Treating Breast Cancer
Improved diagnostic techniques and targeted treatments offer help and hope
When it comes to breast cancer, the bad news is that 8,907 Georgians were diagnosed with the disease last year alone – and the chance of receiving that feared diagnosis has been increasing. In the United States, a woman’s chance of being diagnosed with breast cancer in her lifetime is one in eight – up from one in 11 just three decades ago.
Scientists cite a number of possible reasons for this increased risk: Two key ones are the trend of delayed childbearing and rising rates of obesity. Not having children or having your first child after age 30 increases your risk for breast cancer, and fat tissue associated with obesity produces excess levels of estrogen, which have been associated with breast cancer risk.
Yet another reason is the fact that more cancers are being detected due to improved awareness and screening, says Thomas A. Samuel, M.D., associate professor of medicine in hematology/oncology at Georgia Regents University in Augusta and founder and co-leader of the Georgia Health Sciences Uni-versity Multidisciplinary Breast Cancer Program. “We know that mammogram screening has in-creased in the last 20 years, so a lot of earlier cancers are being picked up,” Dr. Samuel says. “Some of these may be one of these situations of if we didn’t find it, we may have never known about it. I think that is why incidence has gone up to some extent.”
Often screenings reveal cancerous lesions long before a woman would have felt a lump, and in many cases while the cancer is still highly treatable. That, says Dr. Samuel, is part of the good news about breast cancer. “We are detecting it at an earlier stage when we have a chance to do something of benefit.”
More good news: Improved diagnostic and screening techniques and targeted treatments are often more effective than more conventional treatment – and less invasive. Here are some of the major advances helping Georgians with breast cancer today as well as a look at what’s ahead.
For three decades, a mammogram has been the standard screening tool for breast cancer. The procedure involves flattening the breast between two plates and taking X-ray images. X-rays can show lumps or masses in the breast or calcifications (deposits of calcium) that could be a sign of cancer. Increasingly, however, medical centers are using more advanced tools such as magnetic resonance imaging (MRI), ultrasound or computed tomography (CT) scans to screen for or diagnose breast cancer, particularly for women at highest risk.
At Georgia Regents University, a technique called 3-D tomographic mammographic screening is available to all pa-tients who come for breast cancer screening, says Dr. Samuel. In women having this kind of screening, X-ray machines take pictures of thin slices of the breast from different angles. Computer software then uses the different images to construct a 3-D image of the breast similar to the way a CT scanner produces images of structures in the body.
A study published in January 2013 in the journal Radiology shows that adding 3-D tomography to traditional mammo-graphy increases the rate of cancer detection by as much as 40 percent, while reducing false positive results by 15 percent.
This 3-D tomography, says Dr. Sam-uel, “is a very advanced way of looking at mammograms to try to detect lesions that we have not been able to pick up with [traditional] mammograms. That is a huge advancement now.”
When abnormalities are found through traditional mammograms or 3-D tomo-graphy, increasingly doctors are referring their patients for an MRI or ultrasound of the breast before sending them to a surgeon.
“If something is thought to be a problem on mammogram, MRI or ultrasound will confirm that or, more importantly, not confirm it, relieving patients of having to go through a biopsy,” Dr. Samuel says.
For a woman with confirmed or suspected breast cancer, surgery is almost always a component of treatment, but advances over the years have been steadily reducing the trauma of surgery for most women. The biggest advance has been the shift from radical mastectomy – removal of the breast, underlying chest muscle and nearby lymph nodes, as was commonly done prior to the late 1980s – to lumpectomy, removal of the tumor and the immediate surrounding tissue while leaving the rest of the breast intact.
Yet even women who have been able to keep their breasts have often had to endure the pain and other risks of having their axillary (underarm) lymph nodes removed.
Traditionally, breast surgeons removed the lymph nodes under the arm on the side of affected breasts out of concern that the cancer may have spread to them, says Matthew Pugliese, M.D., a medical oncologist at Georgia Regents University Cancer Center. However, doing so often meant removing healthy lymph nodes and unnecessarily subjecting women to risks such as lymphedema (swelling and fluid retention) and increased risk of infection.
That began to change in the 1990s, when researchers discovered a way to identify so called sentinel lymph nodes, the first few lymph nodes into which a tumor drains. The procedure, referred to as axillary mapping, involves injecting two types of dye into the breast tissue during surgery. The dyes are taken up by the lymph system of the breast and travel to those most important lymph nodes, says Dr. Pugliese. While the patient is still on the operating table, doctors are able to identify the sentinel nodes by the accumulation of dye and remove only those nodes for examination.
“Historically, we believed that if the [sentinel] lymph node was normal, all of the other lymph nodes were going to be normal, too,” says Dr. Pugliese. “That has turned out to be a very accurate predictor. If that sentinel node is normal, then we can leave the rest of the lymph nodes alone.”
For about 80 percent of patients, the sentinel nodes are normal, which means that in recent years only 20 percent of patients have had to have all their axillary lymph nodes removed, a procedure known as axillary dissection. Now research findings are helping doctors reduce that percentage even further.
“What was happening was when we found a tumor in the sentinel node and then removed the other nodes, a large number of patients didn’t have tumor in any of the rest of the lymph nodes,” says Dr. Pugliese. “What we wanted to know is how to predict who was going to be helped by this operation and who was not, and that led to a whole new round of studies that have shed light on which patients are safe not having their other lymph nodes removed.”
Additional patients deemed safe to forgo axillary dissection are those who have had a lumpectomy, only one or two positive sentinel nodes, and no extranodal extension, which is a tumor growing out of the lymph nodes into the surrounding tissue, says Dr. Pugliese. They must also have plans for radiation following their lumpectomy.
“Twenty years ago, we would have removed all the lymph nodes in 100 percent of patients with breast cancer,” he says. “Now we are removing them in only 10 percent.”
One of biggest potential advances in reducing surgical trauma could mean the elimination of surgery altogether for some women, says Ray Rudolph, M.D., a breast cancer surgeon at Memorial University Medical Center in Savannah. Memorial is currently involved in a multi-center clinical trial treating ductal carcinoma in situ (DCIS) with drugs called aromatase inhibitors. DCIS is a cancer confined to the lining of the milk ducts of the breasts. Aromatase inhibitors are drugs that block an enzyme called aromatase that changes other hormones into cancer. By blocking the enzyme, they reduce levels of estrogen that fuel the growth of some breast cancers.
Traditionally, women with DCIS have been treated with lumpectomy followed by radiation. In the trial, however, they are given an aromatase inhibitor instead of immediately being scheduled for surgery, says Dr. Rudolph. After three months of treatment with an aromatase inhibitor, doctors repeat a breast MRI. If the cancer hasn’t gotten any worse, the women receive the drug for another six months, then have a repeat MRI followed by a lumpectomy.
“This is an initial trial to try to show that aromatase inhibitors by themselves may be effective in helping downgrade DCIS into a nonmalignant lesion perhaps,” says Dr. Rudolph. “That may mean that eventually, after years of study and evaluation, we could wind up with a medical treatment for DCIS instead of surgical treatment. It would be great if you found out you needed no surgery or radiation whatsoever for that type of cancer.”
Like surgery, the need for radiation therapy is a given in almost all cases of breast cancer. Studies show that women who forgo radiation after a lumpectomy have a 40 percent chance of their cancer recurring, but receiving conventional (external beam) radiation can be a time-consuming process, usually requiring 33 sessions over the course of six and a half weeks, says Dr. Rudolph. Side effects can include reddening of the skin and hardening and shrinkage of the breast tissues as well as the potential risks of subjecting healthy underlying tissue to the effects of radiation.
A new procedure called intraoperative radiation therapy (IORT), however, is minimizing the need for post-surgical radiation by administering a targeted dose right at the time of surgery – and right where it is needed to kill cancer cells, while sparing healthy tissue. The procedure involves placing a device into the cavity where the lump was removed while the patient is still asleep on the operating table. “The radiation oncologist comes into the operating room, calculates the dose of radiation and gives it in the operating room for approximately 20 to 35 minutes while the patient is still asleep,” he says. “When they are done, we remove the device, sew them up and send them home.”
The first center in Georgia to offer IORT, Memorial has used it on 37 patients thus far, and Dr. Rudolph calls the results “excellent.”
For some women, IORT reduces the time for post-surgery radiation from six to four weeks, but for another group it eliminates the need for further radiation completely. “If you have no positive margins, no positive nodes and are over 45, then your radiation therapy is done and complete,” says Dr. Rudloph.
New research shows that patients who undergo IORT have a slightly increased risk of cancer recurrence than those who undergo a full course of traditional external beam radiation after surgery, yet the death rate for patients receiving IORT is actually lower, Dr. Rudolph says. “We think that might be due to minimal heart and lung effects [due to radiation therapy], because IORT is given exactly in the spot.”
Targeted Drug Therapies
While the chance of a breast cancer diagnosis has increased in recent decades, so fortunately has the life expectancy and, importantly, the quality of life for women who receive that diagnosis.
That is due in large part to targeted therapy that minimizes not only the trauma of surgery but also the trauma of strong drugs used to control cancers.
“The emphasis of medical treatment has been moving away from ‘let’s destroy the tumor with a jackhammer-type of approach’ to using more targeted chemotherapy,” says Dr. Samuel. “I use the analogy [that] we are using sniper methods instead of using the IED [improvised explosive device] kind of method that we used in the past. We are targeting tumors to create less collateral damage, less of the severe side effects that gave chemotherapy a bad name.”
An important advance that has made this possible is technology that enables doctors to categorize breast tumors into three different types: estrogen-dependent or estrogen-driven breast cancer, human epidermal growth factor receptor 2 (HER-2/neu)-positive or dependent, and triple negative.
“In women who have estrogen-positive breast cancer, we have medications that are targeting the estrogen pathways, and those drugs are very important in increasing the likelihood that a woman with early breast cancer is cured,” says Hillary Hahm, M.D., Ph.D., a medical oncologist and breast cancer specialist with North-west Georgia Oncology Centers in Marietta.
HER-2/neu is a protein on the surface of some cancer cells that is an important part of the pathway for tumor growth and survival. A major step in treating HER-2/neu-positive cancer came a decade ago with the approval of trastuzumab (Herceptin®), the first drug to target the HER-2/neu pathway. Since then, a number of other HER-2/neu drugs have become available, and others are still in development, including one called T-DM1, which could be approved by the FDA by press time.
T-DM1 is a protein that targets the HER-2/neu receptor – which is like an antenna on the outside of a cancer cell – attached to a very potent chemotherapy drug, says Dr. Hahm. “This drug is so potent that by itself it is too toxic to be used in patients,” she says. “But by linking it to this protein and targeting it to the cancer cell, that chemotherapy is only released within the cancer cell itself. This makes it a very effective drug in killing off the cancer cell, but it doesn’t have a lot of toxicity because it is not released outside the cancer cell. It is kind of a smart delivery.”
The hardest-to-treat breast cancers are the triple-negative cancers. “The holy grail in breast cancer right now is finding a specific target for triple-negative breast cancer,” says Dr. Samuel. “We haven’t found it, but there are a lot of good candidates.” Among the most promising candidates are drugs that target a pathway called P1K3 to help keep cells from proliferating and to induce cell death. Research shows that these drugs may also be helpful add-ons to therapy for women with HER-2/neu-positive cancers that have become resistant to HER-2/neu-targeting agents.
In addition to finding ways to deliver chemotherapy to specific cells, re-searchers are trying to determine which patients can best benefit from chemo-therapy in hopes that the others can be spared chemotherapy altogether.
“Chemotherapy is a dangerous treatment,” says Dr. Rudolph. “Besides losing your hair and getting sick, there is a known mortality rate – some patients die of infection while receiving chemotherapy, and a substantial number of people many years later will develop lymphoma or leukemia. If we can get chemotherapy to patients who need chemotherapy and not give it to those who don’t, we are much better off and the patient is much better off.”
Scientists envision a day when there is a machine that analyzes tumor tissue and determines the best type of treatment for it. “We’ll take the tumor specimen, put it into one side of a machine, and the machine spits out on the other side ‘this is the ideal therapy for this particular tumor,’” says Dr. Samuel.
The ideal therapy most likely will include a drug that targets a pathway inside the cancer cells. “These drugs are not chemotherapy,” says Dr. Hahm. “They are turning off a switch, turning off a pathway that is important to the cancer cell. There are different molecular pathways, and we have a lot of clinical trials for oral agents that are targeting these pathways.”
“The idea is you come in with a breast cancer, and instead of a one-size-fits-all approach, you’ll get a treatment targeted specifically for your breast cancer,” says Dr. Samuel. “We don’t do that quite like that today, but that is what we are headed for.”