In the not so distant past, a diagnosis of breast cancer frequently yielded a standard prescription: tumor removal via mastectomy or sometimes lumpectomy, usually followed by radiation and sometimes chemotherapy.
While the approach clearly worked for some women, it didn't work for all -- leaving doctors puzzled.
"It was difficult to understand why some women thrived after breastcancercancer treatment while others perished," says Julia Smith, MD, director of the Lynne Cohen Breast Cancer Preventive Care Program at the NYU Cancer Institute in New York City.
The reason became increasingly clear, say experts, when they stopped looking at why a woman wasn't responding to treatment, and instead examined why the cancer didn't respond.
What they discovered: The concept of tumor biology. In short, not all breast tumors are alike -- or respond to the same treatment.
"We realized breast cancer isn't just one disease -- it's at least three different diseases, each requiring a different treatment approach," says Cliff Hudis, MD, chief of breast cancer medicine service at Memorial Sloan-Kettering Cancer Center in New York City.
These differences have now morphed into a full-fledged treatment approach: target-specific drugs aimed not just at killing cancer cells, but in some instances, disrupting and dismantling the entire tumor-creating mechanism. Usually paired with more traditional treatments such as lumpectomy -- and sometimes radiation -- these new treatments are helping to ensure that even the most stubborn cancers now have a chance to be cured.
Targeting Breast Cancers
Among those benefiting most from this approach are women with tumors identified as HER2 positive.
Affecting one in every three women who develop breast cancer, Smith says HER2-positive tumors occur when a genetic glitch causes an overproduction of the HER2 protein. This protein promotes the growth of cancer cells.
"This is a very aggressive cancer and there was little we could offer in terms of treatment," says Smith.
The target-specific drug that changed all that is Herceptin -- a treatment that attaches itself to the cancer-promoting proteins and slows or shuts down production.
Hudis tells WebMD that Herceptin not only increases survival rates but also reduces the likelihood of tumor recurrence.
"Now we can not only offer treatment for something that was untreatable before, we can also help prevent what once was an incurable disease," says Hudis.
Herceptin is FDA approved for metastatic breast cancer that is positive for HER2. However, a number of clinical trials conducted in 2005 revealed that when combined with chemotherapy, Herceptin is similarly effective in treating early-stage HER2-positive breast cancer.
For those who can't take Herceptin, (there is, for example, some evidence it may cause cardiovascular problems in some users), the experimental drug Tykerb may help. Although it works in a slightly different manner, experts say it accomplishes similar results -- and may have treatment advantages of its own.
Although still in clinical trials, Hudis says results are impressive and may facilitate a fast track to FDA approval.
Hormone-Positive Cancers
As research into tumor biology continued, doctors soon discovered the hormone-positive breast cancer malignant cells that rely on the female sex hormones, predominantly estrogen, to flourish and grow.
And again, target-specific drugs seemed to be the answer. The first in this category was tamoxifen, which Smith says works by blocking the tumor's ability to use estrogen. While it worked well against hormone-positive cancers, side effects were troubling -- including the risk of blood clots and even other cancers.
More recently, the STAR trial, led by researchers at the University of Texas M.D. Anderson Cancer Center, found an alternative -- the osteoporosisosteoporosis drug Evista. Although this trial focused on prevention of breast cancer, it appears that Evista accomplishes results similar to tamoxifen, with fewer side effects. Experts say it may become another treatment option for some women with hormone-positive breast cancer.
Today, excitement is growing over an even newer approach: drugs known as aromatase inhibitors.
"Aromatase is an enzyme that helps convert steroids to estradiol -- a form of estrogen that makes some breast cancers grow," says Smith. Aromatase inhibitors, she says, are drugs that knock out that enzyme so estradiol can't be made at all, thus inhibiting tumor growth.
The one caveat, says Smith, is that these drugs only work in postmenopausal women, whose estrogen supply comes from this steroid conversion process.
"In premenopausal women ovaries are the prime producers of estrogen, and they are not affected by aromatase inhibitors," says Smith.
In a number of clinical breast cancer trials, newer aromatase inhibitors (such as Femara, Aromasin, and Arimidex) have been compared with tamoxifen and found to be more effective, show greater survival rates, and in many cases have more tolerable side effects overall.
A 2006 analysis of 23 studies showed women with advanced breast cancer lived longer if they took aromatase inhibitors instead of tamoxifen. Researchers found women with advanced breast cancer who had an expected survival rate of 2.5 years lived an additional four months when treated with newer aromatase inhibitors. The analysis was published in the Journal of the National Cancer Institute.
The American Society of Clinical Oncology now recommends the use of aromatase inhibitors for the treatment of hormone-positive breast cancer in postmenopausal women.
Targeting the Future
If doctors are right, the future of breast cancer treatment may involve drugs that don't target tumor cells at all, but instead work to disrupt the support system that helps them grow.
In a process known as angiogenesis (creation of new blood vessels), cancer cells utilize growth factors made naturally in the body to develop a blood supply that enables them to thrive. New drugs known as "antiangiogenisis" treatments interfere with that process and, says Smith, "Cut off tumor growth in its embryonic stage."
So far, at least one drug -- Avastin -- is accomplishing this in some lung and colon cancers. Hudis says clinical trials have also yielded impressive results in breast cancer, although the drug is not yet approved for breast cancer treatment.
"What's really exciting about this method is that it is generic enough in its approach to work for all types of cancer," says Hudis.
Extreme Cures
In addition to target-specific drugs, new ways to use standard breast cancer treatments have resulted in still more treatment advances. Two of the newest hit extremes that cover both ends of the healing spectrum.
In line with the minimalist approach to breast conservation -- treatment that includes lumpectomy over mastectomy -- comes a minimal form of radiation therapy. One such technique is known as MammoSite.
Unlike traditional treatment, which blankets the entire breast with radiation from an outside source, MammoSite uses a process known as brachytherapy - the delivery of radiation direct to the site of the tumor bed from inside the body.
Dan Chase, MS, DABR, a board-certified radiological physicist at the Thompson Cancer Survival Center in Knoxville, Tenn., explains.
"We enter the same cavity where the lump was removed and insert a small, soft balloon attached to a thin catheter (tube)," says Chase.
The balloon is inflated, he says, and a computer-controlled machine delivers the radiation down the tube into the balloon. Here, it acts on adjacent tissue. The total radiation exposure is similar to what would be traditionally administered, but in a much more confined space.
Treatment time is also shorter; just 10 minutes, twice a day for a total of five days. That's compared with five days of treatment per week -- for up to seven weeks -- with traditional radiation therapy.
As good as it sounds, however, Smith cautions that a lack of long-term data means treatment should be confined to a clinical trial.
And while trials are ongoing, treatment is also being offered nationwide by many facilities; Chase says women should think twice before saying yes.
"In some universities partial breast radiation is thought of as the next big thing in breast cancer treatment. But until we know more, women should get a second opinion before accepting this treatment," says Chase.
Aggressive Chemotherapy and Radiation
On the other end of the spectrum is a nod to the past, with an extremely aggressive use of both chemotherapy and radiation combined.
"We now treat all women with stage II breast cancerbreast cancer or higher with chemotherapy prior to surgery, and if there is breast conservation, we follow with radiation, sometimes followed by more chemotherapy," says Therese B. Bevers, MD, medical director of the Cancer Prevention Center and Prevention Outreach Programs at M.D. Anderson.
Bevers says she believes chemotherapy prior to surgery shrinks tumors, allowing some women to have a lumpectomy instead of a mastectomy. Moreover, she says, "It also ensures that any renegade cancer cells that may be floating in the body are killed prior to surgery."
Bevers believes the extra kick of chemo reduces cancer recurrences.
"We are seeing fewer women developing this disease again down the road," says Bevers.
Not everyone, however, agrees. Hudis says several clinical trials show chemotherapy before surgery does not prolong survival or decrease cancer recurrences. Smith believes it's best used only for large tumors when the chance of cancer spreading is greatest.
"The downside of chemotherapy can be enormous. This is not something you want to use unless you are certain it's going to make a significant difference," says Smith.
Predicting Future Care
According to Cheryl Perkins, MD, director of clinical affairs for the Susan G. Komen Breast Cancer Foundation, determining who benefits most from chemotherapy may soon be a cancer-care reality.
"Right now a screening known as Oncotype DX uses a panel of 21 genes to evaluate the likelihood that a woman's breast cancer will recur, and some of that information may be used to determine who benefits most from chemotherapy," says Perkins.
Indeed, a new clinical trial known as TailorRx is using Oncotype DX to see if some of the genes involved in breast cancer recurrence can also determine the need for chemotherapy -- and more importantly, who will do better without it.
"We may soon know exactly who benefits most from these treatments and who should avoid them," says Perkins.
"Ultimately the goal is personalized treatment for every woman with breast cancer and a prescription that is targeted specifically for her."
