What Doctors Know About Breast Cancer by AudioLearn

What Doctors Know about Breast Cancer www.AudioLearn.com

Molecular Typing of Breast Cancer ............................................................................... 84 Metastatic Breast Cancer ............................................................................................... 87 Breast Cancer Staging ....................................................................................................88 Wrap Ups from this Section .......................................................................................... 90 Symptoms of Breast Cancer ...................................................................... 91 Wrap Ups from this Section .......................................................................................... 97 Diagnosis of Breast Cancer ....................................................................... 98 Breast Biopsies ............................................................................................................... 99 Breast Cancer Receptor Testing .................................................................................. 102 HER2 Testing ............................................................................................................... 106 Genomic Testing .......................................................................................................... 109 Diagnostic Tests for Metastatic Breast Cancer ............................................................. 117 Wrap Ups from this Section ......................................................................................... 121 Treatment Options for Breast Cancer ...................................................... 122 Surgery ......................................................................................................................... 122 Breast Reconstruction.................................................................................................. 125 Lymph Node Dissection ............................................................................................... 129 Prophylactic Surgeries ................................................................................................. 132 Cryotherapy .................................................................................................................. 133 Chemotherapy .............................................................................................................. 133 Radiation Therapy ....................................................................................................... 135 Hormonal Therapy....................................................................................................... 138 Targeted Therapies ....................................................................................................... 141 Immunotherapy ............................................................................................................ 141

Wrap Ups from this Section ........................................................................................ 146 Living with Breast Cancer ........................................................................ 147 Managing Side Effects related to Treatments ............................................................. 147 General Health Measures after Cancer ....................................................................... 153 Fertility and Pregnancy with Breast Cancer ................................................................ 156 The Immune System after Breast Cancer .....................................................................157 Wrap Ups for this Section ............................................................................................ 160 Current Research on Breast Cancer ......................................................... 161 Wrap Ups for this Section ............................................................................................ 167 The Future of Breast Cancer Care ........................................................... 168 Wrap Ups from this Section .........................................................................................172 Conclusion ............................................................................................... 173

PREFACE It was not too long ago when getting the diagnosis of breast cancer was greatly feared because it meant surgical disfigurement, dangerous medical therapies, and radiation without any assurance of being alive at the end of such extreme treatment. The breast itself is such a symbol of femininity and beauty; this fact only added to the distress of having this particular body part involved in such a serious disease. Breast cancer has been known and experienced by women since the beginning of time. It has only been in the last several decades that real progress has been made in understanding what causes this type of cancer, how it spreads in the body, and how best to treat it in order to not only preserve life but to preserve as much normal breast tissue as possible. Something amazing has happened in the study and progress made with regard to breast cancer. Because it is the most common cancer among women worldwide with so many mothers, daughters, and siblings affected, large amounts of money and time has been spent by researchers everywhere to understand its roots, prevent the disease if possible, detect it as early as possible, and affect lasting cure for as many affected individuals given the diagnosis of this serious disease. As you will see in the discussions we will have on breast cancer in this audiobook, the understanding and management of this disease have come a long way since it was first described in the Edwin Smith Surgical Papyrus, which may have been written by the Egyptian physician Imhotep between 3000 and 2,500 BCE. During those years and for centuries to follow, breast cancer was a mysterious and terrible disease that meant almost certain disfigurement and death to the men and women who suffered from it. Maybe it’s because it’s such a common disease and maybe because it has affected so many mothers throughout the world, large amounts of research time and effort have been devoted to understanding breast cancer—possibly more than has happened for any other type of cancer known. This has led to great strides in helping the breast cancer

patient survive their cancer and live as long and as normally as possible after receiving the diagnosis. In this audiobook, we will talk about what doctors now know about breast cancer. Did you know, for example, that there are several different types of breast cancer that differ greatly in their appearance and overall survivability? There has been a great deal of research done in understanding the different types and how best to treat them once a specific diagnosis has been made. There are also several different risk factors for breast cancer that were once not known about. Some of these risk factors are what we call “modifiable”, meaning you can change your risk of getting the disease simply by changing aspects of your lifestyle. Other risk factors are considered “nonmodifiable”, which means you cannot do anything about them. Even so, knowing you have a nonmodifiable risk factor does not mean you are helpless to do anything. There are things that can be done, including stepped-up surveillance, that can reduce your overall risk of dying from this disease. We will also talk about the different ways of detecting breast cancer and about those things that work and those things that have been found to be less helpful in finding an early breast cancer. You may be confused about things like breast self-examinations, mammography, and clinical breast examinations by your doctor and you have every reason to feel this way. As research has progressed about the disease, recommendations about these things have changed dramatically. They may even change again as more is understood about the risks and benefits of detecting breast cancer at the different stages. You may have certain ideas about the symptoms of breast cancer, including whether there are symptoms you can expect at all. As it turns out, the symptoms of breast cancer range from having no symptoms at all to becoming severely debilitated by the disease process. It depends on what type of breast cancer is involved and where a person is with regard to the disease processes in the body. We will talk extensively about the treatment of breast cancer, mostly because it has changed so much in recent years. No longer does treatment focus solely on removal of the breast and destruction of remaining breast cancer cells. Huge advancements have

been made in the molecular understanding of breast cancer that have helped to determine who is at the greatest risk of developing it and how best to treat the various forms of the disease. These things depend greatly on the genetics and cellular aspects of breast cancer, which fundamentally change the treatment processes. We will also discuss living with breast cancer, including living after your breast cancer has been technically cured. No one is more concerned about getting the disease than those who have already suffered through the experience of having had it. Even if the disease has not been cured, there are things a person can do to help the body function at its best even when breast cancer is still a part of it. Finally, we will talk about the research currently being done on the different aspects of breast cancer and about the future of breast cancer in the world. No one in the world of breast cancer research feels that we know everything there is to know about the disease process or its treatment. Breast cancer research is unfolding every day and you should know, too, that research on breast cancer has opened doors for the understanding of how to manage other kinds of cancer besides that of the breast itself. Will there be a time when breast cancer is no longer a disease to worry about or fear? This remains to be seen but you should know that a great deal of effort is being expended every day toward this goal. Sure, we have learned a lot about breast cancer since the days of ancient Egypt but there is still so much to be uncovered. There are few human diseases for which so much passion about curing it is attached than breast cancer. It is unlikely that research efforts will stop unless ways are found to prevent the disease as much as possible and to cure those people who find themselves afflicted with it. Stay tuned, for you have much to learn.

HISTORY OF BREAST CANCER Even though we now know that it is certainly possible for a man to have breast cancer, the disease itself has been linked mostly to women. The presence of breast cancer has always been considered to be an affront to the beauty, femininity, and ability to nurture one’s infant—all characteristics symbolized by the female breast. In ancient times, cancer was mainly treated with the surgical removal of the cancerous tissue, which led to the added distress of having the diseased breast further disfigured by the surgeon’s knife. This has led to a long and complicated effort to treat breast cancer with a number of modalities that did not always involve extreme disfigurement but that would also lead to adequate treatment of the disease. While a great deal has been learned about the effect of genetics and hormones on the development of breast cancer and its treatment, none of this could have been understood by the ancient physician who knew only that a woman’s only chance at prolonged survival from this disease meant that the cancer and the breast itself had to be surgically removed. While we now think of breast cancer as a “lump in the breast”, this was not always the case, particularly in ancient times. At that time, most women might not have even noticed such a subtle change in the breast or, even if they did, there was nothing that could be done about it anyway that wouldn’t be further disfiguring. Back then, cancers grew out of control, through the skin of the breast, and into the armpit before anything was done about it. Naturally, this meant that the woman already had an incurable disease. As mentioned, breast cancer has been written about since at least 3000 years BCE. The texts spoke of incurable breast cancer being defined as a breast that was “cool to the touch” and “bulging”—spread throughout the entire breast and often rising to the surface as a mass that looked much like a fungus coming up out of the breast tissue. Such presentations are fortunately rarely seen today because the cancer rarely becomes so far advanced.

While there certainly some physician surgeons who sought to remove the cancerous breast tissue in ancient times, much of the treatment of the disease focused on divine intervention. Votive offerings in the shape of the human breast were placed in Greek temples of the house of Asclepius, the Greek god of medicine. In 400 BCE, Hippocrates himself wrote about breast cancer as being an imbalance of the various causes of all diseases. Such imbalances involved the four humors, which were phlegm, blood, yellow bile, and black bile. Of course, no one today believes these things but that was just how it was once believed diseases were said to occur. Hippocrates also wrote carefully about the different stages of progression of breast cancer because there was no known treatment and almost everyone died of their disease. Some steps toward actual medical treatment were made about the first century AD, when Leonides of Alexandria, another ancient physician, first wrote about removal and cauterization of breast cancer tumors. He believed that a wide margin of healthy tissue should be removed around the cancer, which is something doctors today sometimes still strive to do in order to improve the cure rate for cancers of all types. The physician Galen in 200 AD felt again that black bile accumulation in the body led to the development of breast cancer. He felt that breast cancer wasn’t actually a localized disease process but involved the body as a whole. At that time, it was also believed that breast cancer had something to do with menopause or the stoppage of menstrual periods, leading to the idea that breast cancer was mainly a disease of older women. Because it was believed that the dreaded black bile accumulation was part of why breast cancer started in the first place, when Galen and his cohorts removed the cancerous tumors, the surgical margins were never sutured shut but were allowed to freely bleed so the black bile could get out of the breast as part of the treatment process. Galen also made use of castor oil, sulfur, licorice, and other salves to treat breast cancer and used opium to manage breast cancer pain. From ancient times, the diagnosis of breast cancer was extremely embarrassing and was a taboo topic to talk about. Because of this, practically nothing was written about it other than could be found in medical books and there was no talk of ways to detect it as

early as possible or what to do when the disease was discovered unless it was already in its advanced stages and virtually incurable. As you will learn, it has only been recently, when much of the taboos have been listed and when efforts were made by women themselves to bring breast cancer to the forefront of discussion that real progress has been made. The Middle Ages did nothing to advance a woman’s prospects after being diagnosed with breast cancer. Christians of the era believed in miracles and faith healing. They believed surgery was barbaric and not likely to have any added benefit toward survival. Instead it was the Islamic doctors who revived what had been uncovered by the Ancient Greeks and who developed certain potentially helpful therapies. They invented caustic pastes applied to breast tumors, which were designed along the same theories used by later doctors in the development of chemotherapy treatments for breast cancer. Surgical instruments were created to help remove cancerous lesions of the breast. Very little progress was made in the understanding of breast cancer until the late 1600s, when a French doctor, Francois de la Boe Sylvius, started to think differently about the disease. He no longer believed in the “black bile excess” theory of breast cancer and felt that the cancer had something to do with chemical changes in the lymphatic fluids. A few years later, the idea that breast cancer was a systemic disease was rejected as well, in favor of the idea that breast cancer happened when glandular and nerve tissue mixed with lymph fluids in the body. In 1713, a doctor named Bernardino Ramazzini hypothesized that the reason breast cancer happened to such a high degree among nuns was because they did not have sex. He indicated that the reproductive organs required regular sexual activity in order to function well and without that, cancer could develop. An alternative theory was proposed by others who suggested that having sex too vigorously could lead to blockage of lymph vessels and the development of cancer. Still others of the time thought that curdled milk, inflammation of the breast, sedentary lifestyles, and depression were causative of breast cancer. Around 1750, a famous French surgeon, Henri Le Dran, was the first to indicate that breast cancer could only be effectively treated by removing both the affected breast and

the lymph nodes of the armpit on the same side of the breast cancer. Other surgeons came to believe this as well and were of the mindset that surgery was the only viable method of treating the disease. Very little progress was made to counter this until the latter part of the Twentieth Century. Prior to that time, women with breast cancer were basically only offered the option of undergoing a radical mastectomy, which involved removal of the entire breast, the underlying muscle tissue, and the nearby lymph nodes for the treatment of their cancer. Surgery itself was not well developed as a viable option until the middle of the nineteenth century. Before then, the lack of antiseptic surgical practices meant it was nearly as likely to die from the surgery for breast cancer as it was to die from the cancer alone. Eventually, antiseptic practices were developed, anesthesia became a viable surgical option, and blood transfusions in the treatment of surgical patients meant that one could conceivably survive this type of surgery. Along with the vast degrees of surgical advancements to the treatment of breast cancer made in the nineteenth century, other doctors were able to identify breast cancer cells under the microscope. German doctors, Muller and Virchow no longer believed in body humors and declared definitively that breast cancer came from individual living but abnormal cells that traveled along the lymphatic system near the breast in order to later metastasize and become systemic diseases. More focus was placed on the lymphatic system, which included the necessity of removing the axillary or underarm lymph nodes in order to prevent the spread of the disease. Dr. William Halstead, who was the Professor of Surgery at Johns Hopkins in Baltimore, became perhaps one of the most famous and important doctors of the era when it came to breast cancer treatment. He was the one to devise the radical mastectomy in 1894, which stressed the importance of removing all at one time the entire breast, the pectoralis major muscle of the chest wall, and the axillary lymph nodes. He felt that leftover pieces of cancerous tissue could lurk in these nearby tissues, only to later spread to become metastatic breast cancer, even if the main block of breast cancer had already been removed.

Interestingly, at the time it was believed that it was important not to violate the tumor by getting a biopsy of it beforehand, even if it meant removing the entirety of a woman’s breast and other tissues without actually knowing that the lump was even cancerous. It was felt that the diagnosis of breast cancer could be made by a clinical diagnosis alone without benefit or risk of biopsy. By now, however, surgery had also advance so that no one believed these cancerous areas should be left open to drain and wounds were finally closed with sutures. This greatly reduced the risk of a postoperative infection of the breast. It’s hard to believe that much of the twentieth century was dominated by the use of the radical mastectomy for the treatment of nearly all breast cancers. While it was clear that this type of procedure did help a person live longer after a diagnosis of breast cancer, it was an extremely disfiguring treatment that not only left deformities of the chest but usually meant a woman suffered from debilitating pain and swelling of the affected arm, called lymphedema, after this type of surgery. Frankly, some women chose not to undergo this surgery because of the side effects left behind after having it. By the early twentieth century, the idea that hormones were involved in breast cancer growth and spread was purely hypothetical. Discoveries made about the fact that some breast cancers had estrogen-responsive receptors on them didn’t happen until 1967. What was known, however, was that younger women who still had plenty of female hormones in their bodies had a much more aggressive disease process when they developed breast cancer. This naturally led to attempts to reduce the levels of female hormones in breast cancer patients at all costs. An additional discovery was made in 1895 by George Beatson, a surgeon out of Scotland. He discovered that one of his patients had shrinkage of her breast cancer after her ovaries were removed. This led to other surgeons choosing to remove the woman’s ovaries along with her breast in order to better the chances of surviving the disease. We now know this might be helpful in situations where the breast tumor is fed by the estrogen made by the ovaries. In 1952, this idea was further advanced when some doctors decided that the estrogen made by a woman’s adrenal glands might also feed the existing breast cancer cells. This led to the extreme surgical intervention of also removing the adrenal glands in order to prolong the woman’s life. 8

Remember when the ancient doctors believed that breast cancer was a systemic disease? This theory was somewhat revived in 1955, when Dr. George Crile also suggested that breast cancer was a systemic disease process. Others further refined the idea by noting that breast cancer probably began as a local disease but that it had the capacity to metastasize or spread to other body areas. By 1976, Bernard Fisher began using less drastic surgical treatments for the removal of breast cancer and added things like chemotherapy and radiation treatments to the treatment of this disease. In the twentieth century, gradual changes were made by surgeons and others in the treatment of breast cancer. Some believed that there was more to breast cancer treatment than Halsted’s radical procedures. Things like sentinel node dissection were developed. What this involves is the checking and removal of the lymph nodes most likely first receive cancerous cells in the axilla. If just these sentinel nodes were removed, the idea was that the other lymph nodes could be left behind with fewer aftereffects than radical surgery. Other things used by surgeons in the early treatment of breast cancer through surgery were focused on trying to fix the cosmetic disfigurement left behind after cancer surgery. One French surgeon transferred healthy breast tissue from the normal, unaffected breast in order to restore the woman’s appearance. Others transferred muscle tissue in order to reduce the defect. This led to the development of the TRAM procedure, which stands for transverse rectus abdominis myocutaneous flap repair. Parts of the abdominal rectus abdominis muscle are flipped around to replace the defect left behind after breast removal. Still other surgeons used glass balls, petroleum jelly, rubber prostheses, sponges, ivory, and silicone implants as prostheses to help the breast cancer patient look more normal after surgery. What about nowadays? Fewer than 10 percent of patients with breast cancer need to have any type of mastectomy. Instead, breast conserving surgery is used along with modern treatments that involve biological and hormonal therapies directed at individualizing the management of breast cancer. With these types of treatments, survival from breast cancer is better than ever.

There have been other major research milestones in the detection and management of breast cancer that are less related to the wealth of surgical options that became the cornerstone of breast cancer treatment for so many decades. For example, the first xray of any kind was taken in 1895. It wasn’t until 1966, however, that the first compression mammography techniques were developed. These used low-dose x-rays in order to find small calcium deposits in the breast often associated with breast cancer. Marie and Pierre Curie first discovered the radioactive elements polonium and radium in 1898. The destructive nature of these radioactive substances were soon uncovered and doctors started using radium implants in the local treatment of some types of cancer. By 1937, radiation therapy was added to the surgical regimen of the treatment of breast cancer. It started by first removing all visible signs of cancer and then injecting radium through needles into the breast and near the lymph nodes to destroy the remaining cancerous cells. External beam radiation treatments were later developed and were directed at the remaining chest wall. In 1978, the US Food and Drug Administration or the FDA first approved the drug called tamoxifen for the treatment of breast cancer. Tamoxifen was originally thought to be a good method for birth control but, because it opposes estrogen in the body, it was believed to help slow the growth of those breast cancers that relied on estrogen for maximal growth. Tamoxifen is a selective estrogen receptor modulator or SERM and is one of several similar drugs still used today to treat certain breast cancers. By 1984, researchers first discovered a genetic mutation in rats for which a similar version was found in women with breast cancer. This was called the HER2 gene. Having a breast cancer that exhibited overexpression of the HER2 gene was called HER2-positive breast cancer. It was soon determined that these types of breast cancers tended to be more aggressive and were harder to treat with traditional drugs available. This led to a whole new field of breast cancer research directed specifically at detecting and specifically treating HER2-positive breast cancers. When 1985 rolled around, it was already commonplace to be able to find breast cancers through screening mammograms even before the cancer could be felt by the woman or her doctor. This led to the discovery that, when these women were treated with breast-

conserving lumpectomies along with radiation, the survival rates were just as good as when a woman had a mastectomy alone. This revolutionized the treatment of most cases of breast cancer so that no longer were women expected to have their entire breast removed even when the cancer itself was small. Doctors were able to identify and clone certain tumor suppressor genes related to breast cancer in 1995. Tumor suppressor genes do exactly what you’d think they would do: they suppress the growth of certain tumors. If a person is born with a mutation of one of these genes, they cannot suppress cancers from starting and later growing so the risk of cancer is greater. The tumor suppressor genes BRCA1 and BRCA2 are inherited from one generation to another. If the inherited genes are abnormal in any way, the risk of breast cancer and other cancers is increased. Knowing one’s status with regard to these genes means that the affected person with a mutated gene can step up surveillance or have certain treatments that reduce their overall risk of cancer. The years between 1996 and 2006 brought great strides in individualizing breast cancer therapy. Anastrozole was approved as an estrogen blocking drug for the management of some types of breast cancer. Tamoxifen was also found to be a reasonable way of reducing the risk of breast cancer among high-risk women who didn’t yet have cancer. Trastuzumab was a biological therapy directed at cancers that express the HER2 gene, approved by the FDA in 1998 for the treatment of these traditionally difficult to treat cancers. Raloxifene was another drug approved in 2006 for postmenopausal women at a higher risk for breast cancer who couldn’t tolerate the side effects seen when tamoxifen is taken by some people.

WRAP UPS FROM THIS SECTION •

Breast cancer has likely existed from the dawn of mankind and womankind.

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In ancient times, nearly everyone died of breast cancer, which grew uncontrollably without any available treatments.

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It was once believed that excesses of black bile led to breast cancer, while many laypeople turned to divine intervention to treat the disease.

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The first strides toward breast cancer treatment involved surgery, which was made more practical in the 19th century when general practices in surgical interventions meant a better chance of survival from surgical remedies.

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The most accepted early practice of treating breast cancer was the radical mastectomy, which involved the removal of the entire breast and other nearby tissues in order to maximize the chances of a cure.

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The hormonal linkage between female hormones and breast cancer were at first hypothesized and later proven, which led the way for the hormonal treatment of certain cancers.

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By the twentieth century, radical mastectomies were gradually replaced with less aggressive surgical procedures combined with radiation and chemotherapy to address the systemic aspects of the disease.

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More recent advances in the genetic and molecular biology aspects of breast cancer have opened the door for a wide variety of prevention and treatment strategies that are more individualized to the person’s specific form of cancer.

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