ASCO 2010-ROUTINE USE OF IHC NOT NEEDED IN EARLY BREAST CANCER

June 15, 2010 (Chicago, Illinois) — The routine use of immunohistochemistry (IHC) to evaluate sentinel lymph nodes and bone marrow lacks clinical utility in early breast cancer, according to a study presented here at the American Society of Clinical Oncology (ASCO) 2010 Annual Meeting.

IHC is used to detect micrometastases that might be missed by standard pathology.

In a large observational study of women who had undergone a lumpectomy and had clinically node-negative disease, the investigators found that overall survival was not affected by the use of IHC.

"We believe that routine examination of sentinel lymph nodes by IHC is not supported in this patient population," concluded Kelly Hunt, MD, who presented the Z10 study on behalf of the American College of Surgeons Oncology Group (ACSOG). Dr. Hunt is from the University of Texas M.D. Anderson Cancer Center in Houston.

All the women in the trial had either T1 or T2 N0 M0 breast cancer.

The trial design called for all of the women to undergo sentinel lymph node biopsies (n = 5210). The women with negative nodes on standard hemotoxylin and eosin (H&E) testing (n = 3995) were further evaluated with IHC to determine if micrometastases were present but undetectable by the standard H&E pathologic technique. A total of 349 women (10%) were ultimately found to have positive nodes on IHC.

The median 5-year overall survival rate was 95.1% for women who were node negative on H&E (and subsequently either positive or negative on IHC) and 92.8% for women with positive lymph nodes detected by standard H&E (P = .0009).

"There is no added clinical benefit" to performing IHC on H&E-negative sentinel lymph nodes, said William Wood, MD, from Emory University School of Medicine in Atlanta, Georgia. Dr. Wood acted as discussant of the study at ASCO.

Dr. Wood said that neither the College of American Pathologists nor ASCO should change their recommendations that IHC is not needed when sentinel nodes are negative on H&E.

After the ASCO 2009 meeting, it appeared that those recommendations might need to be altered, suggested Dr. Wood.

He was referring to the MIRROR (Micrometastases and Isolated Tumor Cells: Relevant and Robust or Rubbish?) study from the Netherlands, which found that IHC-detected isolated tumor cells in sentinel lymph nodes had "significant prognostic importance."

However, Dr. Wood pointed out that the ACSOG Z10 study was a "real-world" trial. In ACSOG Z10, the patients were treated with current clinical norms — 68% had adjuvant hormonal therapy and 53% had adjuvant chemotherapy. In MIRROR, however, none of the patients, who were evaluated retrospectively, had received any adjuvant treatment. Dr. Wood mentioned that when the MIRROR investigators later added in data on patients who had received adjuvant therapies, their outcome with regard to the value of IHC was "reversed."

Bone Marrow Results

Many of the women in the ACSOG Z10 study had IHC testing of the bone marrow (n = 3413), regardless of the status of their lymph nodes. The testing in the study was originally optional and then became mandatory, reported Dr. Hunt.

Only 3% of the women (n = 104) had bone marrow specimens that were positive on IHC. The percentage was low but in keeping with the disease stage, which was "very, very early" breast cancer, and the small average tumor size, Dr. Hunt explained.

Dr. Wood pointed out that this meant that only 1 in 33 bone marrows were positive on IHC in this population of women.

Dr. Hunt reported that the median 5-year survival rate for women with IHC-positive bone marrow was 90.2%, compared with 95.1% for women with IHC-negative bone marrow; the difference was statistically significant (P = .015).

The detection of bone marrow metastases with IHC turned out not to be predictive of overall survival in multivariate analysis, added Dr. Hunt.

The multivariable analysis, which included sentinel node and bone marrow status, estrogen-receptor status, progesterone-receptor status, grade, size, and age, showed that IHC-detected micrometastases in sentinel node (P = .66) or bone marrow (P = .08) were not independent predictors of overall survival.

The fact that bone marrow metastases identified by IHC were "associated" with an increased risk for death was supportive of findings of earlier studies, the study authors note.

"What does this add?," asked Dr. Wood about the fact that the median 5-year survival rate for women with IHC-positive bone marrow was lower than that for women with IHC-negative bone marrow.

In answering his own question, Dr. Wood pointed out that the survival difference (90.2% vs 95.1%) did not seem large but, in fact, was statistically significant.

However, Dr. Wood also noted that among the subset of women who were originally sentinel-lymph-node negative (on H&E) but were found to have IHC-detected metastases in the bone marrow, there was not a statistically significant overall survival value (P = .16). This is important, he said, because these are the very patients who "might not receive cytotoxic chemotherapy."

"I'm grateful that it appears to lack clinical utility," said Dr. Wood about the bone marrow findings. He said that the opposite finding would require him and other clinicians to do 33 bone marrow aspirations among sentinel-lymph-node negative women to find the 1 patient with bone micrometastases.

Dr. Wood noted that the finding about disease spread in the bones is important because it might support the idea that what matters most in survival is the biology of the tumor and not its micrometastastic spread.

Dr. Hunt and Dr. Wood have disclosed no relevant financial relationships.

American Society of Clinical Oncology (ASCO) 2010 Annual Meeting: Abstract CRA504. Presented June 7, 2010.