SAN FRANCISCO – The use of aromatase inhibitors (AIs) in the adjuvant setting appears to delay the development of contralateral breast cancer, and this effect was particularly prevalent among breast cancer patients who were BRCA positive, according to findings presented here at the 2015 Breast Cancer Symposium.
“AI use was suggestive of a decreased risk in all patients with a P value of .08, which was not statistically significant,” said Dr. Maryam Nemati Shafaee, from the University of Texas M.D. Anderson Cancer Center, Houston, who presented the results of her study. “However among patients with BRCA mutation, AI use was significantly associated with a smaller hazard of developing contralateral breast cancer with a P value of .04.”
Dr. Maryam Nemati Shafaee
“This may give these patients an option other than prophylactic mastectomy,” she said.
The risk of contralateral breast cancer in women who are carriers of BRCA1 and 2 mutations is up to 64%. Those with estrogen receptor positive (ER+) disease are offered tamoxifen or AIs adjuvantly. Some studies have suggested that tamoxifen might be able to reduce the risk of contralateral breast cancer in this population, but results have been conflicting.
“There is no final conclusion on the use of tamoxifen in preventing contralateral breast cancer in BRCA mutation carriers,” said Dr. Shafee, “And there are no such data on the effect of AIs.”
Dr. Shafee and her colleagues identified 2,520 patients known to carry a BRCA mutation from a prospectively maintained database, and, of that number, 486 breast cancer patients with known BRCA status were included in the final analysis.
Of these patients, the majority were diagnosed under the age of 50 years, and the majority had not undergone prophylactic mastectomy. Most patients had received tamoxifen only (60%), 21% had received tamoxifen and AIs sequentially, and 16% had received AIs only.
The median follow up 8.6 years.
Upon univariate analysis, only BRCA status was associated with a risk of contralateral breast cancer (P= .04). “Interestingly AI use was suggestive to lead to decreased risk (P value of .08) but did not reach statistical significance,” said Dr. Shafee.
In multivariate analysis, BRCA status was significantly associated with an increased risk of contralateral breast cancer. AI was again suggestive of a decreased risk (P= .08).
BRCA mutation status was also significantly associated with shorter time to the development of contralateral breast cancer (P= .047), compared with patients who were BRCA negative. AI treatment was marginally significantly associated with time to the development of contralateral breast cancer (P= .088), as compared with patients who didn’t receive this treatment. Those who received AI therapy had a smaller hazard of cancer development in the other breast.
The effect on risk of cancer in the second breast was not statistically associated with age, HER2 status, TNM stage, and tamoxifen use.
Dr. Shafee noted that the study had several limitations, one being the relatively small sample size of BRCA 1&2 mutation carriers with hormone positive tumors. “Validation of our findings based on a larger cohort of BRCA mutation carriers who have received endocrine therapy in adjuvant setting is recommended,” she said.
Dr. William J. Gradishar, of the Lurie COmprehensive Cancer Center of Northwestern University, Chicago, noted that while the data are impressive, he agreed with Dr. Shafee that the “numbers are simply too small to make any sweeping recommendations based on these data.”
In his discussion of the popular, he also posed the question if these patients are really a reflection of BRCA mutation carriers, being that they are largely ER+. “The conclusions are intriguing and value further evaluation, and I would caution the use of this broadly in this use of individuals,” noted Dr. Gradishar.