Educational Information: Treatments - New Findings

For Young Women, Breast Conserving Surgery May Be Acceptable Alternative to Mastectomy

Women under age 40 who had breast-conserving surgery (BCS) did not have higher rates of local recurrence or poorer overall survival compared with women who underwent mastectomy, according to results from two retrospective studies. Young age at diagnosis is thought to be a risk factor for disease recurrence, and many young women with breast cancer choose mastectomy for treatment.

The research was presented at the 2011 American Society of Clinical Oncology Breast Cancer Symposium in San Francisco. “These studies support [the idea] that breast conserving surgery with lumpectomy and radiation is an excellent option for young women, and may be the preferred approach,” commented Dr. Jo Anne Zujewski, head of Breast Cancer Therapeutics in NCI’s Division of Cancer Treatment and Diagnosis, who was not involved in the research.

In the first study, researchers led by Dr. Julliette Buckley of Massachusetts General Hospital reviewed the medical records of 628 young women with stage I to stage III breast cancer treated at their hospital between 1996 and 2008. The median follow-up time after treatment was 6 years. During the study period, 7.1 percent of women who had breast conserving therapy and 7.5 percent of women who underwent mastectomy had a local recurrence—a difference that was not statistically significant.

The local recurrence rates seen in this study are lower than in previous studies, stated the researchers. These new results suggest “that lumpectomy is indeed a safe option for young women,” said Dr. Buckley during a press briefing. “We believe that awareness of the genetic risk of breast cancer, advances in the screening for breast cancer, and improvements in systemic and radiation therapy have contributed to the longer overall survival for young women with breast cancer that we have demonstrated,” she explained.

In the second study, investigators led by Dr. Usama Mahmood of the University of Texas M. D. Anderson Cancer Center examined data from NCI’s Surveillance, Epidemiology, and End Results database for 14,760 women between the ages of 20 and 39 who were diagnosed with stage I or stage II breast cancer between 1990 and 2007. All patients who received BCS underwent radiation therapy. The 10-year overall survival rate was virtually identical between the two groups: 83.5 percent for women who had BCS and 83.6 percent for women who had mastectomy.

“We found similar survival with either breast conservation therapy or mastectomy in the treatment of young women with early-stage breast cancer,” said Dr. Mahmood. “This serves as a reminder that women should be counseled appropriately regarding their treatment options and should not choose mastectomy based on an assumption of improved survival.”

Dr. Andrew Seidman, of Memorial Sloan-Kettering Cancer Center, who moderated the press conference, added: “It’s very important that we periodically revisit conventional wisdom, and…this is an important revisitation of the conventional wisdom that young women who have breast cancer really need to have mastectomy.”

Cancer research shows survival improvements over past 30 years.

The CBS Evening News (9/20, lead story, 3:10, Pelley) reported that the American Association for Cancer Research issued a "milestone" report showing that "there has been remarkable progress on some cancers, but nearly no improvement in others." Medical editor Dr. Jon LaPook said, "Over the last 30 years, death rates for all cancer dropped by 22% for men and 14% for women, resulting in almost 900,000 fewer deaths in the US." American Association for Cancer Research's Dr. Judy Garber noted, "Cancer is probably 200 diseases, not one disease. And we can cure cancer, we just can't cure all cancer." LaPook also noted a call for more federal funding, saying that "despite all the progress, as people live longer...cancer will soon overtake heart disease as the number-one killer in the United States."

HealthDay (9/21, Goodwin) reports some of the most successful advances: "Breast cancer deaths fell about 28 percent," and "deaths from cervical cancer have dropped nearly 31 percent. Colorectal deaths have fallen 28 percent in women and 33 percent in men; deaths from leukemia have fallen nearly 15 percent in women and 10 percent in men; and deaths from stomach cancer have fallen 34 percent in women and 43 percent in men." Prostate cancer deaths have also decreased 39 percent. However, "certain cancers -- pancreatic, ovarian and lung, for example -- remain very deadly and are often caught after they've already spread, making them more difficult to treat."

MedPage Today (9/21, Walker) reports, "The report was released by the AACR to commemorate the 40th anniversary of the signing of the National Cancer Act in 1971. That law 'set the Nation on a course to conquer cancer,' according to the report authors, by laying the groundwork for funding research grant programs through the National Institutes of Health (NIH) and the National Cancer Institute." The report's authors still cautioned that "for all of these scientific successes, we are continually humbled by cancer's ability to defy expectations and change and adapt in response to treatment," and that "cancer's complexity still stands as a major challenge in cancer research."

FDA's Maisel says breast implants are safe.

The New York Times (9/1, Harris, Subscription Publication) reports, "After two days of discussion and testimony about silicone breast implants, ... Dr. William Maisel, chief scientist for the Food and Drug Administration's Center for Devices, said silicone breast implants were safe." Dr. Maisel noted the existence of risks "including ruptures, a hardening of the area around the implants, the need to remove the implants, scarring, pain, infection and asymmetry." One expert said that "the two companies that manufacture silicone breast implants - Johnson & Johnson [Mentor] and Allergan - had done a poor job of studying patients who got the implants," and "Dr. Maisel agreed that the studies conducted by the two companies had failed to follow as many patients as the agency had hoped."

The Wall Street Journal /Dow Jones (9/1, Subscription Publication) quotes Dr. Maisel saying, "FDA continues to believe currently approved devices are safe and effective," and adding, "There is a significant complication rate." The article explains that the follow-up studies being conducted have not followed enough of the patients to authoritatively answer questions about safety. Dr. Maisel said that the FDA would work with the companies to improve the studies.

MSNBC (9/1, Rubin) also quotes Dr. Maisel saying, "We believe that the benefits and risks are sufficiently well understood." Regarding follow-up studies, "Mentor has three-year data for only one out of every five women in its study, while Allergan has two-year data for three out of every five, according to the FDA."

CNN (9/1, Young) also says, "Makers of silicone breast implants have not followed up on thousands of women who received them as required by the Food and Drug Administration as a condition of approval."

MedPage Today (9/1, Walker) reports, "The FDA's General and Plastic Surgery Devices Panel, which wrapped up a two-day meeting Wednesday afternoon, said that current data collection demands are too onerous."

Lymph-node removal may not be necessary for all breast cancer patients.

ABC World News (2/8, story 5, 1:25, Sawyer) reported, "For many women with breast cancer, a new study finds doing less surgically may be just as effective." ABC (Besser) explained, "It used to be the standard of care: A doctor would go in and remove that tumor but they would also go in and remove all the lymph nodes under the arm, as many as 15 or 20. ... This study says you don't need to do that." NBC Nightly News (2/8, story 2, 2:40, Snyderman) added, "Doctors now know that if they take out one or two or three of the lymph nodes closest to the tumor, that's all they need."

USA Today (2/9, Szabo) reports, "Some women with early breast cancers can safely opt for less surgery, greatly reducing the risk of painful long-term complications," according to a study in the Journal of the American Medical Association. NPR (2/9, Knox) says the results were initially "presented last spring at a meeting of the American Society of Clinical Oncology," and many "specialists have been waiting for formal publication."

The Washington Post (2/9, Stein) reports that the analysis of "nearly 900 women who were treated at 115 sites across the country, found that those who did have their lymph nodes removed were no more likely to survive five years after the surgery than those who did not." Gary Lyman of the American Society of Clinical Oncology "said the findings will probably prompt the group to revise its recommendations for breast cancer patients accordingly." The panel that issues those guidelines is "currently reviewing its recommendations."

The Los Angeles Times (2/9, Roan) notes that all the women in the study had evidence of cancer in one or two "sentinel lymph nodes. In about half of the women, however, doctors also removed at least 10 axillary lymph nodes." The five-year survival rate was "91.8% in the women with axillary-node removal, compared with 92.5% with sentinel-node-only removal," a difference "not statistically significant." The AP (2/9, Tanner) adds that all of the women in the study were "treated with lumpectomies to remove their tumors and a common type of radiation that covers the breast and underarm area." Most also had "chemotherapy, hormone treatment, or both."

According to a front-page story in the New York Times (2/9, A1, Grady), removing the "lymph nodes proved unnecessary because the women in the study had chemotherapy and radiation, which probably wiped out any disease in the nodes," the researchers said. They concluded that removing nodes has no advantage in "about 20 percent of patients, or 40,000 women a year in the US."

Meanwhile, CNN / (2/9, Harding) points out that some breast cancer patients will "continue to need the more extensive lymph node removal." The authors "note that the procedure 'remains standard practice' in women who have had a mastectomy or who receive partial (as opposed to whole-breast) radiation. ... 'I wouldn't be too quick to apply this information to women who don't have the exact situation,'" said the lead researcher Armando Giuliano, M.D., of the John Wayne Cancer Institute in California.

The Houston Chronicle (2/9, Ackermans) adds that the researchers said patients whose cancerous lymph nodes would still require surgery include those with Stage 3 cancer and those who "had chemotherapy before surgery, a sign the cancer may be more resistant and might not be killed by radiation." MedPage Today (2/8, Bankhead) and HealthDay (2/8, Gardner) also covered the story.

Four Breast Cancer Trials with Clinical Implications

At the recent American Society of Clinical Oncology (ASCO) annual meeting in Chicago, Dr. William Wood of Emory University discussed four NCI-supported clinical trials in breast cancer, each with clinically important results. He said that he could not remember a series of four consecutive reports at ASCO “with as clear conclusions that were consequential for practice” as these.

The first trial found that a commonly used test to identify rare cells in the sentinel lymph nodes or bone marrow of patients with breast cancer may not provide useful information for patients and physicians. The test, a method for staining cells called immunohistochemistry (IHC), can detect small numbers of cells, or micrometastases, that would not typically be picked up by a pathologist’s examination of a tissue specimen on a slide.

The researchers hypothesized that IHC could help identify patients at risk of recurrence and determine which ones might need systemic chemotherapy, but the results suggested otherwise. “We had thought that finding micrometastases using immunohistochemistry would portend a worse prognosis, but we did not find that,” said co-investigator Dr. A. Marilyn Leitch, of the University of Texas Southwestern Medical Center at Dallas.

This prospective multicenter trial included more than 5,000 women with early-stage, clinically node-negative (without palpable metastases in the lymph nodes under the arm) breast cancer who had undergone lumpectomy. The women also underwent sentinel lymph node biopsies and bone marrow aspiration to determine whether micrometastases were present.

“In general, as a result of this study, these special stains should probably no longer be done in women with newly diagnosed breast cancer,” said Dr. Eric Winer of Harvard Medical School, who moderated a press briefing. The findings should have an impact on care because IHC is routinely done at many medical centers, he noted.

Regarding the bone marrow test, there was a suggestion of worse outcome in women who were found to have tumor cells in the bone marrow as detected by IHC. But this approach requires further investigation, said Dr. Winer. “I don’t think any of us would recommend that a woman with newly diagnosed breast cancer undergo a bone marrow examination as part of her routine evaluation,” he added.

Improving Quality of Life

Another study in the session was NSABP B-32, a large randomized phase III trial that compared sentinel lymph node biopsy with axillary dissection in clinically node-negative women with breast cancer. The study concluded that, in these women, axillary lymph node dissection did not add a benefit to sentinel node biopsy alone.

“When the sentinel node is negative, sentinel node surgery alone with no further axillary dissection is an appropriate, safe, and effective therapy for breast cancer patients with clinically negative lymph nodes,” said Dr. David N. Krag of the Vermont Cancer Center, who presented the findings. “This is clear evidence of a study that adds benefit to a woman’s quality of life and is also cost-saving.”

Dr. Wood praised the trial’s design and focus on surgical quality control, and he agreed with its conclusion, calling the evidence “definitive.”

In a related trial, researchers found that removing additional axillary lymph nodes to look for more breast cancer cells in women with limited disease that had spread to the sentinel node did not improve survival. These findings are important because many physicians routinely opt for axillary node dissection in women with metastases in the sentinel lymph node, the researchers said.

Axillary lymph node removal has been the standard approach for women with micro- and macrometastases in the sentinel node, explained lead author Dr. Armando Giuliano, director of the John Wayne Cancer Institute Breast Center in Santa Monica, CA. The results are not definitive, noted Dr. Winer, because the study did not meet its goal in accrual.

But the findings suggest that there may not be a benefit to removing more lymph nodes than the sentinel node in such cases, and that many women can avoid the risk of additional side effects associated with more extensive lymph node removal, Dr. Giuliano said. Axillary lymph node dissection will still be needed in some cases, but these findings show it may be necessary for far fewer women, he added.

Helping Older Patients

A fourth trial found that some older women can forgo radiation after surgery for breast cancer. Women 70 years of age or older with early-stage breast cancer did not benefit from the addition of radiation therapy to breast-conserving surgery and tamoxifen, according to the results from a phase III randomized trial. (See the full NCI Cancer Bulletin article.)

“These clinical trials, which were made possible only through government funding, will spare many women the side effects of unneeded treatment without compromising their survival,” said Dr. Jo Anne Zujewski, head of Breast Cancer Therapeutics in NCI’s Division of Cancer Treatment and Diagnosis. “They will also help save health care dollars.”

Dr. Wood concluded his discussion of the four reports by saying: “These are practice-changing results. And it’s also interesting to see scientific hypotheses proven, even if it’s only the null hypothesis.”

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