Nearly 30 years ago, when Judy Macon was diagnosed with breast cancer, she had surgery followed by radiation and chemotherapy to destroy the malignant cells left behind. The chemo she got was essentially the same as for any other woman with breast cancer.
Today, doctors recognize that the one-size-fits-all approach may have been more onerous than her particular tumor required. But it worked. She remained cancer-free for 26 years, until she was diagnosed with a new breast cancer in 2009.
This time, her treatment was tailored to fit her particular tumor. Molecular diagnostic tests revealed that the cells inside her right breast were of a particularly deadly sort that doctors call “triple negative.” But her tumor was only 1 centimeter across, small enough for her oncology team to feel comfortable skipping one of the chemo drugs, Adriamycin, that is usually used on triple-negative cancers. Macon, a 59-year-old nurse and cancer educator in Bethesda, Md., was relieved to learn she could avoid it, because Adriamycin can cause heart damage.
“I really feel lucky to have been able to have some choices like that,” says Macon, who began doing cancer outreach in the early 1980s as a result of her personal experience with the disease. “I’m thrilled that in all aspects of medicine we’re getting out of this cookie-cutter mentality that what’s good for one person is good for everybody.”
As scientists have learned more about the molecular underpinnings of breast cancer, doctors have come to see it not as a single disease but as a family of ailments for which they can tailor therapies accordingly. The increasingly detailed knowledge is transforming the way breast cancer is treated.
“Breast cancer is a more complicated disease than we used to think,” says Dr. Armando E. Giuliano, a surgical oncologist and co-director of the Breast Center at Cedars-Sinai Medical Center in Los Angeles. “By looking at the markers and molecular sub-types, we see major differences in how you might treat them.”
Tumors are discovered in the breasts of nearly 290,000 women in the U.S. each year, according to the American Cancer Society. Until 40 years ago, women were treated more or less uniformly, with radical mastectomy, radiation and some form of primitive hormone therapy, such as removal of the pituitary gland.
“Everybody was treated the same way, despite the fact that we knew some patients did well no matter what we did and other patients did poorly and died no matter what we did,” says Dr. C. Kent Osborne, director of the Breast Center at Baylor College of Medicine in Houston.
That approach began to change in the late 1970s, when studies revealed that about 70% of breast cancers grew in the presence of estrogen. These tumors could be treated by suppressing the body’s production of estrogen and starving them of the hormone. Not long after, doctors were using this information to tailor hormonal therapies for patients.
“That was really the beginning,” Osborne says.
In the 1980s, scientists discovered that between 20% and 30% of breast cancers make too many HER2 receptors, which causes them to grow more quickly. Though these tumors are considered aggressive, they are now highly treatable because they respond well to targeted therapy that interferes with the receptors and blocks tumor growth.
And in the last decade, new diagnostic tests have made it possible to assess all of the genes in a tumor cell at the same time, allowing doctors to identify all manner of abnormalities and determine the optimal treatments for patients.
“Not all cancers are the same,” says Dr. Otis Brawley, the American Cancer Society’s chief medical and scientific officer in Atlanta. “There’s varying biologic behavior, and we can vary our aggressiveness of treatment.”
Some doctors are optimistic that by learning more about the molecular characteristics of breast cancers, they’ll be able to classify them more narrowly and do a better job of matching tumors to treatments. That could make certain types of breast cancer as manageable as chronic illnesses like diabetes, they say.
For instance, within the next 10 years, post-menopausal women with breast cancers that need hormones to grow will be able to keep their tumors in check by using increasingly refined combination therapies, says Dr. Carlos L. Arteaga, director of the breast cancer program at Vanderbilt-Ingram Cancer Center in Nashville.
Even better, he says, aggressive breast cancers that are fueled by HER2 are on their way to being wiped out in the developed world. Studies in the last few years have found that a drug called Herceptin binds to these receptors, putting the brakes on tumor growth. A 2005 report in the New England Journal of Medicine found that combining Herceptin with standard chemotherapy reduced the risk of recurrence over a two-year period from 16% to 8% and cut the risk of death over that time from 5.5% to 3.7%.
“We’re going to be discovering an increasing complexity of these tumors,” and those discoveries will guide doctors in selecting the right drugs for patients, Arteaga says.
The approach is already paying off for some patients, like Nicki Boscia Durlester, who was diagnosed with breast cancer in 2009. The tumor in her right breast was estrogen-receptor positive, meaning that it grew in the presence of the hormone estrogen. A biopsy found cancer cells in a sentinel lymph node, and the standard follow-up treatment was chemotherapy. In preparation for the inevitable hair loss, she had her long hair lopped into a short bob.
But two weeks before she was set to start her first round of chemotherapy, Durlester received a call from her surgeon’s office. She had analyzed her tumor with a genetic test called MammaPrint, and the results predicted there was only a small risk that her stage 2 cancer would spread. Then she had a similar test, called Oncotype DX, which suggested there was a low risk that the tumor would return.
Based on these results, a team of cancer experts concluded that Durlester would have little to gain from chemotherapy and that she could safely skip it.
“Although I did not get off scot-free, I escaped the potential ravages of chemotherapy,” says Durlester, a 55-year-old headhunter in Los Angeles. She had a double mastectomy and breast reconstruction surgery and is now taking a drug called Femara to block estrogen synthesis.
Surgery too is becoming much more refined. For the last 100 years, nearly every breast cancer patient has had the lymph nodes under her armpit removed regardless of whether a biopsy showed evidence of cancer there. But most women with early-stage breast cancer do not have it in those lymph nodes, says Giuliano of Cedars-Sinai.
“You do a radical procedure that has significant consequences — loss of mobility, arm swelling, shoulder pain — but you don’t remove any cancer,” he says. “We thought that was no good.”
So Giuliano and his colleagues took a closer look. They found that for certain groups of women — including those whose tumors were no more than 5 centimeters wide and whose cancer had not spread beyond more than two sentinel nodes — survival rates after chemo and radiation were better than 90% after five years regardless of whether the nodes were removed. That realization meant that about 40,000 women in the U.S. could skip this procedure each year. The results were published this year in the Journal of the American Medical Assn.
Eventually, a personalized assessment of a woman’s risk for breast cancer will make it possible to prevent many cases of breast cancer altogether, says Dr. M. William Audeh, medical director of the Samuel Oschin Cancer Center at Cedars-Sinai. The idea isn’t that different from using blood pressure and cholesterol levels to identify people who are at greatest risk for a heart attack and intervening with preventive drugs and lifestyle changes.
“You don’t wait for a cancer to happen — that’s the equivalent of waiting for a heart attack to happen,” Audeh says. “You try to understand what are the risk factors, whether they’re genetic or lifestyle or things like that, and do something about it.”
Women with certain mutations in two genes called BRCA1 and BRCA2 already know they have a heightened risk of developing breast cancer. In some cases, the risk is so high that women remove their breasts and ovaries as a preventive measure.
Audeh hopes that one day drugs will make it possible to help these women prevent breast cancer without drastic surgeries. Currently, there are three estrogen-blocking drugs — Tamoxifen, Raloxifene and Exemestane — that can be taken to reduce the risk of breast cancer. But they can only prevent cancers that feed on the hormone.
Audeh is involved in clinical trials of a drug called olaparib. In two 2010 proof-of-concept studies published in the journal Lancet, Audeh and an international team of researchers reported that olaparib — a pill that is much less toxic than chemotherapy and appears to cause few side effects — can inhibit tumor growth in women with BRCA mutations who have advanced cases of breast or ovarian cancer.
Though olaparib has not been shown to stop cancer from occurring in the first place, the drug offers promise as a prevention strategy that could be tailored to a person’s genetic background, Audeh says. “It’s just a matter of learning what those genes are and being able to identify who has them.”