Wednesday, May 18, 2011

Lapatinib plus Herceptin May Target Estrogen-Negative, Her2-Positive Breast Cancer

News from the Baylor College of Medicine:

HOUSTON -- (May 18, 2011) -- A subset of breast cancer patients who have tumors overexpressing a protein called the human epidermal growth factor receptor 2 (HER-2 positive) may benefit from a combination of targeted treatments and may not need chemotherapy, said researchers from the Lester and Sue Smith Breast Center at Baylor College of Medicine on behalf of the Translational Breast Cancer Research Consortium in an abstract released today by the American Society of Clinical Oncology.

Dr. Jenny Chang, previously with the Smith Breast Center and now director of the Methodist Cancer Center in Houston, will present the results of this clinical study (TBCRC 006) in an oral presentation at the annual ASCO meeting in Chicago in June.

The clinical trial involved 64 women with large tumors that tested positive for HER-2 and some that were also estrogen-receptor positive. Using two drugs – lapatinib and trastuzumab – that target HER-2 in different ways, physicians were able to eradicate tumors in 38 percent of estrogen-receptor negative patients and 21 percent of estrogen receptor-positive patients, said Dr. C. Kent Osborne, director of the Smith Breast Center and a senior author of the report. Estrogen-receptor positive patients were also given an aromatase inhibitor to stop production of estrogen.

Preclinical models developed at BCM

"We have shown in preclinical models that complete blockage of the HER-2 family including HER-1, 2 and 3 with the drugs lapatinib and trastuzumab leads to eradication of HER-2 positive tumors in mice," said Dr. Mothaffar Rimawi, medical director of the Smith Breast Center and current principal investigator on the study. "These drugs alone only partially inhibit the pathway, quickly resulting in resistance to treatment." Rimawi developed this model in 2004 as a fellow in the laboratory of Osborne and Dr. Rachel Schiff, associate professor in the Smith Breast Center and a co-author on the paper.

"We conducted two prior clinical studies over the last ten years that show that lapatinib and trastuzumab are effective as single agents but our preclinical data suggested they would likely work better when used together," said Chang.

The research team at Baylor College of Medicine sought to translate these findings to patients, so they initiated a multicenter clinical trial through the TBCRC.

The same response (eradication of tumors) that Rimawi and his team observed in preclinical models in the laboratory was also seen in many patients in this clinical trial, Osborne said.

Study design

The TBCRC 006 trial recruited a total of 64 patients through the Smith Breast Center (at the Baylor Clinic and Ben Taub General Hospital sites), the Vanderbilt University School of Medicine, the University of Alabama at Birmingham, the University of Chicago, and the Mayo Clinic College of Medicine.

The patients had large (average of 6 cm) HER-2 positive tumors in the breast when they were initially diagnosed. They were given a combination of lapatinib (Tykerb®) daily and trastuzumab (Herceptin®) once weekly for 12 weeks before surgery without standard chemotherapy. Lapatinib is a pill that blocks the enzyme activity of HER-2 and its close family member HER-1. Trastuzumab is an antibody administered intravenously that blocks HER-2 in a different way. Some patients’ tumors were also estrogen-receptor positive (grow in the presence of the hormone estrogen). These patients were given an aromatase inhibitor to stop production of estrogen.

"With this combination, we are able to block all of the cancer-promoting signals from the HER family, which we know is crucial for growth of this kind of breast cancer," said Osborne, also director of the NCI-designated Dan L. Duncan Cancer Center at BCM. "Each of these drugs hits a different receptor, thereby shutting down the pathway responsible for the breast cancer’s growth."

No patients were given chemotherapy during that 12-week period. Tumor biopsies were gathered at study entry, 2, 8 and 12 weeks (the time of surgery) to study how the drugs were working.

Study results

After 12 weeks, 38 percent of the estrogen-receptor negative, HER-2 positive patients had eradication of invasive breast cancer from the breast – "the type of breast cancer that can spread beyond your breast and invade healthy, surrounding tissue, and other organs," said Rimawi.

A significant benefit was also observed in the estrogen-receptor positive group, Rimawi said. "Twenty-one percent of these patients had complete disappearance of their tumors and another 34 percent had near eradication with only small amounts of tumor left after treatment."

"We have seen similar results in other recently reported studies using the lapatinib/trastuzumab combination, but this is the first study not to use chemotherapy," said Osborne. "The side effects of chemotherapy can be significant and eliminating the need for chemotherapy in certain patients would represent a groundbreaking approach to treatment."

Another strong point of this trial was the representation of minority women in the study group. Of the group, 33 percent were Hispanic and 21 percent were African-American, Rimawi said.

Next steps in research

"Our next step with this research will be to determine the optimal duration of treatment," said Rimawi. "In an upcoming multicenter TBCRC clinical trial led by us at Baylor College of Medicine, we will compare 12 weeks with 24 weeks of treatment." Studies are underway now to identify which patients can be safely treated without chemotherapy for this subtype of breast cancer which used to be considered difficult to treat.

For more information on enrolling in that trial, please contact Anne Pavlick at 713-798-7814 or

This study was supported by GlaxoSmithKline and the Translational Breast Cancer Research Consortium.

Monday, May 16, 2011

Coffee may reduce ER- risk, study says, but....

Research from Sweden’s Karolinska Institute shows a connection between significant caffeine intake—more than five cups a day—and a reduction in the risk of hormone-negative breast cancer. The study, published in Breast Cancer Research, was on 6,000 post-menopausal women, who saw a 57 percent reduced estrogen-negative breast cancer risk, no matter whether on not they used hormone-replacement therapy or alcohol, and independent of their educational status. Researchers suggest that compounds in coffee, such as trigonolline, may provide some level of protection. Hormone-receptor status was available for only 65 percent of those studied, however. And they did not specify types of coffee, so women could have been drinking decaf or different blends that are available outside of Sweden.

Some things to remember: This research was on postmenopausal women, and TNBC is more likely to affect premenopausal women, so the effects on that population are not clear. Likewise, other dietary effects may come into play here—it could be that these women had a healthier overall diet, or a healthier lifestyle otherwise, so the effects of caffeine were mediated by other factors.

Whatever the case, too much caffeine in general is not good for you. In fact, reducing caffeine can improve your overall health. Who needs the extra nervousness that coffee brings, when you are already stressed? Switching to decaf coffee can help, but while decaf has less caffeine, it is not caffeine-free. Researchers at the University of Florida compared caffeine in decaf coffee and found that different brands had from 8.6 mg to 13.9 mg, compared to an average of 85 mg for caffeinated coffee.

Source: Li, Jingmei, Seibold, Petra, Claude, Jenny C., Janys, Dieter F., Liu, Jianjun, Czene, Kamila, Humphreys, Keith Hall, Per, 'Coffee consumption modifies risk of estrogen-receptor negative breast cancer', Breast Cancer Research , vol. 13, no. 3, R49+ (2011). Find the full article at

Five Years Cancer-Free

I made it to five years--and to Machu Picchu! At present I am too tired from the trip to say more, so I will let these two wonderful facts stand on their own.

Tuesday, May 3, 2011

Off to celebrate five years--almost

On May 16, I will be five years past diagnosis. Yes! So, as a pre-celebration, we are going to Machu Picchu. I'll be off this site for at least a couple of weeks. See you after I soak up the Inca's sacred sites.