When you or a loved one are diagnosed with cancer, it is important to know all of the treatment options available in order to make the best decision about your cancer treatment. This may include clinical trials, which are research studies designed to evaluate new cancer treatment options. Clinical trials test the safety and effectiveness of treatments, many of which are only available through participating in a clinical trial. Trials evaluate new anti-cancer drugs, unique approaches to surgery and radiation therapy, and new combinations of treatments. In the United States, the Food and Drug Administration (FDA) oversees the conduct of clinical trials. What does the FDA do? The FDA is a government agency that is responsible for making certain that the food we eat and the drugs we take are safe. The FDA does not make drugs or directly test drugs to determine if they are safe and effective. The FDA's role is to oversee the research conducted by pharmaceutical companies, university research centers, and physicians to make certain that federal regulations governing research are being followed. The FDA requires that the drug company's plan must be reviewed by community research review board (IRB), and that patients participating in the clinical trial are informed about the trial and consent to participate. Once the drug company has completed its clinical trials, the data are tabulated and submitted to the FDA in an application known as a New Drug Application (NDA). The FDA evaluates the outcomes reported in the NDA and determines whether the new drug will be approved and made available to patients in the United States. In order to be approved, the drug must be safe and effective. Can I get a drug before it is approved by the FDA? Until a drug receives FDA approval, it cannot be sold and the drug company may only provide it to patients through clinical trials. Furthermore, each clinical trial has specific criteria that patients must meet to be included. Occasionally, a cancer patient who is not eligible for a clinical trial may receive a promising unapproved drug, if the patient's doctor, the drug company, and FDA each agree. The FDA's primary interest is helping to ensure that the drug company's research will not subject cancer patients in the clinical trial to undue risks. The FDA drug review process guarantees that the risks and benefits of a cancer drug have been carefully considered before it is approved and helps to ensure the public that marketed drugs are safe and effective. How can I learn more about a drug that has been approved? The FDA requires that all drugs have an information document for healthcare providers and consumers called a “package insert.” This document is a summary of the essential scientific information needed for the safe and effective use of the drug. You can ask your doctor for this information. Also, most package inserts are available on the internet. A package insert typically includes the following information: • Chemical structure It is important to understand that once it has been determined that a drug is safe and it is approved by the FDA, physicians often use the drug for the treatment of medical conditions other than the specific condition that the FDA has approved it for. Are all clinical trials the same? Development of new anticancer drugs and treatment strategies occurs in four phases. Each phase is designed to determine specific information about the potential new treatment such as its risks, safety, and effectiveness compared to standard therapy. The hope is that the new therapy will be an improvement over the previous standard therapy. Phase I Trials: This phase is probably the most important step in the development of a new drug or therapy. Phase I therapy may produce anti-cancer effects and a small number of patients may benefit, however, the primary goals of this phase are to determine safety issues, which include: • The maximum tolerated dose of the treatment, Phase I trials usually involve a small number of patients for whom other standard therapies have failed or no known alternative therapy is available. Upon completion of phase I trials, the information that has been gathered is used to begin phase II trials. Phase II Trials: Phase II trials are designed to determine the effectiveness of the treatment in a specific patient population at the dose and schedules determined in phase I. These trials usually require a slightly higher number of patients than phase I trials. In general, all of the patients participating in a phase II trial will receive the treatment that is being investigated. Drugs or therapies that are shown to be active in phase II trials may become standard treatment or be further evaluated for effectiveness in phase III trials. Phase III Trials: Phase III trials compare a new drug or therapy with a standard therapy in a randomized and controlled manner in order to determine proof of effectiveness. Phase III trials require a large number of patients to measure the statistical validity of the results because patient age, sex, race, and other unknown factors could affect the results. To obtain an adequate number of patients, several physicians (investigators) from different institutions typically participate in phase III clinical trials. Phase IV Trials: Once the drug or treatment is approved and becomes part of standard therapy, the manufacturer of the drug may elect to initiate phase IV trials. This phase includes continued evaluation of the treatment effectiveness and monitoring of side effects as well as implementing studies to evaluate usefulness in different types of cancers. There is currently no single source of all clinical trials. The following are clinical trial resources that patients may wish to visit:
• Information about how the body absorbs, distributes, metabolizes, and excretes the drug
• Results from some clinical trials
• What specific circumstances the drug is used for
• Dosing and administration schedules
• Side effects
• Contraindications
• The manner in which the drug works in the body,
• The toxic side effects related to different doses, and
• Whether toxic side effects are reversible.
Jumat, 28 November 2008
A Word about Clinical Trials
Questions to Ask Your Doctor about Cancer Treatment
Being educated and informed will help you make the best decisions about your cancer treatment. Get all the information you can as early as possible concerning your evaluation, treatment, and possible side effects. The sooner you know about side effects and possible treatments, the more likely you are to protect yourself against them, or manage them more effectively. Your doctor and nurse are your best sources of information, but you must remember to ask questions. There is no such thing as a dumb question. Don’t be afraid to ask anything that is on your mind. To make the most of your opportunities to learn from your health care providers, read as much as you can and make a list of questions before each appointment. Also, ask family, friends, and your support team to help you remember the questions. These approaches will help you talk more effectively with your doctor or nurse. Finally, you or your caregiver should consider taking notes during your visit to ensure you remember what you learned. The following are some questions, grouped by topic, which you may wish to ask your nurse or physician: Your Cancer Cancer Treatment Tests Side Effects of Treatment Protecting Against Infection Daily Activities What to Expect After Treatment
• Do you typically treat patients with my diagnosis?
• What stage is my cancer?
• Is there anything unique about my cancer that makes my prognosis better or worse?
• Should I get a second opinion?
• What is the goal of treatment?
• To cure my cancer or stop it from growing?
• What are my treatment options?
• How can each treatment option help me achieve my goal of therapy?
• What risks or potential side effects are associated with each treatment?
• What research studies (“clinical trials”) are available?
• Are there any clinical trials that are right for me?
• How long will I receive treatment, how often, and where?
• How will it be given?
• How will I know if the treatment is working?
• How might a disruption in my chemotherapy dose or timing affect my results?
• How and when will I be able to tell whether the treatment is working?
• What are the names of all the drugs I will be taking?
• Can I talk with another of your patients who has received this treatment?
• Are there any resources or Web sites you recommend for more information?
• What types of lab tests will I need?
• Will I need x-rays and scans?
• Can you explain the results of my complete blood count (CBC)?
• Are there tests for the genetic make-up of my cancer?
• Will I benefit from having my cancer evaluated for its genetic make-up?
• How frequently will I get the tests?
• What possible side effects should I prepare for?
• When might they start?
• Will they get better or worse as my treatment goes along?
• How can I prepare for them or lessen their impact?
• Are there treatments that can help relieve the side effects? What are they? Do you usually recommend or prescribe them?
• Which risks are most serious?
• Will I require blood transfusions? Why?
• How can I best monitor myself for complications related to either my disease or my treatment?
• Will my type of chemotherapy put me at risk for a low white blood cell count and infection?
• Can I help protect myself against infection right from the start of chemotherapy, instead of waiting until problems develop?
• Am I at special risk for infection?
• What are the signs of infection?
• How serious is an infection?
• How long will I be at risk for infection?
• What should I do if I have a fever?
• How are infections treated?
• How will my cancer treatment affect my usual activities?
• Will I be able to work?
• Will I need to stay in the hospital?
• Will I need someone to help me at home?
• Will I need help taking care of my kids?
• Are there any activities I should avoid during my chemotherapy?
• What happens after I complete my treatment?
• How can I best continue to monitor myself for complications related to either my disease or my treatment?
• What kind of lab tests will I need?
• How frequently should I get those lab tests?
• What types of x-rays and scans will I need?
• How often do I need to come in for checkups?
• When will you know if I am cured?
• What happens if my disease comes back?
Optimizing Your Treatment
By proactively understanding and managing aspects of your treatment, you can help ensure the best possible outcome from treatment and maintain some degree of control in your life. Things you can do to optimize treatment of cancer are: • Get informed Don’t forget that fighting cancer is not a challenge you should face alone. It is a team effort that involves family, friends, and your healthcare team. Don’t overlook the strength that can come from having your support network by your side. In order to ensure optimal treatment, consider the following: Get informed: A new diagnosis of cancer can be a shock, making you feel out of control and overwhelmed. Getting informed can help alleviate these feelings. Seek out many resources to investigate your treatment options for your type and stage of cancer. Resources should include your healthcare team, second opinions, books, the internet, and other patients with your disease. As you learn, identify the specific questions that only your doctor can answer. Most importantly, work toward understanding your diagnosis and stage of disease, goals of therapy, treatment plan, benefits of treatment, and possible side effects. Following a diagnosis of cancer, the most important step is to accurately define the stage of your disease. Staging is a system that describes how far the cancer has spread. (Keep in mind that some cancers, such as leukemia, may not be staged.) Each stage of cancer may be treated differently. In order for you to begin evaluating and discussing treatment options with your healthcare team, you need to find out from your doctor the correct stage of your cancer. Stay organized: Develop a system for keeping all the information that you gather organized, such as laboratory and test results, admissions and consultation information, and additional instructions. Keep a folder or three-ring binder with all your information in one location. Discussing the effectiveness of treatment: It is important that you and your caregivers are able to evaluate treatment options and to understand how cancer treatments are compared so that you can work with your healthcare team to make informed treatment choices. Understanding the goals of a specific therapy, as well as the risk and benefits it poses, will help you decide which treatment is most appropriate for your situation. Patients typically receive cancer treatment in order to cure the cancer, prolong the duration of their life or alleviate symptoms caused by the cancer and improve their quality of life. These potential benefits of treatment must be balanced against the risks of treatment. Some risks posed by various cancer treatments may include time away from family and friends, uncomfortable side effects of therapy and/or long-term complications or death. The most common term used to describe the effectiveness of cancer treatment is remission. Remission means that the cancer has disappeared and can no longer be measured using existing technology. Oncologists use the terms partial and complete remission to describe partial or complete disappearance of cancer after treatment. A cancer cannot be cured if a remission is not obtained; however, a remission does not always ensure that a cancer is cured. The best ways to evaluate the benefits of treatment are to examine the duration of remission, survival, and disease-free survival (cure). Since it often takes many years to determine whether a new treatment is better than a previous treatment, remission rates may be useful for comparing therapies when patients have not been evaluated long enough to know whether the chance of cure or survival is improved. Treatment of cancer is associated with risks. It is important that you evaluate the risks and benefits of treatment within the context of the overall goal of receiving cancer therapy. Cancer treatment may be inconvenient, prolonged, or unavailable close to home. These are important considerations when evaluating treatment options, but not typically mentioned in medical journals reporting the results and benefits of new treatments.
• Stay organized
• Discuss the effectiveness of treatment
• Work with your physician to select the best treatment for you
Select your optimal treatment: Cancer treatment varies depending upon your type of cancer, stage of cancer, and overall condition. Additionally, treatment options may vary depending on whether or not the goal of treatment is to cure the cancer, keep the cancer from spreading, or to relieve the symptoms caused by cancer. You and your physician will consider all of these factors as you work on selecting your optimal treatment.
Introduction to Cancer Treatment
Choice of cancer treatment is influenced by several factors, including the specific characteristics of your cancer; your overall condition; and whether the goal of treatment is to cure your cancer, keep your cancer from spreading, or to relieve the symptoms caused by cancer. Depending on these factors, you may receive one or more of the following: One or more treatment modalities may be used to provide you with the most effective treatment. Increasingly, it is common to use several treatment modalities together (concurrently) or in sequence with the goal of preventing recurrence. This is referred to as multi-modality treatment of the cancer. Surgery is used to diagnose cancer, determine its stage, and to treat cancer. One common type of surgery that may be used to help with diagnosing cancer is a biopsy. A biopsy involves taking a tissue sample from the suspected cancer for examination by a specialist in a laboratory. A biopsy is often performed in the physician’s office or in an outpatient surgery center. A positive biopsy indicates the presence of cancer; a negative biopsy may indicate that no cancer is present in the sample. When surgery is used for treatment, the cancer and some tissue adjacent to the cancer are typically removed. In addition to providing local treatment of the cancer, information gained during surgery is useful in predicting the likelihood of cancer recurrence and whether other treatment modalities will be necessary. Learn more about surgery. Chemotherapy is any treatment involving the use of drugs to kill cancer cells. Cancer chemotherapy may consist of single drugs or combinations of drugs, and can be administered through a vein, injected into a body cavity, or delivered orally in the form of a pill. Chemotherapy is different from surgery or radiation therapy in that the cancer-fighting drugs circulate in the blood to parts of the body where the cancer may have spread and can kill or eliminate cancers cells at sites great distances from the original cancer. As a result, chemotherapy is considered a systemic treatment. More than half of all people diagnosed with cancer receive chemotherapy. For millions of people who have cancers that respond well to chemotherapy, this approach helps treat their cancer effectively, enabling them to enjoy full, productive lives. Furthermore, many side effects once associated with chemotherapy are now easily prevented or controlled, allowing many people to work, travel, and participate in many of their other normal activities while receiving chemotherapy. Learn more about chemotherapy treatment and the management of side effects. Radiation therapy, or radiotherapy, uses high-energy rays to damage or kill cancer cells by preventing them from growing and dividing. Similar to surgery, radiation therapy is a local treatment used to eliminate or eradicate visible tumors. Radiation therapy is not typically useful in eradicating cancer cells that have already spread to other parts of the body. Radiation therapy may be externally or internally delivered. External radiation delivers high-energy rays directly to the tumor site from a machine outside the body. Internal radiation, or brachytherapy, involves the implantation of a small amount of radioactive material in or near the cancer. Radiation may be used to cure or control cancer, or to ease some of the symptoms caused by cancer. Sometimes radiation is used with other types of cancer treatment, such as chemotherapy and surgery, and sometimes it is used alone. For more information, go to Radiation Therapy. Hormones are naturally occurring substances in the body that stimulate the growth of hormone sensitive tissues, such as the breast or prostate gland. When cancer arises in breast or prostate tissue, its growth and spread may be caused by the body’s own hormones. Therefore, drugs that block hormone production or change the way hormones work, and/or removal of organs that secrete hormones, such as the ovaries or testicles, are ways of fighting cancer. Hormone therapy, similar to chemotherapy, is a systemic treatment in that it may affect cancer cells throughout the body. A targeted therapy is one that is designed to treat only the cancer cells and minimize damage to normal, healthy cells. Cancer treatments that “target” cancer cells may offer the advantage of reduced treatment-related side effects and improved outcomes. Conventional cancer treatments, such as chemotherapy and radiation therapy, cannot distinguish between cancer cells and healthy cells. Consequently, healthy cells are commonly damaged in the process of treating the cancer, which results in side effects. Chemotherapy damages rapidly dividing cells, a hallmark trait of cancer cells. In the process, healthy cells that are also rapidly dividing, such as blood cells and the cells lining the mouth and GI tract are also damaged. Radiation therapy kills some healthy cells that are in the path of the radiation or near the cancer being treated. Newer radiation therapy techniques can reduce, but not eliminate this damage. Treatment-related damage to healthy cells leads to complications of treatment, or side effects. These side effects may be severe, reducing a patient's quality of life, compromising their ability to receive their full, prescribed treatment, and sometimes, limiting their chance for an optimal outcome from treatment. Biological therapy is referred to by many terms, including immunologic therapy, immunotherapy, or biotherapy. Biological therapy is a type of treatment that uses the body’s immune system to facilitate the killing of cancer cells. Types of biological therapy include interferon, interleukin, monoclonal antibodies, colony stimulating factors (cytokines), and vaccines. There is no longer a “one-size-fits-all” approach to cancer treatment. Even among patients with the same type of cancer, the behavior of the cancer and its response to treatment can vary widely. By exploring the reasons for this variation, researchers have begun to pave the way for more personalized cancer treatment. It is becoming increasingly clear that specific characteristics of cancer cells and cancer patients can have a profound impact on prognosis and treatment outcome. Although factoring these characteristics into treatment decisions makes cancer care more complex, it also offers the promise of improved outcomes. The idea of matching a particular treatment to a particular patient is not a new one. It has long been recognized, for example, that hormonal therapy for breast cancer is most likely to be effective when the breast cancer contains receptors for estrogen and/or progesterone. Testing for these receptors is part of the standard clinical work-up of breast cancer. What is new, however, is the pace at which researchers are identifying new tumor markers, new tests, and new and more targeted drugs that individualize cancer treatment. Tests now exist that can assess the likelihood of cancer recurrence, the likelihood of response to particular drugs, and the presence of specific cancer targets that can be attacked by new anti-cancer drugs that directly target individual cancer cells. To learn more about personalized cancer care for two common types of cancer, visit the following:Overview of Cancer Treatments
Surgery
Chemotherapy
Radiation Therapy
Hormonal Therapy
Targeted Therapy
Biological Therapy
Personalized Cancer Care
Diagnosing Cancer
What is a cancer diagnosis? A diagnosis is an identification of a particular type of cancer. When making a diagnosis, the initial signs and symptoms are investigated through a variety of tests in order to identify whether cancer is causing them and, if so, what type of cancer it is. For example, breast cancer may be detected when a patient notices a lump, but it must be carefully evaluated with a number of tests in order to determine an accurate diagnosis. The diagnosis describes what type of breast cancer it is (i.e. “ductal” if it started in the ducts of the breast or “lobular” if it started in the lobes) and how advanced it is. What is a cancer stage? How is prognosis determined? Your doctor will evaluate all possible factors to determine your prognosis. Recently, the genetic make-up of cancer is being increasingly recognized as an important prognostic factor. For example, some genes have been associated with an aggressive course or tendency to recur. Identification of these in an early stage cancer may indicate a poor prognosis. Some research suggests that the genetic make-up of the cancer may be even more important for determining prognosis than the stage of the cancer. How is cancer diagnosed? For more information about diagnostic tests, visit the Testing Center. How does diagnosis determine treatment? However, research has indicated that identifying the stage of disease may not be the most accurate technique for determining how aggressive it is. For example, some early stage diseases may recur or progress even after treatment, while some late stage cancers may stay in remission. These findings suggest that there may be factors other than how the cancer looks under a microscope and how far it has spread at the time of diagnosis that may better indicate the likelihood that a given cancer will recur and/or progress. Human genomics, which is the study of the entire genetic material of humans, has provided invaluable tools for identifying the genetic components of cancers. The mapping of the human genome, which consists of 30,000 to 70,000 genes, has laid the ground work for understanding the role those genes play in human health and disease. Cancer is many different diseases; however, one aspect of all cancers that is similar is damage to the DNA resulting in uncontrolled cell growth. Identifying the genes for each cancer type that are involved in the capacity grow and spread may provide valuable prognostic information. As improvements are made in the special laboratory techniques used to identify the genetic make-up of cancers, this genetic information may become a better predictor of cancer aggressiveness and outcome than stage, which has been the diagnostic indicator of choice in the past. Additionally, this genetic information will likely play an increasing role in directing treatment. Specifically, the genes involved in each cancer may indicate more aggressive treatment for some cancers and less aggressive treatment for others.
Diagnosis is not the same as detection. Cancer may be detected when symptoms or abnormalities, such as a lump or growth, are recognized by a patient or doctor. After a cancer is detected, it still must be carefully diagnosed.
Following a diagnosis of cancer, the most important step is to accurately determine the stage of cancer. Stage describes how far the cancer has spread. (Some cancers, such as leukemia, may not be staged.) Each stage of cancer may be treated differently. In order for you to begin evaluating and discussing treatment options with your healthcare team, you need to know the correct stage of your cancer.
There are many staging systems, but TNM is the most common. “T” refers to the size of the tumor, “N” to the number of lymph nodes involved, and “M” to metastasis. TNM staging measures the extent of the disease by evaluating these three aspects and assigning a stage, which is usually between 0-4. Generally, the lower the stage, the better the treatment prognosis (outcome).
The probable course and/or outcome of the cancer is called the prognosis. Identifying factors that indicate a better or worse prognosis may help you and your doctor plan your treatment. There are many factors that help determine your prognosis. Some of these include:
Diagnosing cancer involves the use of a variety of tests that provide details about abnormal cells, which may have been detected through routine medical examinations, self-examination, or reported symptoms. More information about these cells must be gathered in order to identify them as malignant (cancerous) or non-malignant (non-cancerous), and if they are malignant, to determine how serious (aggressive) the particular cancer cells are. Aggressive cancers grow and spread more quickly than less-aggressive or “indolent” cancers. There are many types of tests specifically designed to evaluate cancer:
Historically, a combination of pathological assessment (laboratory evaluation using a microscope) and diagnostic imaging has been used to identify the type of cancer and its stage, and then the treatment. Stage indicates how extensive the cancer is and how much it has spread. Staging usually involves determining the size of the primary tumor and evaluating whether it has remained in the tissue in which it started, whether it has invaded other nearby organs or tissues, and whether cancer cells have spread to distant locations in the body. The cancer is then assigned a stage on a predetermined scale of numbers and letters, for example stage I, II, IIIa, IIIb, IV, etc. The higher number and letter combination indicates more extensive spread, and therefore a more serious condition. Treatment is often selected based on the stage of disease. Higher stage cancers typically receive very aggressive treatments and lower stage disease less aggressive treatment.
WHAT CANCER
What Is Cancer? Newly Diagnosed What is Cancer? A tumor may be benign (non-cancerous) or malignant (cancerous). Cells from cancerous tumors can spread throughout the body. This process, called metastasis, occurs when cancer cells break away from the original tumor and travel in the circulatory or lymphatic systems until they are lodged in a small capillary network in another area of the body. Common locations of metastasis are the bones, lungs, liver, and central nervous system. The type of cancer refers to the organ or area of the body where the cancer first occurred. Cancer that has metastasized to other areas of the body is named for the part of the body where it originated. For example, if breast cancer has spread to the bones, it is called "metastatic breast cancer" not bone cancer. How did I get cancer? What’s next? No one would call cancer a normal experience, but by proactively managing aspects of your treatment, you can maintain a sense of normalcy in your life. Fighting cancer is not a challenge you face alone. It's a team effort that involves family, friends, and your healthcare team. Don't overlook the strength that can come from having your support network by your side.
A new diagnosis of cancer can be a shock, making you feel out of control and overwhelmed. Getting informed can help alleviate these feelings. Remember, very few cancers require emergency treatment; you have time to learn about your diagnosis and treatment options, ask questions, and get a second opinion. This section is designed to help you address your initial questions before you move forward with your treatment.
Cancer is not one disease, but many diseases that occur in different areas of the body. Each type of cancer is characterized by the uncontrolled growth of cells. Under normal conditions, cell reproduction is carefully controlled by the body. However, these controls can malfunction, resulting in abnormal cell growth and the development of a lump, mass, or tumor. Some cancers involving the blood and blood-forming organs do not form tumors but circulate through other tissues where they grow.
Although every patient and family member wants to know the answer to this question, the reason people develop cancer is not well understood. There are some known carcinogens (materials that can cause cancer), but many are still undiscovered. We do not know why some people who are exposed to carcinogens get cancer and others do not. The length and amount of exposure are believed to affect the chances of developing a disease. For example, as exposure to cigarette smoking increases, the chance of developing lung cancer also increases. Genetics also plays an important role in whether an individual develops cancer. For example, certain types of breast cancer have a genetic component.
Following your diagnosis of cancer, your reaction may be one of shock and disbelief. If you have been told that chemotherapy or radiation therapy are an important part of your treatment, many unpleasant images may come to mind. But as you move beyond that initial shock to begin the journey of surviving your cancer, you have many good reasons to be optimistic. Medicine has made—and continues to make—great strides in treating cancer and in making cancer treatment more tolerable, both physically and emotionally.
CANCER BOOK
Mind, Body and Soul is the first comprehensive cancer guide to provide practical patient advice within a “whole person” context. As the name implies, the book offers essential information concerning a broad spectrum of topics - from treatment and medication to soul-serving discussions of philosophical, spiritual and emotional issues.
Beginning from the moment of diagnosis, Mind, Body and Soul gently takes the reader through the cancer process, with a primary focus on patient empowerment via education and understanding.
Unique in both structure and content, Mind, Body and Soul blazes new trails in the cancer, self-help genre. Practical information regarding treatments, pain management, home care and medication is provided in an easy-to-understand fashion, effectively enabling the patient to take an active role in their own care. The often neglected subject of stress reduction and relaxation techniques is also discussed in detail. The apathy and indifference patients often encounter is examined, and countered with indispensable tips to overcome this reality and enhance both the level and nature of care received.
Unlike any book of its kind, Mind, Body and Soul explores cancer through a distinctly personal, human approach. Inspirational, philosophical discussion is featured amidst powerful personal and patient anecdotes. Inevitably, the reader is moved to a higher level of understanding of the multi-dimensional facets of both living with, and fighting against, a cancer diagnosis. Steering patients through a forest of confusion and despair, the book culminates with an affirmation of the power of the human spirit, and a celebration of the inherent majesty of life.
Mind, Body, and Soul is written for cancer patients, their families and friends, and anyone interested in holistic approaches to modern medical care.
“…you must possess an awesome understanding of cancer patients, concerns, and treatment, AND possess a giant of a heart to have written such a beautiful book. I'm positive that not only people with cancer, but those who love them and treat them will be helped immeasurably by your powerful book.”
- Ann Jillian, Emmy & Golden Globe Award winning actress and singer
Take a moment to read the introduction from the Author Nancy Hassett Dahm - Click Here
Breast Cancer
Author: Diane M Opatt, MD, Clinical Instructor of Surgery, Temple University School of Medicine; Assistant Program Director, Department of Surgery, Abington Memorial Hospital
Coauthor(s): Christina Chung, MD, Staff Physician, Department of General Surgery, Tulane University Health Sciences Center; Mary Jo Wright, MD, Associate Professor of Surgery, Chief of Breast Surgery Service, Tulane University School of Medicine; Medical Director, Breast Cancer Center, Medical Center of Louisiana, New Orleans; Krzysztof Moroz, MD, Program Director, Associate Professor, Departments of Pathology and Laboratory Medicine, Tulane University Health Sciences Center; R Edward Newsome, MD, Program Director and Chief of Plastic Surgery, Henderson Chair in Surgery, Assistant Dean for Graduate Medical Education, Tulane University School of Medicine
Editors: Christian Paletta, MD, FACS, Professor, Division Chief and Program Director, Department of Plastic and Reconstructive Surgery, St Louis University School of Medicine; Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine; Saleh M Shenaq, MD†, Former Director and Founder, The International Brachial Plexus Institute; Former Chief, Section of Plastic Surgery, Methodist Hospital, Houston; Nicolas (Nick) G Slenkovich, MD, Practice Director, Colorado Plastic Surgery Center at Swedish Medical Center; Jorge I de la Torre, MD, FACS, Professor of Surgery and Physical Medicine and Rehabilitation, Residency Program Director, Division of Plastic Surgery, University of Alabama at Birmingham; Director, Center for Advanced Surgical Aesthetics
Author and Editor Disclosure
Synonyms and related keywords: mastectomy, radical mastectomy, lumpectomy, radiation therapy, XRT, chemotherapy, benign lesions, malignant lesions, epithelial tumors, intraductal papilloma, adenoma, intraductal carcinoma, invasive carcinoma, Paget disease of the nipple, invasive ductal carcinoma, phyllodes tumor, carcinosarcoma, ductal carcinoma in situ, DCIS, lobular carcinoma in situ, LCIS, Li-Fraumeni syndrome, Muir-Torre syndrome, Cowden disease, Peutz-Jeghers syndrome, BRCA1mutation, BRCA2 mutation, adenocarcinoma, tubular carcinoma, mucinous carcinoma, colloid carcinoma, mucin, medullary carcinoma, mammography
History of the Procedure
Over the greater part of the last century, all forms of breast cancer have been treated by aggressive surgical resection. In 1894, Halsted described the procedure of en bloc removal of all breast tissue, draining lymph nodes and pectoralis muscles for the treatment of breast cancer. This technique of radical mastectomy became the standard of care for decades based on an understanding that cancer growth proceeded in stepwise fashion via the lymphatics, thus could be controlled with surgical excision.
In 1971, Fisher et al challenged this standard and demonstrated in the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-04 trial that radical mastectomy had no survival benefit over mastectomy with radiation or mastectomy with delayed axillary dissection. In a subsequent study, NSABP B-06, patients were randomized to total mastectomy versus lumpectomy and radiation therapy (XRT), and no survival benefit of total mastectomy was found. However, benefit was observed in the decreased rate of local recurrence in women receiving XRT. Development of new chemotherapeutic and hormonal agents has further revolutionized the management of breast cancer.
For excellent patient education resources, visit eMedicine's Cancer and Tumors Center, Women's Health Center, and Imaging Center. Also, see eMedicine's patient education articles Breast Cancer, Mastectomy, Breast Lumps and Pain, Breast Self-Exam, and Mammogram.
Problem
Worldwide, the overall incidence of breast cancer varies markedly but appears to be rising. Far eastern countries such as Japan, which historically have enjoyed low rates in comparison to the United States, are seeing a rapid rise in incidence. Although the United States has the highest reported incidence of breast cancer in the world, several western European nations such as Iceland, Italy, France, Sweden, and the United Kingdom trail closely behind. Incidence has been historically lower in Eastern Europe, the Middle East, and the Far East, but countries such as Japan and Singapore have seen a 2-fold rise over the past few decades.
Frequency
Of American women, 13% will be diagnosed with breast cancer in their lifetimes, making it the most common nonskin cancer among women. In addition, more than 3% will die from the disease. Breast cancer has surpassed lung cancer as the leading cause of cancer death in women worldwide, accounting for more than 400,000 deaths per year. In the United States, breast cancer trails only lung cancer as the second most common cause of cancer death in women. In 2002, more than 1.15 million new cases were diagnosed worldwide. More than 200,000 of these were in the United States alone.
The 1980s saw the greatest rise in incidence, which may have been due to a combination of improvements in screening techniques, data collection, and treatment modalities. Despite this surge in newly-diagnosed cases, mortality rates have been declining over the last decade. The decline is widely attributed to earlier detection via screening mammography and improvements in hormonal therapy and chemotherapy.
Etiology
Risk factors for the development of invasive breast cancer include female gender, age, family history, age at the time of first parturition, personal history of previous breast cancer, hormone replacement therapy, history of atypical hyperplasia or noninvasive lesions, and genetics.
- Female gender: The incidence of breast cancer in women exceeds that in men by 100:1. Overall, 1 of every 8 American women develops breast cancer in her lifetime.
- Age: In American women, risk increases from 1:5900 to 1:290 between the third and eighth decades. A woman aged 60-79 years has a 1:14 chance of developing invasive breast cancer, compared with a woman younger than 39 years, who has a 1:225 probability.
- Age at birth of first child: If aged 30 years or older, relative risk is 2 times that of patients who gave birth when younger than 20 years.
- Personal history of breast cancer: This also is a recognized risk factor. This factor depends on patient age at time of diagnosis. Risk is increased for younger women.
- Noninvasive carcinoma (ductal carcinoma in situ [DCIS]/lobular carcinoma in situ [LCIS]) on previous biopsy: This also is a marker for development of invasive lesions.
- Benign proliferative changes with atypical hyperplasia: These may increase relative risk by 4 times. Atypical hyperplasia may be observed in as many as 10% of specimens from biopsy.
- Early menarche and late menopause: These also are associated weakly with increased relative risk of breast cancer.
- Menopausal hormone replacement therapy: Multiple studies, including the Women's Health Initiative and the Million Women Study in the United Kingdom, have shown an increased risk of breast cancer in postmenopausal women who are either recent or current users of estrogen alone or in combination with progestin. In addition, the combination use of estrogen with progestin has been associated with an even greater risk of breast cancer, particularly of lobular carcinoma. Increased risk is also related to increased duration of use; this risk can be reduced over time, following the termination of hormone replacement therapy.
- Family history: Degree of relativity of the family member with breast cancer affects individual risk. For example, the relative risk of patients with an affected first-degree relative is 1.5-2 times higher when compared to controls without affected family members. Even more significantly, having two first-degree relatives affected (female or male) increases relative risk by more than 4-6 times when compared to patients without this risk factor. Third, age of the affected relative at time of diagnosis also influences risk. A patient with a mother diagnosed when younger than 60 years is at 2 times increased risk. Finally, bilateral cancer in a first-degree relative may increase risk by more than 6 times.
Pathophysiology
The World Health Organization classification of breast tumors organizes both benign and malignant lesions by histologic pattern. Epithelial tumors comprise the largest group, including intraductal papilloma, adenomas, intraductal and lobular carcinoma in situ, invasive (ductal and lobular) carcinoma, and Paget disease of the nipple. Invasive ductal carcinoma is by far the most common type.
Phyllodes tumor, benign and malignant, and carcinosarcoma are rare lesions grouped as mixed connective tissue and epithelial tumors. Other common nonadenocarcinoma lesions of the breast include angiosarcoma and primary lymphoma.
Invasiveness is a key determinant in the prognosis and treatment of breast malignancy. Noninvasive lesions are by definition limited by the basement membrane and may be classified as DCIS or LCIS.
- DCIS is by far more common than LCIS, and more importantly, it should be distinguished as a clearly malignant lesion. Ductal epithelial cells undergo malignant transformation and proliferate intraluminally. Eventually, the cells outstrip their blood supply and become necrotic centrally. This debris can calcify and be detected mammographically. Moreover, the lesions also may be palpable clinically. Five pathologic subtypes have been identified: comedo, papillary, micropapillary, solid, and cribriform. Most lesions represent a combination of at least two of these subtypes. The presence of comedo necrosis is an independent risk factor for subsequent ipsilateral breast cancer (NSABP-B17).
- LCIS also arises from epithelial cells; however, their growth continues in a lobular pattern. In contrast to DCIS, these lesions rarely develop central necrosis, calcify, or become palpable. For this reason, LCIS rarely is detected by examination or mammography preoperatively and usually presents as an incidental finding on histologic review. Clinically, LCIS is considered more of a marker for development of invasive cancer rather than a malignant lesion. The risk of subsequent breast cancer is equal for both breasts irrespective of the index site. Moreover, most invasive cancers that develop are infiltrating ductal, which supports the concept that LCIS is not a malignant lesion.
- Invasive breast cancers usually are epithelial tumors of ductal or lobular origin. Features such as size, status of surgical margin, estrogen receptors (ER) and progesterone receptors (PR), nuclear and histologic grade, DNA content, S-phase fraction, vascular invasion, tumor necrosis, and quantity of intraductal component are all important in deciding on a course of treatment for any breast tumor.
- Infiltrating ductal carcinoma is the most commonly diagnosed breast tumor. This lesion, which accounts for 75% of breast cancers, has no specific histologic characteristics other than invasion through the basement membrane. DCIS may be a frequently associated finding on pathologic examination. It also has a tendency to metastasize via lymphatics.
- Infiltrating lobular carcinoma has a much lower incidence and comprises less than 15% of invasive breast cancer. It is characterized histologically by the Indian file arrangement of small tumor cells. Like ductal carcinoma, these typically metastasize to axillary lymph nodes first. However, it also has a tendency to be more multifocal. Despite this, the prognosis is comparable to that of ductal carcinoma.
Less common histologic subtypes of adenocarcinoma collectively comprise less than 25% of invasive breast cancers.
- The diagnosis of tubular carcinoma requires the presence of tubular formation in at least 75% of the specimen. This pathology is associated with improved prognosis.
- Mucinous (or colloid) carcinoma also has a favorable prognosis when compared with ductal carcinoma. These slow-growing lesions characteristically produce large amounts of mucin, thus are usually bulky. They, like tubular carcinoma, rarely metastasize.
- Medullary carcinoma, despite being a poorly differentiated tumor, also carries an improved prognosis.
ER and PR are valuable as predictors of disease-free survival and response to hormonal therapy. Studies in patients with ER(+) tumors who did not receive chemotherapy suggest they have a higher rate of disease-free survival than patients with ER(-) tumors. The presence of these nuclear steroid receptors on tumor staining should be considered, along with other histologic features, in determining the need for hormonal and adjuvant chemotherapy.
Human epidermal growth factor receptor (Her)-2/neu protein expression is associated with increased incidence of recurrence and shortened overall survival. Her-2/neu is overexpressed in 20-30% of breast cancers. Her-2/neu–positive lesions have also been associated with comedo-type DCIS, another poor prognostic indicator. Patients with Her-2/neu–positive breast cancer are candidates for treatment with combination chemotherapy and monoclonal antibody therapy.
S-phase (proliferative) fraction can be determined by flow cytometry. This fraction represents cells in the synthetic or replication phase of the cell cycle. High S-phase fraction is an indicator of more aggressive disease regardless of nodal status. It has not been shown to predict response to chemotherapy.
Other histologic factors, such as lymphatic invasion, an extensive DCIS component (>25% of the tumor), and Ki-67 staining, continue to be investigated as potential prognostic factors for breast cancer.
Clinical
When evaluating a patient with possible breast cancer, direct questions toward both assessment of risk and narrowing the differential diagnosis. Patient factors associated with increased risk of breast cancer are discussed in Etiology. In addition, inquiry regarding nipple discharge, fever, pain, rapid growth, duration of the mass, and changes with menses may be helpful in directing the workup for breast cancer.
Physical examination should include inspection of the patient in the upright as well as supine positions. With the patient upright, assessment for symmetry and changes in the nipple and skin may be performed. Obvious size discrepancy, nipple inversion, skin dimpling, scaling, and edema (peau d'orange) are suggestive findings. Supraclavicular, infraclavicular, and axillary lymphadenopathy also can be best detected in this position.
Once the patient is in the supine position with the ipsilateral arm extended over the head, the breast parenchyma can be compressed against the chest wall, which allows for improved sensitivity for the examiner. The 2 most common techniques for supine examination are the clockwise radial pattern and the linear pattern. In the clockwise radial technique, examination begins at the 12-o'clock position near the clavicle and proceeds towards the nipple. This is repeated in a clockwise fashion around the entire breast.
The linear technique, when performed correctly, is arguably more sensitive, although time-consuming. Proponents of the linear technique recommend beginning in the axilla at the mid-axillary line, proceeding toward the inferior mammary fold, and then returning to the clavicle in a series of rows (12-15 rows, depending on the size of the breast). Using the pads of 3 fingertips, the examiner should palpate dime-sized circles in 3 different depths at each site before moving one finger width toward the inferior mammary fold and repeating the circular motion at the superficial, medium, and deep levels. Benign lesions are more frequently smaller, rubbery, well-circumscribed, and mobile. Characteristics suggestive of malignancy include skin involvement, fixation to the chest wall, irregular border, firmness, and enlargement.
Compression of the breast or nipple is no longer recommended to assess for discharge. However, visual inspection of the nipple/areola complex should be a routine part of the examination. Only spontaneous discharge should be considered clinically significant. Concerning characteristics include unilateral discharge, nonmilky fluid, and origin from a single duct. Intraductal papilloma, a benign finding, is the most common cause of unilateral bloody nipple discharge. Other benign pathology associated with nipple discharge includes subareolar duct ectasia and fibrocystic changes. Usually, malignant pathology presenting with nipple discharge is also associated with a palpable mass, suggestive mammographic findings, or both.
Breast self-examination, performed monthly, is still generally recommended for women beginning at age 18 years, although no strong statistical data exist to support its efficacy in the early detection of breast cancer. Physicians should examine patients aged 19-40 years approximately every 3 years. The American Cancer Society recommends annual evaluation by physician examination along with screening mammography for women aged 40 years and older, particularly if risk factors are present.
A thorough understanding of the relative anatomy of the breast and axilla is essential to successful and uncomplicated surgical treatment of breast cancer.
The breast is bounded by the clavicle superiorly, the sternum medially, the lateral border of the latissimus muscle laterally, and the inframammary fold inferiorly. The axillary tail of Spence extends into the deep fascia superior and lateral to the breast. The deep pectoral fascia defines the deep margin.
Fibrous bands, known as the suspensory ligaments of Cooper, divide the breast parenchyma into 12-20 separate lobules of glandular tissue. Separate branching lactiferous ducts drain each lobule. These ducts converge just beneath the nipple into sinuses that empty into a single terminal duct. Drainage from individual ducts can be localized for surgical excision.
The lateral pectoral nerve passes medially around the medial pectoralis minor, and the medial pectoral nerve passes laterally around the pectoralis minor. The names are based on the origin of the nerves from the lateral and medial cords of the brachial plexus rather than their orientation to the muscle. Injuries to these nerves are rare.
Injury to the brachial plexus can be avoided by keeping the superior extent of the axillary dissection inferior to the lower border of the axillary vein.
The thoracodorsal nerve is identifiable medial to the thoracodorsal vein running along to enter the latissimus dorsi. Injury may result in slight, if any, clinically evident weakening of the latissimus.
The long thoracic nerve is located more medially in the axilla. It runs just beneath the investing fascia of the serratus anterior, medial to the thoracodorsal complex. Injury to this nerve results in winging of the scapula on arm extension.
The skin of the axilla and upper arm is supplied by the intercostobrachial nerve, which often is sacrificed in the dissection of axillary nodes. Transection may result in numbness in these areas.
Axillary lymph nodes receive most mammary lymphatic drainage. The internal mammary nodes also receive some drainage medially. Axillary nodes are referred to by levels, which are defined by the pectoralis minor muscle. Level I nodes are lateral, II behind, and III medial to the muscle.
The external mammary artery and perforators of the internal mammary artery supply blood to the breast. Venous drainage follows arterial anatomyLab Studies
- For patients undergoing breast biopsy, few, if any, lab tests are necessary. These procedures usually are performed routinely in an outpatient setting under local anesthesia. Order a complete blood count and basic chemistries for more extensive procedures such as modified radical mastectomy requiring general endotracheal anesthesia. Additional testing depends on the individual patient history, age, and comorbid conditions.
- Genetic testing for BRCA1 and BRCA2 can be performed in selected patients with a strong family history of breast or ovarian carcinoma. However, genetic counseling and discussion of subsequent management and treatment options should be performed prior to testing. The criteria for referral for genetic counseling and testing of high-risk individuals include the following:
- Any patient diagnosed with breast cancer who is aged less than 40 years
- Males with breast cancer, especially if they are of Jewish ancestry
- Any patient with 2 or more first-degree relatives, or 2 or more second-degree relatives (on the same side of the family) who meet any of the following conditions:
- Breast cancer diagnosed at in patient aged less than 50 years
- Breast and ovarian cancer in the same bloodline or in the same individual
- Male relative diagnosed with breast cancer when aged less than 50 years
- Family members with bilateral breast cancer
- According to the American Society of Clinical Oncology, serum markers that may be used in the workup for breast cancer include carcinoembryonic antigen (CEA), cancer antigen (CA) 15-3, and CA 27.29. These are not recommended routinely, and indications for their use have not been standardized.
- However, once a diagnosis of breast cancer has been made, additional testing may be performed to determine a patient's likelihood of response to chemotherapy. Specifically, the Oncotype DX assay is a 21-gene assay first announced in 2003 by NSABP researchers. The Oncotype DX provides a score that predicts the likelihood of distant recurrence in a select group of patients who have node-negative and estrogen-receptor–positive breast cancer. Resulting scores may assist in determining the potential benefit or necessity of chemotherapy in these patients.
Imaging Studies
- Mammography has become the standard tool for screening and initial evaluation of breast cancer. Multiple prospective randomized controlled trials have demonstrated that mammography can reduce the mortality from breast cancer in women aged 50-74 years. A great deal of controversy surrounds the use of mammography in younger women, particularly those aged 40-49 years. Currently, the American Cancer Society recommends annual mammography and examination by a physician beginning at age 40 years with no maximum upper age limit. Obviously, this should be taken with the caveat that patients who fall outside these guidelines need to be assessed individually.
For instance, women younger than 40 years who have extensive family histories for breast cancer may benefit from beginning screening earlier. Conversely, older women with significant comorbidities, which may be prohibitive in the treatment of breast cancer, may not derive any benefit from mammography. In addition, the sensitivity of mammography is decreased significantly in young patients with dense breast tissue and possibly with augmentation prosthesis. Mammography seldom is recommended in patients younger than 30 years. - The American College of Radiology established the standard for classification of radiographic abnormalities, known as the Breast Imaging Reporting and Data System (BI-RADS), as follows:
- 0. Incomplete examination - Usually requiring further imaging or evaluation
- I. Normal - With follow-up study recommended in 1 year
- II. Benign - Follow-up study in 1 year
- III. Likely to be benign - Follow-up mammogram in 6 months
- IV. Suspicious - Consider biopsy
- V. Highly suspicious for malignancy - Biopsy recommended
- In addition to evaluating parenchymal masses, mammography can be useful in evaluating the breast for calcifications, architectural distortion, skin thickening, nipple changes, and axillary adenopathy. Enlargement, stellate shape, irregular or spiculated margins, and the presence of pleomorphic calcifications less than 0.5 mm in a given lesion all are suggestive of malignancy.
- As an adjunct to mammography, ultrasonography (US) can be particularly useful in younger patients or women with fibrocystic change. Its main use remains in distinguishing solid from cystic lesions. In the workup of nonpalpable lesions, US can be used to guide a needle biopsy or to place a localizing wire to direct an excisional biopsy. Ultrasonography may also be useful in the workup of palpable masses not visualized by mammography.
- Magnetic resonance imaging (MRI) of the breast is a relatively new modality that is being widely utilized for multiple applications in the screening, diagnosis, and treatment of breast cancer.
- Although little argument exists regarding the utility of MRI in screening patients at high risk, the appropriate interval remains a gray area that is currently under study. Patients at high risk who would be excellent candidates for MRI screening include women with a personal history of breast cancer not visualized by mammography and women with a strong familial or genetic predisposition (carriers of BRCA1 or BRCA2) for breast cancer. In 2004, Kriege et al studied screening modalities in nearly 1,900 women at high risk. MRI was shown to have a significantly increased sensitivity over mammography in the early detection of invasive breast cancer. However, the specificity of MRI was significantly lower than mammography, leading to more than twice as many unnecessary biopsies.
- MRI can also be useful in the evaluation of patients with suspected or known breast cancer. For example, it can be applied to patients with axillary lymphadenopathy and an otherwise undetectable primary tumor. Also, patients with palpable lesions not visualized by diagnostic mammography or ultrasonography should be strongly considered for MRI. In these patients, the advantage of MRI as an adjunct to core biopsy lies in its ability to accurately assess for size, multi-focal disease, and synchronous lesions. As a result, patients would potentially be spared additional surgical procedures for positive margins or multi-focal findings. Finally, MRI may have use in the follow-up with patients who have advanced breast cancer and are undergoing chemotherapy.
- The use of screening and diagnostic MRI in all patients (including those with lesions clearly visualized by standard diagnostic mammography and ultrasonography) remains much more controversial.
- Other imaging modalities include CT and positron emission tomography (PET). CT is primarily used to evaluate for extramammary involvement of the tumor. PET scanning is another tool being increasingly used in the workup for metastatic lesions.
Diagnostic Procedures
- Fine needle aspiration: Fine needle aspiration (FNA) is no longer the criterion standard for initial evaluation of all palpable breast masses. However, it is particularly useful in the evaluation of cystic lesions detected by ultrasonography. FNA results are reported as benign, suggestive of malignancy, or nondiagnostic. Aspiration of a benign cystic lesion should result in collapse of the cavity. Documentation of complete collapse by follow-up ultrasonography may be helpful in decreasing the incidence of recurrence. Persistence of a palpable mass and recurrence following aspiration are general indications for further workup. Importantly, note that the cytopathologist cannot distinguish invasive carcinoma from DCIS. To rule out DCIS, histologic confirmation of invasion with core needle biopsy or excisional biopsy is obtained prior to axillary staging.
- Core needle biopsy: Core needle biopsy (CNB) is a more useful alternative than FNA for initial diagnosis of breast cancer. One advantage is that a surgical pathologist can distinguish between invasive cancer and DCIS based on architectural information provided by the larger tissue sample in CNB. Another advantage to CNB is that a well-trained surgical pathologist can examine the specimen; with FNA, a highly-skilled cytopathologist is required for accurate results. The adoption of image-guided needle biopsy of nonpalpable lesions has defrayed cost and improved patient care by eliminating cosmetic deformity associated with excisional biopsy. Since CNB removes only part of the lesion, one must ensure that the results are concordant with radiographic findings and that proper follow-up is initiated with the patient. With the use of large bore needles and vacuum-assisted devices, adequate sampling of the lesion is much more likely.
- Image-guided breast biopsy: This is an alternative useful for workup of nonpalpable lesions. Ultrasonography, mammography, and MRI may all be used to perform image-guided core needle biopsies. Advantages of this modality include the ability to perform localization and excision in a single procedure. Limitations include cost, availability, and inability to perform biopsy on lesions located close to the chest wall or in patients with small breast volume.
- Excisional biopsy: Complete surgical removal of a palpable breast lesion is referred to as an excisional biopsy. This technique is indicated if (1) neither FNA nor CNB is technically feasible, (2) attempts have produced nondiagnostic results, or (3) pathology is discordant with radiographic imaging. The specimen should always be carefully oriented by the surgeon to aid the pathologist in assessing margins.
Histologic Findings
See Images 6-15.
Staging
The standard staging system is that of the American Joint Committee on Cancer (AJCC). The system is based on primary tumor size (T), lymph node involvement (N), and metastatic disease (M).
- Primary tumor = T
- Tx - Primary tumor cannot be assessed
- T0 - No evidence of primary tumor
- Tis - Carcinoma in situ
- Tis (DCIS) - Only ductal carcinoma in situ
- Tis (LCIS) - Only lobular carcinoma in situ
- Tis (Paget) - Paget disease of the nipple with no tumor (Note: Paget disease associated with a tumor is classified according to the size of the tumor)
- T1 - Tumor £2 cm in greatest dimension
- T1mic - £0.1 cm
- T1a - >0.1cm but <0.5>
- T1b - >0.5 cm but <1>
- T1c - > 1 cm but <2>
- T2 - Tumor > 2 cm but £ 5 cm
- T3 - Tumor > 5 cm
- T4 - Tumor of any size with direct extension to chest wall or skin (including inflammatory carcinoma)
- T4a - Extension to the chest wall, not including the pectoralis muscle
- T4b - Extension to the skin with edema (peau d'orange) or ulceration of the skin or satellite nodules confined to the same breast
- T4c - Both T4a and T4b
- T4d - Presence of inflammatory carcinoma
- Regional lymph nodes (clinical lymph node status) = N
- Nx - Regional lymph nodes cannot be assessed (eg, they were previously removed)
- N0 - No regional lymph node metastases
- N1 - Metastases to ipsilateral axillary lymph nodes without fixation
- N2 - Metastases to ipsilateral axillary lymph nodes with fixation to each other (matted), with fixation to other structures such as the chest wall, or in clinically apparent ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node metastases
- N2a - Metastases in ipsilateral axillary lymph nodes fixed to one another (matted) or to other structures
- N2b - Metastases only in clinically apparent ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node metastases
- N3 - Infraclavicular nodes have metastases with or without axillary lymph node involvement, or clinically apparent ipsilateral internal mammary lymph nodes in the presence of clinically evident axillary lymph node metastases, or metastases in the supraclavicular lymph nodes with or without axillary or internal mammary lymph node involvement
- N3a - Metastases in ipsilateral infraclavicular lymph nodes
- N3b - Metastases in ipsilateral internal mammary lymph nodes and axillary lymph nodes
- N3c - Metastases in ipsilateral supraclavicular lymph nodes
- Regional lymph nodes (pathologic lymph node status)
- pNx - Axillary nodes cannot be assessed (eg, they were not removed during surgery and cannot be viewed)
- pN0 - Lymph nodes do not have metastases
- pN0 (i-) - No regional lymph node metastases histologically, negative immunohistochemistry (IHC)
- pN0 (i+) - No regional lymph node metastases histologically, positive IHC, no IHC cluster >0.2 mm
- pN1 - One to three axillary lymph nodes have metastases or internal mammary lymph nodes with microscopic disease detected by sentinel node but not clinically apparent
- pN1mi - Micrometastasis >0.2 mm but <2.0>
- pN1a - Metastases in 1-3 axillary lymph nodes
- pN1b - Metastases in internal mammary lymph nodes with microscopic disease detected by sentinel lymph node (SLN) dissection but not clinically apparent
- pN1c - Metastases in 1-3 axillary lymph nodes and in internal mammary lymph nodes with microscopic disease detected by sentinel node dissection but not clinically apparent
- pN2 - Four to nine axillary lymph nodes have metastases or in clinically apparent internal mammary lymph nodes in the absence of axillary lymph node metastases
- pN2a - Metastases in 4-9 axillary lymph nodes
- pN2b - Metastases in clinically apparent internal mammary lymph nodes in the absence of axillary lymph node metastases
- pN3 - Ten or more axillary lymph nodes have metastases, or infraclavicular lymph nodes, or clinically apparent ipsilateral internal mammary lymph nodes in the presence of 1 or more positive axillary nodes, or more than 3 axillary lymph nodes with clinically negative microscopic metastases in internal mammary lymph nodes, or ipsilateral supraclavicular lymph nodes
- pN3a - Metastases in 10 or more axillary lymph nodes or metastases in the infraclavicular lymph nodes
- pN3b - Metastases in clinically apparent ipsilateral internal mammary lymph nodes in the presence of 1 or more positive axillary lymph nodes or in more than 3 axillary lymph nodes and in internal mammary lymph nodes with microscopic disease detected by SNL dissection but not clinically apparent
- pN3c - Metastases in ipsilateral supraclavicular lymph nodes
- Distant metastases = M
- Mx - Cannot be assessed
- M0 - No metastases
- M1 - Distant metastases, including ipsilateral supraclavicular lymph nodes
Medical Therapy
Medical therapy for breast cancer can be divided into 3 categories: chemoprevention, neo-adjuvant, and adjuvant therapy.
Chemoprevention
Several classes of drugs, including retinoids, cyclooxygenase (COX) inhibitors, and selective estrogen receptor modulators (SERM), have been studied in the chemoprevention of breast cancer. The NSABP-P1 trial has demonstrated the efficacy of tamoxifen, a SERM, in the prevention of invasive breast cancer. Treatment with tamoxifen reduced the risk of invasive breast cancer by 49%. Moreover, a 50% reduction in the risk of noninvasive cancers was demonstrated.
In terms of prevention, tamoxifen is approved by the US Food and Drug Administration (FDA) for use in healthy women at high risk for the development of invasive breast cancer and in patients with early invasive lesions at risk of secondary contralateral cancer. Dosing should be 20 mg/d for 5 years. Significant relative toxicity from tamoxifen use includes increased risk of endometrial cancer and pulmonary embolism in women older than 50 years. Currently, the NSABP P-2 trial (Study of Tamoxifen and Raloxifene [STAR] trial) is underway to compare the efficacy of tamoxifen with raloxifene, which is a SERM used for treatment of osteoporosis.
A relatively new class of drugs, aromatase inhibitors (AI), is being explored for efficacy in the chemoprevention of breast cancer. Three third-generation aromatase inhibitors (anastrozole, letrozole, exemestane) have already been approved by the FDA for use in adjuvant therapy for postmenopausal women with hormone receptor–positive breast cancer.
However, tamoxifen remains the standard of care for adjuvant endocrine therapy for premenopausal women. In select patients with small tumors and no nodal metastases, tamoxifen may provide a means for systemic treatment without the use of systemic chemotherapy. Conversely, ER(-) tumors are predictive of improved response to chemotherapy and minimal benefit from tamoxifen.
Trastuzumab is a relatively new chimerized mouse/human monoclonal antibody that targets the extracellular portion of the Her-2/neu membrane protein. Two major research studies, NSABP B-31 and North Central Cancer Treatment Group (NCCTG) trial N9831, were closed early because of clinically significant findings of improved disease-free and overall survival in women treated with trastuzumab in addition to chemotherapy. Trastuzumab, in combination with chemotherapy, is now recommended to all patients who have lymph node–positive Her-2–positive breast cancer, unless a clear contraindication exists to treatment. Consideration should be made for the significant cardiotoxicity associated with trastuzumab.
Neoadjuvant therapy for locally advanced breast cancer should involve anthracycline or taxane-based regimens.
Various chemotherapeutic regimens used following surgical treatment include anthracyclines, taxanes, and cyclophosphamide. Choice of the optimal adjuvant chemotherapeutic regimen should be made based on multiple factors including patient age, menopausal status, hormone receptor and Her-2/neu expression, lymph node involvement, and size of the primary lesion.
Multiple guidelines are available to assist clinicians in selecting the most appropriate regimen. They include the National Comprehensive Cancer Network's Breast Cancer Guidelines v 2.2006 and Adjuvant! Online.
Surgical Therapy
Definitions and Techniques
- Ductal excision: Ductal excision may be indicated for suggestive nipple discharge without an associated palpable or radiographic lesion. Bloody discharge and spontaneous clear discharge from a single duct are findings with an increased risk of malignancy. Ductal excision can be performed using a small (4.0) lacrimal duct probe to localize the draining duct. A cone-shaped sample of tissue then should be excised around the probe. The most common histologic findings in this setting are intraductal papilloma or ductal ectasia (approximately 80%). Most of the remaining lesions demonstrate intraductal or infiltrating carcinoma.
- Excisional biopsy or lumpectomy: This should be performed for palpable lesions with suggestive or malignant findings on needle biopsy. Benign or inconclusive findings on needle biopsy also may prompt excisional biopsy in the presence of high clinical suspicion (eg, large mass fixed to the chest wall, atypical epithelial hyperplasia). In general, circumareolar incisions should be made for lesions close to the nipple and radial incisions for lower outer quadrant lesions. All incisions should be made with consideration of potential need for incorporation into subsequent mastectomy incisions. The surgeon should carefully orient specimens with suture for histologic assessment of individual margins. The procedure may be performed safely with local anesthesia and/or monitored intravenous sedation. The need for open biopsy can usually be obviated by the use of CNB as described in Diagnostic Procedures.
- Lumpectomy or wide local excision: Most often performed along with some form of lymph node dissection as part of a breast conservation procedure, lumpectomy involves excision of a palpable malignant breast lesion with adequate margins. In the case of nonpalpable lesions, a needle-localization procedure may precede lumpectomy. This is performed with ultrasonographic or mammographic assistance for nonpalpable, radiographically identified lesions. Following placement of a fine J wire under radiographic guidance, the lesion can be excised surgically. Care must be taken to obtain a solid core of breast tissue around the tip of the wire with margins of at least 1 cm. The specimen should be reevaluated radiographically to confirm excision of the intended lesion prior to completion of the operation.
- Quadrantectomy: This is removal of an entire quadrant of the breast, which is less cosmetically satisfactory than lumpectomy.
- Sentinel lymph node biopsy (SLNB): The sentinel lymph nodes (SLN) are the first nodes that receive drainage from tumors. The technique involves injecting radiocolloid, blue dye, or both in the tissues of the breast. Several techniques of injection are available, including subareolar, peritumoral, intradermal, or intraparenchymal. After injection, an incision is made with consideration of the potential need for subsequent completion lymph node dissection (see next paragraph). Therefore, the incision can be elongated easily if the SLN is positive for metastasis.
- Completion Lymph Node Dissection (CLND): If an SLN is found to be positive on histologic evaluation, a CLND is indicated to assess the degree of lymph node involvement. This can have a significant impact on staging as well as adjuvant treatment.
- Axillary Lymph Node Dissection (AxLND): This procedure is equivalent to SLNB combined with CLND. Axillary lymph node staging provides prognostic information to both the patient and the treating physicians. A formal level I and II axillary lymph node dissection has historically been the standard of care in surgical therapy for the axilla. However, AxLND can result in significant morbidity. Complications of AxLND include pain, paresthesia, seroma, infection, limitation of shoulder motion, and lymphedema.
- Breast conservation therapy: This term is used to describe lumpectomy, quadrantectomy, or segmental mastectomy with or without axillary dissection and adjuvant radiation therapy.
- Total or simple mastectomy: This describes removal of breast parenchyma, including nipple-areolar complex, with no node dissection. It may be performed as a therapeutic or a prophylactic procedure in select patients at high risk.
- Modified radical mastectomy: This procedure involves resection of the breast parenchyma and axillary nodes lateral to and behind the medial border of the pectoralis minor (levels I and II).
- Subcutaneous/skin-sparing mastectomy: This procedure involves subcutaneous removal of breast parenchymal tissue and the nipple-areolar complex and may be accompanied by level I and II axillary dissection; it also is referred to as prophylactic mastectomy when performed in healthy patients with strong risk factors such as LCIS or multiple affected family members.
- Patey modified radical mastectomy: Primarily of historical significance, this involves modified radial mastectomy (MRM) with additional removal of level III nodes requiring division or resection of the pectoralis minor; compared to MRM, this procedure increases lymphedema from 3-10% in the arm.
- Radical (Halsted) mastectomy: This procedure entails removal of all breast, axillary nodes through level III, and both the pectoralis minor and pectoralis major muscles; historically, this was the most commonly performed procedure for breast cancer.
Surgical Indications
Ductal carcinoma in situ
Histologic appearance is one of the most important factors in determining an appropriate treatment plan. Specific cellular characteristics in both noninvasive and invasive breast cancer have significant prognostic value. In DCIS, the presence of various pathologic criteria, such as high nuclear grade and comedo necrosis, have been suggested as risk factors for local recurrence of breast cancer. Lagios et al found that patients with both of these characteristics had 4 times the local failure rate of patients without chemotherapy.
In 1995, Silverstein et al described the Van Nuys classification, which stratified 238 patients into 3 groups based on these 2 factors. Group 1 had low nuclear grade and no comedo necrosis, group 2 also had low nuclear grade but positive comedo necrosis, and group 3 had high nuclear grade with or without comedo necrosis. All patients had been treated with lumpectomy with or without radiation. Retrospective analysis indicated that Groups 1 and 2 were treatable with excision alone. Only Group 3 had significant survival benefit from the addition of XRT.
The Van Nuys Prognostic Index is based on the Van Nuys histologic classification scheme, tumor size, and width of surgical margins. Retrospective analysis of 333 patients, using this index, suggested that local excision alone could be used for definitive treatment of favorable lesions. Conversely, patients with higher scores had high (60%) local recurrence rates despite the addition of XRT. Based on these findings, traditional treatment with mastectomy was recommended for patients with unfavorable histology.
The NSABP B-17 trial prospectively randomized more than 700 women with DCIS to lumpectomy versus lumpectomy and XRT. At the 8-year follow-up point, the Van Nuys classification was applied to their data to determine its role in the assessment for subsequent ipsilateral (recurrent) breast tumors.
First of all, only comedo necrosis independently showed strong predictive value. Surprisingly, other criteria, such as tumor-free margins, multifocality, and nuclear grade, did not prove to be significant independent risk factors.
Secondly, patients in all 3 Van Nuys groups demonstrated a survival benefit from the addition of XRT according to the NSABP B-17 study. Even in Group 1, with favorable histology, a 59% relative risk reduction was observed after treatment with XRT.
Finally, despite a high incidence of subsequent invasive carcinoma, overall mortality of patients treated with lumpectomy and radiation remains less than 2% at 8 years of follow-up study. This is comparable to accepted long-term mortality rates following mastectomy for DCIS. Therefore, the NSABP B-17 investigators emphatically reject the need for mastectomy in patients with DCIS equal to or less than 1 cm. Total mastectomy in the treatment of DCIS greater than 1 cm remains controversial.
Axillary dissection routinely was performed on all patients early in the NSABP-B17 trial. When no nodal involvement was found, the procedure was removed from the protocol. However, the sizes of lesions in this trial were uniformly less than 1 cm. Therefore, the role of axillary dissection in larger lesions requires further study. In general, axillary dissection is not indicated in the treatment of noninvasive lesions but current studies of lymph node morphology may change this recommendation.
Nearly all patients with truly noninvasive ductal carcinoma are candidates for breast conservation surgery and radiation treatment. Additional treatment, including total mastectomy, should be individualized. Tamoxifen should be considered.
Lobular carcinoma in situ
As first described in 1941 by Foote and Stewart, LCIS remains "a rare form of mammary cancer." Most cases of LCIS are discovered incidentally on biopsy for other clinical findings. In 1978, in one of the largest histologic review series, Haagensen et al described LCIS as having no associated palpable mass, higher incidence in premenopausal women, absence of nodal metastases, tendency for multifocal or bilateral disease, and predisposition to carcinoma in either breast. More recently, most of the subsequent breast cancers in these women have been demonstrated to be invasive ductal carcinomas. As a result, LCIS is regarded primarily as a risk factor for malignancy. The NSABP P-1 trial prospectively studied the efficacy of tamoxifen in the prevention of breast cancer and included patients with LCIS. The researchers found a 55% risk reduction in women treated with tamoxifen.
Overall treatment options include observation and close follow-up care with or without tamoxifen and bilateral mastectomy with or without reconstruction. No evidence exists of therapeutic benefit from local excision, axillary dissection, radiation, or chemotherapy. The presence of LCIS in the breast of a woman with ductal or lobular cancer does not require further immediate surgery on the opposite breast. Mirror biopsy of the contralateral breast, once advocated in the treatment of LCIS, is a procedure mainly of historic interest.
Invasive ductal carcinoma
Once the diagnosis of invasive breast cancer has been made, the next step is resection, if clinically feasible. The only exception is locally advanced breast cancer, in which neoadjuvant therapy may precede surgery. The choice of surgical procedure depends on multiple factors, including patient risk factors for contralateral or metachronous cancer, histology, mammographic findings, evidence of nodal or extramammary metastases, comorbidities, and the patient's understanding of the surgical options.
Veronesi et al at the National Cancer Institute in Milan, Italy, evaluated patients with small primary tumors (<2>
Breast conservation therapy is applicable in most patients with stage I and II invasive carcinomas. Relative contraindications include small breast size, large tumor size (>5 cm), and collagen vascular disease. Absolute contraindications include multifocal disease, history of prior radiation to the area of treatment, first or second trimester of pregnancy, and persistent positive margins following attempts at conservation. Factors that often are considered but should not be deterrents include axillary node involvement and tumor location. Consideration of cosmesis, while important, never should outweigh the clinical priority of obtaining negative surgical margins. For instance, lesions involving Paget disease of the nipple may be treated with excision of the nipple-areolar complex and reconstruction. Larger lesions in patients with concerns regarding cosmesis may be better served by standard modified radical mastectomy and concurrent reconstruction.
The primary route of dissemination of breast cancer is via the axillary lymphatics. Therefore, axillary dissection plays an important role in the staging of breast cancer. Guidelines for the use of axillary dissection are somewhat controversial. Current standard of care mandates assessment of the axilla in all cases of invasive breast cancer. The NSABP B-4 trial has demonstrated that axillary dissection improves rates of local control when compared to radiation. Nevertheless, it has failed to have a significant effect on overall survival.
The technique of axillary dissection has evolved on the basis of high morbidity observed following removal of all axillary lymphatic tissue. The significant increase in lymphedema with dissection of level III nodes outweighs the potential benefit of detecting microscopic invasion in them. Invasion into level III nodes without involvement of levels I and II is exceedingly rare and supports the limitation of dissection to the more easily accessible nodes. Randomized controlled trials have confirmed that no improvement in overall survival occurs with complete excision versus axillary sampling.
The sentinel lymph node biopsy (SLNB) is an alternative procedure that allows patients without nodal metastases to avoid axillary dissection. In addition to decreasing morbidity associated with the procedure and being a more cost-effective modality for nodal staging, another advantage of SLNB is that it allows a more focused examination of the lymph node most at risk for metastatic disease.
The technique of injection may not be as important as the skill and experience of the surgeon with the chosen technique and with SLN identification in general. In their initial series, Krag et al demonstrated mapping failure rates of 18% and 35% based on the solitary use of radiocolloid and blue dye, respectively. Subsequent reports by Giuliano have demonstrated a failure rate of 5%. In the initial series of Cox et al, an initial failure rate of 6.6% was noted with a combination technique, which subsequently decreased to 5%.
Most groups would agree that improvement comes with learning and experience. Several factors are thought to contribute to mapping failure, including medial lesions that map to the intramammary nodes without concomitant drainage to the ipsilateral axillary lymph nodes, injection into a cavity with a mature lining, inflammation around a biopsy site that occludes lymphatic channels, obstruction of lymphatic channels by tumor cells, and complete replacement of lymph nodes by tumor. Inaddition, in older patients, the capacity of lymph nodes to retain the radioactive colloid or dye may be reduced because lymph nodes in the elderly tend to be replaced by fat. If physicians fail to identify the SLN, a complete AxLND should be performed. Importantly, SLNB is contraindicated in patients with palpable axillary adenopathy.
The standard of care for breast cancer patients with SLN metastases remains completion axillary lymph node dissection (CLND). Many people have questioned the need for CLND in every patient with detectable SLN metastases, particularly in those with a perceived low additional disease risk. Proponents of CLND argue that the total number of involved nodes is important prognostic information and can guide decisions regarding adjuvant chemotherapy. Proponents also cite the meta-analysis by Orr showing a 5.4% survival benefit associated with CLND.
Opponents of CLND argue that therapeutic benefit is minimal and that half of patients have no further axillary metastases. NSABP Z-11 was designed to answer the question regarding the necessity of CLND after positive SLNB, but the study closed early because of poor accrual. Researchers at Memorial Sloan-Kettering Cancer Center (MSKCC) have developed a nomogram to assist the clinician and patient in determining the likelihood of further axillary metastases before deciding whether or not to proceed with CLND.
Locally advanced breast cancer
Locally advanced breast cancer is, by definition, stage III, thus includes large lesions, with or without lymph node involvement, that have no evidence of distant metastases. Clinically, these lesions frequently involve the skin, are fixed to the chest wall, and/or have palpable gross lymphadenopathy. Core needle biopsy easily can be performed and provides adequate tissue for diagnosis and treatment planning. Standard of care includes neo-adjuvant chemotherapy with a doxorubicin-based regimen, surgical resection, and adjuvant chemotherapy followed by radiation.
Metastatic breast cancer
The prognosis of metastatic breast cancer is dismal, and treatment is aimed primarily at palliation. Surgical palliation may include mastectomy in patients with large and/or erosive breast masses. The role of reconstructive surgery in metastatic breast cancer remains controversial.
Preoperative Details
Preoperative preparation of the patient for breast surgery should include attention to psychosocial as well as surgical issues. Patients may have unexpressed concerns regarding risk of recurrence, need for adjuvant radiation or chemotherapy, surveillance, length of rehabilitation, and particularly cosmesis. In discussing treatment options, it is important not to neglect the options of immediate versus delayed reconstruction and/or augmentation.
From a surgical standpoint, routine preoperative lab testing should be performed based on the patient's age, presence of symptoms, and comorbid conditions. Preoperative administration of a first-generation cephalosporin is a common practice, albeit with no proven benefit.
Intraoperative Details
The keys to successful surgery of the breast include a thorough knowledge of anatomy, accurate assessment of the extent of disease, and recognition of the potential for future operations.
All biopsy incisions should be placed carefully with consideration for the placement of a future mastectomy incision. For instance, a radial incision in the upper inner quadrant does not incorporate into an elliptical mastectomy scar with the same ease as a horizontal or curvilinear incision. However, clearly, adequate surgical margins never should be compromised for the sake of cosmesis. Circumareolar incisions are cosmetically favorable and generally adequate for most central parenchymal lesions.
The axillary incision, if done separately, can be made in a curvilinear or S-shaped fashion based on surgeon preference. Dissection begins with incision of the clavipectoral fascia and identification of the lateral border of the pectoralis minor and the inferior border of the axillary vein. The vein then is traced laterally to the thoracodorsal complex. Once this has been identified with careful preservation of the nerve, attention is turned directly medially to the chest wall where the long thoracic nerve descends to the serratus.
Often, several branches of the intercostobrachial nerve can be identified superficially during axillary dissection. These can be divided if preservation means compromise of the extent of dissection. Level I and II lymphatic tissue is resected with a combination of blunt and careful sharp dissection. Use of electrocautery should be avoided during deep dissection. Hemoclips or sutures are used to divide small vessels or lymphatics to reduce the risk of seroma and/or hematoma formation. Next, an axillary drain, if placed, is brought through a separate stab incision inferiorly.
For a mastectomy, the standard elliptical incision includes the nipple-areolar complex and extends from the lateral border of the sternum to the latissimus dorsi. An umbilical tape or suture may be helpful in measuring the upper and lower sides of the ellipse to ensure even lengths and avoid dog ears, particularly at the lateral corner. Cat's paw retractors or rakes are used to elevate the skin edges, and flaps are raised superiorly and inferiorly using electrocautery. The thickness of the flaps ideally should be approximately 1.0 cm. This relatively avascular plane is readily identifiable with adequate flap traction perpendicular to the chest wall. The breast parenchyma is removed from medial to lateral either sharply or with electrocautery in continuity with the pectoral fascia. Care should be taken to ligate or cauterize any major perforating vessels. The axillary dissection then should proceed as described above through the same incision.
The authors routinely place two drains through separate stab incisions inferior and lateral just above the inframammary fold. One is placed in the axilla and the other in the parenchymal defect. Fine subcuticular suture is used to close the skin.
Postoperative Details
Immediate postoperative care involves assessment for appropriate wound healing and evaluation and treatment of postoperative complications such as seroma, wound infection, bleeding, and nerve damage. Drains are routinely removed when output is less than 30 mL/d. Seromas that develop following drain removal are usually best managed with repeat aspiration. Follow-up of the pathologic specimen should be routine to determine adequacy of margins in the resection of the primary tumor.
Early patient mobility and range of motion exercises should be encouraged postoperatively, although the timing and degree should be tailored to the extent of the procedure performed (ie, lumpectomy vs skin-sparing mastectomy with immediate reconstruction).
Follow-up
Surveillance
Recommendations for surveillance include baseline postoperative mammography of both breasts or of the remaining breast at 6 months and tapered clinical visits. Suggested frequency of clinical assessment during the first 2 years is every 4 months; every 6 months up to the fifth year; then annually for the remainder of the patient's lifetime. Mammography and chest radiographs also should be performed annually. Further workup is not indicated in the absence of suggestive symptoms such as bone pain, headache, or findings on annual routine laboratory chemistry panels.
Complications of all of the described procedures include wound infection, cosmetic disfiguration, and bleeding.
Although the incidence of wound infection is relatively low, the rate may be decreased further with the administration of appropriate prophylactic antibiotics.
Bleeding and hematoma formation should be avoided easily with meticulous hemostasis prior to skin closure. However, seroma formation, usually an adverse postoperative finding, is both expected and cosmetically beneficial after excisional breast biopsies. Inappropriate closure of "dead space" following lumpectomy may prevent accumulation of serous fluid and result in dimpling or distortion of the breast contour. In contrast, placement of drains for modified radical mastectomy prevents accumulation of serous/lymphatic fluid underneath the breast flaps and in the axilla and may decrease the likelihood of wound infection and dehiscence.
Unfortunately, lymphedema is one of the more common and debilitating complications of axillary node dissection. The incidence of lymphedema, using current techniques for axillary dissection, has decreased significantly. Removal of level III axillary nodes can increase the incidence from 3-10% when compared with limited level I and II dissection.
Neurologic injuries vary widely from mild traction neuralgias to major brachial plexus injuries. The brachial plexus may be spared by keeping dissection inferior to the axillary vein. The most common neurologic complaint postoperatively is numbness of the axillary skin and upper medial arm. This is secondary to transection of the intercostobrachial nerve as it crosses the axilla.
Necrosis of the skin flaps is an uncommon complication following mastectomy. Simple use of the standard horizontal incision for mastectomy, careful attention to flap thickness, and tension-free closure of the wound can prevent this unpleasant complication.
Survival in breast cancer depends on multiple social, biologic, and independent patient factors.
Accessibility to medical care, compliance with screening, level of education, and socioeconomic status all can impact the stage at which breast cancer first is diagnosed, which therefore influences survival.
Race has been associated with mortality from breast cancer in American women. The National Cancer Institute reported a 57% survival for black women versus 71% for white women.
Genetic predisposition also can influence outcome. Once diagnosis has been achieved, tumor size, receptor status, and axillary node involvement can affect prognosis.
A 20-year follow-up study from the BCDDP found overall 20-year survival rates regardless of age, stage, or treatment to be greater than 78%. For women aged 40-49 years, survival rate was 80% without accounting for stage and treatment. Older women (60-69 y) had a lower overall survival rate of 76%.
Tumor size clearly is associated with higher mortality. Lesions greater than 5.0 cm were associated with a 50-60% 20-year survival rate compared to those less than 1 cm, which had a 93-98% 20-year survival rate. The BCDDP also found, predictably, that nodal involvement also negatively influenced survival rates.
Choice of treatment modality also has significance with respect to survival. As discussed above, no statistically significant difference in survival was noted for patients with stage I and II breast cancers treated with breast conservation versus mastectomy.
For 2006, the 5-year survival rates for women in the United States have improved to 98% for disease localized to the breast. With nodal involvement, this decreases to 81%, and with distant metastases, the 5-year survival is only 26%.
Metastatic disease
Median survival for metastatic breast cancer is approximately 2 years. Post-menopausal patients are candidates for treatment with endocrine therapy with an AI, SERM, or agents such as fulvestrant, megestrol acetate, fluoxymesterone, or ethinyl estradiol. Chemotherapy regimens for all patients may include anthracyclines and taxanes similar to the recommended regimens for adjuvant treatment. Trastuzumab, when used in combination with chemotherapy, has been shown to improve overall survival time as well as time to disease progression.
Preliminary data had indicated potential benefit from stem cell rescue, cytotoxic chemotherapy, and autologous bone marrow transplant; however, currently no conclusive results support routine use of these therapies.
The standards of preoperative, operative, and adjuvant treatment require continuous reassessment in randomized controlled clinical trials.