Introduction: Mark Pegram, MD
Director, Stanford Breast Cancer Oncology Program
October 16, 2014
After skin cancer, breast cancer is the most common cancer diagnosed in women in the United States and the most common invasive cancer in women worldwide. According to the Centers for Disease Control and Prevention, more than 210,000 women in the U.S. are diagnosed each year and close to 40,000 die annually from the disease. Awareness of the disease, along with earlier detection and new scientific insights, has improved breast cancer survival rates dramatically over the past few decades.
The Stanford Women’s Cancer Center recognized October as National Breast Cancer Awareness Month by bringing together several specialists to discuss the latest screening and treatment advances in breast cancer.
Genetic Testing for Hereditary Breast Cancer
Courtney Rowe-Teeter, CGC
Certified Genetics Counselor
Inherited cancers begin in the DNA, the body’s cellular blueprint. Each cell contains two sets of chromosomes—one from the father and one from the mother—that replicate each time a cell divides. Chromosomes package genetic information in the form of genes, the blueprints that tell our bodies how to grow develop and function. Therefore it is always important to assess for a history of breast and other cancers on both sides of the family.
The genes tested in the Stanford hereditary cancer clinic are considered tumor suppressor genes. When working correctly they prevent cells from growing out of control or inhibit tumor development. And individual who inherits a mutation within one of these tumor suppressor genes has a higher lifetime risk to develop cancers associated with those mutated genes..
Most breast cancer diagnoses are sporadic, developing by chance, and are not due to an inherited gene mutation. Only about 5 to 10 percent of breast cancers are thought to be due to a single underlying inherited gene mutation. Inherited mutations in the BRCA1 and BRCA2 genes are the most common cause for hereditary breast cancer; mutations in these genes primarily lead to increased risk for breast, ovarian, prostate, and pancreatic cancer. Recent research has identified more genes that contribute to hereditary breast cancer.
Next-generation sequencing technologies now allow for clinical analysis of multiple genes simultaneously. Panel testing is a more comprehensive—and cost-effective—approach than testing one gene at a time. “The BRCA genes do not work in a vacuum; there are other genes and a cascade process involved,” said genetic counselor, Courtney Rowe-Teeter. “Panel testing allows us to cast a wide net to catch a broader range of gene mutations that could be underlying a history of breast and other cancers.”
Most inherited gene mutations that predispose to cancer development are inherited in an autosomal dominant manner. That means each individual with the mutation has a 50 percent chance of passing it along. When a specific mutation has been identified, targeted testing for that specific mutation becomes available to family members.
The ultimate goal of genetic testing is to identify individuals with an inherited predisposition to cancer so they can be proactive in developing a focused medical management plan with their physicians to allow for early detection and prevention. Genetic counselors are a critical component to the genetic testing process. They help patients and their families understand the genetic contributions to developing cancer, what type of information genetic testing could yield, and in collaboration with physicians create personalized plans to manage their risk regardless of the test result. “We translate the information we find to help women and men make educated choices,” she said.
Breast Surgery: We’ve Come a Long Way
Amanda Wheeler, MD
Clinical Assistant Professor of Surgery
The breast contains milk-producing glands called lobules that are connected to the nipple by ducts. Much of the rest of the breast is composed of fatty tissue which is usually in proportion to the rest of your body. Cancer that begins in the milk duct, known as ductal carcinoma, is the most common; cancer that begins in the lobules is known as lobular carcinoma.
Surgical treatment of breast cancer involves a multidisciplinary team of specialists, from radiologists to microvascular surgeons. How the cancer is treated depends on the size of the tumor, whether the cancer is invasive or non-invasive, whether lymph nodes are involved, and whether the cancer has spread. There are additional elements that also must be factored in to determine the most appropriate surgical approach.
For example, improved screening from mammograms and breast imaging has led to a dramatic increase in early detection and smaller tumor size. “The size of the tumor at diagnosis has decreased over time due to regular screening mammograms,” said Dr. Wheeler. “The smaller a tumor is when first detected, the better the cosmetic results.”
The goal of breast surgery is to remove the tumor which can be made significantly smaller following chemotherapy. Strategies have changed over the years, and today surgeons can spare much of the overlying skin and nipple area for a more normal-appearing mastectomy. Oncoplastic surgery and advances in micro-reconstruction also are leading to better cosmetic outcomes.
“Breast cancer is an emotional diagnosis for women, but the techniques for surgical treatment are greatly improved, especially with early detection,” Dr. Wheeler said.
Reconstructive Surgery: Rebuilding After Breast Cancer
Rahim Nazerali, MD
Clinical Assistant Professor of Plastic and Reconstructive Surgery
For the one in eight American women dealing with the aftereffects of breast cancer treatment, such as a mastectomy or lumpectomy, reconstructive surgery can restore their body’s natural shape and form, and improve self-esteem.
Some women prefer to have breast reconstruction immediately, which has improved aesthetic results but can delay follow-up therapy if complications occur. Others choose to wait after the initial surgical procedure. Research has shown that the more an institution performs a procedure, the better the results are, so be sure to ask your doctor how many reconstructions he or she has done. Additionally, ensure your surgeon is board certified by the American Board of Plastic Surgery and ask about areas of expertise and specialized training. The surgeon should be trained and have expertise in microsurgery to be able to provide you the comprehensive set of options for reconstruction.
The most common breast reconstruction option is implants, which is considered an extremely safe procedure with a rapid recovery time. It requires only a brief surgery but involves a two-step process. The reconstruction first requires tissue expansion, a gradual process that stretches the chest skin and expands tissue to make room for the implant. The expander is then exchanged for a permanent implant made of either silicone or saline. Although nipple sparing procedures are becoming more common, if that is not an option during the mastectomy, local tissue rearrangement and tattooing can create a similar appearing nipple as an outpatient procedure.
Women can also use tissue transplanted from another part of the body, a process called autologous reconstruction. A flap of tissue composed of skin, fat, and sometimes muscle is detached with its blood supply, usually from the abdomen, thighs, or butt. This tissue is then moved to the chest, where it is reattached and formed into the shape of a breast.
Using specialized microsurgery techniques, the vessels are stitched into place. Breast reconstruction using transplanted tissue lasts a lifetime and looks natural. In addition, the patient gets an added bonus of a tummy tuck or butt lift depending on where the tissue was taken, Dr. Nazerali said. However, the procedure can be lengthy, involves specialized surgical expertise, and requires a longer recovery time.
Jafi Lipson, MD
Assistant Professor of Radiology
Technological advances have made a great impact on imaging, an essential resource for assessing risk, improving early detection, directing pre-operative localization, and tracking outcomes. It requires special expertise to interpret mammograms, MRIs, and other imaging modalities to help target deep breast tumors and spare nearby healthy tissue. Stanford has been a long-time pioneer in developing and refining the field of radiology.
Every major breast care organization recommends having a mammogram annually starting at age 40, unless the woman is at high risk, in which case screening mammography may start at a younger age. If a screening test result is abnormal, the patient will be called back for additional mammographs and possible diagnostic breast ultrasound. If suspicious findings persist, a minimally invasive breast biopsy will be recommended. Biopsied tissue is sent to the pathology lab for analysis, and the lab’s findings will be correlated with the radiologist’s reading. After diagnosis, some women will undergo a dynamic contrast-enhanced breast MRI, a noninvasive imaging scan that can identify additional sites of disease.
Radiologists also play an important role during surgery, placing a pre-op wire into the tumor to guide the surgeon to the exact location to excise and reviewing a specimen X-ray during the procedure to ensure that the entire tumor is removed. They also provide follow-up surveillance with mammograms during and after treatment.
A new imaging breakthrough called breast tomosynthesis offers a more accurate image compared to standard mammography. Used in conjunction with two-dimensional digital mammography, the technology takes multiple low-dose images and then reconstructs the slices into a three-dimensional image volume. Breast radiologists can see through layers of tissue and examine areas of concern from all angles, which helps to improve breast cancer detection rates and reduce the patient callback rate.
Another promising new breast imaging tool, soon to be tested in clinical trials at Stanford, is called contrast-enhanced digital mammography (CEDM), a detection modality that uses low levels of radiation and an iodine-based contrast agent to visualize vascular tumors. The resulting images compare a regular mammogram and the contrast information. Preliminary studies have shown that CEDM to be a low-cost, well-tolerated option and may approach the diagnostic accuracy of breast MRI.
“We continue to develop and refine patient-centered solutions,” said Dr. Lipson.
Breast Cancer Oncology
Mark Pegram, MD
Director of the Stanford Breast Cancer Oncology Program
Cancer by its very nature is genetically unstable and can mutate rapidly, scrambling chromosomes at a rapid pace. This process makes it hard to treat—the cancer becomes a moving target in terms of treatment options. The situation becomes even more complex because there can be multiple mutations in one tumor, adding yet another level of complexity. There also can be a lack of cellular uniformity in mutation profiles even within the same tumor from the same patient (molecular heterogeneity).
Because breast cancer genes are so complicated and easily altered, early detection and prevention is a real key to treating the disease, he said. There is also a direct link between heterogeneity and drug resistance.
“Most of the complexity [in breast cancer] has already occurred by the time of diagnosis,” said Dr. Pegram, who is co-director of Stanford’s Molecular Therapeutics Program. “Consequently, a theoretical ideal would be to intervene as early as possible in the evolution of a cancer, before the it acquires the ability to spread.”
For example, one recent study found a 98 percent relapse-free survival rate in HER2-positive breast cancer patients (human epidermal growth factor receptor 2) is a protein that, when overexpressed, promotes aggressive cancer growth], who were treated early with taxol plus Herceptin. Herceptin is an antibody that binds to HER2 and prevents just those cells from multiplying.
Other studies at Stanford are looking at therapeutic antibodies that use the body’s natural immune system defense mechanisms to target and destroy cancer cells. In one ongoing study, researchers are employing engineered antibodies (with more potent immune stimulating capabilities) to enhance anti-tumor response. These types of immune-enhancing strategies may hold promise for patients who do not respond to standard treatments.
To learn more about breast cancer research and treatment innovations, please visit the following websites: