By Scott Dance, The Baltimore Sun
4:44 PM EDT, October 20, 2012
If there ever was a right time to be diagnosed with breast cancer, Beth Thompson found one.
In February 2006, the pea-size tumor in her right breast was too small for a clinical trial of Herceptin, a targeted therapy that had proved effective in advanced stages of the aggressive cancer Thompson had. She underwent a lumpectomy and chemotherapy. When the cancer continued to show signs of growth, she had a double mastectomy.
But soon after, her doctor, buoyed by promising trial results, encouraged her to consider Herceptin, developed by Genetech to target the protein that fuels the cancer's growth. Six years later, Thompson, now 47, is in remission and so healthy that she takes no prescription medications at all.
Unlike chemotherapy, which kills all rapidly growing cells, from cancer to bone marrow and hair follicles, targeted cancer therapies home in on just cancer cells and the molecules that help them multiply and spread. Soon even more targeted therapies — either already approved or about to be —will be available for newly diagnosed breast cancer patients, offering hope that it can become more of a manageable chronic disease and less of a killer.
Targeted breast cancer treatments date to the 1980s, when hormone therapy was first applied to the most common types, in which estrogen or progesterone fuel cancer growth. But as more is learned about the intricacies of breast cancer types, researchers are finding new ways to halt the spread of cancer, boosting survival rates, lengthening remission times and, in some cases, eliminating the need for other treatments that can have powerful side effects but aren't as effective.
"Early on, just knowing that this was a diagnosis of breast cancer, and this is the size of the tumor, and it has or has not spread outside the breast, that's what we called part of the staging assessment. That information alone was all we needed to make treatment decisions," said Dr. Antonio Wolff, a professor of oncology at the Johns Hopkins University School of Medicine and Thompson's physician.
But decades of research investment, Wolff said, have "translated into real and palpable improvements in the lives of women who unfortunately are still diagnosed with breast cancer."
The latest fruits of that research are Perjeta, used along with Herceptin to treat what is known as HER-2 positive breast cancer, which Thompson had, and Affinitor, a drug already used for kidney cancer and shown to be an effective supplement to hormonal treatments for the most common type of breast cancer. Both received FDA approval this year for advanced cases of breast cancer and are undergoing clinical trials in early-stage cases.
Another new therapy showing promising results in trials, known as T-DM1, combines Herceptin and chemotherapy drugs but delivers them directly to cancer cells, eliminating many of chemo's side-effects, including hair loss. The Herceptin carries the chemotherapy drug, ImmunoGen's DM1, directly to the cancer cells before it is released. T-DM1 could earn FDA approval next year.
For some patients, the treatments mean they could lead normal lives with normal life expectancies. For others, it could mean that when one treatment's effectiveness begins to wane, there are other options that can keep cancer in check for longer.
"The aim is that you have someone on an effective treatment as nontoxic and non-troublesome as possible," said Dr. Roisin Connolly, an assistant professor of oncology at Hopkins.
A study published last month in the journal Nature laid out many of the findings that are informing targeted therapies. While doctors said the study summed up previous findings, a New York Times article on the research called it "the first comprehensive genetic analysis of breast cancer."
The research laid out four distinct types of breast cancer:
• Luminal A and luminal B, two types of hormone-driven cancers that receive similar treatments but can have vast differences in tumor size and likelihood of spreading or recurring;
• HER2-enriched cancer, in which patients, like Thompson, are found to have an excess of a gene known as HER2 that promotes the cancer's spread;
• What are known as "triple-negative" cancers, which test negative for the other three types. Oncologists theorize that this category could eventually be broken down into further subtypes because of variation among "triple-negative" tumors. Most are known as "basal-like" because they are similar to the basal cells that line mammary ducts. Basal-like cancer behaves similarly to ovarian cancer. Such cancer is more prevalent among both younger and black women.
An estimated 227,000 women are expected to be diagnosed with breast cancer this year, with 40,000 deaths, according to the National Cancer Institute.
As treatments have improved and awareness has increased, mortality rates from breast cancer have fallen in recent decades. For white women, the annual rate fell from about 31 per 100,000 in 1987 to about 22 in 2007, according to the cancer institute. The rate didn't fall as much among black women, dropping from 35 per 100,000 in 1987 to about 31 in 2007.
Research to continue those improvements is focused on increasing what is known about breast cancer types and developing targeted therapies.
Other efforts seek to improve genetic testing to provide more insight on patients' individual cancer risks, but that work may not be as useful as learning more about the disease itself, said Dr. Katherine Tkaczuk, director of the breast evaluation and treatment program at the University of Maryland's Greenebaum Cancer Center.
"It's not ever going to be possible to look at every gene, although we'd like to be personalized eventually," Tkaczuk said.
Developing better profiles of each breast cancer type, which Tkaczuk said she expects to number more than just the four outlined in the Nature study, can establish a better "common ground" to apply to all patients, she said.
In the realm of cancer research, much is known about breast cancer relative to other cancers, making targeted therapies more advanced, said Dr. Otis Brawley, chief medical officer for the American Cancer Society. But more could be done, he said, pointing out that the federal cancer institute funds only about 10 percent of research proposals.
"In breast cancer, we understand more about the targets than almost any other cancer," Brawley said. "I see a lot of progress. I'm not at all satisfied with the pace of that progress."
Part of the difficulty is that the deeper researchers delve into breast cancer types, the fewer patients their findings may help, doctors said. That also makes it difficult for researchers to get a large enough sample of patients from which to draw conclusions. Studies pull from hospital cancer centers across the country to gather a large enough pool of cases.
The treatments also are costly and not a quick fix. For Herceptin, for example, a full course is administered for a year and costs about $50,000. Combined with Perjeta, the new companion drug, the price rises above $100,000.
Still, patients are eager to embrace new treatments, Thompson said. A former nurse, Thompson started working as a nurse educator and navigator at Hopkins' breast center after completing her treatment, helping others learn more about their options.
Many go to their oncologists after doing their own research, asking specifically about targeted therapies that are in clinical trials, despite the time and costs involved.
"A year seems like a long time to not be able to put cancer behind you, but at the same time, they're glad to have that arrow in their quiver," Thompson said. "This is the best shot for what we call a curative paradigm."
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