here in Chicago and all designed to understand breast cancer better and achieve its control. Personally, I believe that the control of breast cancer is a rational pursuit and is not chimerical.

I congratulate Dr. Dodd, Chairman of the Program Planning Committee; Dr. Schweitzer, Vice Chairman; the members of the Program Committee; and all of you in attendance for what I am sure will be the very best and most productive National Conference on Breast Cancer in the history of the American Cancer Society.

Because of people like those of you in our audience today, the sky never really falls in on the cancer patient, no matter how bleak the prospects. And that sky does not fall because there are sincere, interested, and dedicated men and women who will raise their hands against the sky, who will hold up the very heavens and give the patient with cancer room to breathe, room to accomplish, space in which to live, and hope and resources necessary to help them cope with their illness.

I trust we have finally learned to place human priorities above all other priorities, because the greatest asset we have in the U. S. is our people. And the greatest threat to our future comes not from bombs, not from missiles, but from those times when we no longer care for each other.

As the more energetic and younger physicians take over, I wish them luck and Godspeed in all their good works. May I also remind them, whenever they are feeling de- pressed and everything seems to be going wrong with pa- tient care or research, that even a stopped watch is right twice a day.

My time is up. I have now completed the three main functions of a keynote speaker:

1. Allow more time to register. 2. Permit a short nap before the program begins. 3. Set the stage for the real experts who will follow.

Thank you.

REFERENCES

1. Cameron CS. Cancer control: Challenge or Chimera. The James Ewing Lecture. Cancer 1974; 33:402-413.

2. Lewison EF. Breast Cancer and the Diagnosis and Treatment. Bal- timore: Williams and Wilkins, 1955.

3. First National Conference on Breast Cancer, May 8-10, 1969, Washington, D. C. Sponsored by the American Cancer Society, Inc., Cancer Control Program, United States Public Health Service in con- junction with the VIII Annual Symposium on Mammography and Dis- eases of the Breast of the American College of Radiology and the Cancer Control Program. Cancer December 1969; 24 (Suppl):l101-1355. The above issue of Cancer published the results of the conference. I refer to a number of the presentations made.