Breast Cancer: Real Questions, Real Answers

Preface

THE ULTIMATE QUESTION: What do women who have been diagnosed with breast cancer want from health care providers? My experience has been that the first thing they want from us is answers: clear, accurate, up-to-date, thorough but concise information they need to help them comprehend as much as possible what has happened and decide upon and implement a course of action that is right for them. To adequately meet this need, physicians treating breast cancer must be scientifically well-informed and clinically experienced, but also patient, compassionate, and forthright communicators, willing to devote sufficient time to providing the answers. This is a tall order, but an essential first step in securing the best possible outcome for each patient.

I have known Dr. David Chan since our medical school days, and have had the privilege of practicing academic oncology for twenty years in Southern California, where he is one of the most sought-after and respected clinical oncologists. Unflaggingly for all those years, Dave has been an integral and valued participant in our breast cancer program at UCLA, generously contributing his valuable time to our outpatient clinics and teaching conferences, helping us to fill the tall order for our patients, and sharing with the next generation of physicians his extensive knowledge and experience. Remarkably, in addition to providing his patients and ours with the answers they need, Dave has also been an active participant in our breast cancer research efforts, helping to generate new answers to questions for which we had none. Dave’s work with UCLA has served as a model of what a relationship between a research center and an oncology practice can and should be.

No encounter between a patient and a physician is ever perfect and there is always the question unasked or the answer forgotten. That’s the unfilled niche this book will fill. In a unique question and answer format, Dr. Chan provides clear, concise, and accurate answers to questions that he hears from patients on a daily basis. Women and their loved ones who are confronting breast cancer will find the information he provides empowering in preparing for or reflecting on their meetings with physicians. It will help them understand what has happened, what options exist and their rationale, what is known and unknown. Most important, it will support them in the process of making decisions that are right for them, choosing an approach they are comfortable will secure the best possible outcome. This book will help us fill the tall order.

JOHN GLASPY, MD, MPH
Professor of Medicine
Sanders Chair in Cancer Research
Director, Clinical Research Unit
Jonsson Comprehensive Cancer Center
UCLA School of Medicine
Los Angeles, California

Introduction

AS SOMEONE WHO has treated breast cancer for almost four decades, I have seen a marked shift from performing a mastectomy as the sole primary treatment of breast cancer to the current strategy of treating the entire patient. Breast surgery is now only one of a number of therapies used in a modern breast cancer treatment program. The advances in treatment over the last decade have been most impressive and I would like to highlight the major ones in this preface.

Today breast surgery is still an essential component of the treatment plan. There is, however, a very noticeable reduction in the number of mastectomies. The majority of women no longer need to lose their breast. In addition to surgical treatment, almost every newly diagnosed breast cancer patient receives some form of medical treatment such as hormonal therapy or chemotherapy to lower her chance of breast cancer relapse. This combination of reduced surgery and increased use of hormonal and chemotherapy has resulted in higher cure rates, reduced suffering, and better quality of life.

This last decade has been very important in virtually every aspect of breast cancer diagnosis and treatment, both for women with breast cancer and also for women who are at high risk of getting breast cancer. Even though analyses show a higher number of breast cancers now compared to ten years ago, the number of women dying today from the disease has significantly decreased as a direct result of improvements in diagnosing breast cancer earlier and in treating the disease.

It has been less than ten years since the first breast cancer susceptibility gene, BRCA1, was discovered and analyzed. This led to the discovery of a second gene, BRCA2, and the rapid development of a commercially available test permitting women in high-risk families to undergo genetic testing for risk assessment. Researchers studying these high-risk families have discovered that this genetic abnormality also increases a woman’s chance of getting cancer of the ovary. In the past several years, more effective strategies for screening and prevention for high-risk women have been developed.

We have learned a lot about breast cancer risk reduction. We have known for decades that estrogen use could increase breast cancer risk but the degree of risk was often debated and difficult to estimate until recent studies were completed. It is now clearly established that postmenopausal use of estrogen increases a woman’s chance of getting breast cancer and that with the addition of progesterone, the risk is increased even more. With recognition of important risk factors, the concept of breast cancer prevention has also emerged. We now know that taking Tamoxifen for five years can reduce the risk of breast cancer by almost 50 percent. Within just the past several years, we have also learned that another type of hormonal treatment, aromatase inhibitors, may be as effective in preventing breast cancer and possibly more so and with less side effects. These treatments offer very meaningful reductions in breast cancer risk and are now often used in higher risk women.

Imaging techniques for the early and more accurate diagnosis of breast cancer have improved considerably. It is common today to have mammograms scanned by computer-assisted analyzers to reduce reading errors. Additionally, the development of digital images can help make mammograms easier to read and lessens the chance of missing a cancer. Improvements in mammography have resulted in a decrease in the size of breast cancers diagnosed over the last decade and this will lead to higher cure rates. Recent developments in MRI analysis of the breast have added a new way to image the breast. MRI has the advantage of not using X-ray and is currently being used to screen high-risk women or women with dense breasts where mammograms are less helpful. Newer biopsy techniques allow most biopsies to be performed with a needle, reducing the need for surgical excisions of abnormalities seen on mammography or other imaging methods.

Advances in surgery have allowed many women to avoid an axillary dissection, a surgery that can lead to long-term discomfort and sometimes significant swelling of the arm. This important recent surgical advance is termed sentinel lymph node mapping, and replaces the standard axillary dissection. This surgery is just as accurate in assessing risk of cancer spread. Most breast cancer patients can now have sentinel lymph node mapping to test whether spread of the cancer has occurred, with a much lower risk of discomfort and swelling. In addition, major surgical advances include new breast reconstruction techniques such as the skin sparing mastectomy, which have significantly improved the appearance of the breast after mastectomy. There was a time when women were afraid of having breast reconstruction for fear that breast implants could be harmful by causing autoimmune diseases. Many studies of this question now show no harm from implants. Today, the vast majority of women who have had a mastectomy can have some form of breast reconstruction, either with implants or various procedures that use tissue from another area of the body to reconstruct the breast. These approaches have been a significant advance for women who need mastectomy. However, most women today will not require a mastectomy because breast cancer is now found earlier, permitting breast conservation with lumpectomy and radiation. The wide availability of expert radiation centers has given many women the opportunity of replacing mastectomy with breast radiation.

In the past decade, major advances have occurred in the use of chemotherapy and hormonal therapy in treatment of both newly diagnosed breast cancer and recurrent or advanced breast cancer. This has resulted in both improved cure rates and also improved quality of life for breast cancer patients. An important new class of chemotherapy drugs, the taxanes, was developed and is now in widespread use with significant improvement in cure rates and survival. New forms of drugs that exploit biochemical pathways are showing promise to enhance cure and prolong survival with minimal toxicity.

There have also been important changes in the way chemotherapy is now given. Twenty-five years ago, some women received prolonged courses of chemotherapy to prevent relapse. Over time, many clinical trials showed equal effectiveness with much shorter courses of treatment. This shortening of chemotherapy treatment has resulted in less toxicity without lowering cure rates. This process of performing comparitive clinical trials on breast cancer chemotherapy was also very influential in establishing the type of scientific study needed to prove that a cancer treatment was unquestionably effective, rather than relying on intuition or individual experience. Clinical trials in breast cancer have established a firm scientific base that demonstrates that chemotherapy and hormonal therapy improve cure rates.

For women with advanced breast cancer, there have also been major improvements in treatment, leading to improved durations of survival and better quality of life. Newer hormonal therapies have been developed, giving patients more and better options for hormonal treatment. These newer therapies can control breast cancer for longer periods of time and with fewer side effects. Likewise, new chemotherapy drugs such as taxanes, gemcitabine, and capecitabine are effective additions to the chemotherapy armamentarium with high rates of response and very tolerable side effects. The introduction of Herceptin, a new biological agent, has improved survival when combined with chemotherapy in certain groups of patients with advanced breast cancer. A new class of drugs, bisphosphonates, has been introduced to lessen the extent of breast cancer spread into the bones and significantly reduces discomfort as well. The next several years will see the introduction of new and important therapies that are currently making their way down the research pipeline.

Chemotherapy is also now much easier to receive. The immediate toxicities of treatment have been reduced and many of the side effects typically associated with treatment have been ameliorated. This has coincided with the introduction of new medications that prevent nausea and that reduce blood count problems. In the past, these were both major side effects for patients receiving chemotherapy. Solutions for these problems have made chemotherapy easier to take, permitting more patients to receive treatment with a corresponding improvement in survival for all stages of breast cancer.

Newer testing methods on a patient’s breast cancer allow doctors to more accurately select treatments for each individual patient. Assays are now routinely used to detect the presence of hormone receptors for estrogen and progesterone on every breast cancer, indicating whether or not a patient is likely to benefit from hormonal treatment. An even more recent test analysis for Her2 identifies which patients are appropriate candidates to receive a new treatment, trastusamab (Herceptin). The recent introduction of molecular analyses is now providing more refined methods for analyzing each individual breast cancer to assess risk and permit more accurate treatment planning. I anticipate that within a few years, these tests and other tests for gene expression will be widely used.

Supportive care is now recognized as having important value in minimizing the distress that goes with the diagnosis of breast cancer. Group and individual session therapy have become widely encouraged and accepted. Such care can help patients through their treatments and have very positive effects on their interactions with family and friends.

There is a bright future for breast cancer care, building on these and other findings discussed in this book. The strategies developed over the last forty years are now bearing fruit, resulting in women being diagnosed with smaller breast cancers, in surgeries that are less disfiguring, and in treatments that are easier to receive, which all lead to higher cure rates. I see new strategies evolving, including targeted therapies in which specific growth pathways within a cancer are blocked; newer hormonal treatments that will prevent breast cancer from growing; a rise in biological methods of cancer treatment; new applications of breast radiation with shorter treatments; new diagnostic tests using information from the human genome project; refinements in breast imaging that more specifically identify whether or not a cancer is present; and new laboratory tests which will distinguish low- from high-risk patients, preventing the use of unneeded chemotherapy.

Breast Cancer: Real Questions, Real Answers tells of the progress that has led to the wide-ranging improvements in breast cancer care that have emerged. Among the topics covered are breast cancer risk and strategies of risk reduction, breast imaging and biopsy, breast surgery, use of chemotherapy and hormonal treatments, new molecular technologies to estimate severity of risk with a new breast cancer, breast reconstructive surgery, radiation therapy, and supportive care.

These are only some of the important issues covered in an informative, reader-friendly way within this book. Unlike many of the books written for women or family members concerned about breast cancer, this book takes the approach that questions are the best way to gather information about this disease. The questions posed are those that I hear most often in taking care of patients. The format of this book can provide a framework to be used for understanding the issues involved in breast cancer care and as a basis for talking with your doctor or family members.

The format of Breast Cancer: Real Questions, Real Answers is straight-forward and you can skip from question to question and read the parts of interest. Topics can be pursued in sequence or you can skip over topics as needed because the book is internally cross-referenced for ease of navigation. Unlike other books, Dr. Chan includes not only his own view on areas of controversy but also the views of other cancer specialists. This is rather unique in a book for the lay reader.

The sections on chemotherapy and hormonal therapy are very detailed, and provide understanding of this complex topic central to breast cancer care. Lifestyle and psychosocial issues are addressed with practical suggestions and without exaggerating or overstating the benefits of lifestyle change, or of vitamin and supplement alternative therapies. This book is written by an experienced physician and the views expressed are those common among breast cancer experts. It will be useful to those concerned about breast cancer, to women who have developed breast cancer, to their families, and, I suspect, to many physicians concerned with the practical aspects of care.

FRANK E. STOCKDALE, MD, PHD
Professor of Biological Sciences
Maureen Lyles D’Ambrogio Professor of Medicine, Emeritus
Founding Director, Combined Modalities
Breast Cancer Program
Stanford University Cancer Center
Stanford, California

1

How Did I Get
Breast Cancer?

Q Why did I get breast cancer?

A There is no simple answer to this question. The American Cancer Society estimates that in the United States, over 275,000 new cases of breast cancer will be diagnosed each year. Breast cancer is the leading cause of major cancer in women. Current estimates are that if a woman in the United States lives to be 100 years old, she will have a one in eight chance of developing breast cancer.

Q Is my breast cancer caused by something that I have done?

A I’ll review the main risk factors in this section but the basic answer is that, in all likelihood, your breast cancer is not caused by something that you have done, or something that you had much control over.

Q Then what is the main cause of breast cancer?

A We know that the major risk factor for breast cancer is being a woman who was raised in a high socioeconomic country. Women raised in North America or Western Europe have the highest worldwide risk for getting breast cancer. Women raised in third world countries have the lowest worldwide risk. This is the major risk factor and it obviously isn’t under your control.

Q Why do breast cancer rates differ from one country to another country?

A The differences are actually very dramatic. Many studies of population trends, called epidemiology studies, show that breast cancer is a disease that occurs much more in developed industrialized countries. The very highest rates of breast cancer occur in North America and Western Europe where breast cancer is 5 times as common as in Asia. This is primarily due to dietary and social factors rather than from inherited risks. We know that breast cancer is not primarily genetic or inherited, as a result of studies that evaluate breast cancer risk in women who immigrate. As an example, breast cancer occurs in a much lower rate in Asia than in the United States. However, Asian American women have breast cancer rates similar to those of American women of European descent.

The reasons are complicated but let me give you a brief summary. It’s thought that hormonal stimulation by estrogen during puberty and breast development play an important role in increasing breast cancer rate. In North America and Western Europe, as a result of a high calorie diet and excellent nutrition, puberty occurs several years earlier compared to undeveloped countries. Estrogen stimulates breast development and when puberty occurs earlier, estrogen stimulation of breast tissue occurs earlier as well. Pregnancy and breast-feeding interrupt the estrogen stimulation of breast tissue. In North America and Western Europe, young women tend to delay marriage and child-birth to pursue education and professional opportunities, as opposed to third world countries where multiple pregnancies during teenage years are common. In North America and Western Europe, mothers tend not to breast-feed their infants except for a short period of time, compared to third world countries where breast-feeding commonly extends well beyond one year. Dr. Valerie Beral and her team from Oxford, England, have looked at risk factors and breast cancer in combined studies totaling 150,000 women worldwide. She recently reported that prolonged breast-feeding, as occurs in third world countries, markedly reduces women’s chances of getting breast cancer by almost half. Prolonged breast-feeding does this by lowering estrogen levels for long periods of time.

Therefore, higher socioeconomic background leading to early and uninterrupted stimulation of developing breast tissue by estrogen in young women is thought to play a major part in the increased numbers of breast cancer in the United States and other industrialized countries. It seems that the biggest part of the estrogen story is probably during puberty and early adult life and leads to higher risks of breast cancer in the later decades, which is when breast cancer usually occurs.

Q Why do the effects of prolonged and uninterrupted estrogen exposure occur so many years later?

A Cancers occur as a result of changes in DNA. In essence, DNA is the blueprint plans of your body that controls the growth and function of normal cells. Any error in the DNA, no matter how small, can create a major problem over time. These changes in DNA have been actively studied and are thought to involve multiple cumulative errors, not just one big event. This is why though smoking causes lung cancer, smokers actually don’t get lung cancer immediately and the 10 percent of smokers that get lung cancer do so only after many years of smoking. Similarly most women in the United States, although living in a country with higher breast cancer risk, will not actually get breast cancer despite being exposed to the dietary and social risk factors mentioned above. Even though all women growing up in industrialized countries are at higher risk, the reasons why some women get breast cancer while others do not indicate that there are other risk factors that also play a part in breast cancer development.

KEIKO IS FORTY-TWO and Japanese American. She was born in Japan but came to the United States when she was three. She quickly assimilated life in San Francisco and grew up with multicultural friends. Her favorite foods were pizza, hamburgers, fries, and milkshakes. She was a hardworking, diligent student and graduated at the top of her class from U.C. Berkeley. She followed this with an MBA at the University of Southern California.

Hired right out of college by a large regional bank, Keiko worked her way up to an associate vice president position. She married Kevin, a financial analyst for a brokerage firm, when she was thirty-six. They have no children, travel frequently, and are avid supporters of the L.A. Symphony.

Keiko appears composed but with a trace of nervousness. After some casual conversation, I begin to review with her the biopsy results showing an invasive cancer. She interrupts me and ruefully comments, “I just can’t believe I have breast cancer. This is totally unbelievable. I feel like I’m in a bad dream and I can’t wait to wake up. I try to eat right, don’t drink, never smoked. No one in my family has had breast cancer. Actually, I thought Asians usually don’t get breast cancer. We have small breasts to begin with. What did I do to cause this?”

During the course of our consultation, I explain to Keiko that she has common misconceptions regarding breast cancer risk. Her main risk factor for getting breast cancer is growing up in a high socioeconomic country, not family history, not race, and not breast size. Keiko’s socioeconomic background affected the amount of estrogen stimulation she received during puberty and breast development, which is a key factor for breast cancer risk as an adult. Keiko didn’t do anything to cause her cancer.

Q I always thought that breast cancer is inherited and that because no one in my family has had breast cancer that I would not get it. Why is that not true?

A Contrary to popular belief, most breast cancer is not inherited. Eighty to eighty-five percent of newly diagnosed breast cancer patients do not have a direct relative who has had the disease. About 10 percent of breast cancer is primarily inherited. Two main genes involved in inherited breast cancer have been identified: BRCA1 and BRCA2. BRCA stands for breast cancer susceptibility gene. BRCA will be discussed in more detail in chapter 3.

For most women with breast cancer, no clear hereditary risk can be identified. This is why breast cancer screening is recommended for all women, regardless of family history. All women need mammograms at the appropriate age, not just women who have a family member with breast cancer. The absence of relatives with breast cancer is in no way protective. This is a common misconception.

Q Now that I have breast cancer, does that mean that my daughter will get it?

A Probably not. Unless you are in the 10 percent of breast cancers that are clearly familial and usually related to the BRCA genes, your daughter’s risk is only slightly elevated compared to the average woman. However, you should still remind your daughter to undergo breast screening and she should discuss the timing of when mammograms should start with her physician.

Q Was my breast cancer caused by taking estrogen?

A As mentioned previously, estrogen is certainly important as a risk factor. However the most significant time of risk development probably occurs during breast growth during puberty and young adulthood. Taking estrogen after menopause has also been identified as a risk factor but a relatively small one in comparison. For example, breast cancer is 5 times more common in the United States than in Thailand, an increase in risk of 500 percent. The magnitude of this difference is much greater than the single digit percentage point difference in breast cancer risk between women who take postmenopausal hormones and women who don’t. Taking postmenopausal estrogen is only a very minor risk factor for breast cancer development.

Two studies help to illustrate this point. The first study is called the Nurses’ Health Study, which is a long-term study of nurses by Harvard researchers evaluating a number of different women’s health issues. The nurses complete regular health questionnaires and their health is monitored over many years. One topic of that study is the relationship between estrogen use after menopause and the development of breast cancer. Nurses were questioned about their use of estrogen and then monitored to see if they developed breast cancer. Nurses who took estrogen after menopause had a risk of breast cancer of about 14 percent. Nurses who never took estrogen after menopause had a risk of breast cancer of about 12 percent. Therefore, although postmenopausal estrogen did increase the risk, the overall increase was relatively small and certainly could not be blamed for the large majority of breast cancers.

A second study that sheds light on the small but consistently established increased risk of breast cancer resulting from postmenopausal estrogen replacement therapy is the current Women’s Health Initiative, which is a national study of various health issues in American women. Initial results were reported in 2003. This study also showed that taking estrogen after menopause increased the risk of breast cancer. However the risk was relatively small, estimated at about 0.1 percent (one tenth of one percent) per year of estrogen use.