Today, we know more about breast cancer than ever before. With advances in screening technology and improved treatment options, millions of women with breast cancer are living longer and healthier lives.

Although breast cancer rates are on the decline, public health experts note a disturbing trend: a small but significant decrease in the number of women scheduling annual mammograms for a variety of reasons—cost, insurance, feelings of invulnerability, anxiety, scheduling conflicts, and discomfort, among other issues. Early detection of breast cancer can mean the difference between life and death. Certainly, that was the message of Robin Roberts, popular news anchor of Good Morning America, who recently focused national attention on the issue.

After discovering a lump, the otherwise active, healthy woman faced her fears and immediately saw her doctor, who after biopsy confirmed that Roberts had an early form of breast cancer.

"Hearing the doctor say those words out loud was surreal," recalls Roberts, who underwent successful surgery and follow-up treatment. "I can't stress enough how important it is to get screened and checked for all cancers—and to do self breast exams. I am so blessed that I found this in the early stages, and the prognosis is so promising."

To explore the latest diagnostic and treatment advances, as well as the issue of screening, the Post spoke with Kelly K. Hunt, M.D., F.A.C.S., chair, breast committee of American College of Surgeons Oncology Group and chief of surgical breast section at the world-renowned M.D. Anderson Cancer Center.

Post: Statistics from the CDC confirm that the rates of breast cancer have fallen. What is behind the decline?

Dr. Hunt: It's a combination of factors. Discontinuation of hormone replacement therapy (HRT) appears to be one reason, but the incidence started to decrease before 2002 when the recommendation against routine hormone replacement therapy was given.
Over the past decade, improvements in mammography—both in terms of the technique and radiologists' training in reading the screening, and understanding which patients to call back for additional views and assessment—definitely play a role in the declining mortality rates from breast cancer.

Post: Despite the decline, the National Cancer Institute recently reported that mammography rates are going down in the U.S. Are you witnessing this trend?

Dr. Hunt: Yes. In some cases, older women neglect mammograms because they feel that screening is really not important and perhaps do not completely understand the risk. In contrast, younger women tend to overestimate risk. For example, statistics suggest that one in eight women will develop breast cancer by age 80. Younger women believe that the estimated risk applies to them, even at age 35 or 40, while older women may feel that breast cancer may have skipped them.

I always strongly encourage women to undergo routine mammograms. When we diagnose later-stage breast cancer, it is usually in a woman who missed a year or two of screening. As a result, women who skip scheduled mammograms and then are diagnosed with breast cancer experience tremendous guilt. Breast cancer is unfortunately a very common disease in the United States and Western countries in general. As pap smears became very important in general health screening years ago, the same is true for mammography. Even though women may dislike the discomfort, a mammogram is a brief annual exam.

Post: Would you highlight the important risk factors for the disease?

Dr. Hunt: Age and family history are very important. Among younger women, family history may be more relevant, especially in an individual who has a family history of early onset—30s or 40s—and bilateral breast cancer, because early onset suggests more of a genetic component. While many factors play a role in the development of breast cancer, family history is definitely more critical among younger women. When I see younger women diagnosed with breast cancer who have a family history of early-onset breast cancer, I strongly encourage genetic testing.

In older women, particularly those in their 60s or 70s, we use genetic testing less frequently because the detectable genes responsible for hereditary breast cancer are more commonly seen among women in their 30s and 40s. However, I recently cared for a breast cancer patient in her 60s whose daughter—in her early 40s—was later diagnosed with the disease. We suggested genetic testing. Indeed, the daughter had a genetic mutation and underwent a prophylactic mastectomy and removal of ovaries because the mutation was associated with breast and ovarian cancers. Even through both mother and daughter carried the gene, for some reason it took many more years for the mother to develop the disease. Even though people carry susceptibility genes, that doesn't mean they will definitely get the disease in their 30s or 40s; however, there is a greater risk.

Post: What percentage of breast cancer is believed inherited, and how far have we come in understanding the genetics of breast cancer?

Dr. Hunt: Probably 10 percent—at the most 15—is actually inherited breast cancer.

We've come an amazing distance in the past decade in understanding the genetics of cancer. Today, we are participating in a project called The Cancer Genome Atlas (TCGA) pilot project. In one trial, we use tumor tissues collected during surgery to develop the breast cancer genome. Once completed, we will have made a major advance in understanding the genetics of breast cancer. Over the past decade, we have looked at individual genes, but gains and losses in genes may cause aberrations in pathways important in cell signaling and tumor growth. When the breast cancer genome is complete, we will have much more information.

Post: Will genetics be useful in selecting treatment?

Dr. Hunt: Genetic profiling is definitely going to be critical in treatment decisions. Our committee at the American College of Surgeons Oncology Group has ongoing trials using prognostic and predictive factors like the estrogen receptor and HER-2/neu oncogene. We use these predictive markers to select and guide treatment. Genetic profiling on individual tumors—gains and losses in the DNA content of the tumor—helps us understand which pathways are activated, or knocked out, in an individual tumor. For example, if a tumor has HER-2/neu overexpression, we know what drug to use because we know what pathway is in place. That knowledge is absolutely critical. Now, we routinely test for HER-2/neu in the tumor. Within five to ten years, genetic profiling of tumors before determining treatment will be routine.

Post: Do you use positron emission tomography (PET) and magnetic resonance imaging (MRI) scans?

Dr. Hunt: In my own practice, PET scans are definitely useful for patients with more advanced disease. PET scans help identify individuals who have early sites of metastatic deposits that we wouldn't detect through a standard CT scan.
Eventually, MRI will be a great tool. While there's a lot of excitement about the use of MRI, we haven't figured out how to deal with so many benign findings in the breast that an MRI detects—which can initially be interpreted as suspicious for cancer.

Post: Is breast self-examination still important?

Dr. Hunt: Many women detect breast cancers during a breast self-exam. But breast self-examination is less relevant as an important focus in routine breast health, because data do not suggest that we can improve breast cancer survival by teaching women breast self-examination. While not every cancer can be found this way, it is an easy step women can and should take for themselves.
Self-exams are important to educate women about what to look for. Through self-exams, we may find cancer at its earliest stage. Many women are uncertain what they are looking for, but should get comfortable with their own breasts and know how they usually feel and appear. If something feels different, a woman should contact her doctor. For example, when getting dressed, women may notice redness of the skin or puckering of the tissue. A close inspection of the breast may reveal noticeable changes to breast tissue that could be early signs that there's something wrong, prompting them to visit a physician earlier.

Post: Why is inflammatory breast cancer (IBC) difficult to diagnose?

Dr. Hunt: In IBC, there's usually not a specific mass that you can identify. In most women at time of examination, IBC is a very acute finding where, say, last week they were perfectly normal, then all of a sudden they experience swelling and redness of the breasts. The first thought is that the swelling and redness may be an infection, like mastitis, which many women have had. With mastitis, patients are treated with antibiotics and dismissed. On a mammogram of a patient with IBC, radiologists may notice skin thickening and edema but cannot identify specific masses within the breast. No one does a biopsy if they don't see a specific area to biopsy. As a result, IBC can go undiagnosed for weeks or months until someone finally does a skin biopsy—the easiest way to confirm diagnosis. You can do a punch biopsy of the skin, similar to what a dermatologist would do for a skin lesion, and find tumor cells within the lymphatic channels—a finding that aids diagnosis.

Post: Can you outline the role of prevention and steps women can take to reduce their risk of developing breast cancer?

Dr. Hunt: There is an easily accessible risk assessment program on the NCI website (http://www.cancer.gov/bcrisktool). One can input age, family history, and any breast biopsies performed in the past, then receive an assessment of risk—both lifetime and five-year risk assessments. A nurse, nurse practitioner, physician, or other healthcare professional who understands risk assessment can help discuss strategies for risk reduction. Risk can change. Obviously, family history changes when members are diagnosed or undergo breast biopsies that show some abnormal, proliferative changes in breast tissue. Using the free NCI website, women can get a risk assessment, which they should do as part of their general health screening. If they are found to be at higher risk than the general population, women can participate in many different types of activities. Diet and exercise are certainly important, but some drugs, such as raloxifene and tamoxifen, are available for breast cancer prevention. We definitely can reduce the incidence of breast cancer using proven risk-reduction strategies. Women should find out what their individual risk is and decide with the advice of their physician if they should employ some type of risk reduction.

Post: What is the link between diet and the risk of breast cancer?

Dr. Hunt: There is a tremendous amount of information in the scientific literature, but it's murky. The really solid data suggest that high-fat diets contribute to breast cancer, and obesity is certainly an important risk factor. It's a really challenging area of study, because of today's fast-paced lifestyle and reluctance to adhere to a healthy diet.

Post: Do you advocate supplementation of certain vitamins or minerals?

Dr. Hunt: A multivitamin usually has all the necessary supplements. The ongoing and emerging studies are important, but questions remain as to when women should start utilizing specific supplements. Vitamin D and calcium are important, especially in reducing the incidence of breast cancer in premenopausal women. We still have a lot to learn.

Post: Are tests available to determine potential relapse?

Dr. Hunt: Yes and no. Some tests help to risk-stratify women. For instance, in women who have estrogen-receptor positive (ER+) breast cancer that has not spread to the lymph nodes, a test can be performed on the tumor tissue to rank them in low-, intermediate- or high-risk categories. The information can also help clinicians decide treatment. If the woman is at very low risk for recurrence, we may not need to administer chemotherapy. The test, however, is really only valid for the specific subset of estrogen receptor-positive, node-negative breast cancer.

Another test under development looks at circulating tumor cells in the blood, a test that has been shown to help predict relapse in women with metastasic breast cancer; it's also being studied in earlier-stage breast cancer. However, there is not yet a definitive test that can say whether you will definitely relapse.

We are also looking at the bone marrow as a site where breast cancer stem cells—the cells that appear to initiate the process—seem to nest. When we detect breast cancer stem cells in the bone marrow, those women are at the highest risk for recurrence. Actually, our team—the American College of Surgeons Oncology Group—just published an article from one study looking at bone marrow, and we have identified these stem cells within the bone marrow. However, we have yet to prove that those stem cells are responsible for treatment failures. While this is an exciting finding, we still don't understand if those cells are definitely the ones that fail to respond to chemo and lead to distant metastasis.

Post: For women undergoing breast reconstruction, are silicone implants a viable and safe option?

Dr. Hunt: The silicone implant is definitely safe, and we offer that option to women, although we have to go through an extensive consent process for them to be able to utilize the silicone implants.

Post: Could you discuss recent advances in breast cancer treatment, such as targeted radiation therapy?

Dr. Hunt: Traditionally, whole breast radiation therapy is given after a lumpectomy to kill any stray cancer cells that might remain in the breast. A form of targeted radiation therapy, partial breast radiation targets only the tumor site and a small area of surrounding tissue. Women who have what appears to be favorable breast cancer—the estrogen receptor-positive, lymph node-negative small breast cancers—do very well with more targeted radiation therapy. In these cases, women have less risk of developing other diseases in the breast.

Post: What is MammoSite, and how does it work? What are the advantages?

Dr. Hunt: The MammoSite was designed as a breast brachytherapy applicator and is used to deliver accelerated partial breast irradiation in patients undergoing breast conserving surgery (lumpectomy). The advantages are that the radiation is delivered over a shorter period (five to seven days as opposed to the standard five to six weeks with whole breast radiation). The data on local recurrence rates and cosmetic outcomes are still being collected. There is a national trial comparing partial breast irradiation (using the MammoSite and other types of partial breast irradiation) versus whole breast irradiation. This is an important trial that will help to define which patients are appropriate candidates for this type of treatment.

Post: Are oncologists using angiogenesis inhibitors to block the formation of new blood vessels that feed and sustain the growing tumor?

Dr. Hunt: Angiogenesis inhibitors are being used in treatment. The one that has received the most attention is bevacizumab (Avastin), but other agents are in clinical trials. We know that angiogenesis—the process of developing new blood vessels—is very important to sustain tumor growth and spread. The question is how we can safely administer the therapy, because it has side effects that affect other systems in the body. Earlier anti-angiogenesis studies utilized a blanket approach, which had an impact on the entire body. Today, the consensus is that we need a targeted approach. Tumors are associated with specific types of cells important for growth of blood vessels. The goal is to develop targeted agents that reach only tumor-nurturing blood vessels and not blood vessels in other important areas of the body.

Post: Would you comment on the potential side effects of angiogenesis inhibitors recently noted in animal studies?

Dr. Hunt: There are definitely some side effects even in the human trials that have been performed. Hypertension is one that has been noted. It is still early in the process of clinical trials, and the animal studies are helpful but may not be definitive—especially the animal model that was used in this study, which was bred specifically to knock out all the activity of a specific gene involved in blood vessel growth. Angiogenesis is important in normal tissues as well as cancer, and so the key is to determine how to specifically target the vasculature within the cancer.

Post: Is tamoxifen still one of our most important therapeutic tools?

Dr. Hunt: During the past three decades, tamoxifen has probably cured more breast cancers than any other breast cancer treatment. We now know that tamoxifen is only useful in estrogen receptor-positive disease and is only effective for five years. Most studies have suggested that if tamoxifen is used longer than five years, the treatment can actually be detrimental. The medication has many potential side effects—uterine cancer, deep vein thrombosis, increased rate of cataract formation (especially in older women), hot flashes and vaginal dryness, and quality-of-life issues. Tamoxifen is falling out of favor, especially in the postmenopausal patient group where we observe more significant rates of uterine cancer, cataract formation, and deep vein thrombosis.

Aromatase inhibitors—Arimidex, letrozole, and exemestane, for example—that lower the amount of estrogen have emerged as the favored therapy in postmenopausal women, even after use of tamoxifen therapy. We now use Arimidex at M.D. Anderson Cancer Center as a frontline therapy for postmenopausal women who have estrogen receptor-positive breast cancer. If the patient has difficulty tolerating Arimidex or an issue with bone health, we will use tamoxifen because people on aromatase inhibitors do have a higher incidence of osteoporosis and musculoskeletal fractures.

Post: What other treatment advances are emerging?

Dr. Hunt: Another huge advance in the past few years is trastuzumab (Herceptin), which is the antibody to the HER-2/neu oncogene that appears to be important in approximately 20 to 30 percent of breast cancers. Over the past decade and in multiple trials, we've found that using chemotherapy with Herceptin in women whose tumors have the HER-2/neu gene leads to a marked improvement in chemotherapy response and a major reduction in the risk of recurrence of breast cancer.

Post: Is it important for women to enroll in ongoing clinical trials?

Dr. Hunt: The only way we'll be able to continue to improve our treatments is for women to participate in ongoing clinical trials for all types of breast cancer. I encourage as many women as possible to participate in these trials because that's where we've made all the advances. These women are the real heroes: not the doctors who do the trials but the patients who participate in them, because that's where we learn.

Post: What is the focus of your research?

Dr. Hunt: My research is on cell cycle as an important aspect of breast cancer growth. The cell cycle is what regulates the growth of cells, and there's a specific pattern that cells go through before they divide. In breast cancer specifically, a type of aberration occurs where too much of a specific cell cycle regulator called cyclin E promotes cells to continue to grow, divide and make more cells. It appears important in about 30 percent of breast cancers, so it's similar to the HER-2/neu oncogene and very important in identifying breast cancers that will not respond to hormonal therapies, such as tamoxifen and aromatase inhibitors. We're actually developing agents similar to Herceptin to make breast cancer cells more sensitive to breast cancer therapies.

Post: You so often hear women say, "I ate right, I exercised, I always stayed the perfect weight, there's no family history—how could I have breast cancer?"

Dr. Hunt: I hear that quite frequently. We're still missing important information and research, which highlights why genetic research, understanding risk, and the role of diet, exercise, and family history are so important.
We are getting closer. The progress is amazing. When I started practice many years ago, improvements were just incremental, but today we are witnessing huge improvements in breast cancer detection, treatment, and understanding, because of the technology that's available to us now. We're going to see major advances in the next five to ten years.