Stronger role for a breast cancer drug

SAN ANTONIO — A recently approved breast cancer drug called lapatinib may serve as a valuable partner for letrozole, a standard frontline drug for the disease, according to a study of patients whose cancer has spread.

Patients with metastatic breast cancer are destined to return to chemotherapy, and this drug combination seems to significantly delay that day for patients who have a certain form of the disease, says medical oncologist Stephen Johnston of the Royal Marsden NHS Foundation Trust in London.

He presented the findings December 11 at the San Antonio Breast Cancer Symposium.

The trial included 1,286 post-menopausal women who had hormone receptor-positive breast cancer. In such women, the hormone estrogen — and less commonly progesterone — binds to receptor proteins in breast cells and instigates malignant growth. Most breast cancers are estrogen-receptor positive. For that reason, standard frontline drugs such as tamoxifen and letrozole have proved extremely valuable, since both drugs interfere with estrogen’s proliferative effects.

But in roughly one in six of the women in this study, the malignancy had also taken an alternative path in fueling runaway cell growth. In these women, a gene encoding a receptor protein called HER2 — for human epidermal growth factor receptor type 2 — mutates and begins overproducing the HER2 receptor protein. This induces aberrant growth in the cell in a process that is still being elucidated.

Thus, in many breast cancers, just when estrogen suppression seems to get a cancer under control, HER2 production runs amok.

Johnston and his colleagues identified 219 women in the trial population who were indeed HER2-positive in addition to being hormone receptor-positive. The researchers randomly assigned some women to get a daily regimen of letrozole to quell the pro-growth hormone effects, plus a placebo. Others received letrozole plus lapatinib, an anti-HER2 drug.

The researchers monitored patients for two years on average. During that time, volunteers getting lapatinib were 29 percent less likely to see their cancer worsen, compared with the others, Johnston says. Specifically, those getting both drugs went an average of eight months without showing any cancer progression, compared with only three months to relapse among these getting letrozole alone, he reports.

Lapatinib, called Tykerb by its maker GlaxoSmithKline, gained Food and Drug Administration approval as a breast cancer drug in 2007 for its ability to thwart HER2’s proliferative effects. But at that time, lapatinib was cleared only for use with the chemotherapy drug capecitabine.

“In patients who are estrogen receptor-positive and HER2-positive … I think you need to use agents for both pathways,” says Carlos Arteaga, a physician at Vanderbilt-Ingram Cancer Center in Nashville, Tenn. “It’s a very reasonable thing to do.”