Tamoxifen Patients Monitored With Office Biopsies

April 1, 1996

NEW ORLEANS--In presentations at the Society of Gynecologic Oncologists meeting, Canadian researchers confirmed a small increased relative risk for uterine cancer in patients taking tamoxifen (Nolvadex), while investigators from Memorial Sloan-Kettering Cancer Center showed that office endometrial biopsies may be sufficient to protect tamoxifen users by findings abnormalities early.

NEW ORLEANS--In presentations at the Society of Gynecologic Oncologistsmeeting, Canadian researchers confirmed a small increased relativerisk for uterine cancer in patients taking tamoxifen (Nolvadex),while investigators from Memorial Sloan-Kettering Cancer Centershowed that office endometrial biopsies may be sufficient to protecttamoxifen users by findings abnormalities early.

For their metaanalysis, researchers at the Hamilton Research CancerCenter, Ontario, reviewed 13 trials, including 8 randomized controlledtrials involving 4,449 patients, said William Boyd, MD, who isnow with the National Maternity Hospital, Dublin, Ireland. Analysiswas performed on the entire group and again after adjustmentsto exclude women who lacked a uterus or were postmenopausal.

Putting Risk into Perspective

For both the adjusted and nonadjusted analyses, the relative riskfor uterine cancer was 2.81 for breast cancer patients receivingtamoxifen for 1 year or more. To put this into perspective, Dr.Boyd pointed out that the relative risk of patients taking unopposedestrogen has been shown to be 2.3.

"This is slightly lower than our patients on tamoxifen,"Dr. Boyd said, adding that most of the endometrial cancers inthe tamoxifen group were early, low-risk lesions.

Dr. Boyd recommended that all patients on tamoxifen who are havingabnormal vaginal bleeding undergo endometrial biopsy and long-termfollow-up. "In the asymptomatic patient," he added,"the picture is less clear."

Richard Barakat, MD, of Memorial Sloan-Kettering, reported thatmonitoring for endometrial cancer with office biopsies will safeguardthe majority of patients taking tamoxifen.

"All hyperplastic lesions were detected in patients havingat least 12 months of tamoxifen exposure," he said. "Longerfollow-up is required to determine the value of routine endometrialbiopsies, but this study provides some confirmation that officebiopsies can safely detect abnormalities in these patients."

Four Abnormal Biopsies

The prospective study sought to determine the frequency at whichpatients taking tamoxifen develop pathologic changes in the endometrium.Subjects were entered into the study upon initiating adjuvanttamoxifen for breast cancer confined to the breast and axillarynodes. Office biopsies were obtained at baseline and every 6 monthsfor 2 years.

Of 126 patients enrolled in the study, 101 were evaluated, fora total of 296 biopsies and a median surveillance time of 16 months.In these 101 patients, four biopsies (4%) were abnormal, as confirmedby dilation and curettage (D&C). These included two complexhyper-plasias, one complex atypical hyperplasia, and one withan abnormal amount of histiocytes, Dr. Barakat said.

Six additional patients required D&C for persistent bleedingdespite benign biopsies. Findings included polyps and pseudodecidualization;one case was normal. Three patients underwent hysterectomy forcomplex atypical hyperplasia, pelvic mass, or complex hyperplasiawith extensive mucinous change. All had taken the drug for atleast a year.