New data may alter frequency and surgical procedure for lymph node biopsies in early-stage breast cancer
Research results from the “Era of Hope” Department of Defense Breast Cancer Research Program meeting
iopsy is the standard tool to determine whether small breast tumors have invaded nearby lymph nodes, a signal that additional therapy is called for to destroy roving cancer cells. But the traditional procedure for nodal biopsy is, itself, major surgery with serious potential complications, and many women with early-stage cancer have no biopsy or follow up therapy, putting them at risk for recurrence from undetected metastatic disease.
At the “Era of Hope” Department of Defense Breast Cancer Research Program meeting, investigators present three studies with findings that may change clinical practice by making it possible to identify likely metastasis without nodal biopsy, demonstrating the accuracy of a less invasive technique when biopsy is called for, and confirming the importance of determining nodal status for all women diagnosed with early-stage breast cancer.
Advanced Technology May Detect Breast Cancer and Define Prognosis Without Surgery
A new technology developed by Australian researchers may enable women to learn — within minutes and without surgery — if a breast abnormality is benign or malignant and, if they have early breast cancer, whether or not the cancer has spread to the lymph nodes.
“This technology could eliminate a lot of unnecessary surgery in women with breast abnormalities by providing both a diagnosis and a prognosis before surgery,” said Cynthia L. Lean, Ph.D., scientific director of the Institute for Magnetic Resonance Research in Sydney, Australia, and a member of the team that developed the technology.
The technique, known as magnetic resonance spectroscopy (MRS), works by analyzing the chemicals present in a small cluster of cells removed with a fine needle from the suspicious area of the breast. If a malignancy is found, a computer program evaluates the likelihood that the tumor has spread to the lymph nodes.
The group has conducted multiple laboratory tests using breast cancer cells that have shown that MRS can identify benign and malignant tumors and the presence or absence of lymph node involvement with a high degree of accuracy. Clinical testing of the technology is set to begin within a year in Australia, Sweden, and the United States.
Currently, women in whom other diagnostic tests are inconclusive may need a surgical biopsy to determine whether a breast abnormality is benign or malignant — and it may take several days to get the biopsy results. “In most cases, the abnormality turns out to be benign, but the woman has had to undergo surgery as well as days of uncertainty to obtain that diagnosis,” explained Dr. Lean.
In women with early breast cancer, the presence or absence of lymph node involvement is a crucial factor in determining how their disease is treated. However, surgical removal of lymph nodes to determine if they contain cancer can cause lymphedema — swelling in the arms or legs due to excess fluid accumulation, which remains a risk after the procedure, and after breast cancer has been successfully treated.
“We hope that MRS will ultimately eliminate the need for lymph node surgery and the associated risk of lymphedema,” Dr. Lean said.
Less-Invasive Biopsy to Detect Metastasis Found Suitable for More Patients
New data support expanding the pool of women with breast cancer who are potential candidates for sentinel node biopsy (SNB), a less-invasive procedure to determine whether the disease has spread to the lymph nodes, according to interim results from an ongoing clinical trial reported here. The study also provides early indications that the type of test conducted on the SNB sample may enhance the accuracy of the results.
“SNB has dramatically better benefits than axillary node dissection because it is less invasive and more accurate at finding whether the tumor has spread,” said Lorraine Tafra, M.D., director of the Breast Center at the Anne Arundel Medical Center in Annapolis, MD. “This and other multicenter studies have shown that the surgeons experience with the procedure is critical. Now were investigating the role of other factors that might widen the applicability of the technique and further improve reliability.”
SNB is replacing axillary node dissection as the procedure of choice to determine whether cancer has migrated beyond the breast for recently diagnosed patients. With axillary dissection, 10-30 lymph nodes under the arm next to the affected breast are removed in a procedure that involves surgery around nerves and the nearby major vein. The rate of complications, primarily fluid collection, infection, and loss of sensation in the arm, can be as high as 25%-50%. However, only a few of these axillary lymph nodes actually drain from the breast and are appropriate first-line indicators of metastatic disease. Most women have one or two such “sentinel” nodes.
With SNB, the surgeon injects one or more agents around the tumor, which then travel through the lymphatic pipes, highlighting the lymph nodes most likely to contain metastatic disease; no major nerves or vessels are disturbed. If the sentinel node does not contain cancer cells, the chance of the disease being in the remaining lymph nodes should be very small, explained Dr. Tafra.
In this study, scientists compared biopsy results from over 1,200 patients who had SNB, the majority of whom also then had the standard axillary node dissection procedure, to see whether they could identify any patient-specific factors that might be related to a “false-negative” SNB reading — one that misses cancer in the sentinel node but finds cancer in an axillary node. The data showed no association between a false-negative reading and patient age, tumor type or location, multiple versus single cancer sites in the breast, or preoperative chemotherapy, thus making thousands of women eligible for SNB who were previously excluded. What initially appeared to be a higher false-negative rate for women who had had a partial mastectomy, compared with open or core biopsy, disappeared with subsequent analysis of a larger group of patients.
“The sentinel node will not accurately reflect the other lymph nodes in less than one percent of patients, and its clear that SNB will be both more accurate and less traumatic than the axillary node procedure for the vast majority of patients,” Dr. Tafra said.
Furthermore, the study is finding evidence that the technique used to analyze the SNB tissue may be an important factor in the accuracy of the results. When 36 false-negative SNB specimens from 18 patients were examined with a molecular test called RT-PCR, tumor cells were detected in 61% of these nodes. RT-PCR amplifies the signal from the tumor so that detection of metastatic cells is much more sensitive than with H&E, the standard pathology test. Additionally, in this study, tissue for RT-PCR was sampled throughout the sentinel node. Pathologists usually are able to examine only a few central sections of each lymph node, especially with the large number of nodes from standard axillary dissection, Dr. Tafra explained.
Early data from this study reveal a statistically significant increase in disease-free survival for patients whose nodal biopsies were negative for cancer on both pathology tests, suggesting that the cancer really was confined to the breast, compared with those whose biopsies were negative with H&E but positive with the more sensitive RT-PCR test.
“Thus far weve done RT-PCR analysis for less than half the patients enrolled in the study, but were optimistic that another 12 months of data will demonstrate that even very small amounts of disease detected only by molecular methods can have clinical significance,” Dr. Tafra concluded.
Lumpectomy Without Nodal Biopsy Linked to Poorer Survival in Older Women
Older women who have breast-conserving surgery (BCS) without lymph node biopsy or radiation therapy have poorer survival rates than those who have this procedure plus biopsy, radiation therapy, or both, according to results of a large retrospective study reported today. “We focused our study on women age 65 and older because even though breast cancer risk rises with age, appropriate treatment for cancer generally decreases with age,” explained Xianglin Du, M.D., Ph.D., University of Texas Medical Branch and Sealy Center on Aging, Galveston, TX.
The Galveston team matched treatment with outcomes in two databases for 31,618 women who had BCS, also called lumpectomy, for early-stage breast cancer. Over 27% of these women, or 9,006, had BCS without nodal biopsy, and 74% of these women were at least 65 years old. Of the women who had BCS without biopsy, 62% had no radiation therapy and 98% had no chemotherapy. Numerous clinical trials have documented that post-surgical chemotherapy is appropriate for breast cancer patients only to the age of 69, but there are no such age restrictions for radiation therapy or hormone therapy.
Nodal biopsy was strongly associated with higher seven-year survival rates and higher rates of post-surgical radiation or chemotherapy to kill any errant cancer cells. Survival rates were similar for women who had either nodal biopsy or radiation therapy and those who had both procedures, reported Dr. Du.
“Survival of older breast cancer patients hasnt improved for 20 years. Our study suggests that one key reason may be the growing popularity of BCS for early-stage disease without nodal dissection, which can lead to under-staging and under-treatment, ultimately leading to higher recurrence and higher mortality,” Dr. Du concluded.
Dr. Du cautioned that the study is limited by his groups inability to control for post-surgical hormone therapy (e.g. tamoxifen for post-menopausal women with estrogen receptor-positive tumors), because the databases lacked good information on that factor. “Nevertheless, the literature suggests that theres still a large proportion of women who dont receive hormone therapy,” he said.
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