National Cancer Institute NCI Cancer Bulletin: A Trusted Source for Cancer Research News
December 11, 2012 • Volume 9 / Number 24

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Cancer Research Highlights

Chemotherapy after Surgery Improves Survival When Some Breast Cancers Return

Among women whose breast cancer has recurred but not spread beyond nearby tissues, those who received chemotherapy after surgery had better disease-free and overall survival, a new study shows. Patients with estrogen receptor (ER)-negative tumors appeared to derive the greatest benefit. The results, from the CALOR trial, were presented December 6 at the San Antonio Breast Cancer Symposium.

"This is the first randomized controlled study that shows that adjuvant chemotherapy works in these patients," Dr. Stefan Aebi, head of the division of medical oncology at Luzerner Kantonsspital in Lucerne, Switzerland, and CALOR co-chair, said in a press release.

Dr. Aebi and his colleagues randomly assigned 162 women who had a local or regional recurrence following prior breast-conserving surgery or a mastectomy to receive adjuvant chemotherapy or not (85 and 77 women, respectively). The trial organizers recommended the use of combination chemotherapy and treatment for 3 to 6 months, but the choice of chemotherapy regimen was left to the discretion of patients' physicians. Treating physicians could also give patients radiation therapy, hormone therapy, or anti-HER2 therapy as appropriate.

Although the trial accrued fewer patients than planned, statistically significant differences were observed. After a median of 5 years of follow-up, the risk of recurrence was 41 percent lower in women treated with chemotherapy than in women who did not receive chemotherapy. And the overall survival rate was higher among patients who received chemotherapy than among those who did not, leading to a 59 percent reduction in the risk of death. (See the table.)

Rate of Disease-Free and Overall Survival, with and without Chemotherapy




P Value
(0.05 and smaller are statistically significant)

Disease-Free Survival at 5 Years

ER negative

ER positive

69 percent

67 percent

70 percent

57 percent

35 percent

69 percent




Overall Survival at 5 Years

ER negative

ER positive

88 percent

79 percent

94 percent

76 percent

69 percent

80 percent




When stratified by tumor type, there was a striking difference in the disease-free survival rate between women with ER-negative tumors who received chemotherapy and those who did not. Women with ER-positive tumors received appropriate hormonal therapy, and there were very few recurrences in that group, regardless of whether they received chemotherapy. Therefore, the majority of benefit was seen in women with ER-negative tumors.

These results show a "dramatic improvement in ER-negative [disease] using common chemotherapy drugs," said Dr. Jo Anne Zujewski, head of Breast Cancer Therapeutics in NCI's Division of Cancer Treatment and Diagnosis, who was not involved in the study. "[This] will be practice changing for a small subset of patients."

This trial was funded in part by NCI (U10-CA-37377, U10-CA-69974, U10-CA-12027, U10-CA-69651, and CA-75362). 

New Targeted Treatment May Slow Disease in Patients with Advanced GIST

A new oral drug, regorafenib (Stivarga), may delay the progression of advanced gastrointestinal stromal tumors (GIST) that are resistant to treatment. Results from an international clinical trial published November 22 in The Lancet demonstrated that patients treated with regorafenib lived longer without their disease progressing than patients who received a placebo.

GIST is a relatively rare cancer that is driven, in most cases, by mutations that activate the KIT or PDGFRA kinase signaling pathways. Because this type of GIST is resistant to standard chemotherapy, most tumors are surgically removed if the disease has not spread.

The tyrosine kinase inhibitor imatinib (Gleevec) was the first drug approved for inoperable GIST. However, most GIST tumors develop resistance to imatinib after about 2 years of treatment. Patients with imatinib-resistant tumors are then treated with sunitinib (Sutent), but the disease usually develops resistance to sunitinib and progresses within 1 year. Patients with advanced GIST that is resistant to both imatinib and sunitinib have no other standard treatment options.

Based on results from an earlier phase II trial, Dr. George D. Demetri of the Dana-Farber Cancer Institute and his colleagues compared regorafenib with placebo in patients with metastatic or inoperable GIST who had been treated previously with imatinib and sunitinib. Regorafenib, which inhibits multiple kinases, was approved in September for metastatic colorectal cancer.

The randomized, placebo-controlled phase III trial included 199 patients with advanced GIST, of whom 133 were randomly assigned to receive regorafenib and 66 to receive a placebo. Those who received regorafenib lived without their cancer progressing for a median of 4.8 months, compared with 0.9 months among patients who received a placebo. There was no difference in overall survival between the patients who initially received regorafenib and those who received the placebo. The authors suggested, however, that this could have been due to crossover: 85 percent of patients assigned to receive the placebo crossed over to receive regorafenib after their disease progressed.

All patients who received regorafenib experienced side effects. Just over 60 percent reported a severe drug-related adverse event, compared with 14 percent of patients who received the placebo.

"The case for routine use of this drug in patients who have failed imatinib and sunitinib is strong," the authors of an accompanying editorial wrote. Dr. Demetri said, "It's encouraging to have developed this third targeted drug to manage a disease that was uniformly untreatable before 2000."

The maker of the drug, Bayer Healthcare Pharmaceuticals, has filed for Food and Drug Administration approval of regorafenib to treat GIST.

This trial was funded in part by Bayer HealthCare Pharmaceuticals and NCI (Gastrointestinal Cancer SPORE Grant 1P50CA127003-05).

Study Explores Why Double Mastectomy Rate Is on the Rise

New results from a population-based study show that about 75 percent of women diagnosed with cancer in one breast who chose to have a double mastectomy did so despite being at low risk of developing a new cancer in the unaffected (contralateral) breast. Greater degree of worry about cancer recurrence was associated with removing the breast not affected by cancer, known as contralateral prophylactic mastectomy (CPM).

Dr. Sarah Hawley of the University of Michigan presented the findings, from a patient survey and analysis of SEER cancer registry data, November 30 at the American Society of Clinical Oncology's (ASCO) Quality Care Symposium in San Diego.

Only a small percentage of women diagnosed with breast cancer have clinical risk factors known to increase their chances of developing a new cancer in the unaffected breast—that is, mutations in the BRCA1 or BRCA2 genes and/or a strong family history of breast or ovarian cancer. Yet several studies, including a previous analysis of SEER data, show that rates of CPM among U.S. women with breast cancer are rising.

To investigate why women may choose CPM, Dr. Hawley and her colleagues surveyed roughly 1,500 ethnically and racially diverse women diagnosed with breast cancer that had been reported to the Detroit and Los Angeles SEER registries. Of the 564 women who received mastectomies, 107 had CPM. The remaining women had breast conserving surgery.

When the researchers compared survey responses in the two groups of women, they found that those who reported being "very worried" about recurrence were about twice as likely to have CPM as those who reported being "somewhat worried" or "not at all worried."

In addition, women who reported that they had tested positive for BRCA1 or BRCA2 mutations were about 10 times more likely to undergo CPM than those who did not have a mutation, and those having two or more first-degree relatives with breast cancer were about 4.5 times more likely to undergo CPM than those who did not have a strong family history of the disease. Although CPM reduces the risk of developing a new cancer in the unaffected breast for women with these clinical risk factors, the procedure has not been shown to reduce the risk of a recurrence of the original cancer.

"Our results suggest that many women are choosing a double mastectomy who really don't need it," Dr. Hawley said. "We want to make sure that women choose CPM…with a good, clear understanding of what it's doing and not doing in terms of risks and benefits…. What you do is a personal decision, but it should be an informed one."

Dr. Hawley and her colleagues are still analyzing the survey data and have not yet examined some other possible reasons that women may be opting for CPM.

"This study suggests that we should re-examine how we communicate with our patients regarding the decision of whether to undergo prophylactic mastectomy," said Dr. Jyoti Patel, an oncologist at Northwestern University who moderated a November 30 ASCO press briefing at the symposium.

This study was funded by NCI (CA088370 and CA109696).

Further reading: "Preventive Double Mastectomies Increasing Despite Some Concerns"

Higher Dose of Breast Cancer Drug Associated with Longer Survival

Women with advanced breast cancer who receive a higher dose of the drug fulvestrant (Faslodex) live longer than women who receive a lower dose, according to updated findings from a large clinical trial. The higher dose, 500 mg, has been in clinical use for a decade, but the new results provide evidence of a survival benefit for some women.

The trial, called CONFIRM, tested the two doses of fulvestrant in postmenopausal women with estrogen receptor (ER)-positive metastatic breast cancer whose cancer had recurred or progressed after previous treatment with endocrine therapy, such as tamoxifen (Nolvadex). Women who received 500 mg of fulvestrant lived for a median of 26.4 months, whereas women who received 250 mg lived for a median of 22.3 months, a statistically significant difference of more than 4 months.

The findings were presented December 5 at the San Antonio Breast Cancer Symposium (SABCS).

More than 700 women were enrolled in the international trial, which randomly assigned participants to receive 500 mg of fulvestrant or 250 mg, the dose initially approved by the Food and Drug Administration (FDA) in 2002.

The FDA approved the 500 mg dose in 2010, based on initial results from the CONFIRM trial that showed a statistically significant improvement in progression-free survival. Overall survival was also improved in the high-dose group, but the difference at that time was not statistically significant.

With longer follow-up, the overall survival benefit became statistically significant. But, the overall survival finding is from an unplanned exploratory analysis, warned the trial's lead investigator, Dr. Angelo Di Leo of the Hospital of Prato in Italy, during an SABCS press briefing.

Even so, when the results of the initial and updated analyses are compared, the two analyses "are perfectly consistent," he continued, "leading to the same conclusion that there is an increased benefit in terms of survival for patients receiving 500 mg" of fulvestrant.

Women who received the higher fulvestrant dose had a slightly higher rate of adverse side effects (8.9 percent versus 6.7 percent), but the difference was not statistically significant.

Following the FDA's 2010 approval, the 500 mg dose became the standard of care for this patient group, "so this study does not change current practice," said Dr. Claudine Isaacs of the Georgetown Lombardi Comprehensive Cancer Center. "However, it does provide further support for this dose and suggests that it may have a survival benefit."

Noninvasive Test for Kidney Cancer May Lessen Need for Surgery

According to a recent study, a new radioactive tracer agent can be used with positron emission tomography/computed tomography (PET/CT) to accurately detect clear cell renal cell carcinomas (ccRCC), the most common type of kidney cancer. The open-label study, conducted at 14 medical centers, was published December 3 in the Journal of Clinical Oncology.

"This study represents (to the best of our knowledge) the first clinical validation of a molecular imaging biomarker for malignancy," the researchers wrote.

The researchers compared results from two imaging methods in 195 patients with renal masses who were scheduled for kidney resections (nephrectomies): iodine-124 (124I)-girentuximab PET/CT and contrast-enhanced CT scans (CECT). 124I-girentuximab binds to an antigen that is found on the cell surface of nearly all ccRCC.

The investigators, led by Dr. Chaitanya Divgi of Columbia University Medical Center, reported that the 124I-girentuximab PET/CT tests were more sensitive than CECT (average sensitivity of 86.2 percent versus 75.5 percent) and more specific (average specificity of 85.9 percent versus 46.8 percent) for detecting ccRCC tumors.

If these results are confirmed by additional studies and the test is approved by the Food and Drug Administration, the new diagnostic test could lessen the need for more invasive procedures, including needle biopsies and nephrectomies, that currently are used to evaluate suspicious renal masses, the researchers suggested. 124I-girentuximab PET/CT may help practitioners decide how best to treat a patient and may have particular benefit for patients who are frail, elderly, or have other health conditions that make surgery risky, they commented.

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