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Three Ways Researchers Are Kicking Breast Cancer’s Butt


New advances in breast cancer diagnosis and treatment bring hope to patients

By Michelle Konstantinovsky


With grim statistics (there are more than 200,000 new cases diagnosed every year), and shocking facts (almost 40,000 people will die from it in 2010), the fear and anxiety surrounding breast cancer runs high. But according to top scientists, there is plenty of hope on the horizon. Contrary to the frightening figures, breast cancer rates have actually been going down, most likely due to early detection and better breast cancer treatment. And thanks to tireless research and groundbreaking discoveries, doctors are optimistic about breast cancer therapies.

"The breast cancer field is moving ahead very rapidly and there are a lot of innovations for many people," said Mark Moasser, MD, an oncologist at the University of California, San Francisco. "There's a lot of hope."

Here are three of the latest scientific breakthroughs sparking such hope about the future of breast cancer diagnosis and treatment.


Breakthrough #1: Targeted therapies

Targeted therapies interfere with specific tumor molecules to block the growth and spread of cancer. One such molecule is a protein known as human epidermal growth factor receptor 2 (HER2). An excess of HER2 caused by a gene mutation is the cause of about one in five breast cancers. These types of cancers, known as HER2-positive breast cancers, tend to be more aggressive and less responsive to treatments.

The good news is that therapies specifically aimed at HER2 are very effective. Herceptin, which was approved in 1998, was the first drug developed to target HER2 and has become a standard treatment for HER2-positive breast cancer. When taken following other types of breast cancer treatment (including chemotherapy, radiation, surgery and hormone therapy), Herceptin significantly lowers the risk of the cancer returning.

According to Moasser, however, research is leading to more effective drugs that target HER2's protein partner, HER3. According to Moasser's research, effectively inactivating the HER2-HER3 team can lead to more successful treatment. The reason has to do with the way in which HER3 works to protect HER2, allowing its biochemical teammate to stimulate the growth of breast cancers.

Moasser, who has done extensive work on HER2 treatments, is currently studying the effects of intermittent, higher-than-standard dosages of new drugs to handicap the HER2-HER3 duo. Administering high doses of drugs works well to break down the partnership, but these elevated quantities can produce toxicities. Moasser and his team however, found that toxicity can be avoided with breaks in treatment.

A clinical trial using a drug targeting HER2 known as lapatinib ditosylate (brand name Tykerb) is currently testing Moasser's new dosing strategy. During the clinical trial, patients are being treated with large, intermittent dosages, along with breaks in treatment to limit side effects.


Breakthrough #2: Predicting the risk of invasive breast cancer

In addition to the ever-evolving improvements within the treatment realm, the important domain of breast cancer risk prediction is also advancing. A recent study led by researchers at UCSF and the San Francisco Veterans Affairs Medical Center may one day change the way patients and doctors interpret treatment options.

The study proves for the first time that it is possible to predict whether women with ductal carcinoma in situ (DCIS), the earliest stage of breast cancer, also known as a type of stage 0 breast cancer, are at risk of developing more invasive tumors later in life. The most common form of non-invasive breast cancer, DCIS rarely leads to breast cancer-related death (only 1-2 percent of women die of the disease within 10 years of diagnosis). Despite the data however, doctors have traditionally prescribed aggressive treatments for DCIS, leading to approximately 35 percent of DCIS patients receiving lumpectomies, 25 percent undergoing complete mastectomies, just 3-5 percent obtaining active surveillance only, and the remainder opting for lumpectomy plus radiation or hormone treatment or both.

"The whole idea behind the study was to try and give women the opportunity to have choices about treatment," said lead author, Karla Kerlikowske, MD, professor of medicine, and epidemiology and biostatics at the UCSF Helen Diller Family Comprehensive Cancer Center, and co-director of the Women Veteran's Comprehensive Health Center at SFVAMC. "Based on the information available, there didn't seem to be good predictors of who would get invasive breast cancer versus who would get DCIS. It's not to say DCIS is not important, but the real risk associated with it is whether or not people with it will later get invasive breast cancer. Those are the people who may want more aggressive treatments."

During the study, Kerlikowske and her team followed the medical histories of 1,162 women aged 40 and older who were diagnosed with DCIS and treated with lumpectomy. Two factors appeared to predict the women's risk of developing invasive breast cancer within eight years of their DCIS diagnosis: how it was detected and whether or not the patient expresses a combination of particular biomarkers. Breast lumps diagnosed as DCIS were more predictive of future invasive cancer than DCIS diagnosed by mammography, as were tumors expressing high levels of biomarkers known as p16, cyclooxygenase-2 and Ki67.

"The goal is that people can use this information to decide what they want to do," Kerlikowske said. "The goal is to focus on how to identify some of the women who we know will go on to have invasive breast cancer."

While experts are working on a commercial DCIS test to screen for the aforementioned biomarkers, one is not yet available. But Kerlikowske is confident about the future. "I think doctors are incredibly optimistic, especially as molecular testing gets more sophisticated," she said. "[Eventually] we'll be able to personalize treatment more and give patients better data on what their risk really is."


Breakthrough #3: Finding the right treatment faster

Though exciting innovations are taking place, the reality still remains: it can take up to $1 billion and 15-20 years to develop a new breast cancer drug. Thankfully, doctors are working to expedite the process and improve results.


A clinical trial known as I-SPY 2 will involve about 800 women with high-risk, fast-growing breast cancers and is a collaborative effort between scientists from the National Cancer Institute, the U.S. Food and Drug Administration (FDA) and nearly 20 major cancer research centers across the country, including UCSF.


The goal of I-SPY 2 is to utilize the latest genetic advances to quickly screen potentially effective drugs and match them with the patients most likely to benefit from them. The trial will enable drug companies to design late-stage trials incorporating much smaller patient populations, more likely to respond to treatment. The molecular makeup of participants' tumors will be taken into account when matching them with medications. This more focused evaluation should effectively speed up the current process of drug approval, drastically reduce costs associated with this process and lead to more FDA-approved, life-saving treatments.


Overall, Kerlikowske believes breast cancer treatment has achieved major milestones recently, and she has no doubt about the potential of future innovations. "The last 10 years have been amazing and I think it's only getting better," she said.


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