Expert Panel Reviews Noncancer Benefits of Adjuvant Tamoxifen

ABSTRACT: An expert panel of seven cancer researchers and a representativeof the National Alliance of Breast Cancer Organizations (NABCO)came together at the San Antonio Breast Cancer Symposium for aroundtable discussion of the use of tamoxifen (Nolvadex), sponsoredby PRR, Inc., publisher of Oncology News International, PrimaryCare & Cancer, and the journal ONCOLOGY. Previous articles in this series have focused on the possiblerisks of secondary cancers with tamoxifen use (February, 1996)and the appropriate duration of tamoxifen treatment (March, 1996).This month, the panel discusses the possible noncancer benefitsof tamoxifen. The last article in the series will deal with managementof tamoxifen-associated side effects.

SAN ANTONIO--The risk-to-benefit ratio for the use of adjuvanttam-oxifen therapy should be considered "outside of the narrowconfines of survival or death from metastatic breast cancer,"Monica Morrow, MD, said at the tamoxifen roundtable.

For women with node-positive breast cancer, "the overwhelmingforce of mortality is always the breast cancer," but in womenwith smaller, node-negative breast cancers, other causes of mortality,eg, cardiovascular disease, complications of osteoporosis, andother cancers, are "a bigger issue," she said.

Dr. Morrow, director of the Comprehensive Breast Program at NorthwesternUniversity Medical School, cited data suggesting that, besidesprevention of breast cancer recurrence, tamoxifen has additionalbenefits that might impact on overall survival.

"Namely, it can lower cholesterol levels and reduce hospitaladmissions for cardiovascular disease, as demonstrated in theStockholm trial," she said, "and, as shown in the Scottishstudies, even in older women, tamoxifen may reduce mortality fromcardiovascular disease."

On the other hand, Dr. Morrow noted, the recent overview analysisof adjuvant tamoxifen from the Early Breast Cancer Trialists'Collaborative Group failed to demonstrate a reduction in non-breastcancer mortality with use of tamoxifen. I. Craig Henderson, MD,of the University of California, San Francisco, said he was "alittle disconcerted" with the overview analysis results,and he remains unconvinced that the current analysis providesthe final word on the subject.

He pointed out that the contributions of various trials to theoverview have not been analyzed. "For example," he said,"the effect on cardiovascular and non-breast cancer mortality,which was rather striking at the last overview analysis, may beless so now because of the inclusion of many more trials withshorter follow-up."

V. Craig Jordan, PhD, DSc, of Northwestern University, who chairedthe tamoxifen roundtable, agreed with Dr. Henderson. He statedthat patients in many of the trials in the metaanalysis have notnecessarily used tamoxifen for 5 years, whereas the data on hormonereplacement therapy in postmenopausal women suggest that "longeris better in regard to maintaining protection against cardiovasculardisease."

Prevention Trial Endpoints

Dr. Jordan also noted that, in some cases, the metaanalsysis wasconducted 15 years after the patients took tamoxifen.

Norman Wolmark, MD, chairman of the NSABP (National Surgical AdjuvantBreast and Bowel Project), said that the current Breast CancerPrevention Trial (BCPT), along with its primary endpoint of breastcancer prevention, has other specific endpoints designed to measurethe benefit of tamoxifen relative to osteoporosis and cardiovasculardisease.

He pointed to two other important benefits associated with tamoxifenbeyond any survival benefits--the reduction in the incidence ofcontralateral breast cancer and the prevention of breast cancerrecurrence in patients who have had lumpectomies.

"In all our studies in which we've used tamoxifen as an adjunctto the treatment of breast cancer, we've noted that the incidenceof breast cancer in the opposite breast over a 10-year periodhas been reduced by 40% to 50%," he said. It was this observationthat provided the background and justification to start the BCPT,which will eventually randomize 16,000 women.

Quality of Life Issue

Use of tamoxifen or chemotherapy in breast conservation patientswho have received radiotherapy reduces the risk of recurrenceby an additional 3% at 10 years. "So the chance of keepingthat breast is significantly improved when tamoxifen or chemotherapyis added to the regimen," he said.

Dr. Morrow commented that whether or not tamoxifen use improvessurvival in this situation, it adds to the quality of life ofthese patients "since those who chose breast preservationdid so because they wanted to keep their breast."

RoundtableParticipants

Moderator: V. Craig Jordan, PhD, DSc, Robert H. Lurie Cancer Center,Northwestern University Medical School, Chicago

Richard R. Barakat, MD, The New York Hospital and Memorial Sloan-KetteringCancer Center, New York City

I. Craig Henderson, MD, University of California, San Francisco

Amy S. Langer, National Alliance of Breast Cancer Organizations(NABCO), New York City

Monica Morrow, MD, Northwestern University Medical School, Chicago

C. Kent Osborne, MD, University of Texas Health Science Center,San Antonio

Joseph Ragaz, MD, Vancouver Cancer Centre, British Columbia CancerAgency, and University of British Columbia

Norman Wolmark, MD, Medical College of Pennsylvania/HahnemannUniversity, Allegheny Campus, Pittsburgh, and Chairman of theNational Surgical Adjuvant Breast and Bowel Project (NSABP)