Goals for Preventing Breast Cancer

By Vera Viner

This fine month of October I set a goal for myself. As we all know, the obesity epidemic is troublesome in this country and remaining at a healthy weight is vital toward reducing our risk of various diseases, including cardiovascular disorders and breast cancer. Along with having a healthy diet, a sure-fire way to keep your weight at a stable level is to exercise. Getting back to my goal, this Breast Cancer Awareness Month, I decided to walk on a treadmill at 3 miles per hour on an elevation for 30 minutes every single day (or at least on as many days as possible).

So far, so good. It is not too difficult to keep to this goal because my gym is right down the street. Another reason I am able to stick to this objective is because I told my husband-to-be about this daily workout goal, which makes me feel more obligated to accomplishing my target. He also keeps me company three times per week, which is when I make sure to take part in some strength training. I am hoping that my fitness routine will stick for much longer than this one month – it’d be the perfect way to stay healthy all through the winter when the snow keeps us indoors indefinitely.

The New York Times reported on October 9 that walking – just walking – can actually reduce a woman’s risk of breast cancer by changing the way her body handles estrogen production and circulation. Researchers from the American Cancer Society studied questionnaire responses from 73,600 postmenopausal women.

The females who walked for one hour a day at 3 miles per hour were found to have a 14 percent reduced risk of breast cancer than those who exercised only 2.5 hours or less every week. Women who exercised vigorously for a total of 10 hours or more per week saw the biggest decline in risk – they were 25 percent less likely to develop breast cancer.

“We think these results are very encouraging,” Alpa V. Patel, senior epidemiologist with the American Cancer Society and senior author of the study, told the source. “Walking is an easy, inexpensive type of exercise. Almost everyone can do it. And for this population of postmenopausal women, it provided a very significant reduction in the risk of breast cancer.”

In addition to walking, make sure to take the extra effort and reduce the amount of BPA, or Bisphenol A, found in our system. This chemical is found in the lining of cans and bottles; it has been linked to a heightened breast cancer risk. USA Today recently reported on the health problems that may be associated with BPA. Try to buy foods that aren’t in metallic or plastic containers and instead are in cartons or glassware. Natural or frozen fruits and vegetables may be the best option to avoiding excess BPA.

These are just some of the ways to prevent breast cancer. This October, or National Breast Cancer Awareness Month, what are you doing to prevent this disease? Do you have a goal of exercising more or eating a healthier diet? Let us know in the comments below!

The Pink Virus 101: Peas, Genes, and Cancer

By Dr. Kathleen T. Ruddy

The next installment in my lecture series on the history of the Pink Virus (i.e., the breast cancer virus) continues …

It was not noisy prejudice that caused the work of Mendel to lie dead for thirty years, but the sheer inability of contemporary opinion to distinguish between a new idea and nonsense.
Wilfred Trotter

Gregor Johann Mendel was a friar, a celibate who never had any children of his own. Yet despite the prohibition against marriage imposed by his religious order, the Augustinians, Mendel created a vast progeny with an impressive legacy, for he is known as the Father of Genetics.

Mendel was born in 1822, the second child of a German family that had lived and farmed the same land located in what is now the Czech Republic for more than four generations. As a child, Mendel kept a garden and raised bees, natural occupations for a farmer’s son. But as Mendel got older he felt a calling to the church and made the decision in late adolescence to become a monk. In 1843 Mendel chose the Order of St. Augustine for his vocation. Augustinian friars pray throughout the day but, unlike cloistered monks who live in a self-sufficient enclave, they are active in the community, typically functioning as teachers and scholars. Mendel enrolled at St. Thomas, a small and beautiful stone abbey . He received his orders eight years later, taking the vows of poverty, chastity, and obedience – otherwise known as the evangelical counsels.

Mendel then moved to Vienna to study physics at the University of Austria. He returned to St. Thomas two years later, where he once again kept a garden, raised bees, and taught physics. His garden and beehives were more than a source of sustenance for Mendel and his fellow friars at the Abbey. They functioned as natural laboratories where Mendel could conduct experiments with God as his mystical assistant. What better way to understand the practical hand of God than to study God revealed in nature? Fueled by a love of mathematics fostered in the study of physics, Mendel began a series of experiments whose goal was to formulate the mathematical principles of what he and others assumed were ‘inherited’ traits. You didn’t need to be a scientific scholar to know that if everyone in a particular family had blond hair and blue eyes, it was unlikely that a child with black eyes and black hair would suddenly appear. And if one did, it would be fair to assume that some dark invader had mustered in. Farmers and breeders of farm animals knew well that traits were inherited and passed along to offspring. Mendel and his relatives must have used this information in the decades they spent on their farm. Everyone involved in farming and animal husbandry must have been well versed in the practical application of inheritance of traits, but Mendel wanted to work out the exact mathematics involved in these observed patterns. Mendel chose to begin his series of experiment using the pea plants in his monastery garden.

Using different colored peas, Mendel bred and crossbred different plants, first to record the results, and then to see if he could create mathematical models to predict the results of the next round of experiments. The experiments and models went very well as long as he confined himself to his garden, but when he turned his sights on bees his experiments took a dangerous turn. Unwittingly, his crossbreeding experiments produced a vicious strain of bees whose queens were notoriously insatiable in their mating behavior. Mendel abandoned the bees and returned to his pea plants to begin a new series of crossbreeding experiments.
Mathematics is often considered to be the language of science, especially of physics. And as a physicist, Mendel was adept at using mathematics to express scientific observations, and even to predict them. Mendel used the data he collected as a result of his crossbreeding experiments in pea plants to generate mathematical models that could explain and predict his observations. After generating his mathematical models based on his experimental observations, he was able to predict the outcome of an experiment in which he would crossbreed, say, a pea plant with a green pod pea with a plant that had a yellow pea pod. It wasn’t long before he was pretty good at predicting results, good enough to formulate some rules of inheritance. This was actually quite clever, for apparently no one had thought to do this before. Without benefit of formal training in biology or botany, per se, Mendel recorded his observations, generated his mathematical models, and discovered that traits were passed from one generation to the next in a mathematically predictable fashion. The field of genetics was thus born in Mendel’s garden. Mendel’s mathematical models of inheritance indicated something else beside a canny ability to predict outcomes of crossbreeding experiments: it was clearly evidence from the experiments that each plant provided exactly one-half of the biologic information needed to form the results observed in its offspring. In fact, Mendel’s models spoke of more than merely numerical outcomes, they spoke of the hidden genes involved in making the oh-so-predictable predictable outcomes so.
Mendel’s experiments and their results, and the mathematical models derived from them allowed him to put forth the first law of inheritance, known as the Law of Segregation: Each trait requires a combination of information, half of which is inherited from one parent, and half from the other. Each parent contributes equally to the traits observed in their offspring. You can depend, and even bet on that.

Mendel increased the complexity of his experiments by crossbreeding peas that differed in two ways. For instance, he took plants with green pods and yellow peas and bred them with plants that had yellow pods and green peas. By making his experiments more complicated via increasing the number of traits being tracked in the crossbreeding studies, Mendel wanted to know whether these individual traits (pod color, pea color) were passed independently or if they were linked together as they made their way up and across the family tree. It didn’t take long for Mendel to discover that individual traits are inherited independent of one another. This became Mendel’s second law of inheritance, known as Independent Assortment. It’s exactly why when you look in the mirror you may see your mother’s nose, your father’s eyes, your grandmother’s hair, and your grandfather’s jaw. It explains the incomparably handsome confluence of features seen in the personage of John F. Kennedy, Jr. – his father’s strong facial bone structure, jaw and brow (Irish traits) and his mother’s dark hair and eyes, which she inherited from her father. His height seems to have been passed down from his mother’s side of the family. We can all agree, it was a sensational combination of inherited traits, indeed; each one passed independently of one another, all converging in one glorious man.

Back at the monastery, Mendel continued to work in his garden laboratory recording observations, collecting data, and generating ever more clever predictions of pea pod inheritance patterns. Mendel created great harvests of food and scientific information, while managing to attend to his other duties as a friar in his monastery. And as long as he was puttering around with peas in the garden, his superiors left him alone. But when Mendel attempted to expand the range of his experiments to include animal studies in mice, his provincial superior, Bishop Anton Schaffgoth, had a fit. Why were peas acceptable as study subjects but not mice, you ask? Though hard to believe by today’s standards, the Bishop balked at experimental studies of inheritance patterns in mice because that would involve, nay encourage, unrestrained copulation. Such wanton behavior, even in mice and even if done to better understand God’s plan for the universe, was unacceptable, intolerable, and out of the question. Amen.

A chastened Mendel retreated to his garden, to the 29,000 peas in his abbey laboratory, and contented himself with the use of non-threatening, non-copulating plants to refine the mathematical formulae that predicted nature’s inheritance patterns.

Mendel published the results of his experiments in 1868, but because of his increasing responsibilities at St. Thomas’s abbey—by then he was its Abbott – he lacked sufficient time, or energy, to submit further papers to the scientific journals. Right from the start, Mendel’s work was well received among the academic community. His work and his data were rarely criticized; but, nevertheless, the results of Mendel’s experiments were cited only three times in the scientific literature over the course of the next thirty-five years. The whole idea of genetics, per se, and the utility of mathematical modeling in predicting inheritance patterns, did not immediately capture the imagination of the broader scientific community. evolutionary ideas almost never explode on the scene all at once, but rather smolder unattended until, after a good long while, a few passers by blow on the embers and, so, set the world on fire. And, thus, Mendel’s research, his data, his mathematical models, and his papers lingered like smoking, glowing ashes well past his death.

Unfortunately, Mendel died of kidney disease in 1884 never knowing what a profound contribution he had made to science. Indeed, today the field of genetics is in the throes of explosive growth, thanks to the work that he did in his garden with his peas.

Mendel’s work was unearthed and recognized as buried treasure around the year 1900, the same year Abbie Lathrop moved to her farm in Granby, Massachusetts. The second coming of his resurrected research created a new religion of its own – genetics – and with it, a stampede to test Mendel’s Laws of Inheritance in animals; and, perhaps one day, in humans too. One of the first men to grasp the importance of Mendel’s mathematical models and laws was a senior at Harvard University, a transfer student in biology who moved to Boston just eight years after Mendel died. His name was William Castle. He was from Ohio and he, too, grew up on a farm. Castle, ever prescient, was intent on making a name for himself in the newly emerging field of genetics, an area that he believed held a vast, uncharted horizon with plenty of room for fame and fortune. Castle studied Mendel’s papers intently and decided to see if Mendel’s Laws of Inheritance applied to animals as well as plants. Fortunately, though Harvard University had been founded by an Anglican minister (John Harvard, of puritan inclination) no one there during Castle’s tenure had any qualms about the role copulation might play in the study of animal genetics.
Castle began breeding small animals: guinea pigs, rats, and mice. Mice were an especially good choice for animal experiments because they bred quickly, reached maturity within three months, and produced several large litters every year thereafter. Just as Mendel’s bishop feared, their natural fecundity yielded abundant data for genetic studies in Castle’s laboratory, a mountain of data he could analyze and compare to Mendel’s results with plants.

After graduation, Castle remained at Harvard to begin a doctoral program in the Department of Biology. He focused his research and doctoral thesis on mammalian patterns of inheritance, what we would call Modern Genetics today. Keep in mind that at the time no one knew that genes even existed or how they worked. They just knew that there were separately inherited traits passed along to offspring from both parents in equal portion, and that these patterns of inheritance fit mathematical models derived from observational data that accurately predict them. It would be years before anyone knew that it was the genes themselves, biologic structures composed of DNA, that carried the information that were made manifest as observable, inherited traits.
Castle was appointed to the faculty at Harvard in 1897, and was then given free rein to launch his career and the field of mammalian genetics. In 1902, as one of a many scientists queuing up outside the gate of Lathrop’s farm in nearby Granby, Castle placed his first order for mice. Over the years, Castle obtained the majority of mice for his experiments from Lathrop, the schoolteacher-turned-entrepreneur who’d engaged a scientist from Philadelphia (Loeb) to study the genetics of breast cancer for herself.
Castle’s mouse experiments soon cluttered the cramped offices he was given in a building on Harvard’s campus in Cambridge. As soon as the opportunity presented itself, he gladly moved his operation to the much larger, open space at Harvard’s Bussey Institute for Applied Biology, located in Forest Hills, a farming community an hour outside of Boston. Bussey had been Harvard’s center for husbandry and agriculture for years. It was the perfect place for Castle and his teeming mice. His move to Bussey also put a safe distance between Castle and a fierce band of competitive colleagues back in Cambridge, many who were enthralled to the real power players in academia, the men who ran Harvard Medical School. The medical men were skeptical about the value of studying mammalian genetics, for they could not see its practical application to the see its to clinical medicine. Altogether, Castle was relieved to be essentially out of the reach of glancing blows from uniformed and not always benignly ignorant academics. He was more than content to be a full day’s drive away in the Massachusetts countryside, free to convert a large, abandoned greenhouse at Harvard’s Bussey Institute into a mouse dormitory, factory, and breeding ground. About as soon as he arrived, he got busy filling his distant empire with mice from Abbie Lathrop’s farm. With no one to stand in his way or slow him down he designed animal experiments in the manner of Mendel’s studies in plants, and than he enthusiastically allowed nature to take its course.
Meanwhile, others were hot on the trail of animal genetics, particularly as it related to cancer. While Castle was busy at Bussey, Loeb continued trying to understand why breast cancer was found in such high rates in certain breeds of mice on Lathrop’s farm. In 1928, ten years after Lathrop died, Loeb published another paper, this one with Ida T. Genther, a pathologist from Washington University School of Medicine in St. Louis. In it Loeb and Genther suggested that there were at least two factors working together to produce breast cancer in Lathrop’s mice. The title of the paper, published in the journal Experimental Biology and Medicine, said it all: “Heredity and Internal Secretion on Origin of Mammary Cancer in Mice.” Loeb and Genther began their paper by stating that “heredity was a factor of very great significance in the origin of cancer in mice. While certain strains had a cancer rate approaching zero, other strains had a rate approaching 80% or more. In successive generations these differences in the rates of breast cancer between different strains of remained approximately constant.” What Loeb and Genther were saying was that breast cancer was, at least in part, an inherited trait; and it was an inherited trait that was variable depending on the strain of mice being studied. But there was something else at work besides pure inheritance. Pink eyes might be inherited by mice in a purely mathematical and predictable fashion, but breast cancer (though inherited in part) had other factors working on it, apart from the genes themselves. Specifically, Loeb and Genther showed (as Loeb and Lathrop had done before) that the ovaries were very much involved in bringing breast cancer to light.
Loeb and Genther stated, “However, in the further analysis of the causes of mammary cancer in mice we found that in addition to heredity, the functional activity of the sex organs played a significant part in the origin of cancer.” Loeb and Genther discovered that if they castrated the mice (surgically removed their ovaries) the risk for breast cancer fell sharply. Furthermore, the earlier in life that castration was performed the more profound the protective effect was observed in preventing breast cancer. “A quantitative relation was thus established between the internal secretion of the ovary and the frequency with which cancer appeared in the breast of mice.” It was pretty clear – the ovaries were linked to breast cancer: no ovaries, no breast cancer.

Lathrop died in 1918, ten years before Loeb published this paper confirming work they’d done together. Loeb’s 1928 paper demonstrated once again that genetics was an important risk factor for the development of breast cancer, but even then they knew that other factors played a role too. Ovarian function appeared to increase the risk for breast cancer in high-risk mice, sometimes to a great extent. Surgical castration to ablate ovarian function caused the risk for breast cancer to plunge. Indeed, when it came to cancer, the clearly ovaries fed the breast tumors. While scientists like Loeb and Genther noted the importance of other confounding variable involved in modulating breast cancer risk in mice, the majority of scientists pursuing the genetic cause of cancer focused almost entirely on identifying the genes involved. Pure genetics, the mathematically pure and simple models and formulations first recorded by Mendel in his monastery garden, became the Holy Grail for cancer research. Many would argue and argue well that it still is. But like the Holy Grail, it was and is more talked about than touched upon.

What You Need to be Aware of During National Breast Cancer Awareness Month

By Vera Viner

As most women know, October is National Breast Cancer Awareness Month. This annual campaign began in 1985 when the American Cancer Society partnered with the pharmaceutical division of Imperial Chemical Industries to promote mammography as the best tool we have to fight breast cancer.

Ever since the beginning, breast cancer awareness has been about early diagnosis, mammography, and treating the disease before it spreads or metastasizes throughout the rest of the body. However, none of this actually prevents the disease.

When it comes to breast cancer, are you aware of the existence of the preventive breast cancer vaccine developed by Dr. Vincent Tuohy and his team at the Cleveland Clinic? Are you aware that we have finally gathered enough funds to start Phase I clinical trials on this vaccine once the FDA gives us the green light?

Also, are you aware that nearly 40 percent of human breast cancers may be linked to the mammary tumor virus? These are the things that Breast Cancer Awareness Month needs to be about.

We need to focus on keeping women from having to go through the pain associated with breast cancer treatment. Radiation, chemotherapy, and surgery are known as “slash, burn, and poison” for a reason. These treatments provide various negative side effects and we should ensure that women no longer have to face the tragedies associated with breast cancer.

Breast Cancer Awareness Month needs to keep women aware of how to stay healthy as well as take part in early diagnosis (yearly mammograms starting at age 40 and monthly self-exams). We need to encourage all females – from young girls to elderly women – to exercise for at least 30 minutes four times per week and eat a plant-based diet full of whole grains, fish, low-fat dairy, and plenty of fruits and vegetables.

Along with diet and exercise, there are some things to avoid such as hormone replacement therapy, excessive drinking, smoking cigarettes, and oral contraceptives. You may want to read this site to learn about some of the dangers of the birth control pill. We at the Breast Health and Healing Foundation wish to provide this imperative information during Breast Cancer Awareness Month so that women are truly aware of how to prevent this disease and learn about the scientific progress surrounding breast cancer prevention.

The Pink Virus 101: A Passion For Mice

The next lecture in this series about the breast cancer virus takes us back 100 years, to a spinster’s farm in rural Massachusetts. 

Dr. John Bittner of the University of the University of Michigan discovered the breast cancer virus in 1936 while working at the Jackson Memorial Laboratory in Bar Harbor Maine under the direction of Dr. Clarence Little of Harvard University.  These eminent scientists with impeccable academic credentials were pointed in the direction of their momentous, albeit surprising discovery by Miss Abbie Lathrop, a spinster who bred small animals to be sold as pets on old chicken farm in Granby, Massachusetts.  If contrast is the key to clarity, there could have been no sharper distinction between the pedigrees of these men and this woman.  Yet they shared one thing in common, a keen intellect driven by laser vision.

Lathrop was born in Illinois in 1868.  Her parents, both teachers, chose to home-school Abbie, their only child, until she was sixteen years old when Abbie decided to become a teacher too.  She attended a year of formal schooling and received a teaching certificate.  Lathrop then took a teaching position at an elementary school but was forced to retire after just a few years because of illness:  she suffered from pernicious anemia, a disease of the lining of the stomach that prevents proper absorption of vitamin B12.  Patients with pernicious anemia suffer from a slowly worsening spectrum of metabolic and neurologic problems that ultimately leads to an early demise.  (Lathrop died at the age of 50.)

Although Lathrop was not strong enough to continue teaching, she felt she had the stamina to run a small chicken farm and so in 1900, she retired to the Massachusetts countryside outside of Boston to begin a new, less demanding life.  But chicken farming did not go well for her either.  Lathrop gave it up after a few years and switched to raising small animals to sell as pets.  She bred guinea pigs, rabbits, ferrets, canaries, and mice.  Yes, mice.  Having mice as pets was all the rage, a cultish pastime that had started in Japan in the 1700’s, made its way west to China, from there to Great Britain via the export trade, and then on to New England.  Mice were raised, bred, and sold just as we breed cats, dogs, and horses today.  Mice were bred for appearance (coat and eye color) and behavior:  “waltzing” mice, born with an inherited dysfunction of the inner ear that made their gait unstable, were the most prized of all.  A waltzing mouse with a sable coat and ruby eyes might fetch a great sum in a demanding market, well worth the time effort a breeder spent producing and raising them.  Mouse conventions, mouse clubs, and mouse newsletters reflected the robust market for pet mice and the expanding opportunity for breeders, especially in New England. At the height of the mouse craze, Lathrop got rid of her chickens and purchased a single pair of waltzing mice.   And with these two little mice Lathrop built an empire.  Years later she confessed she had no idea what she was getting into, for within a few years she had an inventory of more than 11,000 animals and was barely able to keep pace with the growing demand of a growing market.

From the beginning Lathrop intended to expand her product line beyond the original waltzers, and so advertised in local newspapers to purchase other kinds of mice.  In addition to finding new breeding sources she could use to expand her own inventory, she began to receive inquiries from clients, called “mouse fanciers”, who wanted to buy mice from her.  Then, quite unexpectedly, Lathrop began to receive inquiries from scientists who wanted to purchase mice for experiments.  This was a relatively new endeavor – animal experiments using mice – but it was the fastest growing portion of the market.  The demand for experimental mice was growing exponentially, with scientists everywhere scouring the land for mouse breeders.  The scientists at nearby Harvard University were no exception.   Researchers in Harvard’s Department of Biology had just begun to use mice for laboratory experiments, were playing catch-up with other academic institutions around the world, and were keen to have a ready source of experimental animals for their studies.  Lathrop’s farm, with it thousands of mice, was the answer to many prayers.   Her farm became the source of mice for researchers at New York University, the University of Pennsylvania, and nearby Harvard University.  Orders mounted so rapidly that Lathrop began to enlist the help of local schoolchildren, whom she paid seven cents an hour to feed the animals and clean their cages.  Her success produced a steady, handsome income and, more importantly, financial security. But her interest in mice did not end at the bottom of her ledger book, for she developed her own curiosity about the experiments that were being done on her mice.  Despite her lack of formal education – we can assume Lathrop had only a scant knowledge of biology and certainly no knowledge of genetics – she had an alert, curious, and incisive mind worthy of the most prestigious academic institutions in the world.  By discovering what other scientists were doing, and by consulting and collaborating with them in experiments she carried out on her farm, Lathrop pointed men far more educated, but none wiser than she in the direction of one of the most significant discoveries ever made in the field of breast cancer research.

Lathrop noticed that certain strains of mice had a tendency to develop breast lumps that she believed were malignant.  By listening attentively and by asking probing (but, one can imagine, non-threatening) questions, Lathrop was became aware that scientists at Harvard and other universities wanted to understand the genetic causes of cancer by studying the inheritance patterns of cancer in mice.  As soon as she got wind of that, she suggested that if they wanted to learn more about cancer in mice they ought to take a good look at the strains of mice on her farm that had a tendency to develop breast cancer.  Then she sent out letters of inquiry to researchers at other academic institutions offering to send along some of her tumor-prone mice so they might “determine the cause of the malady.”  One of the researchers Lathrop contacted was Dr. Leo Loeb, a pathologist at the University of Pennsylvania, who was more than happy to take a look at Lathrop’s mice.  Loeb confirmed that Lathrop’s mice had breast cancer.  For Loeb, this cold call from a retired, spinster teacher-turned-mouse-breeder was a terrific opportunity to learn more about how and why mice developed breast cancer.  It proved to be an auspicious beginning of a short but productive collaboration between two unlikely strangers who  shared passion for understanding the cause of cancer.  Loeb and Lathrop began experimenting with two strains of mice, those that appeared to be predisposed to breast cancer and those that did not.  Loeb designed the experiments, sent the instructions to Lathrop, who then carried them out on her farm and recorded the results, sending the data back to Loeb for his analysis.  In an arrangement that was highly unusual, they appeared as co-authors in a series of papers published in medical journals between 1907 and 1918 that summarized the results of their experiments on mice with breast cancer.

In a 1915 article, “Further Investigations on the Origin of Tumors in Mice,” Loeb and Lathrop noted that in strains of mice in which the incidence of breast cancer was highest, the tumors also formed at an earlier age.  They concluded that tumor rate and age of tumor onset represented “distinct factors which frequently, but not in all cases, are in some way linked to each other.”  What they were observing was that in the strains of that had a tendency to develop breast cancer, the mice also tended to get breast cancer at an earlier age than that seen in strains of mice in which breast cancer was relatively rare.  They were just beginning to understand, therefore, that a genetic predisposition to breast cancer also tended to drive down the age at which the breast cancer would occur.  Of course, today we know that this is absolutely true:  women who carry a BRCA mutation tend to get breast cancer at a much earlier age than women who do not carry these mutations.  But it was Loeb and Lathrop who, nearly a century before, first observed the notable link between a genetic predisposition for breast cancer and the age of onset of the disease.

In another experiment, Loeb and Lathrop discovered that the age at which mice got breast cancer was linked to the age at which their ovaries began to function.  They noticed that even in strains of mice with a high incidence of breast cancer, the tumors did not appear before adolescence.  Furthermore, Loeb and Lathrop discovered that breast cancer in all strains of mice, but especially in those with a high incidence of breast cancer, could drastically reduced if their ovaries were removed before they reached puberty.  Of course, they really had no idea then what, precisely, the ovaries did in relation to the breasts or breast cancer; but they could readily observe that without their ovaries the mice did not develop breast cancers at all, or at a reduced rate and at a later age.  Without knowing exactly why, Loeb and Lathrop provided that shutting down the ovaries, for the most part, shut down the risk for breast cancer.  It was these two unlikely collaborators, an academician and an amateur, who first opened the door to our present day understanding of the relationship between the ovaries, the breasts, and cancer.

Once they had nailed the ovaries as co-conspirators in the development of breast cancer, Loeb and Lathrop moved on to undertake a series of experiments involving pregnancy and breast cancer.  Using strains of mice with a high and a low risk for breast cancer, they performed studies to better understand how pregnancy affected the incidence of breast cancer in each group.  Loeb and Lathrop observed that strains of mice with a high incidence of breast cancer always developed breast cancer after puberty, usually after several pregnancies.  Pregnancy seemed to have little affect on the incidence of breast cancer in strains with a lower incidence of breast cancer.  Thus, a genetic predisposition, the presence of functioning ovaries following puberty, and whatever other changes occurred as the result of pregnancy seemed to work in concert to increase the onset of breast cancer in susceptible mice.

Loeb and Lathrop published their last paper together in 1918, the year Lathrop died.  In it they revealed their most interesting discovery. They had performed the first experiments cross-breeding strains of mice in which there was a high incidence of breast cancer with mice from strains that didn’t seem to get breast cancer at all.  These crossbreeding studies, later adopted by Harvard researchers, became the nexus for understanding the inheritance patterns – that is, the genetics – of breast cancer.  Loeb and Lathrop took mice from high and low-risk strains, allowed them to crossbreed, and recorded the results to see if they could identify reproducible patterns of inheritance, clues to the genes that might be responsible for the disease.  What they found was both startling and confusing:  The risk of breast cancer tended to follow the mother; the father’s contribution was imperceptibly small.  This didn’t make sense if breast cancer was inherited like any other trait like, say, eye color, in which both parents shared equally in the results observed in the offspring.  Loeb and Lathrop found that cancer was inherited down the maternal line, almost exclusively.  That didn’t fit the patterns of genetic inheritance worked out elsewhere.   Loeb and Lathrop also discovered that once the risk for breast cancer had been inherited (via the mother), the increased risk endured forever:   all subsequent females carried the increased risk in perpetuity; the increased risk for breast cancer could not be diluted over time as can happen with other inherited traits like eye color.

In summary, Loeb and Lathrop showed that breast cancer was, in part, genetic:  certain strains of mice tended toward breast cancer and others seemed immune to it.  They found that breast cancer inheritable, but not in the exact same way as other traits like eye color.  They showed that the ovaries were involved and that pregnancy played a role in breast cancer formation, though they had no idea was, precisely, the ovaries contributed.  (Only later would we discover that what the ovaries contribute is the hormone, estrogen, a strong promoter of breast cancer growth.)  Loeb and Lathrop had discovered hints of breast cancer genes, hints of ovarian involvement, hints of pregnancy-driven breast cancer, but no solid answers about what caused breast cancer in some animals while sparing others.

The experiments that Loeb and Lathrop carried out may seem primitive, even trite, by today’s standards, but they were profoundly important and revealing.  There is no doubt that this unlikely pair, working together as trusted strangers without ever meeting, opened the frontier for research on the genetics and hormonal factors that contribute to breast cancer.  The results of their very clever, prescient experiments – his design and her execution – remain apt and accurate to this very day.

The Pink Virus 101: What Is Cancer Anyway?

By Dr. Kathleen T. Ruddy

As promised, here is the next installment in my fall lecture series about the human breast cancer virus:  Cancer, The Immortal Renegade:  Or, Why You Can’t Catch A Monkey By Chasing It

                 One morning, two women—each thirty-five years old, living in the same town—wake up, take a shower, and find a lump in their breast.  Neither of them has had any breast problems in the past, nor is there a history of breast cancer in their families.  Let’s assume for the sake of argument that both lumps are painless and about the size of a dime.  Both of these women go to their doctors within a week and have a mammogram and breast ultrasound.  The radiologist says the lumps are clearly visible and are solid.    Biopsies are then performed to answer the question, What is causing the lump?  These two women also happen to go to the same hospital for their breast biopsies, and the same pathologist examines their biopsy tissue.  One woman is told she has a benign tumor.  Of course, she is so relieved she can breathe again.  Unfortunately, the other woman is given the worst news anyone who’s had a breast biopsy can hear:   she has cancer.  She doesn’t think she’ll ever be able to take a deep, relaxing breath again.

Exactly what did the pathologist see under the microscope?  Precisely what  distinguishes a benign tumor from the one that is malignant?  Both lumps looked the same on mammogram and ultrasound.  Both were solid and the same size.  From all outward appearances, these two lumps looked identical.  So what was seen down the microscope that rendered one a cancer and the other benign?  , what we are asking is What are the visual and biological characteristics that differentiate benign tumors from those that are diagnosed as cancer?  Understanding the differences between benign and malignant tumors is at the heart of understanding the incredible challenges that face anyone who hopes to cure, or be cured, of cancer.

Let’s start with some common misconceptions about tumors in general, and then we can move on to a more detailed discussion of cancer, per se.  Many people believe that cancers grow fast and benign tumors grow slowly.  But that’s not always true.  Some breast cancers grow very slowly.  I once had an elderly patient whose doctor had been following a mass seen on her mammogram for five years.  The mass, which was not deemed suspicious by the radiologist when it was first seen, and which was not palpable on physical examination (i.e., neither the patient or her doctor could actually feel it) had not changed whatsoever over the course of five years.  Every year, this woman faithfully had her annual mammogram, and every year the mass was there, seemingly immutable as the Rock of Gibraltar, and she and her doctor were told there was nothing to worry about.  Then one day the patient felt a lump in her breast.  The lump happened to be in the same breast that also harbored the “entirely benign” mass seen on her mammogram for the previous five years.  In fact, the lump that she could now feel in her breast corresponded to the mass on the mammogram but it had When her physician referred her to me, the lump felt like cancer.  A repeat mammogram showed a mass just where the old one had been – the one that had been watched for five years – only now the lump was very large and had extended to her axilla (the tissue under her arm.)  I did a biopsy and discovered that she had had cancer all along.  Her tumor, however, appeared suddenly five years before, stopped growing, went into a state of dormancy, and then began growing vigorously.  So grow, whether rapid, slow, or intermittent, is not a reliable way to distinguish a benign from malignant tumors. Indeed, some benign tumors can grow, scaring the daylights out of patients and their primary care physicians.  While rapid growth is often a hallmark of cancer, this is not always the case.  In summary, the difference between benign and malignant cannot be differentiated by virtue of the rate of their growth.

What about pain?  Most women believe painful lumps  benign, and are often relieved to find that a new lump in their breast is painful.  They think, “Oh, good, this isn’t cancer.”   But  15% of breast cancers are painful; o pain is not an accurate  either.

They answer lies at the bottom of the microscope, which is why all breast lumps need a biopsy (or something as reliable) to rule out the presence of a cancer.  under the microscope cancer cells look distinctly difference from normal cells.  It’s as if you see someone with only one eye, not two; or someone with two noses, not one; or someone with three heads.  You’d know right away there was something wrong, for ‘normal’ human beings have one head, two eyes, and one nose.  When a pathologist looks down the microscope at a biopsy specimen, identifying cancer cells is usually not much of a challenge.  (Of course, there are occasions when the cells seen on a biopsy specimen are abnormal but not frankly cancer, at least not yet.  They may or may not be on their way to becoming cancer.  But this situation represents only a minority of cases, and so I keep to my generalization above that cancer cells are pretty easy to spot on a biopsy specimen compared to “benign” tumor cells.)

O.K., so cancer cells look really different – actually, they look bad.  And that’s because they are.  As to behavior, which is the most important consideration, how does the biologic behavior of malignant tumors differ from that of benign tumors?  Generally, hree characteristics that they way behave  from that of normal cells: Cancer cells have the unique ability to invade, metastasize, and live forever.  Let me explain these three characteristics separately so you can fully appreciate what we (patients and doctors) are up against when the pathologist looks down the microscope and then looks up and says “This is cancer.”

First, cancer cells invade.  By this I mean that they do not respect the natural borders set up by other cells and tissues in the body.  As an example, a benign tumor in the lung may grow quite large, pushing and pressing on the surrounding tissue structures like the ribs and heart.  But a benign tumor, even if large and fast growing, will not “eat” into the surrounding tissues.  A benign tumor will surely press up against them, but the tumor and the surrounding structures will be squished together like too many children crammed into the back seat of a car:  shoulder to shoulder and none too happy about it.  On the other hand, a malignancy like lung cancer will grow right into the surrounding tissue.  Not satisfied to merely press up against the surrounding structures, a malignant lung tumor will ‘eat’ into the esophagus, the windpipe, and even the heart – literally strangling the patient to death from the inside out.  This is what’s known as invasion.  Cancer cells invade.  Benign tumor cells just crowd and press up against other cells and structures.  As for breast cancer, it can invade the overlying skin of the breast; it can invade the muscle behind the breast; and I’ve even seen it invade a blood vessel behind the rib of the breast, causing the unfortunate patient to bleed to death.

When the pathologist looks at the biopsy tissue under the microscope cells invading surrounding tissue that these cells are cancerous and not benign.

Second, cancer cells metastasize.  That is, they travel; they ‘hit the road’.    Individual cancer cells can break free of the tumor, say in the breast, and enter the bloodstream and lymphatic channels, moving to other parts of the body.  They circulate throughout the body until they find a favorable environment, like lung, bone, and brain, and create colonies of new tumors in these new locations.  As an example, early in the course of breast cancer, some of the cells may move into the lymph nodes under the arm, which (in and of itself) is an indication of potential metastazing other tissues and organs in the body.  This is the primary reason that many women who are diagnosed with breast cancer will also be asked to have one or more of the lymph nodes under their arms biopsied:  to check for the presence of tumor cells there.

By comparison, benign tumors may grow quickly and to a very large size, but the benign cells will always remain in the same location where they first formed.  Benign cells don’t move around; they never ‘hit the road’.  Cancer cells, on the other hand, are on the move from Day One.

Third, cancer cells live forever.  This is almost unimaginable, but it’s true.  Cancer cells are virtually immortal. Normal cells don’t live forever.  They are programmed to die.  Programmed cell death (also called apoptosis) is part of nature’s master plan, and it actually works very well, for programmed cell death and its corollary, death of the organism, allows for evolutionary change and adaptation.  And so, normal cells to die in order to make way for a new and improved cells, and eventually new and improved  subsequent species.

Cancer cells have found the key to immortality by unhinging programmed cell death. How hard do you think it is, then, to catch up to immortality in a race for a cure?  Really hard.  Now you understand the difficulty patients and doctors face in eradicating this disease.  Even one immortal cell left behind after surgery, radiation, chemotherapy, and targeted therapy is all that is required to set the whole malignant, catastrophic cycle of invasion and metastasis in to motion again.  Cancer’s immortality renders it invincible unless doctors can find a way to kill every cancer cell, or otherwise prevent them from growing or moving around the body.  This is really hard.

Now that you understand what cancer is, it’s nature and characteristics, you might ask,  What causes cancer?  What transforms a normal, law-abiding cell that knows its job and duty to die at the appropriate time, into a malignant, immortal renegade?  When I started medical school in 1985, the favored explanation was that cancer cells arose from normal cells by way of genetic mutation.  This is still the case; the question is, What sorts of mutations trigger invasion, metastasis, and immortality?  Scientists believe that a single cell – that’s all it takes – is transformed by way of genetic mutations, and then grows indiscriminately, dividing and multiplying until its progeny have taken over the entire organism.  This process whereby a single transformed cell leads to an empire of malignant renegades rampaging throughout the body is referred to as “clonal expansion”.  It rests on the assumption that cancer formation takes place over the course of many smaller steps, from normal, to abnormal, to frankly malignant – all reflective of genetic changes that occur inside the cells.

As regards breast cancer, some researchers have recently discovered that cancer cells arise not from just any cell in the breast but from a particular type of cell in the breast called a stem cell.  You may have heard of stem cells, for there is much controversy about them in regards to harvesting such cells from fetuses that have been aborted.  But stem cells live in the human body as well.  They live in the bone marrow, and some scientists believe there are stem cells that reside in the breast.  Stem cells function like the National Guard; they are “on call” to be recruited when new cells need to be made, such as when the breast makes milk for a newborn child.   Stems can undergo malignant transformation.  Scientists now believe that the mutated stem cell sheds malignant cells in the same way that a machine gun fires bullets.  And so, the malignant cells can then form a tumor, invade, metastasize, etc.  This newer research is still under investigation, with not everyone yet buying into the theory of stem cell-driven cancer formation.  But whatever the cause and source of the malignant transformation, the end result is a pack of unruly, misbehaving renegades that run wild throughout the body, changing and morphing by the day in ever more clever ways to avoid all attempts to kill or corral them, and having always on their side immortality as their ultimate weapon.

The Pink Virus 101: Taking An Axe To The Root

By Dr. Kathleen T. Ruddy

The history of the discovery and research on the breast cancer virus is as long and varied as a Shakespearean drama, and every bit as interesting and dramatic!  I’m going to tell you the story about this virus right here on my blog, in a series of lectures I’ll call, “The Pink Virus 101.”

Think of “The Pink Virus 101″ as a free on-line course offered by the Breast Health and Healing Foundation’s Fall Semester catalog, called What You Need to Know.

At the end of every “lecture,” I will invite questions and comments, just as every good professor should.

Hope you like the course.  Now here’s the Introduction to “The Pink Virus 101″.

The cause is hidden, but the result is well known.

                  Ovid

Taking an Axe to the Root

            It was the summer of 1995 and I had just finished my surgical fellowship at the Breast Service of Memorial Sloan-Kettering Cancer Center.  Cancer Treatment Centers of America had hired me to create a similar breast service for one of their partners, Clara Maass Medical Center (now a part of Barnabas Health, the largest healthcare system in New Jersey.)  One of my first patients, who I will call Lisa, was a thirty-four-year-old mother with three young children.  She came to see me about a lump in her breast that she had found six months earlier.  At first it was painless:  just a small lump and nothing more.  Lisa made an appointment to see her gynecologist right away.  This was the same doctor who had delivered her children.  She had an excellent reputation in the community and a large, busy practice to show for it.  The doctor examined Lisa, found the lump as easily as Lisa had, and sent her off for a mammogram. When Lisa showed up at the radiology center for the mammogram, the radiologist suggested she also have a breast ultrasound.  Telephone calls between the radiologist and the gynecologist were exchanged, a prescription for an ultrasound was faxed, and Lisa has both a mammogram and a breast ultrasound that day.

The radiologist looked at the mammogram closely, for Lisa had arrived complaining of a lump in her breast and, so, he was more attentive that usual to the image that appeared on his view box that day.  He interpreted the mammogram images as equivocal, which means they were not exactly normal, not overtly abnormal, but something in between.  You see, there was no distinct mass present on the mammogram, only a slightly increased density – more “whiteness” in one spot than usual – found in the vicinity the lump present in Lisa’s breast.  The ultrasound, on the other hand, was unequivocally, completely, irrefutably abnormal.  No question about it, Lisa had a bad looking ultrasound.  An irregular mass corresponding to the lump in her breast was clearly visible and highly suspicious for malignancy.  (It was taller than it was wide, and it was solid and irregular – the hallmarks of malignancy.)  The radiologist’s dictated his findings in a transcribed and typed report that was sent to Lisa’s doctor.  He was quite clear:  while the mammogram was equivocal, the breast ultrasound was frankly abnormal and the lump should be biopsied because it looked liked cancer.  That’s what he said in the report.  He didn’t call Lisa’s gynecologist to discuss the report.  He trusted that dictating the report and mailing it would be sufficient.  Indeed, the report was mailed to Lisa’s gynecologist and arrived a few days later.

But then something went very wrong.  The report arrived on a timely basis, but rather than being given to the gynecologist for her review, it was immediately filed in Lisa’s chart.  The doctor never saw it.   It was as if it never happened; as if the mammogram and breast ultrasound had never been done.  For without the report, how could this busy gynecologist recall that it had ever been ordered?  She had an office full of patients and women lined up in Labor & Delivery every day and night of the week, year round.   The report of Lisa’s mammogram and breast ultrasound might as well have never arrived at all.  They might as well have never been done for all the good they did, buried and filed away in a forgotten patient’s chart.  Lisa’s lump and the ultrasound report that suggested she had breast cancer were lost amid a throng of patients, endless telephone calls, reams of paper, and a barrage of beeper calls to Labor & Delivery -  all cluttering a cramped, two-exam room office manned by one doctor, two secretaries, one nurse, and two billing agents – all of them oblivious to the huge mistake heating up like an empty coffee pot on a burner no one had time to attend to.

Meanwhile, Lisa assumed that because her gynecologist hadn’t called with the results of the mammogram and ultrasound that, hurrah! her studies must be normal and, therefore, she had nothing to worry about.  Lisa’s anxieties dissipated into the pervading silence like a puff of smoke into a galaxy.    Her spirits rose.  No news was good news, right?  Of course, no news was good news.  Her featherbed – built on wishful thinking, pillowed by denial, and curtained by the cold hand of error – didn’t last long, for her lump got larger, by the week.

Furthermore, Lisa was in no position to absorb bad news.  She had about as much as she could stand.  Lisa was a single mother with three young children, and had been divorced for several years from a physically abusive husband who had returned to his family in the Philippines and left her and the babies behind to fend for himself.  O.K., so that marriage didn’t work out.  Lisa was assigned the task of making the best of her lot and had no visible support to lend a hand.  She had no one to help with the children; her family were all back in the Philippines too.  She received no money from her ex-husband, nor would she ever.  Lisa’s job as a secretary yielded a meager salary, barely enough to keep food on the table and shoes on the children.  She was in no position to take in an ounce more of bad news.  She lived on the brink of collapse.  A lump in her breast was an impossible challenge – though she had sought medical help right away – and she was glad for an eye in the storm, such as it was.  But the winds of worry began to pick up as the lump in her breast started to grow.

I started my career as a breast cancer surgeon six months after Lisa first discovered the lump in her breast.  Cancer Treatment Centers of America (CTCA) had recruited me the week after I completed the first Fellowship on the Breast Service at Memorial Sloan-Kettering to become the Medical Director of the Breast Service at the Clara Maass Medical Center in Belleville, New Jersey.  This happened to be the hospital closest to where Lisa lived.   Upon my arrival in September, 1995, both Clara Maass and CTCA launched a vigorous public relations campaign to market their new Breast Service and me.  When Lisa read about me in the local newspaper she called for an appointment, thinking that perhaps a second opinion might be in order.  In the six months between her first visit to the gynecologist and her first visit with me, the lump in her breast had grown from the size of a walnut to the size of a lemon, and the area under her arm had become swollen and painful.  Denial was no longer an option, silence no longer a comfort, and neglect no longer a solution.  Lisa needed help and she knew it.

I will never forget the day I met Lisa.  Although I was a freshly minted surgeon, platinum-plated from the arguably best cancer institution in the world, one look at her breast was enough for me, or anyone, to know that she had advanced breast cancer.  The upper outer portion of her left breast was visibly swollen.  This was especially noticeable when I compared it to the unaffected right breast.  There was a hard mass in Lisa’s breast,  easily felt within the swollen tissue.  The lymph nodes under her left arm were large, hard, and fixed to the surrounded tissues as if they had been crazy-glued in place.

As I examined Lisa’s breasts and the lymph nodes under her left arm, she told me the story of her breast lump, and her presumption that because she had not heard anything from her gynecologist that the mammogram and breast ultrasound she’d had six month prior must have been normal.  She assumed she had nothing to worry about, she said.   But then she told me that she had not been given a follow up appointment.  I was perplexed.  Even a patient who has a normal mammogram and breast ultrasound should be seen again if she has a lump in her breast.  After all, doesn’t everyone know that 10-15% of patients with breast cancer have completely normal mammograms?  Doesn’t everyone know that women with breast lumps need to be followed as closely as Al Qaeda suspects?

Lisa’s story didn’t make sense to me.  I wasn’t so concerned about the likelihood that her mammogram was read as normal.   Young women with breast cancer frequently have normal mammograms.   You see, in older women, breast cancer is typically very dense compared to the softer, normal, fatty breast tissue that surrounds it.  But if, as in young women, the surrounding breast tissue is also dense, then it’s very difficult to tell one from the other.   So, young women with breast cancer have dense breasts and dense breast cancers – and it’s hard to tell the difference between the two:  so, a “normal” mammogram seemed within the realm of possibility in Lisa’s case.  But not a “normal” ultrasound.  In young women, breast cancers can be readily seen on breast ultrasounds.  A solid mass that is taller than it is wide, and that has irregular borders, can easily been seen in even the youngest breast.  So Lisa’s distinctly palpable breast mass was highly unlikely to produce a completely normal breast ultrasound.  As for the lack of a phone call from the gynecologist to discuss the results of the studies – normal or abnormal –  and the absence of a follow up appointment to make sure the lump had gone away, well that was peculiar, indeed.

I fully intended to get to the bottom of this confusing story, but unraveling this mystery had to wait, for this was an urgent case:  Lisa needed help, and fast.

Naturally, Lisa was worried.  The painless lump in her breast had doubled in size in six months, and to make matters worse, it was now painful and had spread to under her arm.   No doubt, Lisa could see beneath my calm facade a profound concern for her welfare and that of her children.  All told, I think she was glad to have found a doctor who could provide the care she needed no matter what the cost.

Because six months had elapsed between Lisa’s initial mammogram and ultrasound, I decided to repeat the studies to see what, if anything, had changed.  I also did my best to comfort her.   I quietly told her she would need a breast biopsy to determine the cause of the lump, and as soon as we had that information we could begin treating it.  Then I gave her an appointment to come back to see me again in two days.  (No patient ever leaves my office without a follow up appointment unless I am formally discharging her from my practice.  That way I never lose track of anyone.  If a patient chooses not to come back, that’s her choice:  but I always have a record and a paper trail so that no one ever falls through a crack coughed up by error or oversight.)

As soon as Lisa left, I called her gynecologist, who I will call Dr. Smith.  Of course, I wanted to introduce myself and discuss what looked like a very ugly case of advanced breast cancer in an alarmingly young woman.  In the first few minutes of our conversation, as I recounted Lisa’s story of her lump and her belief that because she hadn’t heard anything that her mammogram and ultrasound were completely normal,  the gynecologists seemed as bewildered as I.  While I described the history and the physical findings,  I could here her rifling through Lisa’s chart.  Then there was silence.  A long pause in which nothing was said.  The gynecologist had discovered the mammogram and ultrasound reports.  She immediately recognized that they had been filed away in the chart without her ever seeing them.  Understandably, she was horrified.  And I was horrified for her.  I had recently come from Memorial Sloan-Kettering where a notable neurosurgeon had operated on the wrong side of a patient’s brain, leaving her incapable of having the life-saving surgery she needed on the other side!  That devastating news, which had scorched my beloved institution like wild fire, still burned in my memory.  The lesson was, no matter how hard you try, no matter how many fail safe mechanisms you install in your practice or hospital, inevitably mistakes happen.  And some of them cost lives.  In the sixteen years I’ve been in practice, with 6,000 patients under my care, mistakes have happened in my office – and I’m a crazy compulsive person about paperwork and charts!  I always come close to a heart attack when I find a report in a chart I haven’t seen, despite the fact that I’ve instituted two mechanisms in my practice to avert this mistake.  But mistakes happen.  They always happen.  They happen to me, and when they do I feel awful, just like Dr. Smith did.  Fortunately, the filing mistakes that have occurred in my office over the past 18 years have never resulted in harm to any of my patients, but only a bad case of rattled nerves for my staff and me.

I sympathized with Dr. Smith as I listened to her hold her breath on the other end of the phone.  It was a silence that shrieked of mistake and grief, a silence that was soon followed by muttering and sputtering.  Amid the unfolding drama rising like a fetid odor in the debris of remorse the ominous truth emerged:  this avoidable mistake had resulted in a delay in diagnosis of Lisa’s breast cancer.  It might cost Lisa her life and her children their mother.  Six months had passed.  What now?

I reassured Dr. Smith just as I had reassured Lisa:  I would get right on it, obtain a definitive diagnosis, and begin treatment as soon as possible.  Life has no rewind button, have you noticed?  There is only unidirectional time, relentlessly unfolding to what comes next.  So be it.  The task, then, is to decide, What is the next best thing to do?  In my opinion, the next best thing to do was to repeat the studies, perform a biopsy to obtain a definitive pathologic diagnosis, and quickly begin appropriate treatment.  That meant ‘full speed ahead’ for everyone.

We, the entire team assembled to form the Breast Service – radiologists, oncologists, surgeons, pathologists, and social workers – had to proceed speedily, with hope and resolve, as if a cure was achievable, as if there was no doubt that we would catch up to Lisa’s tumor (despite the fact that it had a six-month head), and work like heaven to cast it into hell where it belonged.  In the process, I hoped we could save Lisa’s life and save her children a mother too.  There is no more noble cause, and so, we set out to achieve these goals with the fervor of zealots intent on saving the damned.

I performed Lisa’s biopsy two days later, and the pathologist confirmed her tumor was cancer the following day.  Lisa, like thousands of other women, faced her diagnosis with stoic, saintly courage and resolve.  She didn’t blink when I told her what was next:  mastectomy with removal of the lymph nodes under her arm – to physically remove as much tumor as possible – then six months of chemotherapy to eliminate any cancer cells that might be circulating or hiding elsewhere in her body, and then radiation therapy to the chest wall to reduce the risk of local recurrence of the cancer.  Cut, poison, and burn:  that’s how my mentor at Memorial Sloan-Kettering, Professor Jean Petrek, described our land, sea and air attack on breast cancer – an apt, if crude, description of what modern medicine has to offer.  It was the best we could do, so we got busy doing our best.

Like so many brave women, Lisa remained poised and pleasant throughout her ordeal.  She was truly remarkable; a young woman single-handedly supporting three children with no help, no family, and with barely enough money to pay rent and buy food.  She slogged through it all with not a single complaint.  God bless her, she was amazing.

She did well for a year.  Then her cancer returned.  Of course, I wasn’t surprised when it did.  But neither was she.  Surprised or not, we were both devastated:  she, because she knew she was going to die; I, because I knew she was going to die and wondered if she might have been saved if we’d gotten to her sooner, and concerned that I had nothing substantive left to offer her but comfort.

Lisa’s cancer returned with a vengeance, metastasizing (or spreading) to her lungs and liver.  You can live without your breast – millions of women do.  But you can’t live without your lungs or liver.  Unlike most surgeons who operate and then send their well-scarred patients back into the world and on to other specialists for further care, I choose to follow my patients forever – or for as long as they’re willing to let me keep an eye on them.  Of course, I enjoy the excitement and challenge of being in the operating room – it’s Top Gun there everyday, minus the jets  - but  I find that my deepest satisfaction as a healer is found in the art of medicine rather than the craft of surgery. I can cut and sew with the best of them, but I prefer to help women knit up a new life from the threads of disaster that come with cancer. Above all, I appreciate the opportunity to develop long-lasting relationships with my patients, to follow them as their children grow, as they get into the college of their choice (or their second, or third, or last choice), graduate and get their first jobs, as they buy and sell homes, go on vacation, change jobs, retire, travel, get divorced, start dating again, find new old boyfriends, welcome grandchildren, bid good-bye to friends and family who pass, and celebrate each holiday as it comes round every year:  Super Bowl, Valentine’s Day, Lent, Easter, Mother’s Day, Memorial Day, Fourth of July, Labor Day, Back to School, Yom Kippur, Halloween, Thanksgiving, Christmas, New Year’s – where does the time go? We ask.  I can’t tell you how many patients appear in my office with photographs, photo albums, and pictures on their cell phones, all close to hand and laid out on the counter as they sign in at the front desk.  It’s a joy.  Oprah Winfrey never had half the fun.

As a rule, I like to see my patients every two weeks when they are going through chemotherapy and radiation therapy.  Once they are fully recovered, I see them every three months.  This gives me an opportunity to see how they’re doing and to provide emotional support and helpful information, for breast cancer is such a dynamic field that treatments and recommendations can change as fast as the fashionable length of a skirt.  One day the hem is above the knee; the next day it’s mid-calf.  One day it’s perfectly O.K. to take hormone replacement therapy – it won’t cause breast cancer; the next, there’s no question that it causes breast cancer and you better stop!  Try to keep up.    I can, but barely.  So, I would hate for a patient to wait a full year to see me, or not see me at all, and miss getting important advice that could prolong or save her life.

When one of my patient’s has a breast cancer recurrence, she will invariably begin a new round of treatment.   During this time I will see her weekly because I know that her health, both physical and emotional, can change literally overnight.  When Lisa’s breast cancer recurred, her oncologist began treatment with a more toxic drug, but it seemed to have no effect on the growth of the tumors in her lungs and liver. A month later she came to see me for her weekly visit and was extremely distraught.  As she sat on the edge of the examination table, clutching her hospital gown, she told me that the oncologist had given her devastating news: Nothing could be done for her.  She couldn’t believe her ears.  Terrified, she began to plead with me, “Isn’t there anything you can do for me, Dr. Ruddy?  Please, I have three children.  I am all they have.”

Lisa’s pleading supplication for help, and the searing memory I have of her anguished words haunt me to this day.

For the most part, medical schools teach students how to identify, diagnose, treat and cure disease.  For clinicians, patients are little more than stages upon which illness plays out its varied stories:  heart attack, stroke, cancer, trauma, chronic disease – each with its own characteristic plot that seldom varies.  And if it does, well that just makes the whole thing that much more interesting, doesn’t it?  Not to the patients, of course, but to the doctors who take care of them.  Residency training takes over where medical schools leave off, honing the skills of newly minted doctors so they can apply the principle of cure as far as possible.  Then what?  What if there is no cure?  What if there isn’t even a race for a cure?   What frequently happens is that patients are told there’s nothing more that can be done, and then they are sent home to live out their days unattended by the doctors who have cared for them for so long; or they are removed to long-term facilities with short-term horizons where they are kept clean and comfortable and left to die.  In truth, medical school and residency programs offer little, if any, guidance about how to proceed when the doctor’s black bag is empty.  Think you’re going to find the answers of what to do next in a book?  Think again.  Surgical textbooks are void on the subject of what to do when nothing more can be done.  As an example, the textbook compiled by the American College of Surgeons, ACS Surgery, 6^th Edition, published in 2007, with its seven editors and 308 contributing authors, says not a word about what to do for the dying patient.  Rather, the College confines its discussion of death to: 1) how to define it, and 2) how to declare it.  Well, that wasn’t going to help me or Lisa or her children. 

Personally, I have found there’s a lot that can be done at the end of life, a lot that is useful and memorable.  Courage, kindness, and tender support—and simply spending time with the patient—provide plenty of comfort at the end of life, comfort that the patient and family need and appreciate.  When Lisa asked me if there was anything more I could do, I told her I would try.  I called her medical oncologist to ask if there were any clinical trials for which she might be eligible.  He said, “No, there’s nothing.”  I told Lisa that there was no other medicine that could be given, but that I would continue to make inquiries at other research centers.  Oft times, clinical trials involving investigational drugs can be found at research hospitals like Memorial Sloan-Kettering.  But when I searched, there were none for which she was a candidate.  I then asked Lisa, who knew she was approaching the end, what plans she had made for the care of her children.  She told me that she had “not gotten that far” because she was simply incapable of facing the dreadful possibility that she might die and leave behind three motherless children.  I told her I would help her deal with it, and we discussed several options.

I brought the matter to the attention of the team I had assembled as Medical Director of Breast Service at Clara Maass Hospital.  I was fortunate to have an array of capable, compassionate, and resourceful professionals to help me figure out how best to assist and care for Lisa and her children. As Woodrow Wilson once said, “I not only use all the brains I have, but all the brains I can find.”  With our help Lisa arranged to have her extended family in the Philippines take custody of the children.  Fortunately, by working together we were able to relieve a great deal of her suffering and anguish.

This deeply troubling case, presented to me so early in my career, was a personal and professional challenge that left me wondering, as never before,Why did Lisa get breast cancer to begin with?  She, like the majority of women diagnosed with breast cancer, had no risk factors—none whatsoever.   She was young.  She was healthy.  She didn’t smoke.  She didn’t drink.  No one in her family had ever had breast cancer.  No one had even had a breast biopsy!  She didn’t carry a BRCA mutation (which confers as much as an 85% lifetime risk of breast cancer.)  Why, then, did Lisa get breast cancer? Despite the promise President Nixon made in his inaugural address to end every form of cancer by 1976 – in time for the nation’s bicentennial – or the Race for a Cure that Nancy Brinker started running in 1982  – a race with no finish line in sight – the cause of Lisa’s breast cancer remains a mystery wrapped in a pink ribbons that serve more as a shroud to her death than an answer to what caused her disease in the first place.

It is now 2013.  Even with a promise, a race, a ribbon, and a king’s ransom spent on research,  a woman is diagnosed with breast cancer somewhere in the world every twenty seconds and another one dies every minute, each one falling like a petal from a “wet black bough.”   And, still, we don’t know why.

It wasn’t until 2006 that I first learned that a virus might lay at the heart of a large portion of this disease.  This virus was discovered in 1936.  That’s a long time for a murder suspect to roam free.