MDedge ObGyn

Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."

Follow-up from two of the WHI’s randomized trials have found that estrogen alone in women with prior hysterectomy significantly increased ovarian cancer incidence and mortality in postmenopausal women. Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)

In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.

Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
 

Ovarian Cancer Incidence Doubles with Estrogen

At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.

Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).

Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”

Care of Ovarian Cancer Survivors Should Change

The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.

In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.

“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.

“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.

Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.

“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.

Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.

“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”

Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”

These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”

When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”

Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.

Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."

Follow-up from two of the WHI’s randomized trials have found that estrogen alone in women with prior hysterectomy significantly increased ovarian cancer incidence and mortality in postmenopausal women. Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)

In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.

Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
 

Ovarian Cancer Incidence Doubles with Estrogen

At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.

Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).

Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”

Care of Ovarian Cancer Survivors Should Change

The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.

In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.

“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.

“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.

Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.

“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.

Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.

“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”

Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”

These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”

When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”

Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.

Two decades after the landmark Women’s Health Initiative (WHI) changed the way clinicians thought about hormone therapy and cancer, new findings suggest this national health study is "the gift that keeps on giving."

Follow-up from two of the WHI’s randomized trials have found that estrogen alone in women with prior hysterectomy significantly increased ovarian cancer incidence and mortality in postmenopausal women. Estrogen and progesterone together, meanwhile, did not increase ovarian cancer risk, and significantly reduced the risk of endometrial cancer. Rowan T. Chlebowski, MD, PhD, of The Lundquist Institute in Torrance, California, presented these results from the latest WHI findings, at the annual meeting of the American Society of Clinical Oncology in Chicago.

Dr. Chlebowski and his colleagues conducted an analysis from two randomized, placebo-controlled trials, which between 1993 and 1998 enrolled nearly 28,000 postmenopausal women aged 50-79 years without prior cancer from 40 centers across the United States. (The full WHI effort involved a total cohort of 161,000 patients, and included an observational study and two other non-drug trials.)

In one of the hormone therapy trials, 17,000 women with a uterus at baseline were randomized to combined equine estrogen plus medroxyprogesterone acetate, or placebo. In the other trial, about 11,000 women with prior hysterectomy were randomized to daily estrogen alone or placebo. Both trials were stopped early: the estrogen-only trial due to an increased stroke risk, and the combined therapy trial due to findings of increased breast cancer and cardiovascular risk.

Mean exposure to hormone therapy was 5.6 years for the combined therapy trial and 7.2 years for estrogen alone trial.
 

Ovarian Cancer Incidence Doubles with Estrogen

At 20 years’ follow up, with mortality information available for nearly the full cohort, Dr. Chlebowski and his colleagues could determine that ovarian cancer incidence doubled among women who had taken estrogen alone (hazard ratio = 2.04; 95% CI 1.14-3.65; P = .01), a difference that reached statistical significance at 12 years’ follow up. Ovarian cancer mortality was also significantly increased (HR = 2.79 95% CI 1.30-5.99, P = .006). Absolute numbers were small, however, with 35 cases of ovarian cancer compared with 17 in the placebo group.

Combined therapy recipients saw no increased risk for ovarian cancer and significantly lower endometrial cancer incidence (106 cases vs. 140 HR = 0.72; 95% CI, 0.56-0.92; P = .01).

Conjugated equine estrogen, Dr. Chlebowski said during his presentation at the meeting, “was introduced in US clinical practice in 1943 and used for over half a century, yet the question about hormone therapy’s influence on endometrial and ovarian cancer remains unsettled. Endometrial cancer and ovarian cancer are the fourth and fifth leading causes of cancer deaths in women ... and there’s some discordant findings from observational studies.”

Care of Ovarian Cancer Survivors Should Change

The new findings should prompt practice and guideline changes regarding the use of estrogen alone in ovarian cancer survivors, Dr. Chlebowski said.

In an interview, oncologist Eleonora Teplinsky, MD, of Valley-Mount Sinai Comprehensive Cancer Care in Paramus, New Jersey, said that apart from this subgroup of ovarian cancer survivors, the findings would not likely have much impact on how clinicians and patients approach hormone replacement therapy today.

“Twenty years ago the Women’s Health Initiative showed that hormone replacement therapy increases breast cancer risk, and everyone stopped taking HRT. And now people pushing back on it and saying wait a second – it was the estrogen plus progesterone that increased breast cancer, not estrogen alone. And now we’ve got these newer [estrogen] formulations.

“Yes, there’s a little bit of an increased risk [for ovarian cancer]. Patients should be aware. They should know the symptoms of ovarian cancer. But if they have indications and have been recommended HRT, this is not something that we would advise them against because of this very slightly increased risk,” Dr. Teplinsky said.

Oncologist Allison Kurian, MD of Stanford University in Stanford, California, who specializes in breast cancer, also noted that the duration of hormone treatment, treatment timing relative to age of menopause onset, and commonly used estrogen preparations had indeed changed since the time the WHI trials were conducted, making it harder to generalize the findings to current practice. Nonetheless, she argued, they still have real significance.

“WHI is an incredibly complex but also incredibly valuable resource,” said Dr. Kurian, who has conducted studies using WHI data. “The first big results came out in 2002, and we’re still learning from it. These are randomized trials, which offer the strongest form of scientific evidence that exists. So whenever we see results from this study, we have to take note of them,” she said.

Because the WHI trials had shown combined therapy, not estrogen alone, to be associated with breast cancer risk, clinicians have felt reassured over the years about using estrogen alone.

“You can’t give it to a person unless they have their uterus removed, because we know it will cause uterine cancer if the uterus is in place. But if the uterus is removed, the feeling was that you can give estrogen alone. I think the new piece that is going to get everyone’s attention is this signal for ovarian cancer.”

Something else the new findings show, Dr. Kurian said, is that WHI is “the gift that keeps on giving,” even after decades. “Some of the participants had a relatively short-term exposure to HRT. They took a medication for just a little while. But you didn’t see the effects until you followed people 12 years. So we’re now going to be a little more worried about ovarian cancer in this setting than we used to be. And that’s going to be something we’re all going to keep an eye on and think twice about in terms of talking to patients.”

These results help demonstrate what happens when a society invests in science on a national scale, Dr. Kurian said. “Here we have a really long-term, incredibly informative study that keeps generating knowledge to help women.”

When the WHI began, it “really was the first time that people decided it was important to systematically study women at midlife. It was a remarkable thing then that society got mobilized to do this, and we’re still seeing the benefits.”

Dr. Chlebowski disclosed receiving consulting or advisory fees from Pfizer. Dr. Teplinsky and Dr. Kurian disclosed no financial conflicts of interest.

An influential US panel may largely reaffirm its current recommendation in favor of screening older women to prevent osteoporotic fractures, while also repeating its call for more research to try to determine whether men would benefit from this kind of routine testing.

The US Preventive Services Task Force (USPSTF) on June 11 released a draft update of its recommendations on osteoporosis screening. The task force will accept comments on the draft through July 8. Federal law gives the USPSTF recommendations extra clout, requiring insurers to cover — without co-pay — services that get top marks “A” or “B” from the task force.

The task force intends to maintain a “B” recommendation on screening of older women, indicating that the evidence gathered to date suggests a moderate net benefit. But the draft includes a shift in the approach to this screening.

The USPSTF proposed saying that it recommends screening for osteoporosis in both women aged 65 years and older and postmenopausal women younger than 65 years who are at an increased risk for an osteoporotic fracture. The current recommendation, finalized in 2018, advises “screening for osteoporosis with bone measurement testing [emphasis added]” for these groups.

The proposed change in language — dropping the phrase “with bone measurement testing” — is intended to expand flexibility for clinicians, Esa Davis, MD, MPH, a member of USPSTF and a professor at the University of Maryland School of Medicine, Baltimore, told this news organization.

USPSTF

University of Chicago Medicine

Insufficient Evidence

The USPSTF’s “I” grade is different from a “D” grade, which is what the task force uses to recommend against the use of a service.

A “D” grade means the USPSTF says there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. (The USPSTF makes it easy to search online for grades given to preventive services, including those that got a “D.”)

The USPSTF is calling for more studies on the benefits and harms of screening for osteoporosis to prevent fractures and related morbidity and mortality in men.

“Men do get osteoporosis,” Dr. Davis said. “But unfortunately, the evidence isn’t there” to allow USPSTF to make a recommendation on screening approaches.

“Any man who has concerns about bone health should certainly talk to his clinician and figure out what is the best form of screening” he might want to do, she said.

There’s been a growing interest in the question of whether to screen men for osteoporosis and bone health. For example, Osteoporosis Canada last year updated a guideline to emphasize the need to assess older patients of both sexes for the risk for fractures. But the Canadian Task Force on Preventive Health Care in 2023 came to a conclusion in line with the USPSTF draft.

The Canadian task force recommended against routine screening in men, while adding that clinicians should be alert to changes in health that may indicate the patient has experienced or is at a higher risk for fragility fracture.
 

Risk Factors, Concerns About Tests

The USPSTF said that risk factors associated with fragility fractures are similar in men and women. These include:

• Increasing age
• Low body mass index
• Excessive alcohol intake
• Current smoking
• Chronic corticosteroid use
• History of prior fractures, falls within the past year, cerebrovascular accident, and diabetes
• Hypogonadism

The process of updating the USPSTF recommendations can serve as a chance to expand public awareness about osteoporosis, as many men may not know to raise the question of their fracture risk during medical appointments, Dr. Davis said.

“Clinicians need to be aware of the risk factors and to be able to have conversations with men,” she said.

Dr. Davis also cautioned about the need to be aware of limitations with clinical risk assessment tools. In the draft recommendation statement, the USPSTF noted that some tools and approaches may be less likely to identify Black, Hispanic, and Asian people as high risk, and subsequently, clinicians may be less likely to offer treatment to them compared with White people of the same age, bone mineral density, and clinical risk profile.

Dr. Davis had no relevant financial relationships. Dr. Jain received research funding from the Amgen Foundation.
 

A version of this article appeared on Medscape.com.

An influential US panel may largely reaffirm its current recommendation in favor of screening older women to prevent osteoporotic fractures, while also repeating its call for more research to try to determine whether men would benefit from this kind of routine testing.

The US Preventive Services Task Force (USPSTF) on June 11 released a draft update of its recommendations on osteoporosis screening. The task force will accept comments on the draft through July 8. Federal law gives the USPSTF recommendations extra clout, requiring insurers to cover — without co-pay — services that get top marks “A” or “B” from the task force.

The task force intends to maintain a “B” recommendation on screening of older women, indicating that the evidence gathered to date suggests a moderate net benefit. But the draft includes a shift in the approach to this screening.

The USPSTF proposed saying that it recommends screening for osteoporosis in both women aged 65 years and older and postmenopausal women younger than 65 years who are at an increased risk for an osteoporotic fracture. The current recommendation, finalized in 2018, advises “screening for osteoporosis with bone measurement testing [emphasis added]” for these groups.

The proposed change in language — dropping the phrase “with bone measurement testing” — is intended to expand flexibility for clinicians, Esa Davis, MD, MPH, a member of USPSTF and a professor at the University of Maryland School of Medicine, Baltimore, told this news organization.

USPSTF

University of Chicago Medicine

Insufficient Evidence

The USPSTF’s “I” grade is different from a “D” grade, which is what the task force uses to recommend against the use of a service.

A “D” grade means the USPSTF says there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. (The USPSTF makes it easy to search online for grades given to preventive services, including those that got a “D.”)

The USPSTF is calling for more studies on the benefits and harms of screening for osteoporosis to prevent fractures and related morbidity and mortality in men.

“Men do get osteoporosis,” Dr. Davis said. “But unfortunately, the evidence isn’t there” to allow USPSTF to make a recommendation on screening approaches.

“Any man who has concerns about bone health should certainly talk to his clinician and figure out what is the best form of screening” he might want to do, she said.

There’s been a growing interest in the question of whether to screen men for osteoporosis and bone health. For example, Osteoporosis Canada last year updated a guideline to emphasize the need to assess older patients of both sexes for the risk for fractures. But the Canadian Task Force on Preventive Health Care in 2023 came to a conclusion in line with the USPSTF draft.

The Canadian task force recommended against routine screening in men, while adding that clinicians should be alert to changes in health that may indicate the patient has experienced or is at a higher risk for fragility fracture.
 

Risk Factors, Concerns About Tests

The USPSTF said that risk factors associated with fragility fractures are similar in men and women. These include:

• Increasing age
• Low body mass index
• Excessive alcohol intake
• Current smoking
• Chronic corticosteroid use
• History of prior fractures, falls within the past year, cerebrovascular accident, and diabetes
• Hypogonadism

The process of updating the USPSTF recommendations can serve as a chance to expand public awareness about osteoporosis, as many men may not know to raise the question of their fracture risk during medical appointments, Dr. Davis said.

“Clinicians need to be aware of the risk factors and to be able to have conversations with men,” she said.

Dr. Davis also cautioned about the need to be aware of limitations with clinical risk assessment tools. In the draft recommendation statement, the USPSTF noted that some tools and approaches may be less likely to identify Black, Hispanic, and Asian people as high risk, and subsequently, clinicians may be less likely to offer treatment to them compared with White people of the same age, bone mineral density, and clinical risk profile.

Dr. Davis had no relevant financial relationships. Dr. Jain received research funding from the Amgen Foundation.
 

A version of this article appeared on Medscape.com.

An influential US panel may largely reaffirm its current recommendation in favor of screening older women to prevent osteoporotic fractures, while also repeating its call for more research to try to determine whether men would benefit from this kind of routine testing.

The US Preventive Services Task Force (USPSTF) on June 11 released a draft update of its recommendations on osteoporosis screening. The task force will accept comments on the draft through July 8. Federal law gives the USPSTF recommendations extra clout, requiring insurers to cover — without co-pay — services that get top marks “A” or “B” from the task force.

The task force intends to maintain a “B” recommendation on screening of older women, indicating that the evidence gathered to date suggests a moderate net benefit. But the draft includes a shift in the approach to this screening.

The USPSTF proposed saying that it recommends screening for osteoporosis in both women aged 65 years and older and postmenopausal women younger than 65 years who are at an increased risk for an osteoporotic fracture. The current recommendation, finalized in 2018, advises “screening for osteoporosis with bone measurement testing [emphasis added]” for these groups.

The proposed change in language — dropping the phrase “with bone measurement testing” — is intended to expand flexibility for clinicians, Esa Davis, MD, MPH, a member of USPSTF and a professor at the University of Maryland School of Medicine, Baltimore, told this news organization.

USPSTF

University of Chicago Medicine

Insufficient Evidence

The USPSTF’s “I” grade is different from a “D” grade, which is what the task force uses to recommend against the use of a service.

A “D” grade means the USPSTF says there is moderate or high certainty that the service has no net benefit or that the harms outweigh the benefits. (The USPSTF makes it easy to search online for grades given to preventive services, including those that got a “D.”)

The USPSTF is calling for more studies on the benefits and harms of screening for osteoporosis to prevent fractures and related morbidity and mortality in men.

“Men do get osteoporosis,” Dr. Davis said. “But unfortunately, the evidence isn’t there” to allow USPSTF to make a recommendation on screening approaches.

“Any man who has concerns about bone health should certainly talk to his clinician and figure out what is the best form of screening” he might want to do, she said.

There’s been a growing interest in the question of whether to screen men for osteoporosis and bone health. For example, Osteoporosis Canada last year updated a guideline to emphasize the need to assess older patients of both sexes for the risk for fractures. But the Canadian Task Force on Preventive Health Care in 2023 came to a conclusion in line with the USPSTF draft.

The Canadian task force recommended against routine screening in men, while adding that clinicians should be alert to changes in health that may indicate the patient has experienced or is at a higher risk for fragility fracture.
 

Risk Factors, Concerns About Tests

The USPSTF said that risk factors associated with fragility fractures are similar in men and women. These include:

• Increasing age
• Low body mass index
• Excessive alcohol intake
• Current smoking
• Chronic corticosteroid use
• History of prior fractures, falls within the past year, cerebrovascular accident, and diabetes
• Hypogonadism

The process of updating the USPSTF recommendations can serve as a chance to expand public awareness about osteoporosis, as many men may not know to raise the question of their fracture risk during medical appointments, Dr. Davis said.

“Clinicians need to be aware of the risk factors and to be able to have conversations with men,” she said.

Dr. Davis also cautioned about the need to be aware of limitations with clinical risk assessment tools. In the draft recommendation statement, the USPSTF noted that some tools and approaches may be less likely to identify Black, Hispanic, and Asian people as high risk, and subsequently, clinicians may be less likely to offer treatment to them compared with White people of the same age, bone mineral density, and clinical risk profile.

Dr. Davis had no relevant financial relationships. Dr. Jain received research funding from the Amgen Foundation.
 

A version of this article appeared on Medscape.com.

TOPLINE:

Isotretinoin was effective in treating acne in individuals undergoing masculinizing gender-affirming hormone therapy in a case series, but more information is needed on dosing and barriers to treatment.

METHODOLOGY:

• Acne can be a side effect of masculinizing hormone therapy for transmasculine individuals. While isotretinoin is an effective treatment option for acne, its effectiveness and safety in transgender and gender-diverse individuals are not well understood.
• This retrospective case series included 55 patients (mean age, 25.4 years) undergoing masculinizing hormone therapy at four medical centers, who were prescribed isotretinoin for acne associated with treatment.
• Isotretinoin treatment was started a median of 22.1 months after hormone therapy was initiated and continued for a median of 6 months with a median cumulative dose of 132.7 mg/kg.
• Researchers assessed acne improvement, clearance, recurrence, adverse effects, and reasons for treatment discontinuation.

TAKEAWAY:

• Overall, 48 patients (87.3%) experienced improvement, and 26 (47.3%) achieved clearance during treatment. A higher proportion of patients experienced improvement (97% vs 72.7%) and achieved clearance (63.6% vs 22.7%) with cumulative doses of ≥ 120 mg/kg than those who received cumulative doses < 120 mg/kg.
• The risk for recurrence was 20% (in four patients) among 20 patients who achieved clearance and had any subsequent health care encounters, with a mean follow-up time of 734.3 days.
• Common adverse effects included dryness (80%), joint pain (14.5%), and headaches (10.9%). Other adverse effects included nose bleeds (9.1%) and depression (5.5%).
• Of the 22 patients with a cumulative dose < 120 mg/kg, 14 (63.6%) were lost to follow-up; among those not lost to follow-up, 2 patients discontinued treatment because of transfer of care, 1 because of adverse effects, and 1 because of gender-affirming surgery, with concerns about wound healing.

IN PRACTICE:

“Although isotretinoin appears to be an effective treatment option for acne among individuals undergoing masculinizing hormone therapy, further efforts are needed to understand optimal dosing and treatment barriers to improve outcomes in transgender and gender-diverse individuals receiving testosterone,” the authors concluded.

SOURCE:

The study, led by James Choe, BS, Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, was published online in JAMA Dermatology.

LIMITATIONS:

The study population was limited to four centers, and variability in clinician- and patient-reported acne outcomes and missing information could affect the reliability of data. Because of the small sample size, the association of masculinizing hormone therapy regimens with outcomes could not be evaluated.

DISCLOSURES:

One author is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Three authors reported receiving grants or personal fees from various sources. The other authors declared no conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

Isotretinoin was effective in treating acne in individuals undergoing masculinizing gender-affirming hormone therapy in a case series, but more information is needed on dosing and barriers to treatment.

METHODOLOGY:

• Acne can be a side effect of masculinizing hormone therapy for transmasculine individuals. While isotretinoin is an effective treatment option for acne, its effectiveness and safety in transgender and gender-diverse individuals are not well understood.
• This retrospective case series included 55 patients (mean age, 25.4 years) undergoing masculinizing hormone therapy at four medical centers, who were prescribed isotretinoin for acne associated with treatment.
• Isotretinoin treatment was started a median of 22.1 months after hormone therapy was initiated and continued for a median of 6 months with a median cumulative dose of 132.7 mg/kg.
• Researchers assessed acne improvement, clearance, recurrence, adverse effects, and reasons for treatment discontinuation.

TAKEAWAY:

• Overall, 48 patients (87.3%) experienced improvement, and 26 (47.3%) achieved clearance during treatment. A higher proportion of patients experienced improvement (97% vs 72.7%) and achieved clearance (63.6% vs 22.7%) with cumulative doses of ≥ 120 mg/kg than those who received cumulative doses < 120 mg/kg.
• The risk for recurrence was 20% (in four patients) among 20 patients who achieved clearance and had any subsequent health care encounters, with a mean follow-up time of 734.3 days.
• Common adverse effects included dryness (80%), joint pain (14.5%), and headaches (10.9%). Other adverse effects included nose bleeds (9.1%) and depression (5.5%).
• Of the 22 patients with a cumulative dose < 120 mg/kg, 14 (63.6%) were lost to follow-up; among those not lost to follow-up, 2 patients discontinued treatment because of transfer of care, 1 because of adverse effects, and 1 because of gender-affirming surgery, with concerns about wound healing.

IN PRACTICE:

“Although isotretinoin appears to be an effective treatment option for acne among individuals undergoing masculinizing hormone therapy, further efforts are needed to understand optimal dosing and treatment barriers to improve outcomes in transgender and gender-diverse individuals receiving testosterone,” the authors concluded.

SOURCE:

The study, led by James Choe, BS, Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, was published online in JAMA Dermatology.

LIMITATIONS:

The study population was limited to four centers, and variability in clinician- and patient-reported acne outcomes and missing information could affect the reliability of data. Because of the small sample size, the association of masculinizing hormone therapy regimens with outcomes could not be evaluated.

DISCLOSURES:

One author is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Three authors reported receiving grants or personal fees from various sources. The other authors declared no conflicts of interest.

A version of this article first appeared on Medscape.com.

TOPLINE:

Isotretinoin was effective in treating acne in individuals undergoing masculinizing gender-affirming hormone therapy in a case series, but more information is needed on dosing and barriers to treatment.

METHODOLOGY:

• Acne can be a side effect of masculinizing hormone therapy for transmasculine individuals. While isotretinoin is an effective treatment option for acne, its effectiveness and safety in transgender and gender-diverse individuals are not well understood.
• This retrospective case series included 55 patients (mean age, 25.4 years) undergoing masculinizing hormone therapy at four medical centers, who were prescribed isotretinoin for acne associated with treatment.
• Isotretinoin treatment was started a median of 22.1 months after hormone therapy was initiated and continued for a median of 6 months with a median cumulative dose of 132.7 mg/kg.
• Researchers assessed acne improvement, clearance, recurrence, adverse effects, and reasons for treatment discontinuation.

TAKEAWAY:

• Overall, 48 patients (87.3%) experienced improvement, and 26 (47.3%) achieved clearance during treatment. A higher proportion of patients experienced improvement (97% vs 72.7%) and achieved clearance (63.6% vs 22.7%) with cumulative doses of ≥ 120 mg/kg than those who received cumulative doses < 120 mg/kg.
• The risk for recurrence was 20% (in four patients) among 20 patients who achieved clearance and had any subsequent health care encounters, with a mean follow-up time of 734.3 days.
• Common adverse effects included dryness (80%), joint pain (14.5%), and headaches (10.9%). Other adverse effects included nose bleeds (9.1%) and depression (5.5%).
• Of the 22 patients with a cumulative dose < 120 mg/kg, 14 (63.6%) were lost to follow-up; among those not lost to follow-up, 2 patients discontinued treatment because of transfer of care, 1 because of adverse effects, and 1 because of gender-affirming surgery, with concerns about wound healing.

IN PRACTICE:

“Although isotretinoin appears to be an effective treatment option for acne among individuals undergoing masculinizing hormone therapy, further efforts are needed to understand optimal dosing and treatment barriers to improve outcomes in transgender and gender-diverse individuals receiving testosterone,” the authors concluded.

SOURCE:

The study, led by James Choe, BS, Department of Dermatology, Brigham and Women’s Hospital, Harvard Medical School, Boston, was published online in JAMA Dermatology.

LIMITATIONS:

The study population was limited to four centers, and variability in clinician- and patient-reported acne outcomes and missing information could affect the reliability of data. Because of the small sample size, the association of masculinizing hormone therapy regimens with outcomes could not be evaluated.

DISCLOSURES:

One author is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases. Three authors reported receiving grants or personal fees from various sources. The other authors declared no conflicts of interest.

A version of this article first appeared on Medscape.com.

Vaccination against human papillomavirus (HPV) is an effective way to prevent HPV infection and cancers typically caused by HPV, including cervical cancer and head and neck cancers, new research showed.

The analysis, featured at a press briefing ahead of the presentation at the American Society of Clinical Oncology (ASCO) 2024 annual meeting, notably found that men who received the HPV vaccine had a 56% lower risk for head and neck cancers.

“We’ve known for a long time that having the HPV vaccine can prevent the development of HPV infection, yes, but importantly, cancer,” primarily cervical cancer, said briefing moderator and ASCO president Lynn Schuchter, MD, Abramson Cancer Center, University of Pennsylvania, Philadelphia. “This is a really important study that extends the information about the impact.”

Using the US TriNetX database, lead investigator Jefferson DeKloe, BS, a research fellow with Thomas Jefferson University, Philadelphia, and colleagues created a matched cohort of 760,540 HPV-vaccinated and unvaccinated men and 945,999 HPV-vaccinated and unvaccinated women.

HPV-vaccinated men had a 54% lower risk for all HPV-related cancers (odds ratio [OR], 0.46; P < .001) and a 56% lower risk for head and neck cancers (OR, 0.44; P < .001) than unvaccinated men. There were not enough cases of anal and penile cancers for analysis.

HPV-vaccinated women had a 27% lower risk for all HPV-related cancers (OR, 0.73; P < .05), a 54% lower risk for cervical cancer (OR, 0.46; P < .05), and a 33% lower risk for head and neck cancers (OR, 0.67; 95% CI, 0.42-1.08) than HPV-unvaccinated women, but this finding was not significant. There were not enough cases of anal cancers for analysis, and the odds of developing vulvar or vaginal cancer was not significantly different in HPV-vaccinated vs unvaccinated women.

Vaccinated women, however, were less likely than unvaccinated women to develop high-grade squamous intraepithelial lesions (OR, 0.44), cervical carcinoma in situ (OR, 0.42), or abnormal Pap findings (OR, 0.87), and were less likely to undergo cone biopsy and loop electrosurgical excision (OR, 0.45).

“This study really highlights the importance of getting the HPV vaccine,” Dr. Schuchter said at the briefing.

“HPV vaccination is cancer prevention,” Glenn Hanna, MD, with Dana-Farber Cancer Institute, Boston, said in an ASCO statement.

Still, HPV vaccination rates in the United States remain relatively low. According to the National Cancer Institute, in 2022, only about 58% of adolescents aged 13-15 years had received two or three doses of HPV vaccine as recommended.

“The goal,” Dr. Schuchter said at the briefing, “is that younger girls and young boys get vaccinated to prevent development of HPV infection, and that should decrease the risk of cancer, which is what we’ve seen.”

Mr. DeKloe agreed and highlighted the importance of improving vaccination rates. “Identifying effective interventions that increase HPV vaccination rates is critical in reducing undue cancer burden in the United States,” Mr. DeKloe said in a statement.

The study had no funding source. Mr. DeKloe had no relevant disclosures. Dr. Hanna has disclosed relationships with Bicara Therapeutics, Bristol Myers Squibb, Coherus BioSciences, and others. Dr. Schuchter had no relevant disclosures.

A version of this article appeared on Medscape.com .

Vaccination against human papillomavirus (HPV) is an effective way to prevent HPV infection and cancers typically caused by HPV, including cervical cancer and head and neck cancers, new research showed.

The analysis, featured at a press briefing ahead of the presentation at the American Society of Clinical Oncology (ASCO) 2024 annual meeting, notably found that men who received the HPV vaccine had a 56% lower risk for head and neck cancers.

“We’ve known for a long time that having the HPV vaccine can prevent the development of HPV infection, yes, but importantly, cancer,” primarily cervical cancer, said briefing moderator and ASCO president Lynn Schuchter, MD, Abramson Cancer Center, University of Pennsylvania, Philadelphia. “This is a really important study that extends the information about the impact.”

Using the US TriNetX database, lead investigator Jefferson DeKloe, BS, a research fellow with Thomas Jefferson University, Philadelphia, and colleagues created a matched cohort of 760,540 HPV-vaccinated and unvaccinated men and 945,999 HPV-vaccinated and unvaccinated women.

HPV-vaccinated men had a 54% lower risk for all HPV-related cancers (odds ratio [OR], 0.46; P < .001) and a 56% lower risk for head and neck cancers (OR, 0.44; P < .001) than unvaccinated men. There were not enough cases of anal and penile cancers for analysis.

HPV-vaccinated women had a 27% lower risk for all HPV-related cancers (OR, 0.73; P < .05), a 54% lower risk for cervical cancer (OR, 0.46; P < .05), and a 33% lower risk for head and neck cancers (OR, 0.67; 95% CI, 0.42-1.08) than HPV-unvaccinated women, but this finding was not significant. There were not enough cases of anal cancers for analysis, and the odds of developing vulvar or vaginal cancer was not significantly different in HPV-vaccinated vs unvaccinated women.

Vaccinated women, however, were less likely than unvaccinated women to develop high-grade squamous intraepithelial lesions (OR, 0.44), cervical carcinoma in situ (OR, 0.42), or abnormal Pap findings (OR, 0.87), and were less likely to undergo cone biopsy and loop electrosurgical excision (OR, 0.45).

“This study really highlights the importance of getting the HPV vaccine,” Dr. Schuchter said at the briefing.

“HPV vaccination is cancer prevention,” Glenn Hanna, MD, with Dana-Farber Cancer Institute, Boston, said in an ASCO statement.

Still, HPV vaccination rates in the United States remain relatively low. According to the National Cancer Institute, in 2022, only about 58% of adolescents aged 13-15 years had received two or three doses of HPV vaccine as recommended.

“The goal,” Dr. Schuchter said at the briefing, “is that younger girls and young boys get vaccinated to prevent development of HPV infection, and that should decrease the risk of cancer, which is what we’ve seen.”

Mr. DeKloe agreed and highlighted the importance of improving vaccination rates. “Identifying effective interventions that increase HPV vaccination rates is critical in reducing undue cancer burden in the United States,” Mr. DeKloe said in a statement.

The study had no funding source. Mr. DeKloe had no relevant disclosures. Dr. Hanna has disclosed relationships with Bicara Therapeutics, Bristol Myers Squibb, Coherus BioSciences, and others. Dr. Schuchter had no relevant disclosures.

A version of this article appeared on Medscape.com .

Vaccination against human papillomavirus (HPV) is an effective way to prevent HPV infection and cancers typically caused by HPV, including cervical cancer and head and neck cancers, new research showed.

The analysis, featured at a press briefing ahead of the presentation at the American Society of Clinical Oncology (ASCO) 2024 annual meeting, notably found that men who received the HPV vaccine had a 56% lower risk for head and neck cancers.

“We’ve known for a long time that having the HPV vaccine can prevent the development of HPV infection, yes, but importantly, cancer,” primarily cervical cancer, said briefing moderator and ASCO president Lynn Schuchter, MD, Abramson Cancer Center, University of Pennsylvania, Philadelphia. “This is a really important study that extends the information about the impact.”

Using the US TriNetX database, lead investigator Jefferson DeKloe, BS, a research fellow with Thomas Jefferson University, Philadelphia, and colleagues created a matched cohort of 760,540 HPV-vaccinated and unvaccinated men and 945,999 HPV-vaccinated and unvaccinated women.

HPV-vaccinated men had a 54% lower risk for all HPV-related cancers (odds ratio [OR], 0.46; P < .001) and a 56% lower risk for head and neck cancers (OR, 0.44; P < .001) than unvaccinated men. There were not enough cases of anal and penile cancers for analysis.

HPV-vaccinated women had a 27% lower risk for all HPV-related cancers (OR, 0.73; P < .05), a 54% lower risk for cervical cancer (OR, 0.46; P < .05), and a 33% lower risk for head and neck cancers (OR, 0.67; 95% CI, 0.42-1.08) than HPV-unvaccinated women, but this finding was not significant. There were not enough cases of anal cancers for analysis, and the odds of developing vulvar or vaginal cancer was not significantly different in HPV-vaccinated vs unvaccinated women.

Vaccinated women, however, were less likely than unvaccinated women to develop high-grade squamous intraepithelial lesions (OR, 0.44), cervical carcinoma in situ (OR, 0.42), or abnormal Pap findings (OR, 0.87), and were less likely to undergo cone biopsy and loop electrosurgical excision (OR, 0.45).

“This study really highlights the importance of getting the HPV vaccine,” Dr. Schuchter said at the briefing.

“HPV vaccination is cancer prevention,” Glenn Hanna, MD, with Dana-Farber Cancer Institute, Boston, said in an ASCO statement.

Still, HPV vaccination rates in the United States remain relatively low. According to the National Cancer Institute, in 2022, only about 58% of adolescents aged 13-15 years had received two or three doses of HPV vaccine as recommended.

“The goal,” Dr. Schuchter said at the briefing, “is that younger girls and young boys get vaccinated to prevent development of HPV infection, and that should decrease the risk of cancer, which is what we’ve seen.”

Mr. DeKloe agreed and highlighted the importance of improving vaccination rates. “Identifying effective interventions that increase HPV vaccination rates is critical in reducing undue cancer burden in the United States,” Mr. DeKloe said in a statement.

The study had no funding source. Mr. DeKloe had no relevant disclosures. Dr. Hanna has disclosed relationships with Bicara Therapeutics, Bristol Myers Squibb, Coherus BioSciences, and others. Dr. Schuchter had no relevant disclosures.

A version of this article appeared on Medscape.com .

The results of a large French study comparing the cancer risk in children conceived through assisted reproductive technology (ART) with that of naturally conceived children were published recently in JAMA Network Open. This study is one of the largest to date on this subject: It included 8,526,306 children born in France between 2010 and 2021, of whom 260,236 (3%) were conceived through ART, and followed them up to a median age of 6.7 years.

Motivations for the Study

ART (including artificial insemination, in vitro fertilization [IVF], or intracytoplasmic sperm injection [ICSI] with fresh or frozen embryo transfer) accounts for about 1 in 30 births in France. However, limited and heterogeneous data have suggested an increased risk for certain health disorders, including cancer, among children conceived through ART. Therefore, a large-scale evaluation of cancer risk in these children is important.

No Overall Increase

In all, 9256 children developed cancer, including 292 who were conceived through ART. Thus, this study did not show an increased risk for cancer (of all types combined) in children conceived through ART. Nevertheless, a slight increase in the risk for leukemia was observed in children conceived through IVF or ICSI. The investigators observed approximately one additional case for every 5000 newborns conceived through IVF or ICSI who reached age 10 years.

Epidemiological monitoring should be continued to better evaluate long-term risks and see whether the risk for leukemia is confirmed. If it is, then it will be useful to investigate the mechanisms related to ART techniques or the fertility disorders of parents that could lead to an increased risk for leukemia.

This story was translated from Univadis France, which is part of the Medscape Professional Network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The results of a large French study comparing the cancer risk in children conceived through assisted reproductive technology (ART) with that of naturally conceived children were published recently in JAMA Network Open. This study is one of the largest to date on this subject: It included 8,526,306 children born in France between 2010 and 2021, of whom 260,236 (3%) were conceived through ART, and followed them up to a median age of 6.7 years.

Motivations for the Study

ART (including artificial insemination, in vitro fertilization [IVF], or intracytoplasmic sperm injection [ICSI] with fresh or frozen embryo transfer) accounts for about 1 in 30 births in France. However, limited and heterogeneous data have suggested an increased risk for certain health disorders, including cancer, among children conceived through ART. Therefore, a large-scale evaluation of cancer risk in these children is important.

No Overall Increase

In all, 9256 children developed cancer, including 292 who were conceived through ART. Thus, this study did not show an increased risk for cancer (of all types combined) in children conceived through ART. Nevertheless, a slight increase in the risk for leukemia was observed in children conceived through IVF or ICSI. The investigators observed approximately one additional case for every 5000 newborns conceived through IVF or ICSI who reached age 10 years.

Epidemiological monitoring should be continued to better evaluate long-term risks and see whether the risk for leukemia is confirmed. If it is, then it will be useful to investigate the mechanisms related to ART techniques or the fertility disorders of parents that could lead to an increased risk for leukemia.

This story was translated from Univadis France, which is part of the Medscape Professional Network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

The results of a large French study comparing the cancer risk in children conceived through assisted reproductive technology (ART) with that of naturally conceived children were published recently in JAMA Network Open. This study is one of the largest to date on this subject: It included 8,526,306 children born in France between 2010 and 2021, of whom 260,236 (3%) were conceived through ART, and followed them up to a median age of 6.7 years.

Motivations for the Study

ART (including artificial insemination, in vitro fertilization [IVF], or intracytoplasmic sperm injection [ICSI] with fresh or frozen embryo transfer) accounts for about 1 in 30 births in France. However, limited and heterogeneous data have suggested an increased risk for certain health disorders, including cancer, among children conceived through ART. Therefore, a large-scale evaluation of cancer risk in these children is important.

No Overall Increase

In all, 9256 children developed cancer, including 292 who were conceived through ART. Thus, this study did not show an increased risk for cancer (of all types combined) in children conceived through ART. Nevertheless, a slight increase in the risk for leukemia was observed in children conceived through IVF or ICSI. The investigators observed approximately one additional case for every 5000 newborns conceived through IVF or ICSI who reached age 10 years.

Epidemiological monitoring should be continued to better evaluate long-term risks and see whether the risk for leukemia is confirmed. If it is, then it will be useful to investigate the mechanisms related to ART techniques or the fertility disorders of parents that could lead to an increased risk for leukemia.

This story was translated from Univadis France, which is part of the Medscape Professional Network, using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article appeared on Medscape.com.

BOSTON — Nearly one in five breast cancer survivors will gain more than 10% of their body weight in the 6 years following their diagnosis, according to new research presented at ENDO 2024, the annual meeting of the Endocrine Society.

Younger age and lower weight at diagnosis were the strongest predictors of this excessive weight gain over time. 

“Weight gain is a common concern after breast cancer diagnosis and treatment,” said Maria Daniela Hurtado Andrade, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, who led the research. “This weight gain in breast cancer survivor increases breast cancer recurrence and mortality, increases cardiovascular disease and mortality, and also increases all-cause mortality.”

Previous studies have found an association between breast cancer survivorship and weight gain, but the reported incidences of weight gain — and the amounts gained — have been highly variable, she added.

In the study, researchers used the Mayo Clinic Breast Cancer Registry to identify 4575 breast cancer survivors and tracked their weight over the course of 6 years following cancer diagnosis. These patients were age-matched to women in the general population selected from the Rochester Epidemiology Project, which contains the medical records of residents of 27 counties in Minnesota and Wisconsin. All controls had no history of cancer or bariatric surgery.

Nearly all patients and controls were White (97%); at breast cancer diagnosis, patients were on average 58 years of age and weighed 76 kg (165.5 lb). Controls had similar ages and baseline weights.

At 6 years following breast cancer diagnosis, average weight gain was modest: Breast cancer survivors gained 1.6% of their body weight, compared with 0.7% in controls (P = .004).

However, 18% of breast cancer survivors had gained at least 10% of their body weight over that time. By comparison, 8% of controls experienced this excessive weight gain during that same time frame (P < .0001). The same trend was observed for 15% and 20% weight gain.

After adjustment for confounding factors, younger age at breast cancer diagnosis and lower baseline weight were the strongest predictors of more than 10% weight gain. BRCA2 mutation and use of systemic chemotherapy treatment were also associated with excessive weight gain.

Several factors could be driving weight gain in these patients, said Zeynep Madak-Erdogan, PhD, at the University of Illinois Urbana-Champaign, who was not involved with the research. Her work focuses on how diet and nutrition affect hormone action in postmenopausal women and breast cancer survivors. Certain therapies can induce temporary or permanent menopause in patients, “and this early menopause might shift balance of estrogens and cause increased weight gain,” she said. Along the same lines, endocrine therapies can also affect estrogen production. 

Stress and exhaustion from treatment — especially compounded by the two previous factors — are also likely culprits in weight gain, she continued.

“These findings highlight importance of lifestyle interventions,” added Dr. Madak-Erdogan. “In addition to changes in the diet (increased vegetable, fruit, [and] whole grain intake; reduction in saturated fats, alcohol, [and] sweetened beverage consumption), survivors should be consulted on importance of regular exercise.”

“These data clearly show we must consider weight changes in breast cancer survivors, and we must find ways of instituting strategies to mitigate these weight gains,” Dr. Hurtado Andrade said. “These women have a lot to think of when they have a breast cancer diagnosis, so we also must find ways of instituting these measures in a way that doesn’t increase the burden of their health.”

Dr. Hurtado Andrade has received research funding from the National Institutes of Health and by Phenomix Sciences. She also is a consultant for Novo Nordisk. These three organizations were not involved with this study. Dr. Madak-Erdogan had no disclosures.

A version of this article first appeared on Medscape.com.

BOSTON — Nearly one in five breast cancer survivors will gain more than 10% of their body weight in the 6 years following their diagnosis, according to new research presented at ENDO 2024, the annual meeting of the Endocrine Society.

Younger age and lower weight at diagnosis were the strongest predictors of this excessive weight gain over time. 

“Weight gain is a common concern after breast cancer diagnosis and treatment,” said Maria Daniela Hurtado Andrade, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, who led the research. “This weight gain in breast cancer survivor increases breast cancer recurrence and mortality, increases cardiovascular disease and mortality, and also increases all-cause mortality.”

Previous studies have found an association between breast cancer survivorship and weight gain, but the reported incidences of weight gain — and the amounts gained — have been highly variable, she added.

In the study, researchers used the Mayo Clinic Breast Cancer Registry to identify 4575 breast cancer survivors and tracked their weight over the course of 6 years following cancer diagnosis. These patients were age-matched to women in the general population selected from the Rochester Epidemiology Project, which contains the medical records of residents of 27 counties in Minnesota and Wisconsin. All controls had no history of cancer or bariatric surgery.

Nearly all patients and controls were White (97%); at breast cancer diagnosis, patients were on average 58 years of age and weighed 76 kg (165.5 lb). Controls had similar ages and baseline weights.

At 6 years following breast cancer diagnosis, average weight gain was modest: Breast cancer survivors gained 1.6% of their body weight, compared with 0.7% in controls (P = .004).

However, 18% of breast cancer survivors had gained at least 10% of their body weight over that time. By comparison, 8% of controls experienced this excessive weight gain during that same time frame (P < .0001). The same trend was observed for 15% and 20% weight gain.

After adjustment for confounding factors, younger age at breast cancer diagnosis and lower baseline weight were the strongest predictors of more than 10% weight gain. BRCA2 mutation and use of systemic chemotherapy treatment were also associated with excessive weight gain.

Several factors could be driving weight gain in these patients, said Zeynep Madak-Erdogan, PhD, at the University of Illinois Urbana-Champaign, who was not involved with the research. Her work focuses on how diet and nutrition affect hormone action in postmenopausal women and breast cancer survivors. Certain therapies can induce temporary or permanent menopause in patients, “and this early menopause might shift balance of estrogens and cause increased weight gain,” she said. Along the same lines, endocrine therapies can also affect estrogen production. 

Stress and exhaustion from treatment — especially compounded by the two previous factors — are also likely culprits in weight gain, she continued.

“These findings highlight importance of lifestyle interventions,” added Dr. Madak-Erdogan. “In addition to changes in the diet (increased vegetable, fruit, [and] whole grain intake; reduction in saturated fats, alcohol, [and] sweetened beverage consumption), survivors should be consulted on importance of regular exercise.”

“These data clearly show we must consider weight changes in breast cancer survivors, and we must find ways of instituting strategies to mitigate these weight gains,” Dr. Hurtado Andrade said. “These women have a lot to think of when they have a breast cancer diagnosis, so we also must find ways of instituting these measures in a way that doesn’t increase the burden of their health.”

Dr. Hurtado Andrade has received research funding from the National Institutes of Health and by Phenomix Sciences. She also is a consultant for Novo Nordisk. These three organizations were not involved with this study. Dr. Madak-Erdogan had no disclosures.

A version of this article first appeared on Medscape.com.

BOSTON — Nearly one in five breast cancer survivors will gain more than 10% of their body weight in the 6 years following their diagnosis, according to new research presented at ENDO 2024, the annual meeting of the Endocrine Society.

Younger age and lower weight at diagnosis were the strongest predictors of this excessive weight gain over time. 

“Weight gain is a common concern after breast cancer diagnosis and treatment,” said Maria Daniela Hurtado Andrade, MD, PhD, of the Mayo Clinic in Jacksonville, Florida, who led the research. “This weight gain in breast cancer survivor increases breast cancer recurrence and mortality, increases cardiovascular disease and mortality, and also increases all-cause mortality.”

Previous studies have found an association between breast cancer survivorship and weight gain, but the reported incidences of weight gain — and the amounts gained — have been highly variable, she added.

In the study, researchers used the Mayo Clinic Breast Cancer Registry to identify 4575 breast cancer survivors and tracked their weight over the course of 6 years following cancer diagnosis. These patients were age-matched to women in the general population selected from the Rochester Epidemiology Project, which contains the medical records of residents of 27 counties in Minnesota and Wisconsin. All controls had no history of cancer or bariatric surgery.

Nearly all patients and controls were White (97%); at breast cancer diagnosis, patients were on average 58 years of age and weighed 76 kg (165.5 lb). Controls had similar ages and baseline weights.

At 6 years following breast cancer diagnosis, average weight gain was modest: Breast cancer survivors gained 1.6% of their body weight, compared with 0.7% in controls (P = .004).

However, 18% of breast cancer survivors had gained at least 10% of their body weight over that time. By comparison, 8% of controls experienced this excessive weight gain during that same time frame (P < .0001). The same trend was observed for 15% and 20% weight gain.

After adjustment for confounding factors, younger age at breast cancer diagnosis and lower baseline weight were the strongest predictors of more than 10% weight gain. BRCA2 mutation and use of systemic chemotherapy treatment were also associated with excessive weight gain.

Several factors could be driving weight gain in these patients, said Zeynep Madak-Erdogan, PhD, at the University of Illinois Urbana-Champaign, who was not involved with the research. Her work focuses on how diet and nutrition affect hormone action in postmenopausal women and breast cancer survivors. Certain therapies can induce temporary or permanent menopause in patients, “and this early menopause might shift balance of estrogens and cause increased weight gain,” she said. Along the same lines, endocrine therapies can also affect estrogen production. 

Stress and exhaustion from treatment — especially compounded by the two previous factors — are also likely culprits in weight gain, she continued.

“These findings highlight importance of lifestyle interventions,” added Dr. Madak-Erdogan. “In addition to changes in the diet (increased vegetable, fruit, [and] whole grain intake; reduction in saturated fats, alcohol, [and] sweetened beverage consumption), survivors should be consulted on importance of regular exercise.”

“These data clearly show we must consider weight changes in breast cancer survivors, and we must find ways of instituting strategies to mitigate these weight gains,” Dr. Hurtado Andrade said. “These women have a lot to think of when they have a breast cancer diagnosis, so we also must find ways of instituting these measures in a way that doesn’t increase the burden of their health.”

Dr. Hurtado Andrade has received research funding from the National Institutes of Health and by Phenomix Sciences. She also is a consultant for Novo Nordisk. These three organizations were not involved with this study. Dr. Madak-Erdogan had no disclosures.

A version of this article first appeared on Medscape.com.

PARIS — Allergic comorbidities such as asthma and rhinitis are common among pregnant women. During the 19th French-speaking Congress of Allergology, Dario Ebode, MD, otolaryngologist and cervicofacial surgeon at Hôpital de la Conception in Marseille, France, described gestational rhinitis and detailed its management.

A Hormonal Rhinitis

The prevalence of rhinitis during pregnancy ranges from 18% to 30%, whether it is pre-existing (eg, allergic or infectious) or newly diagnosed. About half of the cases of pre-existing rhinitis worsen during pregnancy, leading to gestational rhinitis, which has a prevalence of approximately 22%.

“The latter is characterized by its onset in the 2nd or 3rd trimester, a duration of > 6 weeks, an absence of associated allergic symptoms, and complete spontaneous resolution 2-3 weeks after delivery,” said Dr. Ebode.

Uncertainties about the pathophysiology of gestational rhinitis, a “hormonal rhinitis,” remain, he added. Beta-estradiol and progesterone hormones lead to an increase in H1 histamine receptors on epithelial and endothelial cells, which promotes the migration or degranulation of eosinophils.
 

Management

While gestational rhinitis is benign, its symptoms can still be bothersome and can be relieved. In addition to dietary and hygienic (nasal irrigation with large volumes) measures and allergen avoidance, local treatments include nasal corticosteroids, possibly combined with antihistamines, and systemic antihistamines. “During pregnancy, nasal corticosteroids, oral antihistamines [excluding azelastine hydrochloride before 10 weeks], and ipratropium bromide are allowed,” said Dr. Ebode. Regarding sprays that combine corticosteroids and antihistamines, the combination of mometasone furoate and olopatadine is possible but not the combination of azelastine hydrochloride and fluticasone propionate before 10 weeks.

Finally, oral vasoconstrictors (which are found in many over-the-counter medications) should be avoided, as should Kenacort (triamcinolone acetonide), “which also has no place in women outside of pregnancy due to an unfavorable risk-benefit balance in rhinitis,” said Dr. Ebode. Allergen immunotherapy plans should be postponed after delivery.

Dr. Ebode reported a financial relationship with Zambon.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

PARIS — Allergic comorbidities such as asthma and rhinitis are common among pregnant women. During the 19th French-speaking Congress of Allergology, Dario Ebode, MD, otolaryngologist and cervicofacial surgeon at Hôpital de la Conception in Marseille, France, described gestational rhinitis and detailed its management.

A Hormonal Rhinitis

The prevalence of rhinitis during pregnancy ranges from 18% to 30%, whether it is pre-existing (eg, allergic or infectious) or newly diagnosed. About half of the cases of pre-existing rhinitis worsen during pregnancy, leading to gestational rhinitis, which has a prevalence of approximately 22%.

“The latter is characterized by its onset in the 2nd or 3rd trimester, a duration of > 6 weeks, an absence of associated allergic symptoms, and complete spontaneous resolution 2-3 weeks after delivery,” said Dr. Ebode.

Uncertainties about the pathophysiology of gestational rhinitis, a “hormonal rhinitis,” remain, he added. Beta-estradiol and progesterone hormones lead to an increase in H1 histamine receptors on epithelial and endothelial cells, which promotes the migration or degranulation of eosinophils.
 

Management

While gestational rhinitis is benign, its symptoms can still be bothersome and can be relieved. In addition to dietary and hygienic (nasal irrigation with large volumes) measures and allergen avoidance, local treatments include nasal corticosteroids, possibly combined with antihistamines, and systemic antihistamines. “During pregnancy, nasal corticosteroids, oral antihistamines [excluding azelastine hydrochloride before 10 weeks], and ipratropium bromide are allowed,” said Dr. Ebode. Regarding sprays that combine corticosteroids and antihistamines, the combination of mometasone furoate and olopatadine is possible but not the combination of azelastine hydrochloride and fluticasone propionate before 10 weeks.

Finally, oral vasoconstrictors (which are found in many over-the-counter medications) should be avoided, as should Kenacort (triamcinolone acetonide), “which also has no place in women outside of pregnancy due to an unfavorable risk-benefit balance in rhinitis,” said Dr. Ebode. Allergen immunotherapy plans should be postponed after delivery.

Dr. Ebode reported a financial relationship with Zambon.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

PARIS — Allergic comorbidities such as asthma and rhinitis are common among pregnant women. During the 19th French-speaking Congress of Allergology, Dario Ebode, MD, otolaryngologist and cervicofacial surgeon at Hôpital de la Conception in Marseille, France, described gestational rhinitis and detailed its management.

A Hormonal Rhinitis

The prevalence of rhinitis during pregnancy ranges from 18% to 30%, whether it is pre-existing (eg, allergic or infectious) or newly diagnosed. About half of the cases of pre-existing rhinitis worsen during pregnancy, leading to gestational rhinitis, which has a prevalence of approximately 22%.

“The latter is characterized by its onset in the 2nd or 3rd trimester, a duration of > 6 weeks, an absence of associated allergic symptoms, and complete spontaneous resolution 2-3 weeks after delivery,” said Dr. Ebode.

Uncertainties about the pathophysiology of gestational rhinitis, a “hormonal rhinitis,” remain, he added. Beta-estradiol and progesterone hormones lead to an increase in H1 histamine receptors on epithelial and endothelial cells, which promotes the migration or degranulation of eosinophils.
 

Management

While gestational rhinitis is benign, its symptoms can still be bothersome and can be relieved. In addition to dietary and hygienic (nasal irrigation with large volumes) measures and allergen avoidance, local treatments include nasal corticosteroids, possibly combined with antihistamines, and systemic antihistamines. “During pregnancy, nasal corticosteroids, oral antihistamines [excluding azelastine hydrochloride before 10 weeks], and ipratropium bromide are allowed,” said Dr. Ebode. Regarding sprays that combine corticosteroids and antihistamines, the combination of mometasone furoate and olopatadine is possible but not the combination of azelastine hydrochloride and fluticasone propionate before 10 weeks.

Finally, oral vasoconstrictors (which are found in many over-the-counter medications) should be avoided, as should Kenacort (triamcinolone acetonide), “which also has no place in women outside of pregnancy due to an unfavorable risk-benefit balance in rhinitis,” said Dr. Ebode. Allergen immunotherapy plans should be postponed after delivery.

Dr. Ebode reported a financial relationship with Zambon.

This story was translated from the Medscape French edition using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication. A version of this article first appeared on Medscape.com.

Premenopausal patients with hormone receptor positive and human epidermal growth factor receptor 2 negative invasive breast cancer were significantly more likely to respond to chemotherapy plus endocrine therapy if their baseline anti-Müllerian hormone levels were10 pg/mL or higher, a new analysis shows.

The new findings also show that women with low baseline anti-Müllerian hormone (AMH) of less than 10 pg/mL do not benefit from chemotherapy. In fact, AMH levels were a better predictor of chemotherapy benefit than self-reported premenopausal status, age, and other hormone levels.

“We may be overtreating some of our patients” with invasive breast cancer and low AMH levels, Kevin Kalinsky, MD, of the Winship Cancer Institute of Emory University, Atlanta, said in a presentation at the annual meeting of the American Society of Clinical Oncology (ASCO).

The potential implication of the study is that clinicians may be able to stop giving chemotherapy to a subset of breast cancer patients who will not benefit from it, he said in the presentation.
 

New Analysis Singles Out AMH Levels

In a new analysis of data from the RxPONDER trial, Dr. Kalinsky shared data from 1,016 patients who were younger than 55 years of age and self-reported as premenopausal.

The original RxPONDER trial (also known as SWOG S1007) was a randomized, phase 3 trial designed to evaluate the benefit of endocrine therapy (ET) alone vs. ET plus chemotherapy in patients with hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) invasive breast cancer and low recurrence scores (25 or less with genomic testing by Oncotype DX), Dr. Kalinsky said in his presentation.

The researchers found no improvement in invasive disease-free survival (IDFS) with the addition of chemotherapy to ET overall, but significant IDFS improvement occurred with added chemotherapy to ET in the subgroup of self-reported premenopausal women (hazard ratio 0.60).

To better identify the impact of menopausal status on patients who would benefit or not benefit from chemotherapy in the new analysis, the researchers assessed baseline serum samples of serum estradiol, progesterone, follicular stimulating hormone(FSH), luteinizing hormone, AMH, and inhibin B.

The primary outcomes were associations of these markers (continuous and dichotomized) with IDFS and distant relapse-free survival with prognosis and prediction of chemotherapy benefit, based on Cox regression analysis.

Of the six markers analyzed, only AMH showed an association with chemotherapy benefits. “AMH is more stable and reliable during the menstrual cycle” compared to other hormones such as FSH and estradiol. Also, AMH levels ≥ 10 pg/mL are considered a standard cutoff to define normal ovarian reserve, Dr. Kalinsky said in his presentation.

A total of 209 patients (21%) had low AMH (less than 10 pg/mL) and were considered postmenopausal, and 806 (79%) were considered premenopausal, with AMH levels of 10 pg/mL or higher.

Chemotherapy plus ET was significantly more beneficial than ET alone in the premenopausal patients with AMH levels ≥ 10 pg/mL (hazard ratio 0.48), Dr. Kalinsky said. By contrast, no chemotherapy benefit was seen in the patients deemed postmenopausal, with low AMH levels (HR 1.21).

In the patients with AMH of 10 pg/mL or higher, the absolute 5-year IDFS benefit of chemotherapy was 7.8%, compared to no notable difference for those with low AMH levels.

Similarly, 5-year DRFS with chemotherapy in patients with AMH of 10 pg/mL or higher was 4.4% (HR 0.41), with no benefit for those with low AMH (HR 1.50).

The findings were limited by the post hoc design and lack of longitudinal data, Dr. Kalinsky said.

During the question-and-answer session, Dr. Kalinsky said that he hoped the data could be incorporated into a clinical model “to further refine patients who need chemotherapy or don’t.” The results suggest that the reproductive hormone AMH can be used to identify premenopausal women with HR+/HER2- invasive breast cancer and intermediate risk based on oncotype scores who would likely benefit from chemotherapy, while those with lower AMH who could forgo it, Dr. Kalinsky concluded.
 

AMH May Ultimately Inform Chemotherapy Choices

The findings are “thoughtful and intriguing” and may inform which patients benefit from adjuvant chemotherapy and which may not, said Lisa A. Carey, MD, of Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, who served as discussant for the abstract.

Dr. Carey noted as a caveat that AMH is not currently recommended by the American College of Obstetricians and Gynecologists for menopause prediction. However, AMH is “a very credible biomarker of ovarian reserve,” she said in her presentation.

As for clinical implications, the lack of chemotherapy benefit in patients with low AMH at baseline suggests that at least part of the benefits of chemotherapy come from ovarian suppression, Dr. Carey said.

Current assessments of menopausal status are often crude, she noted, and AMH may be helpful when menopausal status is clinically unclear.

Dr. Carey agreed the findings were limited by the post hoc design, and longitudinal data are needed. However, the clinical implications are real if the results are validated, she said, and longitudinal data will be explored in the currently enrolling NRG BR009 OFSET trial.
 

Clinical Challenges of Menopausal Status

Since the original RxPONDER showed a benefit of chemotherapy for premenopausal women, but not for postmenopausal women with the same low recurrence score, the medical oncology community has worked to determine how much of the benefit seen was related to the ovarian suppression associated with chemotherapy, Megan Kruse, MD, of the Cleveland Clinic, said in an interview.

“Determining a woman’s menopausal status can be challenging in the clinic, as many women have had hysterectomy but have intact ovaries or may have significantly irregular periods, which can lead to confusion about the best endocrine therapy to recommend and how to categorize risk when it comes to Oncotype DX testing,” said Dr. Kruse. She was not involved in the RxPONDER study, but commented on the study in a podcast for ASCO Daily News in advance of the ASCO meeting.

“I was surprised that only AMH showed an association with chemotherapy benefit, as we often obtain estradiol/FSH levels in clinic to try to help with the menopausal assessment,” Dr. Kruse said in an interview. However, in clinical practice, the data may help discuss systemic therapy in patients who are near clinical menopause and trying to decide whether the potential added benefit of chemotherapy is worth the associated toxicity, she said.

“My hope is that new data allow for a more informed, individualized decision-making process,” she added.

Potential barriers to incorporate AMH into chemotherapy decisions in clinical practice include the need for insurance coverage for AMH levels, Dr. Kruse said in an interview. “The [AMH] levels also can be dynamic, so checking one point in time and making such a significant clinical decision based on one level is also a bit concerning,” she said.

Looking ahead, Dr. Kruse emphasized the need to complete the NRG BR-009 OFSET trial. That trial is designed to answer the question of whether adjuvant chemotherapy added to ovarian suppression (OS) plus ET is superior to OS plus ET for premenopausal women with early stage high-risk node negative or 1-3 lymph nodes positive breast cancer with an RS score of 25 or lower, she said.

“This extra analysis of the RxPONDER trial helps to further understand how premenopausal women may best benefit from adjuvant treatments,” Malinda T. West, MD, of the University of Wisconsin, Madison, said in an interview. The new study is important because it shows the ability of serum AMH to help predict ovarian reserve and imminent menopause, said Dr. West, who was not involved in the study.

In clinical practice, the study provides further insight into how premenopausal women may benefit from added chemotherapy and the role of ovarian suppression, Dr. West said.

The study was supported by the Breast Cancer Research Foundation, the National Institutes of Health/National Institute of General Medical Sciences/National Cancer Institute, Exact Sciences Corporation (previously Genomic Health), and the Hope Foundation for Cancer Research.

Dr. Kalinsky disclosed that immediate family members are employed by EQRx and GRAIL, with stock or other ownership interests in these companies. He disclosed consulting or advisory roles with 4D Pharma, AstraZeneca, Cullinan Oncology, Daiichi Sankyo/AstraZeneca, eFFECTOR Therapeutics, Genentech/Roche, Immunomedics, Lilly, Menarini Silicon Biosystems, Merck, Mersana, Myovant Sciences, Novartis, Oncosec, Prelude Therapeutics, Puma Biotechnology, RayzeBio, Seagen, and Takeda. Dr. Kalinsky further disclosed research funding to his institution from Ascentage Pharma, AstraZeneca, Daiichi Sankyo, Genentech/Roche, Lilly, Novartis, and Seagen, and relationships with Genentech and Immunomedics.

Dr. Carey disclosed research funding to her institution from AstraZeneca, Genentech/Roche, Gilead Sciences, Lilly, NanoString Technologies, Novartis, Seagen, and Veracyte. She disclosed an uncompensated relationship with Seagen, and uncompensated relationships between her institution and Genentech/Roche, GlaxoSmithKline, Lilly, and Novartis.

Dr. Kruse disclosed consulting or advisory roles with Novartis Oncology, Puma Biotechnology, Immunomedics, Eisai, Seattle Genetics, and Lilly.

Dr. West had no financial conflicts to disclose.

Premenopausal patients with hormone receptor positive and human epidermal growth factor receptor 2 negative invasive breast cancer were significantly more likely to respond to chemotherapy plus endocrine therapy if their baseline anti-Müllerian hormone levels were10 pg/mL or higher, a new analysis shows.

The new findings also show that women with low baseline anti-Müllerian hormone (AMH) of less than 10 pg/mL do not benefit from chemotherapy. In fact, AMH levels were a better predictor of chemotherapy benefit than self-reported premenopausal status, age, and other hormone levels.

“We may be overtreating some of our patients” with invasive breast cancer and low AMH levels, Kevin Kalinsky, MD, of the Winship Cancer Institute of Emory University, Atlanta, said in a presentation at the annual meeting of the American Society of Clinical Oncology (ASCO).

The potential implication of the study is that clinicians may be able to stop giving chemotherapy to a subset of breast cancer patients who will not benefit from it, he said in the presentation.
 

New Analysis Singles Out AMH Levels

In a new analysis of data from the RxPONDER trial, Dr. Kalinsky shared data from 1,016 patients who were younger than 55 years of age and self-reported as premenopausal.

The original RxPONDER trial (also known as SWOG S1007) was a randomized, phase 3 trial designed to evaluate the benefit of endocrine therapy (ET) alone vs. ET plus chemotherapy in patients with hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) invasive breast cancer and low recurrence scores (25 or less with genomic testing by Oncotype DX), Dr. Kalinsky said in his presentation.

The researchers found no improvement in invasive disease-free survival (IDFS) with the addition of chemotherapy to ET overall, but significant IDFS improvement occurred with added chemotherapy to ET in the subgroup of self-reported premenopausal women (hazard ratio 0.60).

To better identify the impact of menopausal status on patients who would benefit or not benefit from chemotherapy in the new analysis, the researchers assessed baseline serum samples of serum estradiol, progesterone, follicular stimulating hormone(FSH), luteinizing hormone, AMH, and inhibin B.

The primary outcomes were associations of these markers (continuous and dichotomized) with IDFS and distant relapse-free survival with prognosis and prediction of chemotherapy benefit, based on Cox regression analysis.

Of the six markers analyzed, only AMH showed an association with chemotherapy benefits. “AMH is more stable and reliable during the menstrual cycle” compared to other hormones such as FSH and estradiol. Also, AMH levels ≥ 10 pg/mL are considered a standard cutoff to define normal ovarian reserve, Dr. Kalinsky said in his presentation.

A total of 209 patients (21%) had low AMH (less than 10 pg/mL) and were considered postmenopausal, and 806 (79%) were considered premenopausal, with AMH levels of 10 pg/mL or higher.

Chemotherapy plus ET was significantly more beneficial than ET alone in the premenopausal patients with AMH levels ≥ 10 pg/mL (hazard ratio 0.48), Dr. Kalinsky said. By contrast, no chemotherapy benefit was seen in the patients deemed postmenopausal, with low AMH levels (HR 1.21).

In the patients with AMH of 10 pg/mL or higher, the absolute 5-year IDFS benefit of chemotherapy was 7.8%, compared to no notable difference for those with low AMH levels.

Similarly, 5-year DRFS with chemotherapy in patients with AMH of 10 pg/mL or higher was 4.4% (HR 0.41), with no benefit for those with low AMH (HR 1.50).

The findings were limited by the post hoc design and lack of longitudinal data, Dr. Kalinsky said.

During the question-and-answer session, Dr. Kalinsky said that he hoped the data could be incorporated into a clinical model “to further refine patients who need chemotherapy or don’t.” The results suggest that the reproductive hormone AMH can be used to identify premenopausal women with HR+/HER2- invasive breast cancer and intermediate risk based on oncotype scores who would likely benefit from chemotherapy, while those with lower AMH who could forgo it, Dr. Kalinsky concluded.
 

AMH May Ultimately Inform Chemotherapy Choices

The findings are “thoughtful and intriguing” and may inform which patients benefit from adjuvant chemotherapy and which may not, said Lisa A. Carey, MD, of Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, who served as discussant for the abstract.

Dr. Carey noted as a caveat that AMH is not currently recommended by the American College of Obstetricians and Gynecologists for menopause prediction. However, AMH is “a very credible biomarker of ovarian reserve,” she said in her presentation.

As for clinical implications, the lack of chemotherapy benefit in patients with low AMH at baseline suggests that at least part of the benefits of chemotherapy come from ovarian suppression, Dr. Carey said.

Current assessments of menopausal status are often crude, she noted, and AMH may be helpful when menopausal status is clinically unclear.

Dr. Carey agreed the findings were limited by the post hoc design, and longitudinal data are needed. However, the clinical implications are real if the results are validated, she said, and longitudinal data will be explored in the currently enrolling NRG BR009 OFSET trial.
 

Clinical Challenges of Menopausal Status

Since the original RxPONDER showed a benefit of chemotherapy for premenopausal women, but not for postmenopausal women with the same low recurrence score, the medical oncology community has worked to determine how much of the benefit seen was related to the ovarian suppression associated with chemotherapy, Megan Kruse, MD, of the Cleveland Clinic, said in an interview.

“Determining a woman’s menopausal status can be challenging in the clinic, as many women have had hysterectomy but have intact ovaries or may have significantly irregular periods, which can lead to confusion about the best endocrine therapy to recommend and how to categorize risk when it comes to Oncotype DX testing,” said Dr. Kruse. She was not involved in the RxPONDER study, but commented on the study in a podcast for ASCO Daily News in advance of the ASCO meeting.

“I was surprised that only AMH showed an association with chemotherapy benefit, as we often obtain estradiol/FSH levels in clinic to try to help with the menopausal assessment,” Dr. Kruse said in an interview. However, in clinical practice, the data may help discuss systemic therapy in patients who are near clinical menopause and trying to decide whether the potential added benefit of chemotherapy is worth the associated toxicity, she said.

“My hope is that new data allow for a more informed, individualized decision-making process,” she added.

Potential barriers to incorporate AMH into chemotherapy decisions in clinical practice include the need for insurance coverage for AMH levels, Dr. Kruse said in an interview. “The [AMH] levels also can be dynamic, so checking one point in time and making such a significant clinical decision based on one level is also a bit concerning,” she said.

Looking ahead, Dr. Kruse emphasized the need to complete the NRG BR-009 OFSET trial. That trial is designed to answer the question of whether adjuvant chemotherapy added to ovarian suppression (OS) plus ET is superior to OS plus ET for premenopausal women with early stage high-risk node negative or 1-3 lymph nodes positive breast cancer with an RS score of 25 or lower, she said.

“This extra analysis of the RxPONDER trial helps to further understand how premenopausal women may best benefit from adjuvant treatments,” Malinda T. West, MD, of the University of Wisconsin, Madison, said in an interview. The new study is important because it shows the ability of serum AMH to help predict ovarian reserve and imminent menopause, said Dr. West, who was not involved in the study.

In clinical practice, the study provides further insight into how premenopausal women may benefit from added chemotherapy and the role of ovarian suppression, Dr. West said.

The study was supported by the Breast Cancer Research Foundation, the National Institutes of Health/National Institute of General Medical Sciences/National Cancer Institute, Exact Sciences Corporation (previously Genomic Health), and the Hope Foundation for Cancer Research.

Dr. Kalinsky disclosed that immediate family members are employed by EQRx and GRAIL, with stock or other ownership interests in these companies. He disclosed consulting or advisory roles with 4D Pharma, AstraZeneca, Cullinan Oncology, Daiichi Sankyo/AstraZeneca, eFFECTOR Therapeutics, Genentech/Roche, Immunomedics, Lilly, Menarini Silicon Biosystems, Merck, Mersana, Myovant Sciences, Novartis, Oncosec, Prelude Therapeutics, Puma Biotechnology, RayzeBio, Seagen, and Takeda. Dr. Kalinsky further disclosed research funding to his institution from Ascentage Pharma, AstraZeneca, Daiichi Sankyo, Genentech/Roche, Lilly, Novartis, and Seagen, and relationships with Genentech and Immunomedics.

Dr. Carey disclosed research funding to her institution from AstraZeneca, Genentech/Roche, Gilead Sciences, Lilly, NanoString Technologies, Novartis, Seagen, and Veracyte. She disclosed an uncompensated relationship with Seagen, and uncompensated relationships between her institution and Genentech/Roche, GlaxoSmithKline, Lilly, and Novartis.

Dr. Kruse disclosed consulting or advisory roles with Novartis Oncology, Puma Biotechnology, Immunomedics, Eisai, Seattle Genetics, and Lilly.

Dr. West had no financial conflicts to disclose.

Premenopausal patients with hormone receptor positive and human epidermal growth factor receptor 2 negative invasive breast cancer were significantly more likely to respond to chemotherapy plus endocrine therapy if their baseline anti-Müllerian hormone levels were10 pg/mL or higher, a new analysis shows.

The new findings also show that women with low baseline anti-Müllerian hormone (AMH) of less than 10 pg/mL do not benefit from chemotherapy. In fact, AMH levels were a better predictor of chemotherapy benefit than self-reported premenopausal status, age, and other hormone levels.

“We may be overtreating some of our patients” with invasive breast cancer and low AMH levels, Kevin Kalinsky, MD, of the Winship Cancer Institute of Emory University, Atlanta, said in a presentation at the annual meeting of the American Society of Clinical Oncology (ASCO).

The potential implication of the study is that clinicians may be able to stop giving chemotherapy to a subset of breast cancer patients who will not benefit from it, he said in the presentation.
 

New Analysis Singles Out AMH Levels

In a new analysis of data from the RxPONDER trial, Dr. Kalinsky shared data from 1,016 patients who were younger than 55 years of age and self-reported as premenopausal.

The original RxPONDER trial (also known as SWOG S1007) was a randomized, phase 3 trial designed to evaluate the benefit of endocrine therapy (ET) alone vs. ET plus chemotherapy in patients with hormone receptor positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) invasive breast cancer and low recurrence scores (25 or less with genomic testing by Oncotype DX), Dr. Kalinsky said in his presentation.

The researchers found no improvement in invasive disease-free survival (IDFS) with the addition of chemotherapy to ET overall, but significant IDFS improvement occurred with added chemotherapy to ET in the subgroup of self-reported premenopausal women (hazard ratio 0.60).

To better identify the impact of menopausal status on patients who would benefit or not benefit from chemotherapy in the new analysis, the researchers assessed baseline serum samples of serum estradiol, progesterone, follicular stimulating hormone(FSH), luteinizing hormone, AMH, and inhibin B.

The primary outcomes were associations of these markers (continuous and dichotomized) with IDFS and distant relapse-free survival with prognosis and prediction of chemotherapy benefit, based on Cox regression analysis.

Of the six markers analyzed, only AMH showed an association with chemotherapy benefits. “AMH is more stable and reliable during the menstrual cycle” compared to other hormones such as FSH and estradiol. Also, AMH levels ≥ 10 pg/mL are considered a standard cutoff to define normal ovarian reserve, Dr. Kalinsky said in his presentation.

A total of 209 patients (21%) had low AMH (less than 10 pg/mL) and were considered postmenopausal, and 806 (79%) were considered premenopausal, with AMH levels of 10 pg/mL or higher.

Chemotherapy plus ET was significantly more beneficial than ET alone in the premenopausal patients with AMH levels ≥ 10 pg/mL (hazard ratio 0.48), Dr. Kalinsky said. By contrast, no chemotherapy benefit was seen in the patients deemed postmenopausal, with low AMH levels (HR 1.21).

In the patients with AMH of 10 pg/mL or higher, the absolute 5-year IDFS benefit of chemotherapy was 7.8%, compared to no notable difference for those with low AMH levels.

Similarly, 5-year DRFS with chemotherapy in patients with AMH of 10 pg/mL or higher was 4.4% (HR 0.41), with no benefit for those with low AMH (HR 1.50).

The findings were limited by the post hoc design and lack of longitudinal data, Dr. Kalinsky said.

During the question-and-answer session, Dr. Kalinsky said that he hoped the data could be incorporated into a clinical model “to further refine patients who need chemotherapy or don’t.” The results suggest that the reproductive hormone AMH can be used to identify premenopausal women with HR+/HER2- invasive breast cancer and intermediate risk based on oncotype scores who would likely benefit from chemotherapy, while those with lower AMH who could forgo it, Dr. Kalinsky concluded.
 

AMH May Ultimately Inform Chemotherapy Choices

The findings are “thoughtful and intriguing” and may inform which patients benefit from adjuvant chemotherapy and which may not, said Lisa A. Carey, MD, of Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, who served as discussant for the abstract.

Dr. Carey noted as a caveat that AMH is not currently recommended by the American College of Obstetricians and Gynecologists for menopause prediction. However, AMH is “a very credible biomarker of ovarian reserve,” she said in her presentation.

As for clinical implications, the lack of chemotherapy benefit in patients with low AMH at baseline suggests that at least part of the benefits of chemotherapy come from ovarian suppression, Dr. Carey said.

Current assessments of menopausal status are often crude, she noted, and AMH may be helpful when menopausal status is clinically unclear.

Dr. Carey agreed the findings were limited by the post hoc design, and longitudinal data are needed. However, the clinical implications are real if the results are validated, she said, and longitudinal data will be explored in the currently enrolling NRG BR009 OFSET trial.
 

Clinical Challenges of Menopausal Status

Since the original RxPONDER showed a benefit of chemotherapy for premenopausal women, but not for postmenopausal women with the same low recurrence score, the medical oncology community has worked to determine how much of the benefit seen was related to the ovarian suppression associated with chemotherapy, Megan Kruse, MD, of the Cleveland Clinic, said in an interview.

“Determining a woman’s menopausal status can be challenging in the clinic, as many women have had hysterectomy but have intact ovaries or may have significantly irregular periods, which can lead to confusion about the best endocrine therapy to recommend and how to categorize risk when it comes to Oncotype DX testing,” said Dr. Kruse. She was not involved in the RxPONDER study, but commented on the study in a podcast for ASCO Daily News in advance of the ASCO meeting.

“I was surprised that only AMH showed an association with chemotherapy benefit, as we often obtain estradiol/FSH levels in clinic to try to help with the menopausal assessment,” Dr. Kruse said in an interview. However, in clinical practice, the data may help discuss systemic therapy in patients who are near clinical menopause and trying to decide whether the potential added benefit of chemotherapy is worth the associated toxicity, she said.

“My hope is that new data allow for a more informed, individualized decision-making process,” she added.

Potential barriers to incorporate AMH into chemotherapy decisions in clinical practice include the need for insurance coverage for AMH levels, Dr. Kruse said in an interview. “The [AMH] levels also can be dynamic, so checking one point in time and making such a significant clinical decision based on one level is also a bit concerning,” she said.

Looking ahead, Dr. Kruse emphasized the need to complete the NRG BR-009 OFSET trial. That trial is designed to answer the question of whether adjuvant chemotherapy added to ovarian suppression (OS) plus ET is superior to OS plus ET for premenopausal women with early stage high-risk node negative or 1-3 lymph nodes positive breast cancer with an RS score of 25 or lower, she said.

“This extra analysis of the RxPONDER trial helps to further understand how premenopausal women may best benefit from adjuvant treatments,” Malinda T. West, MD, of the University of Wisconsin, Madison, said in an interview. The new study is important because it shows the ability of serum AMH to help predict ovarian reserve and imminent menopause, said Dr. West, who was not involved in the study.

In clinical practice, the study provides further insight into how premenopausal women may benefit from added chemotherapy and the role of ovarian suppression, Dr. West said.

The study was supported by the Breast Cancer Research Foundation, the National Institutes of Health/National Institute of General Medical Sciences/National Cancer Institute, Exact Sciences Corporation (previously Genomic Health), and the Hope Foundation for Cancer Research.

Dr. Kalinsky disclosed that immediate family members are employed by EQRx and GRAIL, with stock or other ownership interests in these companies. He disclosed consulting or advisory roles with 4D Pharma, AstraZeneca, Cullinan Oncology, Daiichi Sankyo/AstraZeneca, eFFECTOR Therapeutics, Genentech/Roche, Immunomedics, Lilly, Menarini Silicon Biosystems, Merck, Mersana, Myovant Sciences, Novartis, Oncosec, Prelude Therapeutics, Puma Biotechnology, RayzeBio, Seagen, and Takeda. Dr. Kalinsky further disclosed research funding to his institution from Ascentage Pharma, AstraZeneca, Daiichi Sankyo, Genentech/Roche, Lilly, Novartis, and Seagen, and relationships with Genentech and Immunomedics.

Dr. Carey disclosed research funding to her institution from AstraZeneca, Genentech/Roche, Gilead Sciences, Lilly, NanoString Technologies, Novartis, Seagen, and Veracyte. She disclosed an uncompensated relationship with Seagen, and uncompensated relationships between her institution and Genentech/Roche, GlaxoSmithKline, Lilly, and Novartis.

Dr. Kruse disclosed consulting or advisory roles with Novartis Oncology, Puma Biotechnology, Immunomedics, Eisai, Seattle Genetics, and Lilly.

Dr. West had no financial conflicts to disclose.

For women with early-stage estrogen-receptor positive breast cancer, adjuvant endocrine therapy is known to decrease the likelihood of recurrence and improve survival, while omitting the therapy is associated with a higher risk of death.

For that reason, current guidelines, including those from the National Comprehensive Cancer Network, recommend adjuvant endocrine therapy (AET) for patients with estrogen-receptor positive (ER+) breast cancers.

But these and other guidelines do not make recommendations for a class of tumors deemed estrogen receptor low positive, often referred to as “ER-low,” a category in which ER is seen expressed in between 1% and 10% of cells. This is because benefits of endocrine therapy have not been demonstrated in patients with ER-low disease.

New research presented at the annual meeting of the American Society of Clinical Oncology in Chicago may change how clinicians and patients think about endocrine therapy. The findings showed that omitting endocrine therapy after surgery and chemotherapy was associated with a 25% higher chance of death within 3 years in ER-low patients.

Endocrine therapy, the investigators say, should therefore be offered to all patients with ER-low cancers, at least until it can be determined which subgroups are most likely to benefit.

How Was the Study Conducted?

Grace M. Choong, MD, of the Mayo Clinic in Rochester, Minnesota, and her colleagues, looked at 2018-2020 data from the National Cancer Database for more than 350,000 female patients with stages 1-3, ER+ breast cancer. From among these they identified about 7000 patients with ER-low cancers who had undergone adjuvant or neoadjuvant chemotherapy.

“We specifically wanted to focus on those treated with chemotherapy as these patients have a higher risk of recurrence in our short interval follow-up,” Dr. Choong said during her presentation.

Patients’ median age was 55 years, and three-quarters of them were White. Their tumors were more likely to be HER2-negative (65%), PR-negative (73%), have higher Ki-67 expression, and have a higher clinical stage (73% grade III).

Forty-two percent of patients did not undergo AET as part of their treatment regimen, with various tumor factors seen associated with AET omission. At a median 3 years of follow-up, 586 patients had died. After the researchers controlled for age, comorbidities, year of diagnosis, tumor factors, and pathologic stage, the effect of omitting AET still resulted in significantly worse survival: (HR 1.25, 95% CI: 1.05-1.48, P = .01).

Mortality was driven by patients with residual disease after neoadjuvant chemotherapy, who comprised nearly half the study cohort. In these patients, omission of endocrine therapy was associated with a 27% higher risk of death (HR 1.27, 1.10-1.58). However, for those with a complete pathological response following chemotherapy, omission of endocrine therapy was not associated with a higher risk of death (HR 1.06; 0.62-1.80).

The investigators noted several limitations of their study, including a retrospective design and no information available on recurrence or the duration of endocrine therapy.
 

Why Is Endocrine Therapy So Frequently Omitted in This Patient Group?

Matthew P. Goetz, MD, of the Mayo Clinic, the study’s corresponding author, said in an interview that in Sweden, for example, ER-low patients are explicitly not offered endocrine therapy based on Swedish guidelines.

In other settings, he said, it is unclear what is happening.

“Are patients refusing it? Do physicians not even offer it because they think there is no value? We do not have that granular detail, but our data right now suggests a physician should be having this conversation with patients,” he said.
 

Which ER-Low Patients Are Likely To Benefit?

The findings apply mostly to patients with residual disease after chemotherapy, and underlying biological factors are likely the reason, Dr. Goetz said.

ER-low patients are a heterogeneous group, he explained.

“In genomic profiling, where we look at the underlying biology of these cancers, most of the ER-low cancers are considered the basal subtype of triple negative breast cancer. Those patients should have absolutely zero benefit from endocrine therapy. But there is another group, referred to as the luminal group, which comprises anywhere from 20% to 30% of the ER-low patients.”

Dr. Goetz said he expects to find that this latter group are the patients benefiting from endocrine therapy when they have residual disease.

“We are not yet at the point of saying to patients, ‘you have residual disease after chemotherapy. Let’s check your tumor to see if it is the basal or luminal subtype.’ But that is something that we are planning to look into. What is most important right now is that clinicians be aware of these data, and that there is a suggestion that omitting endocrine therapy may have detrimental effects on survival in this subgroup of patients.”
 

Are the Findings Compelling Enough To Change Clinical Practice Right Away?

In an interview about the findings, Eric Winer, MD, of the Yale Cancer Center in New Haven, Connecticut, cautioned that due to the retrospective study design, “we don’t know how doctors made decisions about who got endocrine therapy and who didn’t.”

The patients with the worst tumors tended not to get endocrine therapy, Dr. Winer noted, and despite attempts to adjust for this, “in any large data set like this, unlike in a randomized trial, you just can’t control for all the bias.”
 

What Should Doctors Tell Patients?

“In the setting of significant side effects from endocrine therapy, we’re still less certain about the benefits of endocrine therapy here than in somebody with an ER-high tumor,” Dr. Winer cautioned.

Nonetheless, he said, the new findings certainly suggest that there may be a benefit for endocrine therapy in patients with ER-low tumors, and doctors should make this known to patients. “It may not be the strongest evidence, but it’s evidence,” he said. “This is very much a question to be raised between the doctor and the patient.”

Dr. Choong and colleagues’ study was funded by a Mayo Clinic Breast Cancer SPORE grant. Dr. Goetz reported consulting fees and research support from pharmaceutical manufacturers, including AstraZeneca, Pfizer, Lilly, and Novartis. Dr. Choong and Dr. Winer reported no financial conflicts of interest.

For women with early-stage estrogen-receptor positive breast cancer, adjuvant endocrine therapy is known to decrease the likelihood of recurrence and improve survival, while omitting the therapy is associated with a higher risk of death.

For that reason, current guidelines, including those from the National Comprehensive Cancer Network, recommend adjuvant endocrine therapy (AET) for patients with estrogen-receptor positive (ER+) breast cancers.

But these and other guidelines do not make recommendations for a class of tumors deemed estrogen receptor low positive, often referred to as “ER-low,” a category in which ER is seen expressed in between 1% and 10% of cells. This is because benefits of endocrine therapy have not been demonstrated in patients with ER-low disease.

New research presented at the annual meeting of the American Society of Clinical Oncology in Chicago may change how clinicians and patients think about endocrine therapy. The findings showed that omitting endocrine therapy after surgery and chemotherapy was associated with a 25% higher chance of death within 3 years in ER-low patients.

Endocrine therapy, the investigators say, should therefore be offered to all patients with ER-low cancers, at least until it can be determined which subgroups are most likely to benefit.

How Was the Study Conducted?

Grace M. Choong, MD, of the Mayo Clinic in Rochester, Minnesota, and her colleagues, looked at 2018-2020 data from the National Cancer Database for more than 350,000 female patients with stages 1-3, ER+ breast cancer. From among these they identified about 7000 patients with ER-low cancers who had undergone adjuvant or neoadjuvant chemotherapy.

“We specifically wanted to focus on those treated with chemotherapy as these patients have a higher risk of recurrence in our short interval follow-up,” Dr. Choong said during her presentation.

Patients’ median age was 55 years, and three-quarters of them were White. Their tumors were more likely to be HER2-negative (65%), PR-negative (73%), have higher Ki-67 expression, and have a higher clinical stage (73% grade III).

Forty-two percent of patients did not undergo AET as part of their treatment regimen, with various tumor factors seen associated with AET omission. At a median 3 years of follow-up, 586 patients had died. After the researchers controlled for age, comorbidities, year of diagnosis, tumor factors, and pathologic stage, the effect of omitting AET still resulted in significantly worse survival: (HR 1.25, 95% CI: 1.05-1.48, P = .01).

Mortality was driven by patients with residual disease after neoadjuvant chemotherapy, who comprised nearly half the study cohort. In these patients, omission of endocrine therapy was associated with a 27% higher risk of death (HR 1.27, 1.10-1.58). However, for those with a complete pathological response following chemotherapy, omission of endocrine therapy was not associated with a higher risk of death (HR 1.06; 0.62-1.80).

The investigators noted several limitations of their study, including a retrospective design and no information available on recurrence or the duration of endocrine therapy.
 

Why Is Endocrine Therapy So Frequently Omitted in This Patient Group?

Matthew P. Goetz, MD, of the Mayo Clinic, the study’s corresponding author, said in an interview that in Sweden, for example, ER-low patients are explicitly not offered endocrine therapy based on Swedish guidelines.

In other settings, he said, it is unclear what is happening.

“Are patients refusing it? Do physicians not even offer it because they think there is no value? We do not have that granular detail, but our data right now suggests a physician should be having this conversation with patients,” he said.
 

Which ER-Low Patients Are Likely To Benefit?

The findings apply mostly to patients with residual disease after chemotherapy, and underlying biological factors are likely the reason, Dr. Goetz said.

ER-low patients are a heterogeneous group, he explained.

“In genomic profiling, where we look at the underlying biology of these cancers, most of the ER-low cancers are considered the basal subtype of triple negative breast cancer. Those patients should have absolutely zero benefit from endocrine therapy. But there is another group, referred to as the luminal group, which comprises anywhere from 20% to 30% of the ER-low patients.”

Dr. Goetz said he expects to find that this latter group are the patients benefiting from endocrine therapy when they have residual disease.

“We are not yet at the point of saying to patients, ‘you have residual disease after chemotherapy. Let’s check your tumor to see if it is the basal or luminal subtype.’ But that is something that we are planning to look into. What is most important right now is that clinicians be aware of these data, and that there is a suggestion that omitting endocrine therapy may have detrimental effects on survival in this subgroup of patients.”
 

Are the Findings Compelling Enough To Change Clinical Practice Right Away?

In an interview about the findings, Eric Winer, MD, of the Yale Cancer Center in New Haven, Connecticut, cautioned that due to the retrospective study design, “we don’t know how doctors made decisions about who got endocrine therapy and who didn’t.”

The patients with the worst tumors tended not to get endocrine therapy, Dr. Winer noted, and despite attempts to adjust for this, “in any large data set like this, unlike in a randomized trial, you just can’t control for all the bias.”
 

What Should Doctors Tell Patients?

“In the setting of significant side effects from endocrine therapy, we’re still less certain about the benefits of endocrine therapy here than in somebody with an ER-high tumor,” Dr. Winer cautioned.

Nonetheless, he said, the new findings certainly suggest that there may be a benefit for endocrine therapy in patients with ER-low tumors, and doctors should make this known to patients. “It may not be the strongest evidence, but it’s evidence,” he said. “This is very much a question to be raised between the doctor and the patient.”

Dr. Choong and colleagues’ study was funded by a Mayo Clinic Breast Cancer SPORE grant. Dr. Goetz reported consulting fees and research support from pharmaceutical manufacturers, including AstraZeneca, Pfizer, Lilly, and Novartis. Dr. Choong and Dr. Winer reported no financial conflicts of interest.

For women with early-stage estrogen-receptor positive breast cancer, adjuvant endocrine therapy is known to decrease the likelihood of recurrence and improve survival, while omitting the therapy is associated with a higher risk of death.

For that reason, current guidelines, including those from the National Comprehensive Cancer Network, recommend adjuvant endocrine therapy (AET) for patients with estrogen-receptor positive (ER+) breast cancers.

But these and other guidelines do not make recommendations for a class of tumors deemed estrogen receptor low positive, often referred to as “ER-low,” a category in which ER is seen expressed in between 1% and 10% of cells. This is because benefits of endocrine therapy have not been demonstrated in patients with ER-low disease.

New research presented at the annual meeting of the American Society of Clinical Oncology in Chicago may change how clinicians and patients think about endocrine therapy. The findings showed that omitting endocrine therapy after surgery and chemotherapy was associated with a 25% higher chance of death within 3 years in ER-low patients.

Endocrine therapy, the investigators say, should therefore be offered to all patients with ER-low cancers, at least until it can be determined which subgroups are most likely to benefit.

How Was the Study Conducted?

Grace M. Choong, MD, of the Mayo Clinic in Rochester, Minnesota, and her colleagues, looked at 2018-2020 data from the National Cancer Database for more than 350,000 female patients with stages 1-3, ER+ breast cancer. From among these they identified about 7000 patients with ER-low cancers who had undergone adjuvant or neoadjuvant chemotherapy.

“We specifically wanted to focus on those treated with chemotherapy as these patients have a higher risk of recurrence in our short interval follow-up,” Dr. Choong said during her presentation.

Patients’ median age was 55 years, and three-quarters of them were White. Their tumors were more likely to be HER2-negative (65%), PR-negative (73%), have higher Ki-67 expression, and have a higher clinical stage (73% grade III).

Forty-two percent of patients did not undergo AET as part of their treatment regimen, with various tumor factors seen associated with AET omission. At a median 3 years of follow-up, 586 patients had died. After the researchers controlled for age, comorbidities, year of diagnosis, tumor factors, and pathologic stage, the effect of omitting AET still resulted in significantly worse survival: (HR 1.25, 95% CI: 1.05-1.48, P = .01).

Mortality was driven by patients with residual disease after neoadjuvant chemotherapy, who comprised nearly half the study cohort. In these patients, omission of endocrine therapy was associated with a 27% higher risk of death (HR 1.27, 1.10-1.58). However, for those with a complete pathological response following chemotherapy, omission of endocrine therapy was not associated with a higher risk of death (HR 1.06; 0.62-1.80).

The investigators noted several limitations of their study, including a retrospective design and no information available on recurrence or the duration of endocrine therapy.
 

Why Is Endocrine Therapy So Frequently Omitted in This Patient Group?

Matthew P. Goetz, MD, of the Mayo Clinic, the study’s corresponding author, said in an interview that in Sweden, for example, ER-low patients are explicitly not offered endocrine therapy based on Swedish guidelines.

In other settings, he said, it is unclear what is happening.

“Are patients refusing it? Do physicians not even offer it because they think there is no value? We do not have that granular detail, but our data right now suggests a physician should be having this conversation with patients,” he said.
 

Which ER-Low Patients Are Likely To Benefit?

The findings apply mostly to patients with residual disease after chemotherapy, and underlying biological factors are likely the reason, Dr. Goetz said.

ER-low patients are a heterogeneous group, he explained.

“In genomic profiling, where we look at the underlying biology of these cancers, most of the ER-low cancers are considered the basal subtype of triple negative breast cancer. Those patients should have absolutely zero benefit from endocrine therapy. But there is another group, referred to as the luminal group, which comprises anywhere from 20% to 30% of the ER-low patients.”

Dr. Goetz said he expects to find that this latter group are the patients benefiting from endocrine therapy when they have residual disease.

“We are not yet at the point of saying to patients, ‘you have residual disease after chemotherapy. Let’s check your tumor to see if it is the basal or luminal subtype.’ But that is something that we are planning to look into. What is most important right now is that clinicians be aware of these data, and that there is a suggestion that omitting endocrine therapy may have detrimental effects on survival in this subgroup of patients.”
 

Are the Findings Compelling Enough To Change Clinical Practice Right Away?

In an interview about the findings, Eric Winer, MD, of the Yale Cancer Center in New Haven, Connecticut, cautioned that due to the retrospective study design, “we don’t know how doctors made decisions about who got endocrine therapy and who didn’t.”

The patients with the worst tumors tended not to get endocrine therapy, Dr. Winer noted, and despite attempts to adjust for this, “in any large data set like this, unlike in a randomized trial, you just can’t control for all the bias.”
 

What Should Doctors Tell Patients?

“In the setting of significant side effects from endocrine therapy, we’re still less certain about the benefits of endocrine therapy here than in somebody with an ER-high tumor,” Dr. Winer cautioned.

Nonetheless, he said, the new findings certainly suggest that there may be a benefit for endocrine therapy in patients with ER-low tumors, and doctors should make this known to patients. “It may not be the strongest evidence, but it’s evidence,” he said. “This is very much a question to be raised between the doctor and the patient.”

Dr. Choong and colleagues’ study was funded by a Mayo Clinic Breast Cancer SPORE grant. Dr. Goetz reported consulting fees and research support from pharmaceutical manufacturers, including AstraZeneca, Pfizer, Lilly, and Novartis. Dr. Choong and Dr. Winer reported no financial conflicts of interest.

Use of combined contraceptive vaginal rings was associated with an increased risk for several types of sexually transmitted infections (STIs), based on data from a pair of studies presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists (ACOG).

Previous research has shown that the use of a combined contraceptive vaginal ring (CCVR) may promote changes in immunity in the female genital tract by upregulating immune-related genes in the endocervix and immune mediators within the cervicovaginal fluid, wrote Amy Arceneaux, BS, a medical student at the University of Texas Medical Branch John Sealy School of Medicine, Galveston, and colleagues.

The infection rates in the female genital tract can vary according to hormones in the local environment and continued safety analysis is needed as the use of CCVR continues to rise, the researchers noted.

In a retrospective chart review, the researchers assessed de-identified data from TriNetX, a patient database, including 30,796 women who received etonogestrel and ethinyl estradiol CCVRs without segesterone and an equal number who were using oral contraceptive pills (OCP) without vaginal hormones. Patients were matched for age, race, and ethnicity.

Overall use of CCVRs was significantly associated with an increased risk for Herpes simplex virus 2 (HSV-2; relative risk [RR], 1.790), acute vaginitis (RR, 1.722), subacute/chronic vaginitis (RR, 1.904), subacute/chronic vulvitis (RR, 1.969), acute vulvitis (RR, 1.894), candidiasis (RR, 1.464), trichomoniasis (RR, 2.162), and pelvic inflammatory disease (RR, 2.984; P < .0005 for all).

By contrast, use of CCVRs was significantly associated with a decreased risk for chlamydia (RR, 0.760; P = .047). No differences in risk appeared for gonorrhea, syphilis, HIV, or anogenital warts between the CCVR and OCP groups.

Another study presented at the meeting, led by Kathleen Karam, BS, also a medical student at the University of Texas Medical Branch John Sealy School of Medicine, Galveston, Texas, focused on outcomes on vaginal health and infection risk in women who used CCVRs compared with women who did not use hormones.

The study by Ms. Karam and colleagues included de-identified TriNetX data for two cohorts of 274,743 women.

Overall, the researchers found a significantly increased risk for gonorrhea, HSV-2, vaginitis, vulvitis, pelvic inflammatory disease, anogenital warts, and candidiasis in women using CCVR compared with those using no hormonal contraception, while the risk for chlamydia, syphilis, and HIV was decreased in women using CCVR compared with those using no hormonal contraception.

“I was pleasantly surprised by the finding that the group of women using the hormonal contraception vaginal ring had decreased risk for HIV and syphilis infections,” said Kathleen L. Vincent, MD, of the University of Texas Medical Branch John Sealy School of Medicine, Galveston, Texas, and senior author on both studies, in an interview. She hypothesized that the estrogen released from the ring might have contributed to the decreased risk for those infections.

The findings of both studies were limited primarily by the retrospective design, but the results suggest a need for further study of the effect of local hormone delivery on the vaginal mucosa, the researchers wrote.

Although the study population was large, the lack of randomization can allow for differences in the behaviors or risk-taking of the groups, Dr. Vincent said in an interview.

“The fact that there were STIs that were increased and some that were decreased with use of the vaginal ring tells us that there were women with similar behaviors in both groups, or we might have seen STIs only in one group,” she said. “Additional research could be done to look at varying time courses of outcomes after initiation of the vaginal ring or to go more in-depth with matching the groups at baseline based on a history of risky behaviors,” she noted.
 

Data Inform Multipurpose Prevention Technology

Dr. Vincent and her colleague, Richard Pyles, PhD, have a 15-year history of studying vaginal drug and hormone effects on the vaginal mucosa in women and preclinical and cell models. “Based on that work, it was plausible for estrogen to be protective for several types of infections,” she said. The availability of TriNetX allowed the researchers to explore these relationships in a large database of women in the studies presented at the meeting. “We began with a basic science observation in an animal model and grew it into this clinical study because of the available TriNetX system that supported extensive medical record review,” Dr. Pyles noted.

The take-home messages from the current research remain that vaginal rings delivering hormones are indicated only for contraception or birth control, not for protection against STIs or HIV, and women at an increased risk for these infections should protect themselves by using condoms, Dr. Vincent said.

However, “the real clinical implication is for the future for the drugs that we call MPTs or multi-purpose prevention technologies,” Dr. Vincent said.

“This could be a vaginal ring that releases medications for birth control and prevention of HIV or an STI,” she explained.

The findings from the studies presented at the meeting have great potential for an MPT on which Dr. Vincent and Dr. Pyles are working that would provide protection against both HIV and pregnancy. “For HIV prevention, the hormonal vaginal ring components have potential to work synergistically with the HIV prevention drug rather than working against each other, and this could be realized as a need for less HIV prevention drug, and subsequently fewer potential side effects from that drug,” said Dr. Vincent.

The studies received no outside funding. The researchers had no financial conflicts to disclose.

Use of combined contraceptive vaginal rings was associated with an increased risk for several types of sexually transmitted infections (STIs), based on data from a pair of studies presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists (ACOG).

Previous research has shown that the use of a combined contraceptive vaginal ring (CCVR) may promote changes in immunity in the female genital tract by upregulating immune-related genes in the endocervix and immune mediators within the cervicovaginal fluid, wrote Amy Arceneaux, BS, a medical student at the University of Texas Medical Branch John Sealy School of Medicine, Galveston, and colleagues.

The infection rates in the female genital tract can vary according to hormones in the local environment and continued safety analysis is needed as the use of CCVR continues to rise, the researchers noted.

In a retrospective chart review, the researchers assessed de-identified data from TriNetX, a patient database, including 30,796 women who received etonogestrel and ethinyl estradiol CCVRs without segesterone and an equal number who were using oral contraceptive pills (OCP) without vaginal hormones. Patients were matched for age, race, and ethnicity.

Overall use of CCVRs was significantly associated with an increased risk for Herpes simplex virus 2 (HSV-2; relative risk [RR], 1.790), acute vaginitis (RR, 1.722), subacute/chronic vaginitis (RR, 1.904), subacute/chronic vulvitis (RR, 1.969), acute vulvitis (RR, 1.894), candidiasis (RR, 1.464), trichomoniasis (RR, 2.162), and pelvic inflammatory disease (RR, 2.984; P < .0005 for all).

By contrast, use of CCVRs was significantly associated with a decreased risk for chlamydia (RR, 0.760; P = .047). No differences in risk appeared for gonorrhea, syphilis, HIV, or anogenital warts between the CCVR and OCP groups.

Another study presented at the meeting, led by Kathleen Karam, BS, also a medical student at the University of Texas Medical Branch John Sealy School of Medicine, Galveston, Texas, focused on outcomes on vaginal health and infection risk in women who used CCVRs compared with women who did not use hormones.

The study by Ms. Karam and colleagues included de-identified TriNetX data for two cohorts of 274,743 women.

Overall, the researchers found a significantly increased risk for gonorrhea, HSV-2, vaginitis, vulvitis, pelvic inflammatory disease, anogenital warts, and candidiasis in women using CCVR compared with those using no hormonal contraception, while the risk for chlamydia, syphilis, and HIV was decreased in women using CCVR compared with those using no hormonal contraception.

“I was pleasantly surprised by the finding that the group of women using the hormonal contraception vaginal ring had decreased risk for HIV and syphilis infections,” said Kathleen L. Vincent, MD, of the University of Texas Medical Branch John Sealy School of Medicine, Galveston, Texas, and senior author on both studies, in an interview. She hypothesized that the estrogen released from the ring might have contributed to the decreased risk for those infections.

The findings of both studies were limited primarily by the retrospective design, but the results suggest a need for further study of the effect of local hormone delivery on the vaginal mucosa, the researchers wrote.

Although the study population was large, the lack of randomization can allow for differences in the behaviors or risk-taking of the groups, Dr. Vincent said in an interview.

“The fact that there were STIs that were increased and some that were decreased with use of the vaginal ring tells us that there were women with similar behaviors in both groups, or we might have seen STIs only in one group,” she said. “Additional research could be done to look at varying time courses of outcomes after initiation of the vaginal ring or to go more in-depth with matching the groups at baseline based on a history of risky behaviors,” she noted.
 

Data Inform Multipurpose Prevention Technology

Dr. Vincent and her colleague, Richard Pyles, PhD, have a 15-year history of studying vaginal drug and hormone effects on the vaginal mucosa in women and preclinical and cell models. “Based on that work, it was plausible for estrogen to be protective for several types of infections,” she said. The availability of TriNetX allowed the researchers to explore these relationships in a large database of women in the studies presented at the meeting. “We began with a basic science observation in an animal model and grew it into this clinical study because of the available TriNetX system that supported extensive medical record review,” Dr. Pyles noted.

The take-home messages from the current research remain that vaginal rings delivering hormones are indicated only for contraception or birth control, not for protection against STIs or HIV, and women at an increased risk for these infections should protect themselves by using condoms, Dr. Vincent said.

However, “the real clinical implication is for the future for the drugs that we call MPTs or multi-purpose prevention technologies,” Dr. Vincent said.

“This could be a vaginal ring that releases medications for birth control and prevention of HIV or an STI,” she explained.

The findings from the studies presented at the meeting have great potential for an MPT on which Dr. Vincent and Dr. Pyles are working that would provide protection against both HIV and pregnancy. “For HIV prevention, the hormonal vaginal ring components have potential to work synergistically with the HIV prevention drug rather than working against each other, and this could be realized as a need for less HIV prevention drug, and subsequently fewer potential side effects from that drug,” said Dr. Vincent.

The studies received no outside funding. The researchers had no financial conflicts to disclose.

Use of combined contraceptive vaginal rings was associated with an increased risk for several types of sexually transmitted infections (STIs), based on data from a pair of studies presented at the annual clinical and scientific meeting of the American College of Obstetricians and Gynecologists (ACOG).

Previous research has shown that the use of a combined contraceptive vaginal ring (CCVR) may promote changes in immunity in the female genital tract by upregulating immune-related genes in the endocervix and immune mediators within the cervicovaginal fluid, wrote Amy Arceneaux, BS, a medical student at the University of Texas Medical Branch John Sealy School of Medicine, Galveston, and colleagues.

The infection rates in the female genital tract can vary according to hormones in the local environment and continued safety analysis is needed as the use of CCVR continues to rise, the researchers noted.

In a retrospective chart review, the researchers assessed de-identified data from TriNetX, a patient database, including 30,796 women who received etonogestrel and ethinyl estradiol CCVRs without segesterone and an equal number who were using oral contraceptive pills (OCP) without vaginal hormones. Patients were matched for age, race, and ethnicity.

Overall use of CCVRs was significantly associated with an increased risk for Herpes simplex virus 2 (HSV-2; relative risk [RR], 1.790), acute vaginitis (RR, 1.722), subacute/chronic vaginitis (RR, 1.904), subacute/chronic vulvitis (RR, 1.969), acute vulvitis (RR, 1.894), candidiasis (RR, 1.464), trichomoniasis (RR, 2.162), and pelvic inflammatory disease (RR, 2.984; P < .0005 for all).

By contrast, use of CCVRs was significantly associated with a decreased risk for chlamydia (RR, 0.760; P = .047). No differences in risk appeared for gonorrhea, syphilis, HIV, or anogenital warts between the CCVR and OCP groups.

Another study presented at the meeting, led by Kathleen Karam, BS, also a medical student at the University of Texas Medical Branch John Sealy School of Medicine, Galveston, Texas, focused on outcomes on vaginal health and infection risk in women who used CCVRs compared with women who did not use hormones.

The study by Ms. Karam and colleagues included de-identified TriNetX data for two cohorts of 274,743 women.

Overall, the researchers found a significantly increased risk for gonorrhea, HSV-2, vaginitis, vulvitis, pelvic inflammatory disease, anogenital warts, and candidiasis in women using CCVR compared with those using no hormonal contraception, while the risk for chlamydia, syphilis, and HIV was decreased in women using CCVR compared with those using no hormonal contraception.

“I was pleasantly surprised by the finding that the group of women using the hormonal contraception vaginal ring had decreased risk for HIV and syphilis infections,” said Kathleen L. Vincent, MD, of the University of Texas Medical Branch John Sealy School of Medicine, Galveston, Texas, and senior author on both studies, in an interview. She hypothesized that the estrogen released from the ring might have contributed to the decreased risk for those infections.

The findings of both studies were limited primarily by the retrospective design, but the results suggest a need for further study of the effect of local hormone delivery on the vaginal mucosa, the researchers wrote.

Although the study population was large, the lack of randomization can allow for differences in the behaviors or risk-taking of the groups, Dr. Vincent said in an interview.

“The fact that there were STIs that were increased and some that were decreased with use of the vaginal ring tells us that there were women with similar behaviors in both groups, or we might have seen STIs only in one group,” she said. “Additional research could be done to look at varying time courses of outcomes after initiation of the vaginal ring or to go more in-depth with matching the groups at baseline based on a history of risky behaviors,” she noted.
 

Data Inform Multipurpose Prevention Technology

Dr. Vincent and her colleague, Richard Pyles, PhD, have a 15-year history of studying vaginal drug and hormone effects on the vaginal mucosa in women and preclinical and cell models. “Based on that work, it was plausible for estrogen to be protective for several types of infections,” she said. The availability of TriNetX allowed the researchers to explore these relationships in a large database of women in the studies presented at the meeting. “We began with a basic science observation in an animal model and grew it into this clinical study because of the available TriNetX system that supported extensive medical record review,” Dr. Pyles noted.

The take-home messages from the current research remain that vaginal rings delivering hormones are indicated only for contraception or birth control, not for protection against STIs or HIV, and women at an increased risk for these infections should protect themselves by using condoms, Dr. Vincent said.

However, “the real clinical implication is for the future for the drugs that we call MPTs or multi-purpose prevention technologies,” Dr. Vincent said.

“This could be a vaginal ring that releases medications for birth control and prevention of HIV or an STI,” she explained.

The findings from the studies presented at the meeting have great potential for an MPT on which Dr. Vincent and Dr. Pyles are working that would provide protection against both HIV and pregnancy. “For HIV prevention, the hormonal vaginal ring components have potential to work synergistically with the HIV prevention drug rather than working against each other, and this could be realized as a need for less HIV prevention drug, and subsequently fewer potential side effects from that drug,” said Dr. Vincent.

The studies received no outside funding. The researchers had no financial conflicts to disclose.