NCCN Guidelines Expand Tamoxifen Recommendations

FORT LAUDERDALE, Fla—The National Comprehensive Cancer Center (NCCN) Practice Guidelines for Breast Cancer have been updated to reflect the results of new trials demonstrating the effectiveness of tamoxifen (Nolvadex) as a risk reduction agent for women treated for breast cancer.

The updated guidelines also include new recommendations in other areas, which will be described in an upcoming issue of ONI. Robert W. Carlson, MD, professor of medicine, Stanford University, presented the findings on tamoxifen at the NCCN’s Fifth Annual Conference.

For patients who have been treated for ductal carcinoma in situ (DCIS) with breast-conserving surgery and radiation therapy, the guidelines urge clinicians to “strongly consider” the use of tamoxifen, 20 mg/d for 5 years, as adjuvant treatment. The previous version of the guidelines simply said to “consider” tamoxifen for prevention in this setting.

The new recommendation is based on the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-24 randomized trial, which found a reduction in risk in this setting in women who received tamoxifen. At 5 years, tamoxifen users had about a 5% absolute reduction in the risk of developing breast cancer, compared with placebo, “and that translated into about a 37% relative risk reduction,” Dr. Carlson said.

Reductions in both invasive and noninvasive breast cancers were observed, but no survival advantage for tamoxifen has yet been demonstrated.

In DCIS patients treated with excision alone, high-level evidence is lacking for the use of tamoxifen, but, Dr. Carlson said, there was a uniform consensus within the breast cancer panel to make the recommendation that it be “strongly considered” based on lower-level evidence.

For DCIS patients treated with mastectomy, the recommendation to strongly consider tamoxifen for contralateral risk reduction lacked a uniform consensus. “Panel members agreed that you could use it or not use it in this setting. Practice patterns differ,” Dr. Carlson said.

For women with lobular carcinoma in situ (LCIS), the NSABP Breast Cancer Prevention Trial showed that tamoxifen reduces breast cancer risk in both breasts. Thus, for women with LCIS who are being observed, the guidelines advise “counseling regarding use of tamoxifen for risk reduction.”

The guidelines on adjuvant therapy for stage I, IIA, and IIB invasive breast cancer now include a new column on risk reduction.

“One should consider tamoxifen for contralateral breast cancer risk reduction if tamoxifen was not given as an adjuvant therapy,” Dr. Carlson said. “We have high level evidence from multiple trials that tamoxifen will reduce the contralateral risk. We don’t say that it should be used but, rather, that one should consider its use, because the magnitude of benefit is relatively modest, and cost effectiveness analysis to my knowledge has not yet been done.”

For certain subsets of patients treated for stage I, IIA, or IIB disease, previous guidelines had recommended the optional use of tamoxifen for systemic adjuvant therapy. This has now been replaced with the unequivocal recommendation for its use (with or without chemotherapy) in node-positive patients with stage I, IIA, or IIB disease (1 to 3 cm) who are hormone-receptor positive and in those with node-negative, hormone-receptor positive stage IIA or IIB disease (with adjuvant chemotherapy).