1. Susman, Ed

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SAN ANTONIO-Women who take tamoxifen or aromatase inhibitors to prevent breast cancer recurrence also dramatically decrease their risk of developing cancer in the contralateral breast, researchers reported here at the 38th San Antonio Breast Cancer Symposium (Abstract P5-12-01).

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When compared with women who were not treated with endocrine therapy after breast cancer, women who took tamoxifen for four years or longer had a 61 percent reduced risk of developing another cancer in the opposite breast, stated Gretchen Gierach, PhD, an investigator in the Hormone and Reproductive Epidemiology Branch of the National Cancer Institute, Bethesda, Maryland.


In addition, Gierach reported that women who were just on aromatase inhibitors had a risk reduction of 54 percent when compared with women who were not prescribed tamoxifen or aromatase inhibitors following initial breast cancer diagnosis.


"We find these results encouraging because they are very similar to what was observed in clinical trials," Gierach told OT at her poster presentation, "and this is what is happening in the 'real world.' We have detailed prescription records so we can observe what happens with gaps in treatment over long periods of time."


She and her colleagues reported that "among U.S. patients with invasive breast cancer treated in a general community health plan, adjuvant tamoxifen and aromatase inhibitors significantly reduced contralateral primary breast cancer risk."


"Tamoxifen reduced contralateral primary breast cancer risk during treatment and after cessation, with contralateral primary breast cancer risk progressively decreasing as tamoxifen duration increased," she said. "Stronger effects were observed among women whose first cancer was estrogen receptor-positive.


"Tamoxifen use for more than four years was estimated to result in the prevention of three contralateral primary breast cancers per 100 women by 10 years following an estrogen receptor-positive first breast cancer diagnosis, an absolute reduction in contralateral primary breast cancer which is consistent with findings from clinical trials."


She continued, "If adjuvant endocrine therapy is indicated, our findings, in concert with trial data, suggest that breast cancer patients should be encouraged to complete the full course of therapy."


Study Opinion

In commenting on the study, Eleonora Teplinsky, MD, medical oncologist, Northwell Health Cancer Institute, Lake Success, New York, told OT, "The benefits of adjuvant endocrine therapy in breast cancer treatment are well established. The study presented by Gierach et al. builds on existing data by demonstrating that endocrine therapy decreases the risk of contralateral breast cancer despite gaps in treatment and varying treatment durations."


Study Details

Gierach noted that within 10 years after breast cancer diagnosis, 5 percent of patients will develop a contralateral primary breast cancer. To perform the study, she and her colleagues accessed the records of women treated for breast cancer within the Kaiser Permanente Northwest Center for Health Research in Portland, Oregon, and the Denver-based Colorado health plan between 1990 and 2008. The study included 7,541 patients diagnosed with breast cancer aged 24 to 85 years who survived at least one year after diagnosis and initial treatment and remained at risk for contralateral breast cancer. Of those, 5,951 women were diagnosed with estrogen receptor-positive breast cancer. Women were followed until the earliest of the following events:


* Contralateral primary breast cancer diagnosis,


* Other second cancer diagnosis,


* Exited the Kaiser Permanente plan,


* Death,


* Last tumor-registry follow-up, or


* End of study date in 2011.



In the study, with a median 6.3 years of follow-up, 274 cases of contralateral breast cancer occurred in the patient population. There were 131 of those cancers in the patients who either never used endocrine therapy or were on the treatments for less than 90 days. That group of patients represented 12,852 person-years following initial diagnosis.


Statistical Significance

If women were currently using tamoxifen, a group representing 10,385 person years, there were 33 cases of contralateral breast cancer (RR 0.45 [95%CI 0.28-0.71]), a statistically significant finding, Gierach said.


Former users of tamoxifen who were on the agent for less than a year developed 18 contralateral breast cancers. That group of patients had 2,272 person-years of follow-up. Their risk was less than that of non-users, but the difference did not achieve statistical significance. There were 37 cases of contralateral breast cancer among patients using tamoxifen for one to less than four years, a group that had 5,882 person-years of follow-up, but the risk reduction compared with non-users was not significant.


However, the patients who took tamoxifen for more than four years did have a significant difference in risk reduction when compared to non-users. These long-term users accounted for 29 cases of contralateral breast cancer that occurred during 6,593 person-years of follow-up.


Patients who were treated with aromatase inhibitor but not tamoxifen, representing 3,446 person-years of treatment, had 10 cases of contralateral breast cancer (RR 0.46 [95% CI 0.20-0.94]), which was also statistically significant, Gierach said. Women who were taking both aromatase inhibitors and tamoxifen had 16 cases of contralateral breast cancer. That was a reduced risk compared to non-users; the difference between this group representing 3,385 person-years of experience with the treatment was not statistically significant.


Overall, 58 percent of the women in the study population were prescribed tamoxifen. "The reduced risks associated with four plus years of tamoxifen persisted among patients surviving at least seven years but were attenuated among those with more than 10 years since their first primary diagnosis," Gierach said.


"Adjuvant tamoxifen and aromatase inhibitor therapy considerably reduce the risk of contralateral breast cancer," she said. "Furthermore, our data suggest that tamoxifen protects against contralateral breast cancer while women are being treated and that the protective effect appears to continue after cessation with longer durations of use."