- Email: [email protected]
Breast Cancer after Use of Estrogen plus Progestin in Postmenopausal Women
Capsule Summaries Cumulative Live-birth Rates after In Vitro Fertilization By Malizia BA, Hacker MR, and Penzias AS N Engl J Med 2009;3603:236–243. Occasionally treasure may be found in unlikely sites. Yearly site-specific statistics for in vitro fertilization (IVF) can be accessed online by the general public, even though the process of reporting and data preparation render the results a 3-yearold window, and fertility-based journals are replete with clinic results. But longitudinal data often are hard to come by. This report comes from a busy IVF center at the Boston Beth Israel Deaconess Medical Center and Harvard Medical School, both located in Boston, MA. Live-birth rates among patients undergoing their first fresh-embryo, nondonor egg cycle between 2000 and 2005 were tracked in up to a total of 6 cycles of fresh and/or frozen embryo replacement. A total of 6164 patients in 14 248 cycles were followed up. Live-birth rates were determined by a standard life-table analysis according to 2 different assumptions. The first was the ‘‘optimistic’’ approach, which assumes that patients who discontinued therapy had the same chance for success as those who continued. Because many couples entering IVF therapy have a long history of infertility with unsuccessful treatment, this clearly overestimates the results. The other assumption is a ‘‘conservative’’ model (I would call it ‘‘pessimistic’’) that assumes no live birth after cessation of IVF–clearly an underestimate proved by other studies, but probably closer to reality. I will report the latter assumption in this summary. The other point to keep in mind when interpreting the results is that Massachusetts has a mandatory medical insurance plan that usually covers up to 6 cycles of IVF. This results in a decreased pressure to achieve pregnancy/cycle leading to a reduced number of embryos replaced/cycle, especially now that frozen-thawed cycles have approached fresh cycle replacement results, collectively resulting in a reduction of multiple pregnancy with all its abortion and newborn mortality/morbidity. The live-birth rate for women younger than 35 years after 6 cycles (if necessary) was 65%; for those aged 40 and older the rate was 23%, with the intervening ages between these 2 extremes. The drop-out group included those who transferred to another center, some with poor response to stimulation, and those with age-related factors leading to donor egg cycles. Of the 3126 live births recorded, 70.9% were singleton, 27.3% were twins, and only 1.7% were trip1553-4650/$ - see front matter Ó 2009 AAGL. All rights reserved. doi:10.1016/j.jmig.2009.02.003
lets. Of interest was the fact that the chance for pregnancy decreased with each successive cycle, such that each cycle is not, statistically speaking, an independent event. For the entire group the first cycle success rate was 24.5% but only 13.0% after the sixth cycle. The effect of oocyte age again was clearly demonstrated. Comment: The authors acknowledge that their percycle results are lower than some other clinics, but the reduction in multiple birth rates, in my opinion, more than compensates for this. Remember that multiple birth is not just a 9-month ordeal, but a 21-year (or longer) commitment. Now that blastocyst replacement technology has improved, many centers, especially those in Europe where the number of embryos replaced is often limited by law, routinely return 1 or 2 embryos, keeping the remainder frozen for subsequent use. (In our program we had a successful birth after 8 years of life in liquid nitrogen, so the duration of the freeze seems unimportant.) The article is so clearly written, that I believe many patients can read it and glean important information that will help them in the decision process. Stephen L. Corson, MD doi:10.1016/j.jmig.2009.01.008
Breast Cancer after Use of Estrogen plus Progestin in Postmenopausal Women By Chlebowski RT, Kuller LH, Prentice RP, et al. N Engl J Med 2009;360:573–587. The Women’s Health Initiative (WHI) data have been mined once again. If you recall, the prospective study compared daily administration of 0.625 mg of conjugated estrogens with 2.5 mg of medroxyprogesterone in one group with placebo so far as a possible effect on breast cancer incidence was concerned. Strangely, the active group had fewer cancers in the first 2 years, which then increased compared with the placebo group over the intervention interval of 5.6 years. Continued study of the hormonally active group after cessation of treatment showed a rapid decline from about a twofold risk to essentially the same risk as nonhormonal recipients. The study was halted in July 2002 when the increased risk became statistically noticed. The posttreatment observational study continued until March 31, 2005. All but 4% of the active group ceased any estrogen therapy.
376
Noteworthy is the fact that the frequency of mammograms was the same for both groups. The number of previous hormonal users followed to the end of the posttrial observation was 7466 versus 7190 for the placebo group. During this interval there were 71 diagnosed cases in the drug group and 70 in the placebo group. There is some subgroup analysis, such as looking at those who were or were not hormone users before entry into the trial, but the results do not alter the conclusions. Comment: The numbers are large, the statistical methods are impeccable, the data are robust, and the conclusion is quite straightforward. In the cohort of postmenopausal women studied, compared with placebo, use of the drug combination resulted in a risk of increased breast cancer diagnosis after the second year which remained high, conferring a twofold risk by year 5.6 but with a rapid decline to essentially no increased risk by 2 years after cessation of therapy. I must confess that I am puzzled by the time frame.
Journal of Minimally Invasive Gynecology, Vol 16, No 3, May/June 2009
The biology of breast cancer development is still somewhat murky, but classical teaching is that the lesion diagnosed by mammography today had its onset a year or more in the past, plus or minus the behavior of ‘‘aggressive’’ or ‘‘indolent’’ lesions. One explanation could be (without supporting data) that removal of the hormonal stimulus slowed down development of those lesions that were hormonally sensitive and that they will appear later; or, to go even farther, removal of the hormonal effect brought about a reversal of the malignant process. The latter thought reminds me of treating low grade endometrial lesions with hormonal manipulation. Other theories? Letters to the editor are most welcome. Stephen L. Corson, MD doi:10.1016/j.jmig.2009.02.003
lets. Of interest was the fact that the chance for pregnancy decreased with each successive cycle, such that each cycle is not, statistically speaking, an independent event. For the entire group the first cycle success rate was 24.5% but only 13.0% after the sixth cycle. The effect of oocyte age again was clearly demonstrated. Comment: The authors acknowledge that their percycle results are lower than some other clinics, but the reduction in multiple birth rates, in my opinion, more than compensates for this. Remember that multiple birth is not just a 9-month ordeal, but a 21-year (or longer) commitment. Now that blastocyst replacement technology has improved, many centers, especially those in Europe where the number of embryos replaced is often limited by law, routinely return 1 or 2 embryos, keeping the remainder frozen for subsequent use. (In our program we had a successful birth after 8 years of life in liquid nitrogen, so the duration of the freeze seems unimportant.) The article is so clearly written, that I believe many patients can read it and glean important information that will help them in the decision process. Stephen L. Corson, MD doi:10.1016/j.jmig.2009.01.008
Breast Cancer after Use of Estrogen plus Progestin in Postmenopausal Women By Chlebowski RT, Kuller LH, Prentice RP, et al. N Engl J Med 2009;360:573–587. The Women’s Health Initiative (WHI) data have been mined once again. If you recall, the prospective study compared daily administration of 0.625 mg of conjugated estrogens with 2.5 mg of medroxyprogesterone in one group with placebo so far as a possible effect on breast cancer incidence was concerned. Strangely, the active group had fewer cancers in the first 2 years, which then increased compared with the placebo group over the intervention interval of 5.6 years. Continued study of the hormonally active group after cessation of treatment showed a rapid decline from about a twofold risk to essentially the same risk as nonhormonal recipients. The study was halted in July 2002 when the increased risk became statistically noticed. The posttreatment observational study continued until March 31, 2005. All but 4% of the active group ceased any estrogen therapy.
376
Noteworthy is the fact that the frequency of mammograms was the same for both groups. The number of previous hormonal users followed to the end of the posttrial observation was 7466 versus 7190 for the placebo group. During this interval there were 71 diagnosed cases in the drug group and 70 in the placebo group. There is some subgroup analysis, such as looking at those who were or were not hormone users before entry into the trial, but the results do not alter the conclusions. Comment: The numbers are large, the statistical methods are impeccable, the data are robust, and the conclusion is quite straightforward. In the cohort of postmenopausal women studied, compared with placebo, use of the drug combination resulted in a risk of increased breast cancer diagnosis after the second year which remained high, conferring a twofold risk by year 5.6 but with a rapid decline to essentially no increased risk by 2 years after cessation of therapy. I must confess that I am puzzled by the time frame.
Journal of Minimally Invasive Gynecology, Vol 16, No 3, May/June 2009
The biology of breast cancer development is still somewhat murky, but classical teaching is that the lesion diagnosed by mammography today had its onset a year or more in the past, plus or minus the behavior of ‘‘aggressive’’ or ‘‘indolent’’ lesions. One explanation could be (without supporting data) that removal of the hormonal stimulus slowed down development of those lesions that were hormonally sensitive and that they will appear later; or, to go even farther, removal of the hormonal effect brought about a reversal of the malignant process. The latter thought reminds me of treating low grade endometrial lesions with hormonal manipulation. Other theories? Letters to the editor are most welcome. Stephen L. Corson, MD doi:10.1016/j.jmig.2009.02.003