Revisiting Accepted Wisdom in the Management of Breast Cancer – Part 2

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Popular Concepts Revisited

Today popular conceptions of breast cancer and its management are becoming outmoded as research exposes their lack of merit. Unfortunately, instead of this leading to the modification of common medical procedures, or to the understanding that these protocols are becoming obsolete, many persevere unchanged. Some of the tenets accepted as gospel need revisiting–not only the mastectomy, but also the classification of ductal carcinoma in situ as cancer, the misconception surrounding “early detection,” axillary lymph node dissection, radiation following surgery, and intensive postsurgical follow-up (chest x-ray and bone scans), as well as one of the newer therapies–high-dose chemotherapy with bone marrow or stem-cell transplant.

There is not unanimous agreement about what constitutes breast cancer. Breast anatomy may be helpful in understanding how the disease is defined. Breasts house a series of milk-producing glands that empty into smaller and larger tubes called ductules and ducts. Put simply, breast cancer means uncontrolled growth of cells–tissue that, when removed and analyzed by a pathologist, shows that malignant cells have overrun the anatomical boundary of the duct and extend into the surrounding tissue.

The most common form of breast cancer, referred to as “infiltrating ductal carcinoma,” comprises 70% to 80% of invasive tumors that arise within the mammary ducts and invade the surrounding fatty tissue (called the stroma). The other 20% to 30% are subtypes (invasive lobular, medullary, mutinous, tubular, adenocystic, papillary, carcinosarcoma, inflammatory). This scheme of classification is based on locale and behavior. Americans might be differentiated geographically–as New Yorkers, Southerners, and Californians–but there are plenty of variations within each regional type.

Breast cancer is not a single disease, but an umbrella term for a plethora of diseases. It is no more homogeneous than infectious diseases–mumps and malaria have as little in common as herpes and cholera. Similarly, breast cancers differ strikingly from one another. Within each tumor itself there is enormous heterogeneity. Tumors are as diverse biologically as Manhattan is socially. A tumor is not composed of a single type of cell. It is like a vegetable basket that contains bits of lettuce, carrots, beets, broccoli, and zucchini indiscriminately fused together. Each vegetable has a unique shape, texture, growing pattern, and chemical composition. A tumor is a biological entity unto itself–like the city of Manhattan–yet the inhabitants of the city neither look alike nor behave, eat, or recreate uniformly. Some tumor cells metastasize early; some never do; others do so slowly. Some are accelerated by estrogen; others are not. Some encourage blood vessel growth; some do not. These processes are determined by the genetic material within the myriad cells that comprise the tumor. Even though it may be reasonable to say that two women have breast cancer, when the disease in the two women is compared, there might be so many differences that one begins to question whether they truly do have the same disease. Rate of growth and infiltration may take 3 years in one woman and 40 years in another.

Ductal Carcinoma in Situ Classification

Some abnormalities look like cancer under the microscope but do not act like it, and therefore are not truly breast cancer. One of these discrepancies between anatomy and behavior is “ductal carcinoma in situ” (DCIS), which consists of an abnormal proliferation of ductal cells that do not invade the basement membrane of that duct (hence the term “in situ,” meaning “confined to the site”). Because DCIS does not extend beyond the borders of the duct, it is noninvasive, and does not therefore constitute a true malignancy. In 1934 Halsted’s former resident, Joseph Bloodgood,³² described DCIS as precancerous tissue–a depiction that still applies.

Richard Margolese, surgical oncologist at McGill, says, “The management of ductal carcinoma in situ … is controversial. It is not clear whether all carcinomas are preceded by DCIS or if all DCIS leads inexorably to carcinoma…. A better understanding of the biology of DCIS would lead to better clinical management.”³³ Because of the confusion surrounding the sequelae to DCIS, many current breast cancer studies include women with DCIS, because they regard it as a malignancy; thus the outcomes of these studies are skewed. According to William Silen of Harvard, “Twenty-five or thirty years ago, it was taught that there was no such thing as noninvasive carcinoma of the breast. In pathology, I was taught that if you looked far enough, you’d always find invasion. I’m absolutely convinced that a lot of the so-called cures achieved with radical mastectomy were patients who actually had noninvasive carcinomas of the breast.”^33(p358) Unfortunately, the language does not change appropriately every time the explanatory model shifts. Understandably, this causes confusion. The term “carcinoma” is used both to define malignancy and to describe tumors that are not malignant by virtue of the fact that they neither invade nor spread.

Early Detection

Public misconception abounds concerning the concept of “early detection.” It is perhaps the most mystifying oxymoron within the vocabulary of the breast cancer paradigm. What is early? Ideally, it is before the local malignancy has spread, or metastasized. Although it’s a difficult notion to accept, there is no way of knowing whether malignant cells have spread by the time of detection. Frequently the term “early” is confused with the term “small.” Generally a small lump is preferable to a larger one–but this is not always the case. The significant determinant is biological: whether the cancer has infiltrated beyond local boundaries, how fast it is growing, and where it is growing.

It is known that it takes an average of 10 years for a tumor of the breast to grow to 1 cm (a little less than half an inch) in diameter. It is hypothesized by Judah Folkman³⁴ of Harvard that as the number of blood vessels supplying the tumor increases, so does the likelihood of metastatic disease. It is not known precisely how long it takes for tumors to acquire an adequate blood supply. It takes approximately 5 years from the time a cell becomes malignant (de, shows evidence of uncontrolled growth) to the time that it develops enough vasculature for tumor cells to enter the bloodstream. One cubic centimeter of breast cancer tissue contains roughly one billion cells. Based on the doubling rate of cells, it takes 30 replications for one cell to become one billion. If the time of replication is 120 days, tnen there are 3 replications per annum, so over a 10-year period there are 30 replications. It is thought that in the first 5 years (half of the hypothesized 10-year period), the mass is not sufficiently vascularized (does not have an adequate blood supply) to be able to metastasize. But a palpable mass–or one visualized on mammography that is 1 cm in diameter or more–may have been growing for 10 years. l By this stage it has likely become bloodborne and widely disseminated. Local treatment–mastectomy, lumpectomy, or radiation–will not have any impact on survival if malignant cells have been seeded elsewhere (note 11).

Breast surgeon Susan Love,³⁵ testifying before the Senate in 1991, stated that

The value of”early detection” is complicated by a factor called “lead–time bias.” Namely, women appear to live longer when the disease has been identified earlier, but mortality has not necessarily been affected. There is a widespread collective misunderstanding that if only the lump is found “early,” the problem can be either aborted or “fixed.” This has led to false guilt on the part of women who feel that through their negligence they are responsible for their misfortune, false blame toward doctors even though they could not have discovered the lump sooner (and even if they had, it would not have mattered), and anguish at a cost of millions of dollars in litigation without sound medical foundation.

Not only is the notion of”early” muddled, but the question of what is being detected is also difficult to grasp.³⁶ Nearly one third of the women with tumors undetected by mammogram have positive Iymph nodes–a sign that the disease is already systemic.³⁷ Mammography fails to detect one fifth of all cancers; in women under 50, it misses as much as 40%.³⁸ Unfortunately, having a clear mammogram does not mean that a woman is cancer-free. But because many cases are visualized by mammography, the current recommendation is that, especially for women over 50, it is a useful tool–particularly when a qualified technician uses a reliable mammography machine with a skilled radiologist interpreting the results. As counterintuitive as it sounds, radiologists Samuel Hellman and Jay Harris³⁹ assert that
“[d]etection of cancer at an earlier stage does not necessarily imply an improved cure rate.”

Axillary Node Dissection

Axillary node dissection is another procedure that is no longer routinely justified, yet remains firmly entrenched. Halsted was wrong: cancer does not spread in an orderly fashion via the Iymph system, node by node. Whether nodes are positive or negative does not necessarily foretell whether an individual woman will have a survival advantage. An early hypothesis posited that the presence of malignancy in the Iymph nodes served as a marker for who should receive chemotherapy. But new studies have shown that it is not an accurate prognostic measure. In 1986, Hellman and Harris³⁹ reported the following: “Twenty-five percent of patients without axillary Iymph-node involvement develop metastases while 25 percent of those with axillary Iymph-node metastases never develop distant metastases.” Thirty-eight percent of women with negative Iymph nodes die of the disease, which demonstrates that the positive or negative status of these nodes does not provide reliable prognostic information.

Harvard surgeon Blake Cady urges that “[w]e need to move beyond the latest dogma and convention regarding routine axillary dissection for established functionally equivalent goals” (note 13). In a book called Important Advances in Oncology 1996, Cady writes a chapter titled “Is Axillary Node Dissection Necessary in Routine Management of Breast Cancer? No.” Surgeon Peter Deckers suggests that “[w]ithin the next decade, axillary dissection will be extinct.”^33(p363) Again, it is the cellular biology that is most crucial in determining prognosis and treatment, and this is now the focus of current research. But there is a lag time between the incorporation of new information and the dispatch of old habits.

Fisher’s Protocol B-04 study established that axillary node dissection does not provide survival benefit. When further treatment was dependent on whether the nodes show malignancy, then node dissection was perceived to be a useful procedure. Today, however, we have many biological markers that provide information equivalent to positive or negative node status, rendering this procedure obsolete. If these markers suggest that a tumor is aggressive, women will receive chemotherapy regardless of the status of their axillary nodes. The medical school dictum applies: “If the results of a test do not change what you do, do not do the test.” So why does it continue as routine procedure? Again, one suspects a lag between habit and the adoption of the newer logical thinking. When queried, many oncologists say, “I just feel more comfortable knowing about the nodes.” But unless there is good justification for axillary node dissection, it should be questioned because it does harm.

Lymph node dissection is not only expensive, it disables thousands of women unnecessarily. For example, a woman named Dana had a mastectomy accompanied by removal of the Iymph glands under her arm 8 years ago. In some women, the fluid that would normally drain through the Iymph channels backs up, causing swelling (Iymphedema). Aside from the limited use of her shoulder and limb, Dana suffers from bouts of cellulitis, infections that sometimes arise from mosquito bites or scratches, requiring her to be on long-term antibiotic management to prevent blood poisoning (septicemia). About 20% of the women who have their nodes removed develop measurable Iymphedema (note 14).

Some oncologists recommend a bone marrow transplant if more than 10 nodes are positive. But the value of adjuvant bone marrow transplantation has not been established.

Lymph nodes were once thought to be the instigators of disease, the source of metastatic dissemination. According to Virchow, malignancy, like the tubercle bacillus, traveled through the Iymph channels and proceeded in an orderly, mechanical fashion from the local site, progressing to the glands under the arms, and from there migrating to distant sites. We now know, contrary to Virchow’s theories proposed a dozen decades ago, that the proliferation of malignancy is neither orderly nor mechanical.

Radiation

Radiation is a known carcinogen that can produce irritable, red, inflamed tissue in the short term; and stiff, thickened, desensitized tissue over time. Radiation following lumpectomy has no proven impact on survival, though it does affect local recurrence. Women who recur have an increased mortality, not because of the local tumor, but because recurrence is the manifestation of biologically more aggressive disease. Recurrence, however, is only symptomatic of increased risk of metastases, not the cause of the disease’s spread. Removing the possibility of recurrence no more enhances a woman’s health than removing the speedometer of a car alters its speed.

In rural areas like the outlying plains of North Dakota, where women must travel 6 or 8 hours to receive radiation therapy, mastectomy has been recommended over lumpectomy to prevent local recurrence. But women who do not receive radiation following lumpectomy have the same chance of survival as those who do.^{26, 40,41} The only difference is in the likelihood of local recurrence: 40% of women who do not receive radiation therapy will have a local recurrence within 10 years, whereas 15% who have had radiation following their lumpectomy will have a local recurrence within 10 years. It seems difficult for us to comprehend that how long a woman lives is not dependent on whether the local disease returns. It is not local disease that is life threatening, but the rapidity with which metastatic disease proceeds–something that there is no way to predict as of yet.

Women who recur within 2 years have a 20% chance of living 10 years, whereas women who recur after 5 years have the same chance of survival as those who do not. Recurrence within 2 years may serve as a more valuable marker of disease progression than any other.42 It was shocking when Fisher’s study40 demonstrated that local recurrence did not impact survival. Yet doctors seldom make this clear to patients.^38(p74) Because the value of radiation is questionable, its role following lumpectomy is currently under scrutiny.

Intensive Follow-Up: Chest X-Rays and Bone Scans

The effort to secure medical certainty is costly, elusive, and usually futile. Because elite medical schools are swollen with prestige, power, and funds, and because their libraries bulge with data, there is a public illusion that medicine is equipped to remedy our complaints. Because people think their doctors are so smart, they find it impossible to believe that they don’t know how to help. People want prognostic and diagnostic as well as therapeutic answers.

The belief that an earlier detection of recurrence leads to a higher likelihood of disease control, complete remission, or at least extended survival has led to intensive routine surveillance programs. It now appears that such ardent follow-up screening (chest x-ray and bone scan) for asymptomatic women is a costly measure that has wide acceptance but limited value. Usefulness is a judgment measured by the criteria of quality of life and sur: vival benefit. The early detection of distant metastases has shown no survival advantage. Chest x-rays have not been particularly useful in detecting recurrence, nor has bone-scan surveillance been fruitful in asymptomatic patients.43 After a review of several studies, the following conclusion was reached by Roselli Del Turco et al⁴⁴: “Periodic intensive follow-up with chest [x-rayJ and bone scan should not be recommended as routine policy.”

Chest x-rays were instituted as a public-health protection against tuberculosis: their routine use is considered an expensive and outmoded practice by many. On the other hand, follou-up with a physical exam twice a year and a yearly mammogram are both sensible and cost effective. According to Charles Loprinzi⁴⁵ of the Mayo Clinic, “retrospective studies … do not suggest that patients who had routine follow-up testing did any better than those patients who did not…. A history and physical examination are clearly the best methods for obtaining evidence of recurrent breast cancer. Several studies have reported that 75% to 85% of recurrences are detected this way (even when frequent additional tests are performed).”

Every time Lyra, a 52-year-old woman who had a mastectomy 4 years ago, feels an ache in her calves, she worries. She anticipates bone scans every few months with equal parts dread and hopeful expectation. The usefulness of this intensive surveillance ritual is more than questionable. Metastatic bone disease rarely remains asymptomatic for more than 3 months. If Lyra’s bone scan is negative, it simply means that the part of the bone scanned did not show evidence of disease. If it is positive, there is little advantage in knowing this before actual symptoms of the disease arise. Most bone metastases will become symptomatic within 90 days. Greater power is attributed to diagnostic instruments than is often warranted–scans are imperfect devices that offer relatively crude measurement. Technology has advanced more rapidly than our understanding of how to derive benefit from it.

A savings of $636 million in the United States for the year 1990 was projected for the minimalist surveillance protocol (history, physical exam, mammogram) over the more intensive series (physical exam, blood cell count and chemistry, antigen level. mammogram, chest x-ray, bone scan) currently in routine use.⁴⁶ By the year 2000, the cost savings is estimated to be S1 billion. Again, science can only dubiously cater to the best hopes of patients and doctors. Researchers comment: “In conclusion, although the patient and physician may have an intuition that intensive surveillance will detect recurrence earlier and prolong survival compared with minimal surveillance, this feeling is not borne out….”⁴³ In 1990 breast cancer consumed $6.5 billion–more healthcare dollars than any other cancer. After an exhaustive assessment, Herman Kattlove et al^37(p142) concluded. “Regrettably, it is easier to estimate the expense of medical care than to project the benefit.”

Bone Marrow or Stem-Cell Transplant

In 1995 an independent technology-assessment organization conducted a thorough review of studies, concluding that there is no evidence of any prolonged disease-free or overall survival benefit from the use of either bone-marrow or stem-cell transplants compared with conventional chemotherapy under any circumstances. Reimbursement for these therapies is controversial, and breast cancer patients are seeking insurance coverage ranging between S50,000 and $200,000 for this therapy. Several states have mandated such coverage. This is perhaps another example of both doctors and patients wanting to believe I that if a little is good, more must be better. But 31 studies between 1984 and 1994 showed either no improvement or slightly increased early death rates. Substantial evidence of harm exists for these therapies (note 15).

Making Sense of What We Know: Popular Intuitive Assumptions vs. Counterintuitive Evidence

An advertising concept called “positioning” refers to securing a place for a product in the consumer’s mind that, ideally, I will become identified with the function served. Examples of this are the brand Kleenex, which has become synonomous with tissues, and Xerox, which has become a verb for photocopying. Analogously, the paradigm for the mechanical spread of breast cancer has become fixed securely within doctors’ minds, and “removal before it spreads” has become the corollary kneejerk response. The delusion lingers that if enough malignant tissue is excised, then the cancer can be evicted and the patient cured.

Prior to and in the absence of prospective, randomized, controlled, double-blind studies, treatment protocols are inevitably the fruit of speculative clinical postulates to be tested over time. This holds true for regimens of chemotherapy, radiation, and surgical procedures. When clinical studies throw those habitual behaviors into question, rather than behaviors adapting, studies are often functionally disregarded. Perhaps this is because habits have encouraged theories to be mistaken for facts. It is within this context that the the Office of Technology Assessment issued a report stating that only 17% to 20% of conventional medical practices are based on scientifically validated evidence, and that 80% to 83% are based solely on anecdotal data (Office of Technology Assessment, US Government Printing Office, Washington, DC; 1988).

For example, it was hypothesized that positive axillary nodes served as a predictor for the spread of the disease. When evidence indicated otherwise, only a few doctors altered their clinical behavior. Similarly, bone scans, chest x-rays, and blood work have been shown to be of little use, yet more than half a billion dollars are spent each year when a physical exam, history, and mammogram are sufficient. Even though radiation following surgery reduces local recurrence, it is clearly established that the reduction of local recurrence does not impact survival. Radiation following surgery is akin to the ancient Greek custom of killing the messenger who has delivered bad news. Still, only a few physicians perform lumpectomies without recommending radiation therapy. Finally, though mastectomy is popularly perceived to be the safest treatment, there is comparable survival benefit between mastectomy, lumpectomy with radiation, and lumpectomy alone–women live the same length of time regardless of which intervention they or their doctor choose. Neither mastectomy nor radiation eradicates the possibility of recurrence–they merely reduce it, and local recurrence itself does not suggest that a woman’s chance for a long life is less. Thousands of women and their doctors nevertheless elect mastectomy.

Another major assumption now under question is that people can be separated into two groups: those with metastatic disease and those without. Many leading oncologists now believe that at the time of detection, breast cancer is systemic. In this case, mastectomy plays no role in increasing survival. For the smaller group of women in whom the disease may not be systemic, breast-conserving surgery will remove the local tumor. Finally, when a woman learns that she has breast cancer, and that there is a large probablility the disease is systemic, this does not automatically mean that she will die soon. Roughly 50% to 60% of these women will survive, many for decades. The significant features determining longevity appear to be the biology of the tumor and the resistance of the host.

Times Change… and Remain the Same

Craig Henderson put it simply: “We’re all prisoners of our oncogenes.” He has taken a leave from clinical medicine to work with molecular biologists in the private sector. Molecular biology is now at the hub of inquiry, prompting a review of customary protocols by some, though the bulk of practice remains the same. At the conclusion of a 1994 symposium of carcinoma of the breast, Marvin Gliedman^{33(pp351-362)}, of Albert Einstein College of Medicine queried, “I wonder if breast cancer is a surgical disease any more.” Samuel Hellman and Ralph Weichselbaum” of the University of Chicago say that “[b]ecause of the importance of systemic metastases and the current emphasis on treatments for systemic disease, one may question whether as a regional treatment radiation oncology, like surgery, will have an increasingly restricted role in cancer management.”

Concerning the state of chemotherapy today, oncologists Albert Deisseroth and Vincent DeVita⁴⁸ of the Yale School of Medicine have commented that the most important findings of the last 30 years have been that drugs could cure some forms of cancer–namely leukemias, Iymphomas, and some epithelial cancers. They call it both perplexing and disappointing that 90% of all drug cures occur in only 10% of cancer types. Although it was first thought that cancer cells grow more quickly than do normal cells, this has turned out not to be the case. Instead, cancer is caused by a failure on the part of the cell: instead of deciding to divide, it should, for the sake of the organism, choose to be dormant.⁴⁸

Molecular biology, trumpeted by some as the next great frontier of hope, examines the metabolic pathways that constitute the biochemical basis of all life. Molecular answers are being ardently pursued in order to solve the riddle of why cancer occurs. Life is dependent on proteins, which are themselves a string of amino acids. One focus of this biochemical inquest is upon the regulatory proteins responsible for cell division. This is because cancer is understood as the proliferation of cells without restriction. Somehow the proper regulatory mechanism has been disabled when cells are replicating wildly. It is believed that the coding of the DNA determines the composition of amino acids, which in turn shapes the protein in any given tissue. This DNA is the repository of the genetic code of the organism–that which is passed on to propagate the species and prescribes who someone is structurally and functionally. Part of the DNA is wound tightly and part is unwound. When certain proteins become inappropriately unwound, it is thought to produce uncontrolled cell division. The expectation is that manipulation of these proteins may produce a shut-off valve for the carcinogenic process.

It is remarkable that for all our progress in medicine, a JAMA article⁴⁹ from 1895 reads as though it were from a current journal describing contemporary practice:

[T]he widespread and increasing prevalence of cancer of the breast, its painful and terrifying features, and, above all, the very great attendant mortality, render it one of the most important of surgical conditions and one in which the most strenuous effort should be made to cure…. Operations for cancer of the breast are designed to be curative or are merely palliative, and it is needless to say that the end in view is determined by the extent of the neoplasm…. [M]ammary cancer is a curable disease, and … the keynote to its successful management is to be found in the earliest possible diagnosis, prompt and wide excision and careful observation of the patient during the remainder of her life.

How problems are framed determines which solutions are delivered. In answer to the question, “How can local recurrence be eliminated?” one course of therapy–mastectomy–is mandated. If one asks, instead, “What is the least invasive therapy, will do the least harm, and provide equivalent survival advantage?” another intervention is pursued–lumpectomy. If the question is “What environmental, dietary, hormonal, or genetic factors, if any, contribute to the disease or its amelioration?” this launches the investigator onto other trajectories, such as chemical pollutants that are carcinogenic (some because they mimic estrogens in the body), or fatty diets that appear to increase risk, or genetic predispositions. And if a breast cancer is classified according to its growth rate or the type of cells present, this leads in still another direction–one that does not treat all breast cancers equally, classifying them by many different criteria. Patients have the right of treatment choice, but most women are so poorly informed that they cannot choose wisely.

Personal Story as Metaphor: Medicine as Savior or Slayer

I grew up listening to my father talk about work around the dinner table. Invariably in the middle of a bite of mashed potatoes and green beans, he was summoned to the emergency room to repair the fractured femur and lacerated calves of a teenager whose Harley had slid in the sand. At 10, squeezed onto the end of a bench next to a mammoth high school athlete, I’d watch my father trot onto a muddy New England football field, crunchy with frost, his trench coat flapping behind him like wings One evening after chocolate pudding, eyes shining with zeal, he described new surgical staples that made it possible for him to close bowel resections twice as fast. Often he worked tirelessly into the night while we were asleep. Although usually an energetic optimist, sometimes he’d surprise me with grouchy, venomous criticism. Later, my mother would whisper discreetly that it wasn’t me–that my father had a patient sick with pancreatic cancer and he was desolate because there was nothing he could do. I observed first-hand his distaste for powerlessness in the face of irremediable disease.

Although completely devoted to the practice of his craft, my father was a reluctant patient. At 69, he needed to have cataracts removed but stalled for several years, eventually trading the benefits of improved night vision for his diffidence. Opening his closet door, he was amazed to find that all his suits weren’t the monotone grey he had perceived before the surgery. It was awesome to me that after spending his life wielding the scalpel, he was so wary of it himself.

Some of his cautious hesitation was transmitted to me. When our son was born 22 years ago, with two gaping holes in a distended heart, we deliberated ambivalently about the cardiologist’s urgent plea to go forward with open-heart surgery. Without it his life would have been severely compromised; with it he had a fifty-fifty chance of surviving the surgery. Now the Dacron patches stitched carefully in place by Paul Ebert when our son was 8 months old have enabled him, like the normal kids I envied when he was small, to attend college.

Two years ago I urged my niece, Sherifa Edoga, just after she had graduated with double honors from Stanford, to seek counsel from my son’s cardiologist. She was born without a pulmonary artery, the vessel that carries blood from the heart to the lungs to receive oxygen. Always breathless, her lips and fingernails were permanently stained the color of blackberries, a sign of hypoxia–not enough oxygen in the blood. For anyone else it would be a 2-minute jaunt to the car, but she moved like a snail and for her the trip took 20 minutes. It was with trepidation that Sherifa decided to undergo surgery; she had had two operations as a child that had failed. But the able surgeon felt he could help. In the days before, Sherifa made great gains in quieting her fear. She died 5 days after the operation.

My father always characterizes medicine as an evaluation of the lesser of evils, requiring a cost-benefit analysis accompanied by a willingness to gamble. His awareness of doctor-induced problems (iatrogenesis) led us to be apprehensive about both drugs and procedures. Medicine can mean miracles. It can do harm. Doctors want to ply their trade to the task of genuinely serving, and patients yearn to be saved. Ultimately it is we, not our doctors, who must navigate our vessel. It is our destiny that lies on the shore.

Living With Disease

In 1995, eight million new cases of breast cancer and 3 million deaths were recorded worldwide, Breast cancer is the most common form of cancer in women in the United States, the leading cause of cancer death for black women, and the second leading cause of cancer death for women aged 35 to 54 years. Eighty percent of women diagnosed with it are over the age of 50. More than 70% of cases occur in women without any identifiable risk factors. More than 1.6 million women diagnosed with breast
cancer are alive in America today, and the 5-year survival rate is over 90% (written communication with National Alliance of Breast Cancer Organizations, March 1996). We are always looking toward future progress, toward what’s new that will miraculously transform our capacities for medical management. By looking backward as well as forward, we gain insight, if not the ever-elusive cure.

⁵⁰

we are running

running and

time is clocking us

from the edge like an only

daughter.

our mothers stream before us,

cradling their breasts in their

hands.

oh pray that what we want

is worth this running,

pray that what we’re running

toward

is what we want.

Halsted Holman, professor emeritus at the Stanford School of Medicine, is the son of Emile Holman, who, like Cushing, was I a protege of both Osler and Halsted. Named after his father’s mentor, Halsted Holman oddly echoes Virchow’s social perspecfive, bringing dialogue full circle. In the middle of the 19th century, Virchow claimed that many maladies were the result of aninequitable distribution of social and economic resources, advocating that doctors should exercise their power to abolish the social conditions that are at the root of so many diseases.
Virchow asserted that “physicians are the natural attorneys of the poor.”^11(p316) Similarly, Halsted Holmans51 comments:

Longevity has changed little, and the major illnesses such as malignancy and cardiovascular disease remain unimpeded. Illnesses disproportionately affect the poor, major environmental and occupational causes of illnesses receive little attention and less action, and malpractice charges intensify. Clearly, there is a crisis in health care, both in its effect upon health and in its cost. Simultaneously, medical institutions characterize themselves as excellent. Some medical outcomes are inadequate not because appropriate technicalinterventions are lacking, but because our conceptual thinking is inadequate.

Medicine cannot capitulate to less than a thorough and on-going review of its own habits of mind, as well as its practices. On the disappointing results in the treatment of breast cancer, one of Virchow’s pronouncements spoken in 1896 is still germane: “Indeed, a great deal of industrious work is being done and the microscope is extensively used, but someone should have another bright idea.”14(p107) Psychologist CG Jung⁵² commented that “[tlhe serious problems in life … are never fully solved. If ever they should appear to be so it is a sure sign that something has been lost. The meaning and purpose of a problem seems to lie not in its solution but in our working at it incessantly.”

Although breast cancer is always undesirable and bad, the women who have it are often splendid and good. No one chooses breast cancer as a teacher, but it becomes one. Many women struggling with breast cancer are heroic, powerful, and courageous. How each woman chooses to interact with this disease is as varied as the lives they live. Libby was diagnosed 3 years ago and underwent a modified mastectomy and intensive chemotherapy for a year, which eliminated metastatic liver tumors from view on a CAT scan. The tumors recently recurred. Shirley was told, after 3 years of therapy, that she had only 6 months to live without a bone marrow transplant. She decided not to follow this path, went into remission, and was alive 4 years later. Catherine found a lump while lathering in the shower, had a lumpectomy, and elected not to have her lymph nodes dissected nor undergo radiation or chemotherapy, instead exploring alternative therapies including herbs, a careful diet, yoga, and other activities that gave her pleasure. It is now 5 years that she is alive, though she has evidence of local masses. Erica did not survive a bone marrow transplant. Marilyn did. Breast cancer may be lethal, but we know birth to be an absolutely fatal disease. Many women who are diagnosed with breast cancer will die of other causes, even though they do not get over the disease as if it were a winter cold.

Debra’s acupuncturist, reflecting on her breast cancer, commented, “You’re the sky and the disease is a cloud in the sky.” He is aware of the dualistic perspectives that sometimes have difficulty meeting: attention to the disease mechanism versus regard for the person who has it. Put simply, in one model the doctor is a mechanic fixing a broken body machine, and in the other the doctor is a gardener cultivating a healthy ecology in which the rich soil houses microbes that can combat pests. This is another debate that has echoed through centuries. In mid-19th-century France, Louis Pasteur introduced the idea that disease was located outside the body, in the form of germs. This distracted medicine, encouraging people to think that the invaders could be slain like marauders in a castle. Pasteur’s contemporary Claude Bernard had insisted that it was the milieu interieur–the state of the organism; the relationship between the seed and the soil, the pathogen and its host–that was determinant. Breast conserving pioneer and physician Vera Peters⁵³ comments that “[t]he important influence of the patient’s potential to control her own disease cannot be overlooked. Probably a superior immune mechanism is the major factor allowing the majority to postpone metastatic disease for many years. Their immune potential is reflected by their state of physical and mental health, and by the lymphocyte count.”

Cancer exists on a continuum, with endogenous (internal) causes on one end and exogenous (external) causes on the other. Surgeons are the mechanics and oncologists are the pest controllers. Today the focus is on chemotherapy as a form of pest management; tomorrow there is a promise of medicine being equipped to enhance our self-capacities and eliminate virulence through engineering molecular environments.

Others believe that it is the ambient and ubiquitous burden of toxins in the soup in which we swim daily that foments these changes within. Rather than breast cancer being a local problem, it is a global one. it tends not to have a single regional locus, but becomes universal within the organism; it is more like a virus than a fracture. Struggling against disease with hope is itself believed by many to be therapeutic, but there is not enough known to issue universal prescriptions. Over the centuries, even some of our greatest spiritual teachers have died of cancer.

Surgeon Richard Selzer⁵⁴ commented that after he wrote a medical essay titled “The Exact Location of the Soul,” readers wrote to him, pumping him for more specific information. Upon reflection he answered that if he were to fix the soul in a location, it would be in the wound, that place of tender suffering. Buddhists claim that life is an evolutionary exercise in learning lessons dressed in suffering. One antidote to suffering is glad acceptance–not wishing for things to be other than they are. This entails transcendence of future-oriented desires and instead focuses on experiencing each moment as bliss: exquisitely full, complete, sufficient. The emphasis shifts to the quality rather than the duration of life–more on living better, and less on living longer. Some studies suggest that women who exhibit optimistic determination fare better than do those who are either helpless and hopeless, or those who are anxiously preoccupied.55 Hope can mean tenaciously affirming that life makes sense while encountering the universality of our inevitable death. The best we can do is live well each day, paradoxically accepting what is as we strive valiantly to change.

Harriet Beinfield has practiced acupuncture and Chinese herbal medicine for 24 years at Chinese Medicine Works in San Francisco, Calif. She is the co-author, with Efrem Korngold, of Between Heaven and Earth: A Guide to Chinese
Medicine Malcolm S Beinfield is an associate clinical professor in the Department of Surgery at Yale University School of Medicine and on the staff of the Yale Comprehensive Cancer Center. He has practiced surgery for 45 years and has pub fished numerous articles on clinical breast cancer research.

Acknowledgement

The authors wish to thank Nat Berlin, MD, for his valuable comments during review of this manuscript.

Notes

1. The NCI Consensus Conference concluded that “Breast conservation treatment is an appropriate method of primary therapy for the majority of women with Stage I and 11 breast cancer and is preferable because it provides survival equivalent to total mastectomy and axillary dissection while preserving the breast…. Breast conserving treatment Idefined as lumpectomy and axillary dissection followed by irradiation! is preferable because it provides survival equivalent to total mastectomy and axillary dissection while preserving the breast” (NIH Consensus Development Panel. Consensus development conference on the treatment of early-stage breast cancer.J Natl Cancer/nst. 1992:11:1-S).

2. Greater cohesion and homogeneity of the pro&scion were also achieved by the deliberate segregation of Jews, Catholics, women, blacks, and the foreign-born. consolidating the rise of a genteel Protestant medical aristocracy. Medical school admission and operating privileges at hospitals were granted to a closed fraternity of surgeons, qualified more by social caste than by professional achievement Discrimination underlay the building of hospitals with names like Saint Vincent, Saint Mary, Saint Joseph, Beth Israel, Mount Zion, Mount Sinai-places that welcomed Catholic and Jewish patients and doctors.^{10(pp173-177)}

3, Establishing Johns Hopkins as the model for all others to follow was consolidated by the Flexner Report of 1910, which Arced the massive closure of schools that did not conform to the new standards. By 1936, S91 million was steered primaniv from the Rockefeller General Education Board into a select group of schools, Johns Hopkins being among the seven that received more than two thirds of the funds.^10(p121)

4. Curiously, his parents were both the offspring of business partners (his father was a Halsted and his mother was a Haines) and cousins (his mother and father were the children of sisters) (Rutgow 1, William Halsted, his family, and ‘queer business methods.’ Arch Surg. 1996;131:125),

5. In London, Charles Moore formulated the principles of mastectomy in 1867; Joseph Pancoast, prom Philadelphia, recommended removal of the breast and glands all in one piece as early as 1844; Richard von Volkmann in Germany and Theodor Billroth in Vienna both removed the entire breast in the 1870s: and William Handley in London and Willie Meyer were contemporaries of Halsted, who supported his efforts with their own.

6. Halsted demonstrated the use of cocaine as local anesthesia to Koller’s friend, Anton Wolfler, who had been the Viennese surgical giant Theodor Billroth’s first assistant. Later, Wolfler published on the subject (Penfield W. Halsted of Johns Hopkins. JAMA. 1969;210112l:2214-2218). (Reprint of Halsted’s letter to Osler, dated August 23,1918.)

7. In a private letter to Osler, Halsted wrote that three of his associates “acquired the cocaine habit in the course of our experiments on ourselves–injecting nerves. They all died without recovering Prom the habit” (/AMA. 1969:2101121:2217).

8. A lump was the initial symptom in 83% of the women, which by the time of hospitaCzation had become a large mass for many. Ulceration, sometimes extensive. was seen in 68%: only 7% of the women came to the hospital within 6 months of the symptoms. Seventy-one percent delayed for more than 12 months. In 24% of the women, more than 3 years elapsed; in 12%, more than 5 years. The longest delay was 16 years. This contrasts with later practices, in which patients present within 6 months to 1 year after symptoms are noticed. A high percentage of the Middlesex women therefore had advanced disease (Bloom H. Richardson W. Harries E. Natural history of untreated breast cancer 11805-19331, Br Med / Jul
1962:219). According to Diana Fischer, research scientist at Yale School of Medicine, the 50 women who received mastectomies reported upon in Halsted’s study between 1889 to 1894, when compared with the 250 cases at Middlesex Hospital in London between 1805 to 1930, showed no statistically significant survival difference between the surgically managed and untreated women (written communication, March 1996).

9. Farber D. Biologic variations of tumors. Presented at the American Cancer Society; October 11-13, 1991; Pasadena, CaCf (referring to Bloom H. Richardson W. Harries E. Natural history of untreated breast cancer 11805-19331. Br Med J July 28, 1962:213-221).

10. “For virtually all patients who have had a mastectomy, recurrent breast cancer is not a curable disease” (Loprinzi C. It is now the age to define the appropriate follow-up of primary breast cancer patients.JClin OncoL 1994;12(5):881. Editorial).

11. If in 10 years there are 1000 cells within a tumor, in 20 years there are I million; in 30 years, I billion; and in 40 years, I trillion. The human body contains about 11 trillion cells. Death usually results when 10% of the body is replaced by cancer cells. The doubling time of breast cancer cells varies greatly from 9 to 900 days, with an average being 100 to 185 days (spran IS, Spratt JA, Grouth Rates in Cancer of the Breast. 3rd ed. Philadelphia, Pa: WB Saunders; 1988:270-302).

12. Love comments elsewhere: “I think that any breast cancer large enough to be detected has already spread…. The danger of cancer depends on the balance between the cancer and the ability of your body’s immune system to fight it” (Dr Susan Love’s Breast Book Reading, Mass: Addison-Wesley; 1990:212).

13. “Whether lymph node metastases in the axilla or internal mammary drainage basins are removed, radiated, or merely observed, survival is absolutely equivalent” (Cady B. Dilemmas in breast disease. BreastJ 1995:1121:121-124).

14. The National Lymphedema Network, based in San Francisco, and Stanford University are each testing an early therapy for the problem using massage, special armbands, and lifestyle modifications, though elimination ofthe procedure would I absolutely cure the side effects of lymph node dissection.

15. High-dose chemotherapy with autologous bone marrow transplantation and/or blood cell transplantation for the treatment of metastatic breast cancer. Executive Briefing, Emerging Care Research Institute (ECRI), February 1995. ECRI is an independent technology assessment organization located in Plymouth Meeting, Pa. An article about ECRI appears inJAMA (1995;274113]:999-1001).

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