Cancer Research Highlights

Breast Cancer Cells Found by Immunochemistry in Sentinel Nodes Not Associated with Survival

The detection of breast cancer cells in sentinel lymph nodes by immunochemistry—antibody-based techniques to detect cancer cells—in addition to standard tissue staining does not appear to help predict survival after treatment for breast cancer. These results, from the American College of Surgeons Oncology Group (ACOSOG) Z0010 study, were published online July 26 in JAMA.

ACOSOG researchers from 126 hospitals, led by Dr. Armando Giuliano of the John Wayne Cancer Institute in Santa Monica, CA, enrolled 5,119 women with early-stage breast cancer and identifiable sentinel lymph nodes in the prospective observational study between May 1999 and May 2003.

Most of the women had stage I, estrogen receptor-positive breast cancer. Ninety-one percent received whole-breast radiation, 83 percent received chemotherapy, and 68 percent received hormone therapy.

Standard tissue staining found cancer cells in the sentinel lymph nodes of almost one-quarter of the women. Of the remaining women, 85 percent were assessed using immunohistochemistry (IHC). In about 10 percent of those women, IHC found occult (initially undetected) metastases in the sentinel lymph nodes that standard tissue staining had failed to detect. However, the researchers did not see a statistically significant difference in overall survival between women who did and did not have IHC-detected cancer cells in their lymph nodes.

Using a similar test called immunocytochemistry, the researchers found occult metastases in the bone marrow of 104 (3 percent) of the 3,413 women who had samples that could be tested. The presence of these cancer cells was associated with decreased overall survival. However, when other factors, such as age and tumor size, were included in the analysis, the association between occult bone marrow metastases and overall survival disappeared. The small number of women with positive bone marrow findings may explain this absence of statistical significance, noted the authors.

The researchers also pointed out that most patients in the Z0010 trial received adjuvant systemic therapy, which is standard practice in the United States, independent of immunohistochemical findings. “Thus,” wrote the authors, “although the effect of untreated micrometastases is unknown, it is not relevant to current practice” because occult sentinel lymph node metastases treated with adjuvant systemic therapy do not affect survival.

Because IHC of the sentinel nodes did not help predict survival, and the incidence of occult bone marrow metastases was “too low to recommend incorporating bone marrow aspiration biopsy into routine practice” for patients with early-stage breast cancer, the authors concluded that routine immunochemical examination of sentinel nodes and bone marrow is “not clinically warranted” for these women.

“Many laboratories currently do immunohistochemistry to look for sentinel lymph node metastases, and this study does not support this expensive practice,” agreed Dr. Jo Anne Zujewski, head of Breast Cancer Therapeutics in NCI’s Division of Cancer Treatment and Diagnosis.

Radiation Plus Short-Term Hormone Therapy Improves Survival of Men with Early-Stage Prostate Cancer

In men with intermediate-risk, early stage prostate cancer, short-term treatment to lower male sex hormones given in combination with radiation therapy prolonged overall survival compared with radiation therapy alone, according to an NCI-supported clinical trial. The results of the study were published July 14 in the New England Journal of Medicine.

The trial, which was conducted by the Radiation Therapy Oncology Group (RTOG) at 212 centers in the United States and Canada, enrolled nearly 2,000 patients with localized nonmetastatic prostate cancer and with serum prostate-specific antigen (PSA) levels of less than 20 ng/ml. Patients were randomly assigned to treatment with radiation therapy alone or radiation therapy plus short-term (4 months) androgen deprivation therapy (STADT) using drugs that drastically lowered their natural production of testosterone.

The researchers reported a statistically significant improvement in overall survival after 10 years for participants who received STADT plus radiation compared with those who received radiation therapy alone (62 percent versus 57 percent overall survival).

Men who received radiation therapy plus STADT were also less likely than men who received radiation therapy alone to die of prostate cancer (4 percent versus 8 percent). Benefits of the combined treatment were limited mainly to patients with intermediate-risk disease and were not seen for men with low-risk prostate cancer, the researchers said. (Men with intermediate-risk disease have higher Gleason scores, PSA, and clinical stage values than men with low-risk disease.)

The study included nearly 400 black men, who have a higher prostate cancer risk than white men. Benefits from the addition of STADT were similar in white and black men for 10-year overall survival, prostate cancer-specific mortality, and biochemical failure (i.e., a rise in PSA levels after initially lowered levels due to androgen deprivation therapy).  

“This study has important significance for clinical care,” said lead author Dr. Christopher U. Jones, of Radiological Associates of Sacramento, CA. “We now have strong scientific evidence about which patients with early-stage prostate cancer benefit from STADT” added to conventional radiation therapy. But the authors also note that new radiotherapy techniques now make it possible to use higher doses of radiation than were used in this study. A successor RTOG study will investigate the value of adding STADT in men with intermediate-risk disease treated with these new radiation methods.  

In Hodgkin Lymphoma Study, Side Effects Distinguish Treatments

A clinical trial has shown that two strategies for treating advanced Hodgkin lymphoma are nearly equal in their long-term effectiveness, but one is associated with more severe side effects, including a greater risk of treatment-related deaths, infertility, and second cancers. The findings appeared in the July 21 New England Journal of Medicine.

In the study, researchers in Italy compared outcomes in patients randomly assigned to receive one of two multidrug chemotherapy regimens, known as BEACOPP and ABVD, as well as additional therapy for patients in either group who needed it. (Patients who had residual disease after initial therapy or who had a complete response and then relapsed were treated with high-dose salvage chemotherapy with autologous hematopoietic stem-cell transplantation.)  

Dr. Alessandro Gianni of the Milan Cancer Institute and his colleagues found that the 7-year rate of freedom from first progression was 85 percent with BEACOPP versus 73 percent with ABVD. However, the 7-year survival rate for patients in the BEACOPP group was 89 percent, compared with 84 percent for the ABVD group. The difference was not statistically significant. Thus, after salvage therapy, the overall survival outcomes in the two groups were similar, and the ABVD regimen had a clear advantage in terms of side effects.

In the absence of a survival benefit, “patients should be informed of the trade-off involved in choosing between two initial therapies,” the study authors wrote. They noted that the BEACOPP therapy exposes patients who would have been cured by ABVD (i.e., the majority of patients) to an unnecessarily high risk of severe toxic effects, whereas the use of ABVD means that a small proportion (one of eight in this study) of patients will need high-dose salvage treatment, with its associated severe toxic side effects.

Three-quarters of the patients in the ABVD group who responded to treatment were spared infertility, the risk of leukemia, and other toxic effects of the more intense BEACOPP treatment, noted Dr. Joseph Connors, clinical director of the Center for Lymphoid Cancer at the British Columbia Cancer Agency and author of an accompanying editorial. Many patients with this disease are young adults who will have to live with the toxic side effects of their treatments for the rest of their lives.

“This study shows that you cure just as many people with either strategy,” said Dr. Connors. The findings reaffirm what many clinicians are doing, which is to use ABVD as the primary regimen, he noted.

Nonetheless, Dr. Connors continued, deciding which regimen to use has been an open question for the field, and the new study “clarifies the issue substantially.” The ABVD regimen has been used for several decades, and German researchers developed the more intensive BEACOPP regimen during the 1990s.

The new findings also establish an important principle, Dr. Connors added. “For diseases like this one that can often be cured, the proper way to compare outcomes of treatments is to look at overall management strategy as opposed to simply looking at the outcome of the primary therapy,” he said. “You need to look at the whole package.”