HRT Post Oophorectomy Adds No Breast Cancer Risk

CHICAGO – Women who have a BRCA mutation and undergo prophylactic oophorectomy can use hormone replacement therapy to control menopausal symptoms – at least in the short term – without experiencing any increase in the risk of breast cancer, new data suggest.

In an observational cohort study of more than 1,200 BRCA carriers, roughly half of those who underwent risk-reducing salpingo-oophorectomy also used hormone replacement therapy (HRT). The average duration of follow-up was about 3-5 years.

Study results, reported at the annual meeting of the American Society of Clinical Oncology, showed that oophorectomy reduced breast cancer risk as intended, and that HRT users after oophorectomy did not have an elevated risk of breast cancer, compared with nonusers.

"While further data are needed, short-term HRT can at least be considered for mutation carriers undergoing early oophorectomy for ovarian and breast cancer risk reduction," said Dr. Susan M. Domchek, who presented the findings on behalf of the PROSE (Prevention and Observation of Surgical End Points) Consortium.

"I hear a lot from my patients these days that their relatives do not want to come in for genetic testing because they have been told that they are required to have a bilateral mastectomy and oophorectomy, and are not permitted to take HRT," she commented. "If this is dissuading women from coming in, we have to have a real conversation that, although data are limited, this may be an option for patients."

The PROSE database was developed by 20 centers in the United States and Europe who identified and prospectively followed women with a deleterious BRCA1 or BRCA2 mutation. For the study, the investigators focused on those who at ascertainment had at least one ovary, no prior breast or ovarian cancer, no prior bilateral mastectomy, and at least 6 months of follow-up.

Results were based on 1,299 women; 61% had a BRCA1 mutation and 39% had a BRCA2 mutation. (Those with both mutations were excluded.) Overall, 25% underwent risk-reducing salpingo-oophorectomy, and of this group, 45% used HRT afterward.

The mean duration of follow-up was 5.1 years among women who did not have oophorectomy and never used HRT, 3.6 years among women who had oophorectomy and never used HRT, and 5.4 years among women who had oophorectomy and used HRT.

Breast cancer was diagnosed in 22% of the women overall, but in only 13% of the subgroup who underwent oophorectomy.

Study results showed that women who used HRT after oophorectomy did not have an increased risk of breast cancer (and in fact tended to have a decreased risk) whether they were compared with women who did not use HRT after oophorectomy (hazard ratio, 0.78) or with women who did not have oophorectomy and never used HRT (HR, 0.43).

The findings were similar when BCRA1 carriers and BRCA2 carriers were analyzed individually, noted Dr. Domchek of the Abramson Cancer Center at the University of Pennsylvania in Philadelphia.

Additionally, there was no increased breast cancer risk according to the type of HRT taken after surgery, whether combined estrogen-progestin (taken by women who had only their ovaries and fallopian tubes removed) or estrogen only (taken by women who had had a hysterectomy as well).

Finally, in analyses restricted to women who did not undergo oophorectomy, those who used HRT any time after natural menopause did not have an increased risk of breast cancer, compared with their counterparts who never used HRT, and again tended to have a reduced risk (HR, 0.52).

"It’s worth pointing out that the mean age at the start of follow-up is significantly different between these two groups," Dr. Domchek cautioned, at 49 years in the former and 34 years in the latter. "And this really may be a different group that becomes menopausal without any cancer diagnosis."

Dr. Domchek acknowledged that the study was not randomized, that the numbers were small in some subgroups, and that follow-up was limited. But "the perfect can be the enemy of the good at times," she cautioned.

"These women have estrogen floating around their bodies now and want their ovaries out, so they don’t die of ovarian cancer. So even if [HRT] maintains their risk at where it is before their ovaries are out, at least they don’t get ovarian cancer," she said. "I really feel that if we wait [until the data are] perfect, and women won’t have an oophorectomy because they are terrified about menopause, [then] that hasn’t done them any good, either."

Additionally, many women may be fine with short-term use of HRT, which gets around the issue of elevated breast cancer risk seen with longer-term use of combination HRT in the Women’s Health Initiative. "If longer-term use [is desired], then you can have a discussion with women about hysterectomy so that they can take estrogen only," which was not found to increase risk. "I think these are subtleties of the counseling process as well."

Moreover, participants in the Women’s Health Initiative had a median age of 63 years, which was much older than the mean age of 38 years for the BRCA carriers studied. The former "are women who had gone through their whole natural life with estrogen and then [had taken] more, so potentially, it’s not relevant to this population of patients."

Discussant Dr. Lynn Hartmann, an oncologist at the Mayo Clinic in Rochester, Minn., cautioned about the pitfall of unknown biases in observational studies. "I can tell you from participating in cohort studies myself that there are biases that one cannot even imagine that can seep into your study sets," she said.

In the PROSE study, the types of cancers resulting from a BRCA mutation in a family might have influenced which women underwent oophorectomy. And a woman’s breast history (for example, atypia) might have influenced whether her physician offered HRT after oophorectomy.

Dr. Hartmann commended the investigators for developing a large, multi-institutional registry; conducting a high-quality study; and addressing an important, relevant clinical question.

"But I think we do have to have some skepticism when treatment questions are tried to be answered from these types of [study] designs," she said. "I would at least ask the PROSE team ... to consider whether or not they could move into prospective clinical trials with their cohorts."

Dr. Domchek and Dr. Hartmann reported that they had no relevant conflicts of interest.

CHICAGO – Women who have a BRCA mutation and undergo prophylactic oophorectomy can use hormone replacement therapy to control menopausal symptoms – at least in the short term – without experiencing any increase in the risk of breast cancer, new data suggest.

In an observational cohort study of more than 1,200 BRCA carriers, roughly half of those who underwent risk-reducing salpingo-oophorectomy also used hormone replacement therapy (HRT). The average duration of follow-up was about 3-5 years.

Study results, reported at the annual meeting of the American Society of Clinical Oncology, showed that oophorectomy reduced breast cancer risk as intended, and that HRT users after oophorectomy did not have an elevated risk of breast cancer, compared with nonusers.

"While further data are needed, short-term HRT can at least be considered for mutation carriers undergoing early oophorectomy for ovarian and breast cancer risk reduction," said Dr. Susan M. Domchek, who presented the findings on behalf of the PROSE (Prevention and Observation of Surgical End Points) Consortium.

"I hear a lot from my patients these days that their relatives do not want to come in for genetic testing because they have been told that they are required to have a bilateral mastectomy and oophorectomy, and are not permitted to take HRT," she commented. "If this is dissuading women from coming in, we have to have a real conversation that, although data are limited, this may be an option for patients."

The PROSE database was developed by 20 centers in the United States and Europe who identified and prospectively followed women with a deleterious BRCA1 or BRCA2 mutation. For the study, the investigators focused on those who at ascertainment had at least one ovary, no prior breast or ovarian cancer, no prior bilateral mastectomy, and at least 6 months of follow-up.

Results were based on 1,299 women; 61% had a BRCA1 mutation and 39% had a BRCA2 mutation. (Those with both mutations were excluded.) Overall, 25% underwent risk-reducing salpingo-oophorectomy, and of this group, 45% used HRT afterward.

The mean duration of follow-up was 5.1 years among women who did not have oophorectomy and never used HRT, 3.6 years among women who had oophorectomy and never used HRT, and 5.4 years among women who had oophorectomy and used HRT.

Breast cancer was diagnosed in 22% of the women overall, but in only 13% of the subgroup who underwent oophorectomy.

Study results showed that women who used HRT after oophorectomy did not have an increased risk of breast cancer (and in fact tended to have a decreased risk) whether they were compared with women who did not use HRT after oophorectomy (hazard ratio, 0.78) or with women who did not have oophorectomy and never used HRT (HR, 0.43).

The findings were similar when BCRA1 carriers and BRCA2 carriers were analyzed individually, noted Dr. Domchek of the Abramson Cancer Center at the University of Pennsylvania in Philadelphia.

Additionally, there was no increased breast cancer risk according to the type of HRT taken after surgery, whether combined estrogen-progestin (taken by women who had only their ovaries and fallopian tubes removed) or estrogen only (taken by women who had had a hysterectomy as well).

Finally, in analyses restricted to women who did not undergo oophorectomy, those who used HRT any time after natural menopause did not have an increased risk of breast cancer, compared with their counterparts who never used HRT, and again tended to have a reduced risk (HR, 0.52).

"It’s worth pointing out that the mean age at the start of follow-up is significantly different between these two groups," Dr. Domchek cautioned, at 49 years in the former and 34 years in the latter. "And this really may be a different group that becomes menopausal without any cancer diagnosis."

Dr. Domchek acknowledged that the study was not randomized, that the numbers were small in some subgroups, and that follow-up was limited. But "the perfect can be the enemy of the good at times," she cautioned.

"These women have estrogen floating around their bodies now and want their ovaries out, so they don’t die of ovarian cancer. So even if [HRT] maintains their risk at where it is before their ovaries are out, at least they don’t get ovarian cancer," she said. "I really feel that if we wait [until the data are] perfect, and women won’t have an oophorectomy because they are terrified about menopause, [then] that hasn’t done them any good, either."

Additionally, many women may be fine with short-term use of HRT, which gets around the issue of elevated breast cancer risk seen with longer-term use of combination HRT in the Women’s Health Initiative. "If longer-term use [is desired], then you can have a discussion with women about hysterectomy so that they can take estrogen only," which was not found to increase risk. "I think these are subtleties of the counseling process as well."

Moreover, participants in the Women’s Health Initiative had a median age of 63 years, which was much older than the mean age of 38 years for the BRCA carriers studied. The former "are women who had gone through their whole natural life with estrogen and then [had taken] more, so potentially, it’s not relevant to this population of patients."

Discussant Dr. Lynn Hartmann, an oncologist at the Mayo Clinic in Rochester, Minn., cautioned about the pitfall of unknown biases in observational studies. "I can tell you from participating in cohort studies myself that there are biases that one cannot even imagine that can seep into your study sets," she said.

In the PROSE study, the types of cancers resulting from a BRCA mutation in a family might have influenced which women underwent oophorectomy. And a woman’s breast history (for example, atypia) might have influenced whether her physician offered HRT after oophorectomy.

Dr. Hartmann commended the investigators for developing a large, multi-institutional registry; conducting a high-quality study; and addressing an important, relevant clinical question.

"But I think we do have to have some skepticism when treatment questions are tried to be answered from these types of [study] designs," she said. "I would at least ask the PROSE team ... to consider whether or not they could move into prospective clinical trials with their cohorts."

Dr. Domchek and Dr. Hartmann reported that they had no relevant conflicts of interest.

CHICAGO – Women who have a BRCA mutation and undergo prophylactic oophorectomy can use hormone replacement therapy to control menopausal symptoms – at least in the short term – without experiencing any increase in the risk of breast cancer, new data suggest.

In an observational cohort study of more than 1,200 BRCA carriers, roughly half of those who underwent risk-reducing salpingo-oophorectomy also used hormone replacement therapy (HRT). The average duration of follow-up was about 3-5 years.

Study results, reported at the annual meeting of the American Society of Clinical Oncology, showed that oophorectomy reduced breast cancer risk as intended, and that HRT users after oophorectomy did not have an elevated risk of breast cancer, compared with nonusers.

"While further data are needed, short-term HRT can at least be considered for mutation carriers undergoing early oophorectomy for ovarian and breast cancer risk reduction," said Dr. Susan M. Domchek, who presented the findings on behalf of the PROSE (Prevention and Observation of Surgical End Points) Consortium.

"I hear a lot from my patients these days that their relatives do not want to come in for genetic testing because they have been told that they are required to have a bilateral mastectomy and oophorectomy, and are not permitted to take HRT," she commented. "If this is dissuading women from coming in, we have to have a real conversation that, although data are limited, this may be an option for patients."

The PROSE database was developed by 20 centers in the United States and Europe who identified and prospectively followed women with a deleterious BRCA1 or BRCA2 mutation. For the study, the investigators focused on those who at ascertainment had at least one ovary, no prior breast or ovarian cancer, no prior bilateral mastectomy, and at least 6 months of follow-up.

Results were based on 1,299 women; 61% had a BRCA1 mutation and 39% had a BRCA2 mutation. (Those with both mutations were excluded.) Overall, 25% underwent risk-reducing salpingo-oophorectomy, and of this group, 45% used HRT afterward.

The mean duration of follow-up was 5.1 years among women who did not have oophorectomy and never used HRT, 3.6 years among women who had oophorectomy and never used HRT, and 5.4 years among women who had oophorectomy and used HRT.

Breast cancer was diagnosed in 22% of the women overall, but in only 13% of the subgroup who underwent oophorectomy.

Study results showed that women who used HRT after oophorectomy did not have an increased risk of breast cancer (and in fact tended to have a decreased risk) whether they were compared with women who did not use HRT after oophorectomy (hazard ratio, 0.78) or with women who did not have oophorectomy and never used HRT (HR, 0.43).

The findings were similar when BCRA1 carriers and BRCA2 carriers were analyzed individually, noted Dr. Domchek of the Abramson Cancer Center at the University of Pennsylvania in Philadelphia.

Additionally, there was no increased breast cancer risk according to the type of HRT taken after surgery, whether combined estrogen-progestin (taken by women who had only their ovaries and fallopian tubes removed) or estrogen only (taken by women who had had a hysterectomy as well).

Finally, in analyses restricted to women who did not undergo oophorectomy, those who used HRT any time after natural menopause did not have an increased risk of breast cancer, compared with their counterparts who never used HRT, and again tended to have a reduced risk (HR, 0.52).

"It’s worth pointing out that the mean age at the start of follow-up is significantly different between these two groups," Dr. Domchek cautioned, at 49 years in the former and 34 years in the latter. "And this really may be a different group that becomes menopausal without any cancer diagnosis."

Dr. Domchek acknowledged that the study was not randomized, that the numbers were small in some subgroups, and that follow-up was limited. But "the perfect can be the enemy of the good at times," she cautioned.

"These women have estrogen floating around their bodies now and want their ovaries out, so they don’t die of ovarian cancer. So even if [HRT] maintains their risk at where it is before their ovaries are out, at least they don’t get ovarian cancer," she said. "I really feel that if we wait [until the data are] perfect, and women won’t have an oophorectomy because they are terrified about menopause, [then] that hasn’t done them any good, either."

Additionally, many women may be fine with short-term use of HRT, which gets around the issue of elevated breast cancer risk seen with longer-term use of combination HRT in the Women’s Health Initiative. "If longer-term use [is desired], then you can have a discussion with women about hysterectomy so that they can take estrogen only," which was not found to increase risk. "I think these are subtleties of the counseling process as well."

Moreover, participants in the Women’s Health Initiative had a median age of 63 years, which was much older than the mean age of 38 years for the BRCA carriers studied. The former "are women who had gone through their whole natural life with estrogen and then [had taken] more, so potentially, it’s not relevant to this population of patients."

Discussant Dr. Lynn Hartmann, an oncologist at the Mayo Clinic in Rochester, Minn., cautioned about the pitfall of unknown biases in observational studies. "I can tell you from participating in cohort studies myself that there are biases that one cannot even imagine that can seep into your study sets," she said.

In the PROSE study, the types of cancers resulting from a BRCA mutation in a family might have influenced which women underwent oophorectomy. And a woman’s breast history (for example, atypia) might have influenced whether her physician offered HRT after oophorectomy.

Dr. Hartmann commended the investigators for developing a large, multi-institutional registry; conducting a high-quality study; and addressing an important, relevant clinical question.

"But I think we do have to have some skepticism when treatment questions are tried to be answered from these types of [study] designs," she said. "I would at least ask the PROSE team ... to consider whether or not they could move into prospective clinical trials with their cohorts."

Dr. Domchek and Dr. Hartmann reported that they had no relevant conflicts of interest.