The study reviewed here found that some HER2-positive, estrogen-receptor-negative breast cancer cells became estrogen-receptor-positive after being exposed to the targeted therapy Herceptin (chemical name: trastuzumab). This study was done on groups of cells in a lab, not in people.
While the results are very promising, more research is needed so doctors can better understand exactly how Herceptin affects the hormonal status of some breast cancers.
A healthy breast cell has estrogen receptors on its surface. These receptors act like antennae that receive signals from the hormone estrogen. Many breast cancers also have estrogen receptors on the surface of their cells. When breast cancer cells have hormone receptors, estrogen helps the cancer grow and spread. Hormonal therapy medicines reduce the risk of hormone-receptor-positive breast cancer coming back by blocking estrogen's effect or reducing the amount of estrogen produced in the body. Tamoxifen, the aromatase inhibitors, and Femara (chemical name: letrozole) are all hormonal therapy medicines.
Some breast cancer cells don't have hormone receptors or may stop making hormone receptors as time passes and the cancer progresses. About 25% of breast cancers are hormone-receptor-negative. Hormonal therapy medicines don't work on hormone-receptor-negative breast cancers.
Herceptin is used to treat HER2-positive breast cancers, regardless of the cancer's hormone-receptor status. Herceptin wasn't thought of as a treatment that could affect hormone-receptor status. But in the lab, this study showed that exposing HER2-positive, estrogen-receptor-negative breast cancer cells to Herceptin made some of the cancer cells start making estrogen receptors again (called upregulation). The study also found that the growth of the cancer cells that became estrogen-receptor-positive was slowed when the cells were then exposed to a hormonal therapy medicine. The researchers aren't sure how Herceptin causes estrogen-receptor-negative breast cancer cells to become estrogen-receptor-positive.
It's important to remember that this study was done with cancer cells in a lab, not in people. Still, the results suggest that Herceptin could make some breast cancers change from hormone-receptor-negative to hormone-receptor-positive and be able to be treated with hormonal therapy. Other research also suggests this can happen. A small study done in Italy found that 3 of 10 women diagnosed with HER2-positive, estrogen-receptor-negative, advanced-stage breast cancer had the cancer's hormonal status switch to estrogen-receptor-positive after being treated with Herceptin. Two of these women were then successfully treated with the hormonal therapy Femara. An ongoing U.S. study is looking at how Herceptin affects breast cancer hormone-receptor status.
Stay tuned to Breastcancer.org for the latest information about research on possible new breast cancer treatments.
WASHINGTON, June 18 (MedPage Today) -- A drug used to treat breast cancer carrying the HER2 receptor made cells sensitive to hormonal therapy, suggesting a new strategy for treating the disease, an investigator reported here.
Estrogen receptor-negative, human epidermal growth factor receptor-2 (HER2)-positive breast cancer cells converted to ER-positive status after exposure to trastuzumab (Herceptin).
After three days of exposure to trastuzumab in vitro, the previously ER-negative cells exhibited upregulation of ER±, Gauri Sabnis, PhD, of the University of Maryland in Baltimore, said at the Endocrine Society meeting.
Moreover, trastuzumab-stimulated cells responded to the growth-inhibiting effects of antiestrogens and aromatase inhibitors.
"This strategy may offer a new avenue for treatment of breast cancer patients with ER-negative and HER2-positive tumors," Dr. Sabnis concluded.
About 25% of breast cancers are ER negative: typically they're treated with chemotherapy and radiation only, because endocrine therapy usually has no growth-inhibiting activity in such tumors.
In previous studies, Dr. Sabnis and colleagues found that breast cancer cells and tumors resistant to an aromatase inhibitor had reduced levels of ER± and increased levels of HER2.
The aromatase inhibitor-resistant cells had been derived from an ER-positive cell line, leading investigators to examine whether HER2 inhibition would lead to upregulation of ER± in ER-negative, HER2-positive cells.
Dr. Sabnis and colleagues added trastuzumab at a concentration of 50 mcg/mL to ER-negative cells and evaluated ER expression after 72 hours.
Investigators then treated the cells with different concentrations of estradiol and the estradiol precursor androstenedione. The hormones triggered proliferation of the formerly ER-negative cells.
Subsequently, the investigators evaluated the effects of aromatase inhibitors and antiestrogens on trastuzumab-pretreated ER-negative cancer cells.
They observed significant growth inhibition -- comparable to what occurs when ER-positive cells are exposed to aromatase inhibitors or antiestrogens.
The inhibition was significantly greater than treatment with an aromatase inhibitor or antiestrogen alone -- or with trastuzumab alone.
For example, letrozole (Femara) had an IC50 of 3 nmol, which is similar to the growth inhibiting response the aromatase inhibitor has in ER-positive cells, said Dr. Sabnis.
A literature review uncovered evidence that trastuzumab might also upregulate ER± in humans with ER-negative breast cancer.
Italian investigators gave trastuzumab to 10 patients with HER2-positive, ER-negative breast cancer. Three of the 10 subsequently had upregulation of ER±, and two of the three were treated with letrozole monotherapy and remained progression free for as long as three years (Breast Cancer Res 2006; 8(6): 407).
Moreover, a clinical trial initiated at the University of Michigan in Ann Arbor is evaluating trastuzumab's ability to induce ER expression in patients with ER-negative, HER2-positive breast cancer.
Dr. Sabnis reported no disclosures. Co-investigator Angela Brodie, PhD, disclosed a financial relationship with Syndax.
Primary source: The Endocrine Society Source reference: Sabnis G, Brodie A "Trastuzumab sensitizes ER negative, HER-2 positive breast cancer cells (SKBr-3) to endocrine therapy" ENDO 2009; Abstract OR38-02.
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