Targeted breast cancer therapies coming to the forefront in treatment
Researchers uncovering more effective methods as they learn more about intricacies of disease
Beth Thompson, a breast cancer survivor, now works as a counselor to breast cancer patients, helping guide their treatment at Johns Hopkins. (Lloyd Fox, Baltimore Sun / October 20, 2012)
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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.