Researchers continue to test the mettle of breakthrough breast cancer drugs, three decades after tamoxifen changed the medical landscape by drastically reducing the risk of recurrences in women with estrogen receptor-positive tumors.
Encouraging findings on several different drugs were presented Thursday at the CTRC-AACR San Antonio Breast Cancer Symposium in Texas.
First in the line-up, the osteoporosis drug zoledronic acid (Zometa) appears to shrink breast tumors in patients who undergo chemotherapy.
The drug is already approved to treat breast cancer that has spread to the bone and, earlier this year, was reported to lower the risk of breast cancer recurrence in pre-menopausal women with early estrogen- or progesterone-positive tumors.
In an analysis of slightly more than 200 women, those who received Zometa in addition to chemotherapy had better results than those receiving chemotherapy alone. After compensating for variables such as estrogen receptor status and treatment duration, residual invasive tumor size was 42.4 millimeters in the chemotherapy alone group, and 28.2 millimeters in the combination group.
"This data suggests that zoledronic acid is doing something more than protecting bone," said study senior author Dr. Robert Coleman, a professor of medical oncology at the University of Sheffield in England. "It's not practice-changing. It's hypothesis-generating, which will lead to the design of new trials to look at this in detail. But this is the first patient-related evidence."
Coleman spoke, along with researchers involved with other trials, at a Thursday teleconference. Other studies showing promise included:
Postmenopausal women with estrogen receptor- and/or progesterone receptor-positive breast cancer who took the aromatase inhibitor exemestane (Aromasin) had a 15 percent relative reduction in recurrences and a 19 percent reduction in the risk of distant metastasis, compared with those taking tamoxifen alone. "Exemestane is very effective at preventing recurrences," said Dr. Stephen Jones, medical director of U.S. Oncology Research in Houston. Exemestane, like other aromatase inhibitors, blocks production of estrogen, while tamoxifen, long the gold standard in breast cancer therapy, inhibits the hormone's effects in the body.
Seventy percent of women receiving Herceptin (trastuzumab), a drug used to treat HER2-positive breast cancer, plus chemotherapy before surgery survived three years without a recurrence. Only slightly more than half of women receiving chemotherapy alone survived that long. The incidence of major heart problems was low. "Herceptin given before surgery with chemotherapy significantly [reduces the likelihood] of a recurrence in patients with advanced HER2-positive cancer, and most likely will translate into a benefit in terms of survival," said Dr. Luca Gianni, director of medical oncology at the National Cancer Institute in Milan, Italy. "We think that this data establishes preoperative Herceptin with chemotherapy as a standard treatment option for women with advanced HER2-positive breast cancer."
Combining lapatinib (Tykerb), another HER2 inhibitor, with an aromatase inhibitor (in this case, letrozole) prolonged progression-free survival from three months among those taking letrozole (Femara) alone to 8.2 months in women taking both drugs. These patients had HER-2-positive metastatic breast cancer. "The combination shows benefits in controlling the disease and controlling it for longer than using endocrine therapy alone," said Stephen Johnston, a consultant in medical oncology and reader in breast cancer medicine at Royal Marsden Hospital and Foundation in the United Kingdom. "The suggestion is that combined therapy may be the best approach."
Finally, aromatase inhibitors may be poised to replace tamoxifen as standard treatment to prevent breast cancer recurrence in women who have already undergone conventional therapy, according to a new meta-analysis. The analysis looked at two groups: women with postmenopausal estrogen receptor-positive breast cancer who took tamoxifen for five years after standard treatment and women who took tamoxifen but then switched to an aromatase inhibitor after initial treatment. "The data are still early but it does show a statistically significant advantage in [women who were switched from tamoxifen to an aromatase inhibitor] but not in [women who took tamoxifen for the full five years]," said Dr. James Ingle, director of the breast cancer program at the Mayo Clinic, in Rochester, Minn. "But you have to remember our experience with tamoxifen. It took 10 to 15 years to see the full effect of tamoxifen."