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Few women identify breast density as a breast cancer risk

Article Type
Changed
Thu, 03/16/2023 - 11:35

A qualitative study of breast cancer screening–age women finds that few women identified breast density as a risk factor for breast cancer.

Most women did not feel confident they knew what actions could mitigate breast cancer risk, leading researchers to the conclusion that comprehensive education about breast cancer risks and prevention strategies is needed.

The study was published earlier this year in JAMA Network Open.

“Forty [percent] to 50% of women who undergo mammography fall into the two highest breast density categories,” said the study’s lead author Christine Gunn, PhD, of the Dartmouth Institute for Health Policy and Clinical Practice, N.H. “Breast cancer risk increases from 1.2-4.0 times depending on the level of breast density. By comparison, a first-degree family history of breast cancer, particularly in premenopausal women, confers a two-fold higher breast cancer risk.”

Dr. Gunn’s study is based on a survey of 2,306 women (between 40 and 76 years old) that was conducted between 2019 and 2020. The goal was to determine how well women understood cancer risks associated with dense breast tissue. The final analysis included 1,858 women (9% Asian, 27% Black, 14% Hispanic, 43% White, and 7% other race or ethnicity).

Breast density was thought to be a greater risk than not having children, drinking daily, and having had a prior breast biopsy, according to 52%, 53%, and 48% of respondents, respectively. Breast density was believed to be a lesser breast cancer risk than having a first-degree relative with breast cancer by 93% of women, and 65% of women felt it was a lesser risk than being overweight or obese.

Of the 61 women who completed follow-up interviews, 6 described breast density as a contributing factor to breast cancer risk. And, 17 women did not know whether it was possible to reduce their breast cancer risk.
 

Doctors must notify patients in writing

Breast tissue falls under one of four categories: fatty tissue, scattered areas of dense fibroglandular tissue, many areas of glandular and connective tissue, or extremely dense tissue. The tissue is considered dense if it falls under heterogeneously dense or extremely dense, and in those cases, follow-up testing with ultrasound or MRI may be necessary. This is important, Dr. Gunn said, because dense tissue can make “it harder to find cancers because connective tissue appears white on the mammogram, potentially masking tumors.”

Prior studies have found that many clinicians are uncomfortable counseling patients on the implications of breast density and cancer risk, the authors wrote.

However, under the Mammography Quality Standards Act, which was updated on March 10, the Food and Drug Administration requires that patients be provided with a mammography report summary that “identifies whether the patient has dense or nondense breast tissue.” The report, which should be written in lay language, should also specify the “significance” of the dense tissue.

While some states mandate notification regardless of the density level, most only notify women if heterogeneously dense or extremely dense tissue has been identified, Dr. Gunn said. But the rules are inconsistent, she said. In some facilities in Massachusetts, for example, women may receive a mammography report letter and a separate breast density letter. “For some, it has been really confusing. They received a letter saying that their mammography was normal and then another one saying that they have dense breasts – resulting in a lot of uncertainty and anxiety. We don’t want to overly alarm people. We want them to understand their risk,” she said.

Breast density can be considered among other risk factors, including alcohol use, obesity, diet, parity, prior breast biopsy, and inherited unfavorable genetic mutations. “If the total lifetime risk is above 20%, that opens up further screening options, such as a breast MRI, which will catch more cancers than a breast mammogram by itself,” Dr. Gunn said.

“The challenges for physicians and patients around collecting and understanding breast density information in the context of other risk factors can potentially lead to disparities in who gets to know their risk and who doesn’t,” Dr. Gunn said. It would be possible, she speculated, to create or use existing risk calculators integrated into medical records and populated with information gathered in premammography visit questionnaires. Ideally, a radiologist could hand the patient results in real time at the end of the mammography visit, integrating risk estimates with mammography findings to make recommendations.

This study was supported by grant RSG-133017-CPHPS from the American Cancer Society.
 

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A qualitative study of breast cancer screening–age women finds that few women identified breast density as a risk factor for breast cancer.

Most women did not feel confident they knew what actions could mitigate breast cancer risk, leading researchers to the conclusion that comprehensive education about breast cancer risks and prevention strategies is needed.

The study was published earlier this year in JAMA Network Open.

“Forty [percent] to 50% of women who undergo mammography fall into the two highest breast density categories,” said the study’s lead author Christine Gunn, PhD, of the Dartmouth Institute for Health Policy and Clinical Practice, N.H. “Breast cancer risk increases from 1.2-4.0 times depending on the level of breast density. By comparison, a first-degree family history of breast cancer, particularly in premenopausal women, confers a two-fold higher breast cancer risk.”

Dr. Gunn’s study is based on a survey of 2,306 women (between 40 and 76 years old) that was conducted between 2019 and 2020. The goal was to determine how well women understood cancer risks associated with dense breast tissue. The final analysis included 1,858 women (9% Asian, 27% Black, 14% Hispanic, 43% White, and 7% other race or ethnicity).

Breast density was thought to be a greater risk than not having children, drinking daily, and having had a prior breast biopsy, according to 52%, 53%, and 48% of respondents, respectively. Breast density was believed to be a lesser breast cancer risk than having a first-degree relative with breast cancer by 93% of women, and 65% of women felt it was a lesser risk than being overweight or obese.

Of the 61 women who completed follow-up interviews, 6 described breast density as a contributing factor to breast cancer risk. And, 17 women did not know whether it was possible to reduce their breast cancer risk.
 

Doctors must notify patients in writing

Breast tissue falls under one of four categories: fatty tissue, scattered areas of dense fibroglandular tissue, many areas of glandular and connective tissue, or extremely dense tissue. The tissue is considered dense if it falls under heterogeneously dense or extremely dense, and in those cases, follow-up testing with ultrasound or MRI may be necessary. This is important, Dr. Gunn said, because dense tissue can make “it harder to find cancers because connective tissue appears white on the mammogram, potentially masking tumors.”

Prior studies have found that many clinicians are uncomfortable counseling patients on the implications of breast density and cancer risk, the authors wrote.

However, under the Mammography Quality Standards Act, which was updated on March 10, the Food and Drug Administration requires that patients be provided with a mammography report summary that “identifies whether the patient has dense or nondense breast tissue.” The report, which should be written in lay language, should also specify the “significance” of the dense tissue.

While some states mandate notification regardless of the density level, most only notify women if heterogeneously dense or extremely dense tissue has been identified, Dr. Gunn said. But the rules are inconsistent, she said. In some facilities in Massachusetts, for example, women may receive a mammography report letter and a separate breast density letter. “For some, it has been really confusing. They received a letter saying that their mammography was normal and then another one saying that they have dense breasts – resulting in a lot of uncertainty and anxiety. We don’t want to overly alarm people. We want them to understand their risk,” she said.

Breast density can be considered among other risk factors, including alcohol use, obesity, diet, parity, prior breast biopsy, and inherited unfavorable genetic mutations. “If the total lifetime risk is above 20%, that opens up further screening options, such as a breast MRI, which will catch more cancers than a breast mammogram by itself,” Dr. Gunn said.

“The challenges for physicians and patients around collecting and understanding breast density information in the context of other risk factors can potentially lead to disparities in who gets to know their risk and who doesn’t,” Dr. Gunn said. It would be possible, she speculated, to create or use existing risk calculators integrated into medical records and populated with information gathered in premammography visit questionnaires. Ideally, a radiologist could hand the patient results in real time at the end of the mammography visit, integrating risk estimates with mammography findings to make recommendations.

This study was supported by grant RSG-133017-CPHPS from the American Cancer Society.
 

A qualitative study of breast cancer screening–age women finds that few women identified breast density as a risk factor for breast cancer.

Most women did not feel confident they knew what actions could mitigate breast cancer risk, leading researchers to the conclusion that comprehensive education about breast cancer risks and prevention strategies is needed.

The study was published earlier this year in JAMA Network Open.

“Forty [percent] to 50% of women who undergo mammography fall into the two highest breast density categories,” said the study’s lead author Christine Gunn, PhD, of the Dartmouth Institute for Health Policy and Clinical Practice, N.H. “Breast cancer risk increases from 1.2-4.0 times depending on the level of breast density. By comparison, a first-degree family history of breast cancer, particularly in premenopausal women, confers a two-fold higher breast cancer risk.”

Dr. Gunn’s study is based on a survey of 2,306 women (between 40 and 76 years old) that was conducted between 2019 and 2020. The goal was to determine how well women understood cancer risks associated with dense breast tissue. The final analysis included 1,858 women (9% Asian, 27% Black, 14% Hispanic, 43% White, and 7% other race or ethnicity).

Breast density was thought to be a greater risk than not having children, drinking daily, and having had a prior breast biopsy, according to 52%, 53%, and 48% of respondents, respectively. Breast density was believed to be a lesser breast cancer risk than having a first-degree relative with breast cancer by 93% of women, and 65% of women felt it was a lesser risk than being overweight or obese.

Of the 61 women who completed follow-up interviews, 6 described breast density as a contributing factor to breast cancer risk. And, 17 women did not know whether it was possible to reduce their breast cancer risk.
 

Doctors must notify patients in writing

Breast tissue falls under one of four categories: fatty tissue, scattered areas of dense fibroglandular tissue, many areas of glandular and connective tissue, or extremely dense tissue. The tissue is considered dense if it falls under heterogeneously dense or extremely dense, and in those cases, follow-up testing with ultrasound or MRI may be necessary. This is important, Dr. Gunn said, because dense tissue can make “it harder to find cancers because connective tissue appears white on the mammogram, potentially masking tumors.”

Prior studies have found that many clinicians are uncomfortable counseling patients on the implications of breast density and cancer risk, the authors wrote.

However, under the Mammography Quality Standards Act, which was updated on March 10, the Food and Drug Administration requires that patients be provided with a mammography report summary that “identifies whether the patient has dense or nondense breast tissue.” The report, which should be written in lay language, should also specify the “significance” of the dense tissue.

While some states mandate notification regardless of the density level, most only notify women if heterogeneously dense or extremely dense tissue has been identified, Dr. Gunn said. But the rules are inconsistent, she said. In some facilities in Massachusetts, for example, women may receive a mammography report letter and a separate breast density letter. “For some, it has been really confusing. They received a letter saying that their mammography was normal and then another one saying that they have dense breasts – resulting in a lot of uncertainty and anxiety. We don’t want to overly alarm people. We want them to understand their risk,” she said.

Breast density can be considered among other risk factors, including alcohol use, obesity, diet, parity, prior breast biopsy, and inherited unfavorable genetic mutations. “If the total lifetime risk is above 20%, that opens up further screening options, such as a breast MRI, which will catch more cancers than a breast mammogram by itself,” Dr. Gunn said.

“The challenges for physicians and patients around collecting and understanding breast density information in the context of other risk factors can potentially lead to disparities in who gets to know their risk and who doesn’t,” Dr. Gunn said. It would be possible, she speculated, to create or use existing risk calculators integrated into medical records and populated with information gathered in premammography visit questionnaires. Ideally, a radiologist could hand the patient results in real time at the end of the mammography visit, integrating risk estimates with mammography findings to make recommendations.

This study was supported by grant RSG-133017-CPHPS from the American Cancer Society.
 

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Can particles in dairy and beef cause cancer and MS?

Article Type
Changed
Thu, 04/20/2023 - 18:36

In Western diets, dairy and beef are ubiquitous: Milk goes with coffee, melted cheese with pizza, and chili with rice. But what if dairy products and beef contained a new kind of pathogen that could infect you as a child and trigger cancer or multiple sclerosis (MS) 40-70 years later?

Researchers from the German Cancer Research Center (DKFZ) suspect that such zoonoses are possibly widespread and are therefore recommending that infants not be given dairy products until they are at least age 1 year. However, in two joint statements, the German Federal Institute for Risk Assessment (BfR) and the Max Rubner Institute (MRI) have rejected such theories.

In 2008, Harald zur Hausen, MD, DSc, received the Nobel Prize in Medicine for his discovery that human papillomaviruses cause cervical cancer. His starting point was the observation that sexually abstinent women, such as nuns, rarely develop this cancer. So it was possible to draw the conclusion that pathogens are transmitted during sexual intercourse, explain Dr. zur Hausen and his wife Ethel-Michele de Villiers, PhD, both of DKFZ Heidelberg.

Papillomaviruses, as well as human herpes and Epstein-Barr viruses (EBV), polyomaviruses, and retroviruses, cause cancer in a direct way: by inserting their genes into the DNA of human cells. With a latency of a few years to a few decades, the proteins formed through expression stimulate malignant growth by altering the regulating host gene.
 

Acid radicals

However, viruses – just like bacteria and parasites – can also indirectly trigger cancer. One mechanism for this triggering is the disruption of immune defenses, as shown by the sometimes drastically increased tumor incidence with AIDS or with immunosuppressants after transplants. Chronic inflammation is a second mechanism that generates acid radicals and thereby causes random mutations in replicating cells. Examples include stomach cancer caused by Helicobacter pylori and liver cancer caused by Schistosoma, liver fluke, and hepatitis B and C viruses.

According to Dr. de Villiers and Dr. zur Hausen, there are good reasons to believe that other pathogens could cause chronic inflammation and thereby lead to cancer. Epidemiologic data suggest that dairy and meat products from European cows (Bos taurus) are a potential source. This is because colon cancer and breast cancer commonly occur in places where these foods are heavily consumed (that is, in North America, Argentina, Europe, and Australia). In contrast, the rate is low in India, where cows are revered as holy animals. Also noteworthy is that women with a lactose intolerance rarely develop breast cancer.
 

Viral progeny

In fact, the researchers found single-stranded DNA rings that originated in viruses, which they named bovine meat and milk factors (BMMF), in the intestines of patients with colon cancer. They reported, “This new class of pathogen deserves, in our opinion at least, to become the focus of cancer development and further chronic diseases.” They also detected elevated levels of acid radicals in these areas (that is, oxidative stress), which is typical for chronic inflammation.

The researchers assume that infants, whose immune system is not yet fully matured, ingest the BMMF as soon as they have dairy. Therefore, there is no need for adults to avoid dairy or beef because everyone is infected anyway, said Dr. zur Hausen.
 

 

 

‘Breast milk is healthy’

Dr. De Villiers and Dr. zur Hausen outlined more evidence of cancer-triggering pathogens. Mothers who have breastfed are less likely, especially after multiple pregnancies, to develop tumors in various organs or to have MS and type 2 diabetes. The authors attribute the protective effect to oligosaccharides in breast milk, which begin to be formed midway through the pregnancy. They bind to lectin receptors and, in so doing, mask the terminal molecule onto which the viruses need to dock. As a result, their port of entry into the cells is blocked.

The oligosaccharides also protect the baby against life-threatening infections by blocking access by rotaviruses and noroviruses. In this way, especially if breastfeeding lasts a long time – around 1 year – the period of incomplete immunocompetence is bridged.
 

Colon cancer

To date, it has been assumed that around 20% of all cancerous diseases globally are caused by infections, said the researchers. But if the suspected BMMF cases are included, this figure rises to 50%, even to around 80%, for colon cancer. If the suspicion is confirmed, the consequences for prevention and therapy would be significant.

The voice of a Nobel prize winner undoubtedly carries weight, but at the time, Dr. zur Hausen still had to convince a host of skeptics with his discovery that a viral infection is a major cause of cervical cancer. Nonetheless, some indicators suggest that he and his wife have found a dead end this time.
 

Institutional skepticism

When his working group made the results public in February 2019, the DKFZ felt the need to give an all-clear signal in response to alarmed press reports. There is no reason to see dairy and meat consumption as something negative. Similarly, in their first joint statement, the BfR and the MRI judged the data to be insufficient and called for further studies. Multiple research teams began to focus on BMMF as a result. In what foods can they be found? Are they more common in patients with cancer than in healthy people? Are they infectious? Do they cause inflammation and cancer?

The findings presented in a second statement by the BfR and MRI at the end of November 2022 contradicted the claims made by the DKFZ scientists across the board. In no way do BMMF represent new pathogens. They are variants of already known DNA sequences. In addition, they are present in numerous animal-based and plant-based foods, including pork, fish, fruit, vegetables, and nuts.

BMMF do not possess the ability to infect human cells, the institutes said. The proof that they are damaging to one’s health was also absent. It is true that the incidence of intestinal tumors correlates positively with the consumption of red and processed meat – which in no way signifies causality – but dairy products are linked to a reduced risk. On the other hand, breast cancer cannot be associated with the consumption of beef or dairy.

Therefore, both institutes recommend continuing to use these products as supplementary diet for infants because of their micronutrients. They further stated that the products are safe for people of all ages.
 

 

 

Association with MS?

Unperturbed, Dr. de Villiers and Dr. zur Hausen went one step further in their current article. They posited that MS is also associated with the consumption of dairy products and beef. Here too geographic distribution prompted the idea to look for BMMF in the brain lesions of patients with MS. The researchers isolated ring-shaped DNA molecules that proved to be closely related to BMMF from dairy and cattle blood. “The result was electrifying for us.”

However, there are several other factors to consider, such as vitamin D3 deficiency. This is because the incidence of MS decreases the further you travel from the poles toward the equator (that is, as solar radiation increases). Also, EBV clearly plays a role because patients with MS display increased titers of EBV antibodies. One study also showed that people in Antarctica excreted reactivated EBV in their saliva during winter and that vitamin D3 stopped the viral secretion.

Under these conditions, the researchers hypothesized that MS is caused by a double infection of brain cells by EBV and BMMF. EBV is reactivated by a lack of vitamin D3, and the BMMF multiply and are eventually converted into proteins. A focal immunoreaction causes the Schwann cells and oligodendrocytes to malfunction, which leads to the destruction of the myelin sheaths around the nerve fibers.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

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Neurology Reviews - 31(4)
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In Western diets, dairy and beef are ubiquitous: Milk goes with coffee, melted cheese with pizza, and chili with rice. But what if dairy products and beef contained a new kind of pathogen that could infect you as a child and trigger cancer or multiple sclerosis (MS) 40-70 years later?

Researchers from the German Cancer Research Center (DKFZ) suspect that such zoonoses are possibly widespread and are therefore recommending that infants not be given dairy products until they are at least age 1 year. However, in two joint statements, the German Federal Institute for Risk Assessment (BfR) and the Max Rubner Institute (MRI) have rejected such theories.

In 2008, Harald zur Hausen, MD, DSc, received the Nobel Prize in Medicine for his discovery that human papillomaviruses cause cervical cancer. His starting point was the observation that sexually abstinent women, such as nuns, rarely develop this cancer. So it was possible to draw the conclusion that pathogens are transmitted during sexual intercourse, explain Dr. zur Hausen and his wife Ethel-Michele de Villiers, PhD, both of DKFZ Heidelberg.

Papillomaviruses, as well as human herpes and Epstein-Barr viruses (EBV), polyomaviruses, and retroviruses, cause cancer in a direct way: by inserting their genes into the DNA of human cells. With a latency of a few years to a few decades, the proteins formed through expression stimulate malignant growth by altering the regulating host gene.
 

Acid radicals

However, viruses – just like bacteria and parasites – can also indirectly trigger cancer. One mechanism for this triggering is the disruption of immune defenses, as shown by the sometimes drastically increased tumor incidence with AIDS or with immunosuppressants after transplants. Chronic inflammation is a second mechanism that generates acid radicals and thereby causes random mutations in replicating cells. Examples include stomach cancer caused by Helicobacter pylori and liver cancer caused by Schistosoma, liver fluke, and hepatitis B and C viruses.

According to Dr. de Villiers and Dr. zur Hausen, there are good reasons to believe that other pathogens could cause chronic inflammation and thereby lead to cancer. Epidemiologic data suggest that dairy and meat products from European cows (Bos taurus) are a potential source. This is because colon cancer and breast cancer commonly occur in places where these foods are heavily consumed (that is, in North America, Argentina, Europe, and Australia). In contrast, the rate is low in India, where cows are revered as holy animals. Also noteworthy is that women with a lactose intolerance rarely develop breast cancer.
 

Viral progeny

In fact, the researchers found single-stranded DNA rings that originated in viruses, which they named bovine meat and milk factors (BMMF), in the intestines of patients with colon cancer. They reported, “This new class of pathogen deserves, in our opinion at least, to become the focus of cancer development and further chronic diseases.” They also detected elevated levels of acid radicals in these areas (that is, oxidative stress), which is typical for chronic inflammation.

The researchers assume that infants, whose immune system is not yet fully matured, ingest the BMMF as soon as they have dairy. Therefore, there is no need for adults to avoid dairy or beef because everyone is infected anyway, said Dr. zur Hausen.
 

 

 

‘Breast milk is healthy’

Dr. De Villiers and Dr. zur Hausen outlined more evidence of cancer-triggering pathogens. Mothers who have breastfed are less likely, especially after multiple pregnancies, to develop tumors in various organs or to have MS and type 2 diabetes. The authors attribute the protective effect to oligosaccharides in breast milk, which begin to be formed midway through the pregnancy. They bind to lectin receptors and, in so doing, mask the terminal molecule onto which the viruses need to dock. As a result, their port of entry into the cells is blocked.

The oligosaccharides also protect the baby against life-threatening infections by blocking access by rotaviruses and noroviruses. In this way, especially if breastfeeding lasts a long time – around 1 year – the period of incomplete immunocompetence is bridged.
 

Colon cancer

To date, it has been assumed that around 20% of all cancerous diseases globally are caused by infections, said the researchers. But if the suspected BMMF cases are included, this figure rises to 50%, even to around 80%, for colon cancer. If the suspicion is confirmed, the consequences for prevention and therapy would be significant.

The voice of a Nobel prize winner undoubtedly carries weight, but at the time, Dr. zur Hausen still had to convince a host of skeptics with his discovery that a viral infection is a major cause of cervical cancer. Nonetheless, some indicators suggest that he and his wife have found a dead end this time.
 

Institutional skepticism

When his working group made the results public in February 2019, the DKFZ felt the need to give an all-clear signal in response to alarmed press reports. There is no reason to see dairy and meat consumption as something negative. Similarly, in their first joint statement, the BfR and the MRI judged the data to be insufficient and called for further studies. Multiple research teams began to focus on BMMF as a result. In what foods can they be found? Are they more common in patients with cancer than in healthy people? Are they infectious? Do they cause inflammation and cancer?

The findings presented in a second statement by the BfR and MRI at the end of November 2022 contradicted the claims made by the DKFZ scientists across the board. In no way do BMMF represent new pathogens. They are variants of already known DNA sequences. In addition, they are present in numerous animal-based and plant-based foods, including pork, fish, fruit, vegetables, and nuts.

BMMF do not possess the ability to infect human cells, the institutes said. The proof that they are damaging to one’s health was also absent. It is true that the incidence of intestinal tumors correlates positively with the consumption of red and processed meat – which in no way signifies causality – but dairy products are linked to a reduced risk. On the other hand, breast cancer cannot be associated with the consumption of beef or dairy.

Therefore, both institutes recommend continuing to use these products as supplementary diet for infants because of their micronutrients. They further stated that the products are safe for people of all ages.
 

 

 

Association with MS?

Unperturbed, Dr. de Villiers and Dr. zur Hausen went one step further in their current article. They posited that MS is also associated with the consumption of dairy products and beef. Here too geographic distribution prompted the idea to look for BMMF in the brain lesions of patients with MS. The researchers isolated ring-shaped DNA molecules that proved to be closely related to BMMF from dairy and cattle blood. “The result was electrifying for us.”

However, there are several other factors to consider, such as vitamin D3 deficiency. This is because the incidence of MS decreases the further you travel from the poles toward the equator (that is, as solar radiation increases). Also, EBV clearly plays a role because patients with MS display increased titers of EBV antibodies. One study also showed that people in Antarctica excreted reactivated EBV in their saliva during winter and that vitamin D3 stopped the viral secretion.

Under these conditions, the researchers hypothesized that MS is caused by a double infection of brain cells by EBV and BMMF. EBV is reactivated by a lack of vitamin D3, and the BMMF multiply and are eventually converted into proteins. A focal immunoreaction causes the Schwann cells and oligodendrocytes to malfunction, which leads to the destruction of the myelin sheaths around the nerve fibers.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

In Western diets, dairy and beef are ubiquitous: Milk goes with coffee, melted cheese with pizza, and chili with rice. But what if dairy products and beef contained a new kind of pathogen that could infect you as a child and trigger cancer or multiple sclerosis (MS) 40-70 years later?

Researchers from the German Cancer Research Center (DKFZ) suspect that such zoonoses are possibly widespread and are therefore recommending that infants not be given dairy products until they are at least age 1 year. However, in two joint statements, the German Federal Institute for Risk Assessment (BfR) and the Max Rubner Institute (MRI) have rejected such theories.

In 2008, Harald zur Hausen, MD, DSc, received the Nobel Prize in Medicine for his discovery that human papillomaviruses cause cervical cancer. His starting point was the observation that sexually abstinent women, such as nuns, rarely develop this cancer. So it was possible to draw the conclusion that pathogens are transmitted during sexual intercourse, explain Dr. zur Hausen and his wife Ethel-Michele de Villiers, PhD, both of DKFZ Heidelberg.

Papillomaviruses, as well as human herpes and Epstein-Barr viruses (EBV), polyomaviruses, and retroviruses, cause cancer in a direct way: by inserting their genes into the DNA of human cells. With a latency of a few years to a few decades, the proteins formed through expression stimulate malignant growth by altering the regulating host gene.
 

Acid radicals

However, viruses – just like bacteria and parasites – can also indirectly trigger cancer. One mechanism for this triggering is the disruption of immune defenses, as shown by the sometimes drastically increased tumor incidence with AIDS or with immunosuppressants after transplants. Chronic inflammation is a second mechanism that generates acid radicals and thereby causes random mutations in replicating cells. Examples include stomach cancer caused by Helicobacter pylori and liver cancer caused by Schistosoma, liver fluke, and hepatitis B and C viruses.

According to Dr. de Villiers and Dr. zur Hausen, there are good reasons to believe that other pathogens could cause chronic inflammation and thereby lead to cancer. Epidemiologic data suggest that dairy and meat products from European cows (Bos taurus) are a potential source. This is because colon cancer and breast cancer commonly occur in places where these foods are heavily consumed (that is, in North America, Argentina, Europe, and Australia). In contrast, the rate is low in India, where cows are revered as holy animals. Also noteworthy is that women with a lactose intolerance rarely develop breast cancer.
 

Viral progeny

In fact, the researchers found single-stranded DNA rings that originated in viruses, which they named bovine meat and milk factors (BMMF), in the intestines of patients with colon cancer. They reported, “This new class of pathogen deserves, in our opinion at least, to become the focus of cancer development and further chronic diseases.” They also detected elevated levels of acid radicals in these areas (that is, oxidative stress), which is typical for chronic inflammation.

The researchers assume that infants, whose immune system is not yet fully matured, ingest the BMMF as soon as they have dairy. Therefore, there is no need for adults to avoid dairy or beef because everyone is infected anyway, said Dr. zur Hausen.
 

 

 

‘Breast milk is healthy’

Dr. De Villiers and Dr. zur Hausen outlined more evidence of cancer-triggering pathogens. Mothers who have breastfed are less likely, especially after multiple pregnancies, to develop tumors in various organs or to have MS and type 2 diabetes. The authors attribute the protective effect to oligosaccharides in breast milk, which begin to be formed midway through the pregnancy. They bind to lectin receptors and, in so doing, mask the terminal molecule onto which the viruses need to dock. As a result, their port of entry into the cells is blocked.

The oligosaccharides also protect the baby against life-threatening infections by blocking access by rotaviruses and noroviruses. In this way, especially if breastfeeding lasts a long time – around 1 year – the period of incomplete immunocompetence is bridged.
 

Colon cancer

To date, it has been assumed that around 20% of all cancerous diseases globally are caused by infections, said the researchers. But if the suspected BMMF cases are included, this figure rises to 50%, even to around 80%, for colon cancer. If the suspicion is confirmed, the consequences for prevention and therapy would be significant.

The voice of a Nobel prize winner undoubtedly carries weight, but at the time, Dr. zur Hausen still had to convince a host of skeptics with his discovery that a viral infection is a major cause of cervical cancer. Nonetheless, some indicators suggest that he and his wife have found a dead end this time.
 

Institutional skepticism

When his working group made the results public in February 2019, the DKFZ felt the need to give an all-clear signal in response to alarmed press reports. There is no reason to see dairy and meat consumption as something negative. Similarly, in their first joint statement, the BfR and the MRI judged the data to be insufficient and called for further studies. Multiple research teams began to focus on BMMF as a result. In what foods can they be found? Are they more common in patients with cancer than in healthy people? Are they infectious? Do they cause inflammation and cancer?

The findings presented in a second statement by the BfR and MRI at the end of November 2022 contradicted the claims made by the DKFZ scientists across the board. In no way do BMMF represent new pathogens. They are variants of already known DNA sequences. In addition, they are present in numerous animal-based and plant-based foods, including pork, fish, fruit, vegetables, and nuts.

BMMF do not possess the ability to infect human cells, the institutes said. The proof that they are damaging to one’s health was also absent. It is true that the incidence of intestinal tumors correlates positively with the consumption of red and processed meat – which in no way signifies causality – but dairy products are linked to a reduced risk. On the other hand, breast cancer cannot be associated with the consumption of beef or dairy.

Therefore, both institutes recommend continuing to use these products as supplementary diet for infants because of their micronutrients. They further stated that the products are safe for people of all ages.
 

 

 

Association with MS?

Unperturbed, Dr. de Villiers and Dr. zur Hausen went one step further in their current article. They posited that MS is also associated with the consumption of dairy products and beef. Here too geographic distribution prompted the idea to look for BMMF in the brain lesions of patients with MS. The researchers isolated ring-shaped DNA molecules that proved to be closely related to BMMF from dairy and cattle blood. “The result was electrifying for us.”

However, there are several other factors to consider, such as vitamin D3 deficiency. This is because the incidence of MS decreases the further you travel from the poles toward the equator (that is, as solar radiation increases). Also, EBV clearly plays a role because patients with MS display increased titers of EBV antibodies. One study also showed that people in Antarctica excreted reactivated EBV in their saliva during winter and that vitamin D3 stopped the viral secretion.

Under these conditions, the researchers hypothesized that MS is caused by a double infection of brain cells by EBV and BMMF. EBV is reactivated by a lack of vitamin D3, and the BMMF multiply and are eventually converted into proteins. A focal immunoreaction causes the Schwann cells and oligodendrocytes to malfunction, which leads to the destruction of the myelin sheaths around the nerve fibers.

This article was translated from the Medscape German Edition. A version appeared on Medscape.com.

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FDA strengthens mammography regulations: Final rule

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Changed
Mon, 03/20/2023 - 11:17

The Food and Drug Administration has made changes to existing mammography regulations.

A final rule, updating the regulations issued under the Mammography Quality Standards Act of 1992, requires that mammography facilities notify patients about the density of their breasts, strengthens the FDA’s oversight of facilities, and provides guidance to help physicians better categorize and assess mammograms, according to a March 9 press release.

The rule requires implementation of the changes within 18 months.

According to the final rule document, the updates are “intended to improve the delivery of mammography services” in ways that reflect changes in mammography technology, quality standards, and the way results are categorized, reported, and communicated to patients and providers.

For instance, mammography reports must include an assessment of breast density to provide greater detail on the potential limitations of the mammogram results and allow patients and physicians to make more informed decisions, such as the possibility of additional imaging for women with dense breast tissue.

“Today’s action represents the agency’s broader commitment to support innovation to prevent, detect and treat cancer,” said Hilary Marston, MD, MPH, FDA’s chief medical officer, in the agency’s press release. The FDA remains “committed to advancing efforts to improve the health of women and strengthen the fight against breast cancer.”

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

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The Food and Drug Administration has made changes to existing mammography regulations.

A final rule, updating the regulations issued under the Mammography Quality Standards Act of 1992, requires that mammography facilities notify patients about the density of their breasts, strengthens the FDA’s oversight of facilities, and provides guidance to help physicians better categorize and assess mammograms, according to a March 9 press release.

The rule requires implementation of the changes within 18 months.

According to the final rule document, the updates are “intended to improve the delivery of mammography services” in ways that reflect changes in mammography technology, quality standards, and the way results are categorized, reported, and communicated to patients and providers.

For instance, mammography reports must include an assessment of breast density to provide greater detail on the potential limitations of the mammogram results and allow patients and physicians to make more informed decisions, such as the possibility of additional imaging for women with dense breast tissue.

“Today’s action represents the agency’s broader commitment to support innovation to prevent, detect and treat cancer,” said Hilary Marston, MD, MPH, FDA’s chief medical officer, in the agency’s press release. The FDA remains “committed to advancing efforts to improve the health of women and strengthen the fight against breast cancer.”

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

The Food and Drug Administration has made changes to existing mammography regulations.

A final rule, updating the regulations issued under the Mammography Quality Standards Act of 1992, requires that mammography facilities notify patients about the density of their breasts, strengthens the FDA’s oversight of facilities, and provides guidance to help physicians better categorize and assess mammograms, according to a March 9 press release.

The rule requires implementation of the changes within 18 months.

According to the final rule document, the updates are “intended to improve the delivery of mammography services” in ways that reflect changes in mammography technology, quality standards, and the way results are categorized, reported, and communicated to patients and providers.

For instance, mammography reports must include an assessment of breast density to provide greater detail on the potential limitations of the mammogram results and allow patients and physicians to make more informed decisions, such as the possibility of additional imaging for women with dense breast tissue.

“Today’s action represents the agency’s broader commitment to support innovation to prevent, detect and treat cancer,” said Hilary Marston, MD, MPH, FDA’s chief medical officer, in the agency’s press release. The FDA remains “committed to advancing efforts to improve the health of women and strengthen the fight against breast cancer.”

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

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Breast cancer surgery timing matters, but is faster always better?

Article Type
Changed
Wed, 03/08/2023 - 12:11

Most women with breast cancer undergo primary surgery within 8 weeks of diagnosis and any later may be associated with worse overall survival, according to findings from a case series.

With no national quality metrics delineating optimal breast cancer surgery timing, the researchers recommend surgery before 8 weeks from breast cancer diagnosis.

“This time interval does not appear to have a detrimental association with cancer outcomes and allows for multidisciplinary care,” the researchers, led by Alyssa A. Wiener, MD, from University of Wisconsin–Madison, said.

But, in an accompanying editorial, two surgical oncologists questioned whether faster surgery is always better.

“Efficiency might associate with quality, but doesn’t always ensure it,” Rita Mukhtar, MD, and Laura Esserman, MD, with the division of surgical oncology, University of California, San Francisco, said.

The study and editorial were published online in JAMA Surgery.


 

Optimal timing for surgery?

Some studies have found worse survival outcomes for women who experience delays between breast cancer diagnosis and surgical treatment, but the optimal window for surgery and the point at which surgery becomes less advantageous remain unknown.

Using the National Cancer Database, Dr. Wiener and colleagues identified 373,334 women (median age, 61) who were diagnosed with stage I to stage III ductal or lobular breast cancer from 2010 to 2014 and followed up through 2019.

All women underwent surgery as their first course of treatment. Patients with prior breast cancer, those who had neoadjuvant or experimental therapy or missing receptor information, and those who were diagnosed with breast cancer on the date of their primary surgery were excluded.

Most patients had timely surgery. The median time to surgery was 30 days, and 88% of patients underwent surgery before the 57-day time point.

Only 12% of patients had surgery more than 8 weeks after their diagnosis. Factors associated with longer times to surgery included age younger than 45, having Medicaid or no insurance, and lower household income.

The overall 5-year survival for the cohort was high at 90%. On multivariable analysis, the researchers found no statistically significant association between time to surgery and overall survival when surgery was performed between 0 and 8 weeks.

However, women who had surgery 9 or more weeks after diagnosis had a significantly higher rate of death within 5 years, compared with those who had surgery performed between 0 and 4 weeks (hazard ratio, 1.15; P < .001). Performing surgery up to 9 weeks (57-63 days) post diagnosis also did not appear to be negatively associated with survival.

This study “highlights that time to treatment of breast cancer is important,” said Sarah P. Cate, MD, director, Breast Surgery Quality Program, Mount Sinai Health System, New York, who wasn’t involved in the study. “Surgery is only one-third of the treatment of breast cancer, so these patients who had longer delays to the OR may have also not started their postsurgery treatments in time.”

In addition, the study found that socioeconomic status – Medicaid or uninsured status and lower household incomes – was associated with longer times to surgery.

“Socioeconomic factors like these may be independently associated with worse outcomes and may contribute to some of the disparities in cancer outcomes observed for resource-limited patients due to delayed care,” the authors said.

Identifying 8 weeks as a goal for time to surgery can help uncover delays associated with socioeconomic factors and provide adequate time for decision-making, the researchers noted.
 

 

 

Is faster always better?

Dr. Wiener and colleagues cautioned, however, that their findings should be considered “hypothesis generating,” given that decision-making surrounding breast cancer surgery is complex.

Importantly, the authors noted, tumor characteristics, such as tumor size, nodal status, and receptor subtype, appeared to have a pronounced impact on overall survival, compared with timing of surgery. For instance, compared with a tumor size of 2 cm or fewer, larger tumors – those > 2 cm to ≤ 5 cm and > 5 cm – were associated with worse survival (HR, 1.80 and 2.62, respectively).

“This highlights that tumor biology is the primary driver of patients’ breast cancer outcomes,” the authors noted.

In an accompanying editorial, two surgical oncologists highlighted that faster may not always be better.

For instance, Dr. Mukhtar and Dr. Esserman explained, if a patient with a large node-positive, triple-negative breast cancer receives surgery within a week of diagnosis, “one must question whether this timely care represents quality care, as the opportunity to understand tumor response and affect breast cancer survival has been lost.”

The editorialists noted that time to surgery might also matter very little for indolent, screen-detected cancers, and time to treatment start might matter a lot for fast-growing, interval cancers.

In addition, they questioned whether including the socioeconomic factors highlighted in the overall model would “mitigate the association between time to surgery and survival seen in this study.”

Overall, “operating too soon could indicate lack of quality, while operating too late perhaps reflects lack of access to care,” the editorialists said.

This study was supported by grants from the National Cancer Institute and the National Institutes of Health. Dr. Wiener and Dr. Cate report no relevant financial relationships. Dr. Esserman is a member of the Blue Cross Medical advisory panel, is a board member of the Quantum Leap Healthcare Collaborative, and leads an investigator-initiated vaccine trial for high-risk ductal carcinoma in situ, which is funded by Merck.

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

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Most women with breast cancer undergo primary surgery within 8 weeks of diagnosis and any later may be associated with worse overall survival, according to findings from a case series.

With no national quality metrics delineating optimal breast cancer surgery timing, the researchers recommend surgery before 8 weeks from breast cancer diagnosis.

“This time interval does not appear to have a detrimental association with cancer outcomes and allows for multidisciplinary care,” the researchers, led by Alyssa A. Wiener, MD, from University of Wisconsin–Madison, said.

But, in an accompanying editorial, two surgical oncologists questioned whether faster surgery is always better.

“Efficiency might associate with quality, but doesn’t always ensure it,” Rita Mukhtar, MD, and Laura Esserman, MD, with the division of surgical oncology, University of California, San Francisco, said.

The study and editorial were published online in JAMA Surgery.


 

Optimal timing for surgery?

Some studies have found worse survival outcomes for women who experience delays between breast cancer diagnosis and surgical treatment, but the optimal window for surgery and the point at which surgery becomes less advantageous remain unknown.

Using the National Cancer Database, Dr. Wiener and colleagues identified 373,334 women (median age, 61) who were diagnosed with stage I to stage III ductal or lobular breast cancer from 2010 to 2014 and followed up through 2019.

All women underwent surgery as their first course of treatment. Patients with prior breast cancer, those who had neoadjuvant or experimental therapy or missing receptor information, and those who were diagnosed with breast cancer on the date of their primary surgery were excluded.

Most patients had timely surgery. The median time to surgery was 30 days, and 88% of patients underwent surgery before the 57-day time point.

Only 12% of patients had surgery more than 8 weeks after their diagnosis. Factors associated with longer times to surgery included age younger than 45, having Medicaid or no insurance, and lower household income.

The overall 5-year survival for the cohort was high at 90%. On multivariable analysis, the researchers found no statistically significant association between time to surgery and overall survival when surgery was performed between 0 and 8 weeks.

However, women who had surgery 9 or more weeks after diagnosis had a significantly higher rate of death within 5 years, compared with those who had surgery performed between 0 and 4 weeks (hazard ratio, 1.15; P < .001). Performing surgery up to 9 weeks (57-63 days) post diagnosis also did not appear to be negatively associated with survival.

This study “highlights that time to treatment of breast cancer is important,” said Sarah P. Cate, MD, director, Breast Surgery Quality Program, Mount Sinai Health System, New York, who wasn’t involved in the study. “Surgery is only one-third of the treatment of breast cancer, so these patients who had longer delays to the OR may have also not started their postsurgery treatments in time.”

In addition, the study found that socioeconomic status – Medicaid or uninsured status and lower household incomes – was associated with longer times to surgery.

“Socioeconomic factors like these may be independently associated with worse outcomes and may contribute to some of the disparities in cancer outcomes observed for resource-limited patients due to delayed care,” the authors said.

Identifying 8 weeks as a goal for time to surgery can help uncover delays associated with socioeconomic factors and provide adequate time for decision-making, the researchers noted.
 

 

 

Is faster always better?

Dr. Wiener and colleagues cautioned, however, that their findings should be considered “hypothesis generating,” given that decision-making surrounding breast cancer surgery is complex.

Importantly, the authors noted, tumor characteristics, such as tumor size, nodal status, and receptor subtype, appeared to have a pronounced impact on overall survival, compared with timing of surgery. For instance, compared with a tumor size of 2 cm or fewer, larger tumors – those > 2 cm to ≤ 5 cm and > 5 cm – were associated with worse survival (HR, 1.80 and 2.62, respectively).

“This highlights that tumor biology is the primary driver of patients’ breast cancer outcomes,” the authors noted.

In an accompanying editorial, two surgical oncologists highlighted that faster may not always be better.

For instance, Dr. Mukhtar and Dr. Esserman explained, if a patient with a large node-positive, triple-negative breast cancer receives surgery within a week of diagnosis, “one must question whether this timely care represents quality care, as the opportunity to understand tumor response and affect breast cancer survival has been lost.”

The editorialists noted that time to surgery might also matter very little for indolent, screen-detected cancers, and time to treatment start might matter a lot for fast-growing, interval cancers.

In addition, they questioned whether including the socioeconomic factors highlighted in the overall model would “mitigate the association between time to surgery and survival seen in this study.”

Overall, “operating too soon could indicate lack of quality, while operating too late perhaps reflects lack of access to care,” the editorialists said.

This study was supported by grants from the National Cancer Institute and the National Institutes of Health. Dr. Wiener and Dr. Cate report no relevant financial relationships. Dr. Esserman is a member of the Blue Cross Medical advisory panel, is a board member of the Quantum Leap Healthcare Collaborative, and leads an investigator-initiated vaccine trial for high-risk ductal carcinoma in situ, which is funded by Merck.

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

Most women with breast cancer undergo primary surgery within 8 weeks of diagnosis and any later may be associated with worse overall survival, according to findings from a case series.

With no national quality metrics delineating optimal breast cancer surgery timing, the researchers recommend surgery before 8 weeks from breast cancer diagnosis.

“This time interval does not appear to have a detrimental association with cancer outcomes and allows for multidisciplinary care,” the researchers, led by Alyssa A. Wiener, MD, from University of Wisconsin–Madison, said.

But, in an accompanying editorial, two surgical oncologists questioned whether faster surgery is always better.

“Efficiency might associate with quality, but doesn’t always ensure it,” Rita Mukhtar, MD, and Laura Esserman, MD, with the division of surgical oncology, University of California, San Francisco, said.

The study and editorial were published online in JAMA Surgery.


 

Optimal timing for surgery?

Some studies have found worse survival outcomes for women who experience delays between breast cancer diagnosis and surgical treatment, but the optimal window for surgery and the point at which surgery becomes less advantageous remain unknown.

Using the National Cancer Database, Dr. Wiener and colleagues identified 373,334 women (median age, 61) who were diagnosed with stage I to stage III ductal or lobular breast cancer from 2010 to 2014 and followed up through 2019.

All women underwent surgery as their first course of treatment. Patients with prior breast cancer, those who had neoadjuvant or experimental therapy or missing receptor information, and those who were diagnosed with breast cancer on the date of their primary surgery were excluded.

Most patients had timely surgery. The median time to surgery was 30 days, and 88% of patients underwent surgery before the 57-day time point.

Only 12% of patients had surgery more than 8 weeks after their diagnosis. Factors associated with longer times to surgery included age younger than 45, having Medicaid or no insurance, and lower household income.

The overall 5-year survival for the cohort was high at 90%. On multivariable analysis, the researchers found no statistically significant association between time to surgery and overall survival when surgery was performed between 0 and 8 weeks.

However, women who had surgery 9 or more weeks after diagnosis had a significantly higher rate of death within 5 years, compared with those who had surgery performed between 0 and 4 weeks (hazard ratio, 1.15; P < .001). Performing surgery up to 9 weeks (57-63 days) post diagnosis also did not appear to be negatively associated with survival.

This study “highlights that time to treatment of breast cancer is important,” said Sarah P. Cate, MD, director, Breast Surgery Quality Program, Mount Sinai Health System, New York, who wasn’t involved in the study. “Surgery is only one-third of the treatment of breast cancer, so these patients who had longer delays to the OR may have also not started their postsurgery treatments in time.”

In addition, the study found that socioeconomic status – Medicaid or uninsured status and lower household incomes – was associated with longer times to surgery.

“Socioeconomic factors like these may be independently associated with worse outcomes and may contribute to some of the disparities in cancer outcomes observed for resource-limited patients due to delayed care,” the authors said.

Identifying 8 weeks as a goal for time to surgery can help uncover delays associated with socioeconomic factors and provide adequate time for decision-making, the researchers noted.
 

 

 

Is faster always better?

Dr. Wiener and colleagues cautioned, however, that their findings should be considered “hypothesis generating,” given that decision-making surrounding breast cancer surgery is complex.

Importantly, the authors noted, tumor characteristics, such as tumor size, nodal status, and receptor subtype, appeared to have a pronounced impact on overall survival, compared with timing of surgery. For instance, compared with a tumor size of 2 cm or fewer, larger tumors – those > 2 cm to ≤ 5 cm and > 5 cm – were associated with worse survival (HR, 1.80 and 2.62, respectively).

“This highlights that tumor biology is the primary driver of patients’ breast cancer outcomes,” the authors noted.

In an accompanying editorial, two surgical oncologists highlighted that faster may not always be better.

For instance, Dr. Mukhtar and Dr. Esserman explained, if a patient with a large node-positive, triple-negative breast cancer receives surgery within a week of diagnosis, “one must question whether this timely care represents quality care, as the opportunity to understand tumor response and affect breast cancer survival has been lost.”

The editorialists noted that time to surgery might also matter very little for indolent, screen-detected cancers, and time to treatment start might matter a lot for fast-growing, interval cancers.

In addition, they questioned whether including the socioeconomic factors highlighted in the overall model would “mitigate the association between time to surgery and survival seen in this study.”

Overall, “operating too soon could indicate lack of quality, while operating too late perhaps reflects lack of access to care,” the editorialists said.

This study was supported by grants from the National Cancer Institute and the National Institutes of Health. Dr. Wiener and Dr. Cate report no relevant financial relationships. Dr. Esserman is a member of the Blue Cross Medical advisory panel, is a board member of the Quantum Leap Healthcare Collaborative, and leads an investigator-initiated vaccine trial for high-risk ductal carcinoma in situ, which is funded by Merck.

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

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HER2-low breast cancer is not a separate clinical entity: Study

Article Type
Changed
Tue, 03/07/2023 - 17:06

Much attention has been focused recently on the idea that breast cancer with a low expression of HER2 can be treated with HER2-targeted agents. Not surprisingly, manufacturers of these drugs have pounced on this idea, as it opens up a whole new patient population: previously these drugs were only for tumors with a high HER2 expression.

There is a large potential market at stake: HER2-low (also referred to as ERBB2-low), as defined by a score of 0 to 3+ on immunohistochemistry (IHC), is seen in approximately 50%-60% of all breast cancers

However, there is still much debate over whether low-HER2 breast cancer is, in fact, a separate clinical entity.

A new large-scale analysis concludes that it is not.
The authors argued that it actually it represents a series of biological differences from HER2-negative disease that do not have a strong bearing on outcomes.

The analysis was published online in JAMA Oncology.

For the study, researchers from the University of Chicago examined data on more than 1.1 million breast cancer patients recorded as HER2-negative in the U.S. National Cancer Database, and re-classified almost two thirds as HER2-low on further analysis.

They found that HER2-low status was associated with higher estrogen receptor (ER) expression, as well as a lower rate of pathologic complete response, compared with HER2-negative disease. It was also linked to an improvement in overall survival on multivariate analysis of up to 9% in advance stage triple negative tumors.

“However, the clinical significance of these differences is questionable,” the researchers commented.

HER2-low status alone “should not influence neoadjuvant treatment decisions with currently approved regimens,” they added.

These results “do not support classification of HER2-low breast cancer as a distinct clinical subtype,” the team concluded.

Not necessarily, according to Giuseppe Curigliano, MD, PhD, director of the new drugs and early drug development for innovative therapies division at the European Institute of Oncology, Milan. He argued the opposite case, that HER2-low is a separate clinical entity, in a recent debate on the topic held at the 2022 San Antonio Breast Cancer Symposium.

In a comment, Dr. Curigliano said that a “major strength” of the current study is its large patient cohort, which reflects the majority of cancer diagnoses in the United States, but that it nevertheless has “important limitations that should be considered when interpreting the results.”

The inclusion of only overall survival in the dataset limits the ability to make associations between HER2-low status and cancer-specific prognosis, as “survival may lag years behind recurrence.”

The lack of centralized assessment of IHC results is also an issue, as “some of the results may be associated with regional variation in practice of classifying cases as HER2 0 versus HER2 1+.”

“In my opinion, this is a great limitation,” he said, in being able to conclude that there is “no prognostic difference between ERBB2-low and -negative patients.”

He also noted that, from a molecular point of view, “the key determinant of the gene expression profile is the expression of hormone receptors, [and] if we perform a correction for hormone receptor expression, only marginal differences in gene expression are found” between HER2-low and HER2-negative tumors.

“Similarly, large genomic studies have identified no specific and consistent difference in genomic profiles,” Dr. Curigliano said, and so, HER2-low disease, “as currently defined, should not be considered a distinct molecular entity, but rather a heterogeneous group of tumors, with biology primarily driven by hormone receptor expression.”
 

 

 

Analysis quoted by both sides

Senior author of the new analysis, Frederick M. Howard, MD, from the section of hematology-oncology in the department of medicine at the University of Chicago, said that his team’s work was quoted by both sides of the debate at SABCS 2022.

This reflects the fact that, while differences between ERBB2-low and -negative are present, it is “questionable how clinically significant those differences are,” he said in an interview. It’s a matter of “the eye of the beholder.”

Dr. Howard does not think that clinicians are going to modify standard treatment regimens based solely on HER2-low status, and that low expression of the protein “is probably just a reflection of some underlying biologic processes.”

Dr. Howard agreed with Dr. Curigliano that a “caveat” of their study is that the IHC analyses were performed locally, especially as it has shown that there can be discordance between pathologists in around 40% of cases, and that the associations they found might therefore be “strengthened” by more precise quantification of HER2 expression.

“But, even then,” Dr. Howard continued, “I doubt that [ERBB2-low status] is going to be that strong a prognostic factor.”

He believes that advances in analytic techniques will, in the future, allow tumors to be characterized more precisely, and it may be that HER2-low tumors end up being called something else in 5 years.
 

Renewed interest in this subgroup

In their paper, Dr. Howard and colleagues pointed out that, as a group, HER2-low tumors are heterogeneous, with HER2-low found in both hormone receptor–positive and triple-negative breast cancers. Also, various studies have come to different conclusions about what HER2 low means prognostically, with conclusions ranging from negative to neutral and to positive prognoses.

However, new research has shown that patients with HER2-low tumors can benefit from HER2-targeted drugs. In particular, the recent report that the antibody-drug conjugate trastuzumab deruxtecan doubled progression-free survival versus chemotherapy in ERBB2-low tumors led to “renewed interest in the subgroup,” the researchers noted.

To examine this subgroup further, they embarked on their analysis. Examining the National Cancer Database, they gathered information on more than 1.1 million U.S. patients diagnosed with HER2-negative invasive breast cancer in the 10-year period 2010-2019, and for whom IHC results were available.

The patients were reclassified as having HER2-low disease if they had an IHC score of 1+, or 2+ with a negative in situ hybridization test, while those with an IHC score of 0 were deemed to be HER2-negative. They were followed up until Nov. 30, 2022.

These patients had a mean age of 62.4 years, and 99.1% were female. The majority (78.6%) were non-Hispanic white. HER2-low was identified in 65.5% of the cohort, while 34.5% were HER2-negative.

The proportion of HER2-low disease was lower in non-Hispanic black (62.8%) and Hispanic (61%) patients than in non-Hispanic White patients, at 66.1%.

HER2-low disease was also more common in hormone receptor–positive than triple-negative tumors, at just 51.5%, rising to 58.6% for progesterone receptor–positive, ER-negative, and 69.1% for PR-positive, ER-positive tumors.

Multivariate logistic regression analysis taking into account age, sex, race and ethnicity, comorbidity score, and treatment facility type, among other factors, revealed that the likelihood of HER2-low disease was significantly with increased ER expression, at an adjusted odds ratio of 1.15 for each 10% increase (P < .001).

Non-Hispanic Black, Asian, and Pacific Islander patients had similar rates of HER2-low disease as non-Hispanic White patients after adjustment, whereas Native American patients had an increased rate, at an aOR of 1.22 (P < .001), and Hispanic patients had a lower rate, at an aOR of 0.85 (P < .001).

HER2-low status was associated with a slightly reduced likelihood of having a pathologic complete response (aOR, 0.89; P < .001), with similar results when restricting the analysis to patients with triple negative or hormone receptor-positive tumors.

After a median follow-up of 54 months, HER2-low disease was associated with a minor improvement in survival on multivariate analysis, at an adjusted hazard ratio for death of 0.98 (P < .001).

The greatest improvement in survival was seen in patients with stage III and IV triple-negative breast cancer, at HRs of 0.92 and 0.91, respectively, although the researchers noted that this represented only a 2% and 0.4% improvement in 5-year overall survival, respectively.

The study was supported by the Breast Cancer Research Foundation, the American Society of Clinical Oncology/Conquer Cancer Foundation, the Department of Defense, the National Institutes of Health/National Cancer Institute, Susan G. Komen, the Breast Cancer Research Foundation, and the University of Chicago Elwood V. Jensen Scholars Program. Dr. Howard reported no relevant financial relationships. Dr. Curigliano has relationships with Pfizer, Novartis, Lilly, Roche, Seattle Genetics, Celltrion, Veracyte, Daiichi Sankyo, AstraZeneca, Merck, Seagen, Exact Sciences, Gilead, Bristol-Myers Squibb, Scientific Affairs Group, and Ellipsis.

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

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Much attention has been focused recently on the idea that breast cancer with a low expression of HER2 can be treated with HER2-targeted agents. Not surprisingly, manufacturers of these drugs have pounced on this idea, as it opens up a whole new patient population: previously these drugs were only for tumors with a high HER2 expression.

There is a large potential market at stake: HER2-low (also referred to as ERBB2-low), as defined by a score of 0 to 3+ on immunohistochemistry (IHC), is seen in approximately 50%-60% of all breast cancers

However, there is still much debate over whether low-HER2 breast cancer is, in fact, a separate clinical entity.

A new large-scale analysis concludes that it is not.
The authors argued that it actually it represents a series of biological differences from HER2-negative disease that do not have a strong bearing on outcomes.

The analysis was published online in JAMA Oncology.

For the study, researchers from the University of Chicago examined data on more than 1.1 million breast cancer patients recorded as HER2-negative in the U.S. National Cancer Database, and re-classified almost two thirds as HER2-low on further analysis.

They found that HER2-low status was associated with higher estrogen receptor (ER) expression, as well as a lower rate of pathologic complete response, compared with HER2-negative disease. It was also linked to an improvement in overall survival on multivariate analysis of up to 9% in advance stage triple negative tumors.

“However, the clinical significance of these differences is questionable,” the researchers commented.

HER2-low status alone “should not influence neoadjuvant treatment decisions with currently approved regimens,” they added.

These results “do not support classification of HER2-low breast cancer as a distinct clinical subtype,” the team concluded.

Not necessarily, according to Giuseppe Curigliano, MD, PhD, director of the new drugs and early drug development for innovative therapies division at the European Institute of Oncology, Milan. He argued the opposite case, that HER2-low is a separate clinical entity, in a recent debate on the topic held at the 2022 San Antonio Breast Cancer Symposium.

In a comment, Dr. Curigliano said that a “major strength” of the current study is its large patient cohort, which reflects the majority of cancer diagnoses in the United States, but that it nevertheless has “important limitations that should be considered when interpreting the results.”

The inclusion of only overall survival in the dataset limits the ability to make associations between HER2-low status and cancer-specific prognosis, as “survival may lag years behind recurrence.”

The lack of centralized assessment of IHC results is also an issue, as “some of the results may be associated with regional variation in practice of classifying cases as HER2 0 versus HER2 1+.”

“In my opinion, this is a great limitation,” he said, in being able to conclude that there is “no prognostic difference between ERBB2-low and -negative patients.”

He also noted that, from a molecular point of view, “the key determinant of the gene expression profile is the expression of hormone receptors, [and] if we perform a correction for hormone receptor expression, only marginal differences in gene expression are found” between HER2-low and HER2-negative tumors.

“Similarly, large genomic studies have identified no specific and consistent difference in genomic profiles,” Dr. Curigliano said, and so, HER2-low disease, “as currently defined, should not be considered a distinct molecular entity, but rather a heterogeneous group of tumors, with biology primarily driven by hormone receptor expression.”
 

 

 

Analysis quoted by both sides

Senior author of the new analysis, Frederick M. Howard, MD, from the section of hematology-oncology in the department of medicine at the University of Chicago, said that his team’s work was quoted by both sides of the debate at SABCS 2022.

This reflects the fact that, while differences between ERBB2-low and -negative are present, it is “questionable how clinically significant those differences are,” he said in an interview. It’s a matter of “the eye of the beholder.”

Dr. Howard does not think that clinicians are going to modify standard treatment regimens based solely on HER2-low status, and that low expression of the protein “is probably just a reflection of some underlying biologic processes.”

Dr. Howard agreed with Dr. Curigliano that a “caveat” of their study is that the IHC analyses were performed locally, especially as it has shown that there can be discordance between pathologists in around 40% of cases, and that the associations they found might therefore be “strengthened” by more precise quantification of HER2 expression.

“But, even then,” Dr. Howard continued, “I doubt that [ERBB2-low status] is going to be that strong a prognostic factor.”

He believes that advances in analytic techniques will, in the future, allow tumors to be characterized more precisely, and it may be that HER2-low tumors end up being called something else in 5 years.
 

Renewed interest in this subgroup

In their paper, Dr. Howard and colleagues pointed out that, as a group, HER2-low tumors are heterogeneous, with HER2-low found in both hormone receptor–positive and triple-negative breast cancers. Also, various studies have come to different conclusions about what HER2 low means prognostically, with conclusions ranging from negative to neutral and to positive prognoses.

However, new research has shown that patients with HER2-low tumors can benefit from HER2-targeted drugs. In particular, the recent report that the antibody-drug conjugate trastuzumab deruxtecan doubled progression-free survival versus chemotherapy in ERBB2-low tumors led to “renewed interest in the subgroup,” the researchers noted.

To examine this subgroup further, they embarked on their analysis. Examining the National Cancer Database, they gathered information on more than 1.1 million U.S. patients diagnosed with HER2-negative invasive breast cancer in the 10-year period 2010-2019, and for whom IHC results were available.

The patients were reclassified as having HER2-low disease if they had an IHC score of 1+, or 2+ with a negative in situ hybridization test, while those with an IHC score of 0 were deemed to be HER2-negative. They were followed up until Nov. 30, 2022.

These patients had a mean age of 62.4 years, and 99.1% were female. The majority (78.6%) were non-Hispanic white. HER2-low was identified in 65.5% of the cohort, while 34.5% were HER2-negative.

The proportion of HER2-low disease was lower in non-Hispanic black (62.8%) and Hispanic (61%) patients than in non-Hispanic White patients, at 66.1%.

HER2-low disease was also more common in hormone receptor–positive than triple-negative tumors, at just 51.5%, rising to 58.6% for progesterone receptor–positive, ER-negative, and 69.1% for PR-positive, ER-positive tumors.

Multivariate logistic regression analysis taking into account age, sex, race and ethnicity, comorbidity score, and treatment facility type, among other factors, revealed that the likelihood of HER2-low disease was significantly with increased ER expression, at an adjusted odds ratio of 1.15 for each 10% increase (P < .001).

Non-Hispanic Black, Asian, and Pacific Islander patients had similar rates of HER2-low disease as non-Hispanic White patients after adjustment, whereas Native American patients had an increased rate, at an aOR of 1.22 (P < .001), and Hispanic patients had a lower rate, at an aOR of 0.85 (P < .001).

HER2-low status was associated with a slightly reduced likelihood of having a pathologic complete response (aOR, 0.89; P < .001), with similar results when restricting the analysis to patients with triple negative or hormone receptor-positive tumors.

After a median follow-up of 54 months, HER2-low disease was associated with a minor improvement in survival on multivariate analysis, at an adjusted hazard ratio for death of 0.98 (P < .001).

The greatest improvement in survival was seen in patients with stage III and IV triple-negative breast cancer, at HRs of 0.92 and 0.91, respectively, although the researchers noted that this represented only a 2% and 0.4% improvement in 5-year overall survival, respectively.

The study was supported by the Breast Cancer Research Foundation, the American Society of Clinical Oncology/Conquer Cancer Foundation, the Department of Defense, the National Institutes of Health/National Cancer Institute, Susan G. Komen, the Breast Cancer Research Foundation, and the University of Chicago Elwood V. Jensen Scholars Program. Dr. Howard reported no relevant financial relationships. Dr. Curigliano has relationships with Pfizer, Novartis, Lilly, Roche, Seattle Genetics, Celltrion, Veracyte, Daiichi Sankyo, AstraZeneca, Merck, Seagen, Exact Sciences, Gilead, Bristol-Myers Squibb, Scientific Affairs Group, and Ellipsis.

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

Much attention has been focused recently on the idea that breast cancer with a low expression of HER2 can be treated with HER2-targeted agents. Not surprisingly, manufacturers of these drugs have pounced on this idea, as it opens up a whole new patient population: previously these drugs were only for tumors with a high HER2 expression.

There is a large potential market at stake: HER2-low (also referred to as ERBB2-low), as defined by a score of 0 to 3+ on immunohistochemistry (IHC), is seen in approximately 50%-60% of all breast cancers

However, there is still much debate over whether low-HER2 breast cancer is, in fact, a separate clinical entity.

A new large-scale analysis concludes that it is not.
The authors argued that it actually it represents a series of biological differences from HER2-negative disease that do not have a strong bearing on outcomes.

The analysis was published online in JAMA Oncology.

For the study, researchers from the University of Chicago examined data on more than 1.1 million breast cancer patients recorded as HER2-negative in the U.S. National Cancer Database, and re-classified almost two thirds as HER2-low on further analysis.

They found that HER2-low status was associated with higher estrogen receptor (ER) expression, as well as a lower rate of pathologic complete response, compared with HER2-negative disease. It was also linked to an improvement in overall survival on multivariate analysis of up to 9% in advance stage triple negative tumors.

“However, the clinical significance of these differences is questionable,” the researchers commented.

HER2-low status alone “should not influence neoadjuvant treatment decisions with currently approved regimens,” they added.

These results “do not support classification of HER2-low breast cancer as a distinct clinical subtype,” the team concluded.

Not necessarily, according to Giuseppe Curigliano, MD, PhD, director of the new drugs and early drug development for innovative therapies division at the European Institute of Oncology, Milan. He argued the opposite case, that HER2-low is a separate clinical entity, in a recent debate on the topic held at the 2022 San Antonio Breast Cancer Symposium.

In a comment, Dr. Curigliano said that a “major strength” of the current study is its large patient cohort, which reflects the majority of cancer diagnoses in the United States, but that it nevertheless has “important limitations that should be considered when interpreting the results.”

The inclusion of only overall survival in the dataset limits the ability to make associations between HER2-low status and cancer-specific prognosis, as “survival may lag years behind recurrence.”

The lack of centralized assessment of IHC results is also an issue, as “some of the results may be associated with regional variation in practice of classifying cases as HER2 0 versus HER2 1+.”

“In my opinion, this is a great limitation,” he said, in being able to conclude that there is “no prognostic difference between ERBB2-low and -negative patients.”

He also noted that, from a molecular point of view, “the key determinant of the gene expression profile is the expression of hormone receptors, [and] if we perform a correction for hormone receptor expression, only marginal differences in gene expression are found” between HER2-low and HER2-negative tumors.

“Similarly, large genomic studies have identified no specific and consistent difference in genomic profiles,” Dr. Curigliano said, and so, HER2-low disease, “as currently defined, should not be considered a distinct molecular entity, but rather a heterogeneous group of tumors, with biology primarily driven by hormone receptor expression.”
 

 

 

Analysis quoted by both sides

Senior author of the new analysis, Frederick M. Howard, MD, from the section of hematology-oncology in the department of medicine at the University of Chicago, said that his team’s work was quoted by both sides of the debate at SABCS 2022.

This reflects the fact that, while differences between ERBB2-low and -negative are present, it is “questionable how clinically significant those differences are,” he said in an interview. It’s a matter of “the eye of the beholder.”

Dr. Howard does not think that clinicians are going to modify standard treatment regimens based solely on HER2-low status, and that low expression of the protein “is probably just a reflection of some underlying biologic processes.”

Dr. Howard agreed with Dr. Curigliano that a “caveat” of their study is that the IHC analyses were performed locally, especially as it has shown that there can be discordance between pathologists in around 40% of cases, and that the associations they found might therefore be “strengthened” by more precise quantification of HER2 expression.

“But, even then,” Dr. Howard continued, “I doubt that [ERBB2-low status] is going to be that strong a prognostic factor.”

He believes that advances in analytic techniques will, in the future, allow tumors to be characterized more precisely, and it may be that HER2-low tumors end up being called something else in 5 years.
 

Renewed interest in this subgroup

In their paper, Dr. Howard and colleagues pointed out that, as a group, HER2-low tumors are heterogeneous, with HER2-low found in both hormone receptor–positive and triple-negative breast cancers. Also, various studies have come to different conclusions about what HER2 low means prognostically, with conclusions ranging from negative to neutral and to positive prognoses.

However, new research has shown that patients with HER2-low tumors can benefit from HER2-targeted drugs. In particular, the recent report that the antibody-drug conjugate trastuzumab deruxtecan doubled progression-free survival versus chemotherapy in ERBB2-low tumors led to “renewed interest in the subgroup,” the researchers noted.

To examine this subgroup further, they embarked on their analysis. Examining the National Cancer Database, they gathered information on more than 1.1 million U.S. patients diagnosed with HER2-negative invasive breast cancer in the 10-year period 2010-2019, and for whom IHC results were available.

The patients were reclassified as having HER2-low disease if they had an IHC score of 1+, or 2+ with a negative in situ hybridization test, while those with an IHC score of 0 were deemed to be HER2-negative. They were followed up until Nov. 30, 2022.

These patients had a mean age of 62.4 years, and 99.1% were female. The majority (78.6%) were non-Hispanic white. HER2-low was identified in 65.5% of the cohort, while 34.5% were HER2-negative.

The proportion of HER2-low disease was lower in non-Hispanic black (62.8%) and Hispanic (61%) patients than in non-Hispanic White patients, at 66.1%.

HER2-low disease was also more common in hormone receptor–positive than triple-negative tumors, at just 51.5%, rising to 58.6% for progesterone receptor–positive, ER-negative, and 69.1% for PR-positive, ER-positive tumors.

Multivariate logistic regression analysis taking into account age, sex, race and ethnicity, comorbidity score, and treatment facility type, among other factors, revealed that the likelihood of HER2-low disease was significantly with increased ER expression, at an adjusted odds ratio of 1.15 for each 10% increase (P < .001).

Non-Hispanic Black, Asian, and Pacific Islander patients had similar rates of HER2-low disease as non-Hispanic White patients after adjustment, whereas Native American patients had an increased rate, at an aOR of 1.22 (P < .001), and Hispanic patients had a lower rate, at an aOR of 0.85 (P < .001).

HER2-low status was associated with a slightly reduced likelihood of having a pathologic complete response (aOR, 0.89; P < .001), with similar results when restricting the analysis to patients with triple negative or hormone receptor-positive tumors.

After a median follow-up of 54 months, HER2-low disease was associated with a minor improvement in survival on multivariate analysis, at an adjusted hazard ratio for death of 0.98 (P < .001).

The greatest improvement in survival was seen in patients with stage III and IV triple-negative breast cancer, at HRs of 0.92 and 0.91, respectively, although the researchers noted that this represented only a 2% and 0.4% improvement in 5-year overall survival, respectively.

The study was supported by the Breast Cancer Research Foundation, the American Society of Clinical Oncology/Conquer Cancer Foundation, the Department of Defense, the National Institutes of Health/National Cancer Institute, Susan G. Komen, the Breast Cancer Research Foundation, and the University of Chicago Elwood V. Jensen Scholars Program. Dr. Howard reported no relevant financial relationships. Dr. Curigliano has relationships with Pfizer, Novartis, Lilly, Roche, Seattle Genetics, Celltrion, Veracyte, Daiichi Sankyo, AstraZeneca, Merck, Seagen, Exact Sciences, Gilead, Bristol-Myers Squibb, Scientific Affairs Group, and Ellipsis.

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

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FDA expands abemaciclib use in high-risk early breast cancer

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The Food and Drug Administration has expanded the indication for adjuvant abemaciclib (Verzenio) in combination with endocrine therapy for patients with hormone receptor–positive, HER2-negative, node-positive early breast cancer who are at high risk for recurrence.

Abemaciclib was previously approved for this group of high-risk patients with the requirement that they have a Ki-67 score of at least 20%. The new expansion removes the Ki-67 testing requirement, meaning more patients are now eligible to receive this drug. High-risk patients eligible for the CDK4/6 inhibitor can now be identified solely on the basis of nodal status, tumor size, and tumor grade.

The FDA’s decision to expand the approval was based on 4-year data from the phase 3 monarchE trial of adjuvant abemaciclib, which showed benefit in invasive disease-free survival beyond the 2-year treatment course.

At 4 years, 85.5% of patients remained recurrence free with abemaciclib plus endocrine therapy, compared with 78.6% who received endocrine therapy alone, an absolute difference in invasive disease-free survival of 6.9%.

“The initial Verzenio FDA approval in early breast cancer was practice changing and now, through this indication expansion, we have the potential to reduce the risk of breast cancer recurrence for many more patients, relying solely on commonly utilized clinicopathologic features to identify them,” Erika P. Hamilton, MD, an investigator on the monarchE clinical trial, said in a press release.

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

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The Food and Drug Administration has expanded the indication for adjuvant abemaciclib (Verzenio) in combination with endocrine therapy for patients with hormone receptor–positive, HER2-negative, node-positive early breast cancer who are at high risk for recurrence.

Abemaciclib was previously approved for this group of high-risk patients with the requirement that they have a Ki-67 score of at least 20%. The new expansion removes the Ki-67 testing requirement, meaning more patients are now eligible to receive this drug. High-risk patients eligible for the CDK4/6 inhibitor can now be identified solely on the basis of nodal status, tumor size, and tumor grade.

The FDA’s decision to expand the approval was based on 4-year data from the phase 3 monarchE trial of adjuvant abemaciclib, which showed benefit in invasive disease-free survival beyond the 2-year treatment course.

At 4 years, 85.5% of patients remained recurrence free with abemaciclib plus endocrine therapy, compared with 78.6% who received endocrine therapy alone, an absolute difference in invasive disease-free survival of 6.9%.

“The initial Verzenio FDA approval in early breast cancer was practice changing and now, through this indication expansion, we have the potential to reduce the risk of breast cancer recurrence for many more patients, relying solely on commonly utilized clinicopathologic features to identify them,” Erika P. Hamilton, MD, an investigator on the monarchE clinical trial, said in a press release.

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

The Food and Drug Administration has expanded the indication for adjuvant abemaciclib (Verzenio) in combination with endocrine therapy for patients with hormone receptor–positive, HER2-negative, node-positive early breast cancer who are at high risk for recurrence.

Abemaciclib was previously approved for this group of high-risk patients with the requirement that they have a Ki-67 score of at least 20%. The new expansion removes the Ki-67 testing requirement, meaning more patients are now eligible to receive this drug. High-risk patients eligible for the CDK4/6 inhibitor can now be identified solely on the basis of nodal status, tumor size, and tumor grade.

The FDA’s decision to expand the approval was based on 4-year data from the phase 3 monarchE trial of adjuvant abemaciclib, which showed benefit in invasive disease-free survival beyond the 2-year treatment course.

At 4 years, 85.5% of patients remained recurrence free with abemaciclib plus endocrine therapy, compared with 78.6% who received endocrine therapy alone, an absolute difference in invasive disease-free survival of 6.9%.

“The initial Verzenio FDA approval in early breast cancer was practice changing and now, through this indication expansion, we have the potential to reduce the risk of breast cancer recurrence for many more patients, relying solely on commonly utilized clinicopathologic features to identify them,” Erika P. Hamilton, MD, an investigator on the monarchE clinical trial, said in a press release.

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

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Commentary: Looking at Treatment Regimens for HR+ Breast Cancer and Triple-Negative Breast Cancer, March 2023

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Yara Abdou, MD
Adjuvant Aromatase Inhibitor Yields Better Survival Outcomes Than Tamoxifen or Tamoxifen and Aromatase Inhibitor in HR+/HER2+ Breast Cancer

A post hoc analysis of the ShortHER trial, including 784 patients with hormone-positive (HR+) and human epidermal growth factor receptor 2–positive (HER2+) early breast cancer who received adjuvant trastuzumab plus chemotherapy, showed that adjuvant endocrine therapy (ET) with an aromatase inhibitor (AI) was associated with better outcomes than tamoxifen (TAM) or TAM and AI (TAM-AI) in this population. Disease-free survival rates at 8 years were 86.4% for AI vs 79.7% for the TAM/TAM-AI groups, with an absolute difference of 6.7% (log-rank P = .013). This effect was seen independently of menopausal status in a multivariate analysis.

In the exploratory analysis focusing on the premenopausal patients, the addition of gonadotropin-releasing hormone to ET was associated with a significantly better disease-free survival. This was also noted in an exploratory subgroup analysis of the SOFT trial,[1] which showed greater benefit from the addition of ovarian suppression to TAM, as compared with TAM alone, among women with HER2+ disease (hazard ratio 0.41; 95% CI 0.22-0.75).

It is important to note that not all patients in the ShortHER trial received the standard-of-care duration of adjuvant trastuzumab; half of them received only 9-week treatment as opposed to the standard 12 months of adjuvant therapy. It is unclear whether this difference in adjuvant therapy could have affected the results, although the disease-free survival multivariate analysis showed no significant effect of the treatment arm on the role of ET. More studies are needed to verify the optimal adjuvant ET for patients with HR+/HER2+ breast cancer, especially in premenopausal patients.

 

Contralateral Prophylactic Mastectomy Offers No Survival Advantage in Triple-Negative Breast Cancer

There is insufficient evidence that contralateral prophylactic mastectomy (CPM) improves survival in patients with unilateral triple-negative breast cancer (TNBC). A multi-institutional database study, including 796 patients with TNBC, of which 15.5% underwent CPM, showed that CPM did not offer survival benefit to patients with unilateral TNBC. Women who underwent CPM were more likely to be White (P < .001), younger (P < .001), and had had genetic testing performed (P < .001). While there was a borderline improvement in 5-year unadjusted overall survival for patients undergoing CPM compared with no CPM overall (95.1% vs 85.0%; P = .05), no significant improvement was observed for local recurrence-free survival (P = .40) or distant recurrence-free survival (P = .37). Very few (n= 15/673, 2.2%) of the no-CPM patients developed a new primary breast cancer; 3 of the 15 patients were known BRCA1 or BRCA2 mutation carriers. Among the genetic mutation carriers, 5-year overall survival was 97.2% for CPM vs 84.1% for no CPM (P = .35). This study did not demonstrate any statistically significant survival difference between CPM compared with no CPM, regardless of the presence of a BRCA mutation, although prior studies have shown improved outcomes for CPM in BRCA mutation carriers.[2] Larger prospective studies are needed to evaluate the potential benefit of CPM among patients with TNBC, especially patients with BRCA1/2 mutations.

 

Adding Endocrine Therapy to Dual Anti-HER2 Targeted Therapy Beneficial in HER2+/HR+ Metastatic Breast Cancer

The current first-line standard of care for HER2+ metastatic breast cancer is dual anti-HER2 targeted therapy plus chemotherapy, with consideration for maintenance treatment with anti-HER2 therapy and ET for patients with HR+ and HER2+ metastatic breast cancer. The potential benefit of adding ET for patients with HR+/HER2+ metastatic breast cancer has been reported previously, but data overall are limited. This study analyzed the real-world data of 147 patients with HR+/HER2+ metastatic breast cancer from a prospective registry and who received first-line chemotherapy plus trastuzumab and pertuzumab with (n = 91) or without (n = 56) concurrent ET. The findings showed that adding ET resulted in a significant improvement in 5-year progression-free survival (PFS) (hazard ratio 0.59; P = .031) and overall survival (hazard ratio 0.52; P = .018) compared with not adding ET. No new safety concerns were identified when combining HER2+ targeted therapy and ET. While this is a small retrospective analysis, results are certainly encouraging and support the addition of ET to dual anti-HER2 therapy as maintenance therapy post chemotherapy in this subset of patients.

 

High PD-L2 Levels May Predict Worse Clinical Outcomes in ER+ Breast Cancer

Programmed cell death-1 ligand-2 (PD-L2) is a second ligand for programmed cell death-1 (PD-1) and inhibits T-cell activation. A retrospective study including patients with estrogen receptor–positive (ER+) breast cancer looked at PD-L2 protein levels in cancer cells and stromal cells of therapy-naive, locoregional ER+ breast cancer in the main study cohort (n = 684) and in an independent validation cohort (n = 273), and correlated findings with PFS. High levels of PD-L2 protein were present in up to one third (33%) of ER+ tumors and were associated with shorter PFS in the entire cohort of patients with ER+ breast cancer (hazard ratio 2.0; P < .001) and in the subgroup of patients treated with adjuvant chemotherapy (hazard ratio 3.4; P < .001). A multivariable analysis showed that high levels of PD-L2 were an independent prognostic marker in ER+ patients. These findings suggest that high PD-L2 is associated with unfavorable prognosis in ER+ breast cancer and may be a potential biomarker of response to checkpoint inhibitors.

 

Additional References

  1. Francis PA, Pagani O, Fleming GF, et al for the SOFT and TEXT Investigators and the International Breast Cancer Study Group. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med. 2018;379:122-137. Doi: 10.1056/NEJMoa1803164
  2. Li X, You R, Wang X, et al. Effectiveness of prophylactic surgeries in BRCA1 or BRCA2 mutation carriers: A meta-analysis and systematic review. Clin Cancer Res. 2016;22:3971-3981. Doi: 10.1158/1078-0432.CCR-15-1465
Author and Disclosure Information

Yara Abdou, MD
Breast Medical Oncologist
Assistant Professor, Division of Oncology
University of North Carolina at Chapel Hill
Lineberger Comprehensive Cancer Center

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Yara Abdou, MD
Breast Medical Oncologist
Assistant Professor, Division of Oncology
University of North Carolina at Chapel Hill
Lineberger Comprehensive Cancer Center

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Yara Abdou, MD
Breast Medical Oncologist
Assistant Professor, Division of Oncology
University of North Carolina at Chapel Hill
Lineberger Comprehensive Cancer Center

Yara Abdou, MD
Adjuvant Aromatase Inhibitor Yields Better Survival Outcomes Than Tamoxifen or Tamoxifen and Aromatase Inhibitor in HR+/HER2+ Breast Cancer

A post hoc analysis of the ShortHER trial, including 784 patients with hormone-positive (HR+) and human epidermal growth factor receptor 2–positive (HER2+) early breast cancer who received adjuvant trastuzumab plus chemotherapy, showed that adjuvant endocrine therapy (ET) with an aromatase inhibitor (AI) was associated with better outcomes than tamoxifen (TAM) or TAM and AI (TAM-AI) in this population. Disease-free survival rates at 8 years were 86.4% for AI vs 79.7% for the TAM/TAM-AI groups, with an absolute difference of 6.7% (log-rank P = .013). This effect was seen independently of menopausal status in a multivariate analysis.

In the exploratory analysis focusing on the premenopausal patients, the addition of gonadotropin-releasing hormone to ET was associated with a significantly better disease-free survival. This was also noted in an exploratory subgroup analysis of the SOFT trial,[1] which showed greater benefit from the addition of ovarian suppression to TAM, as compared with TAM alone, among women with HER2+ disease (hazard ratio 0.41; 95% CI 0.22-0.75).

It is important to note that not all patients in the ShortHER trial received the standard-of-care duration of adjuvant trastuzumab; half of them received only 9-week treatment as opposed to the standard 12 months of adjuvant therapy. It is unclear whether this difference in adjuvant therapy could have affected the results, although the disease-free survival multivariate analysis showed no significant effect of the treatment arm on the role of ET. More studies are needed to verify the optimal adjuvant ET for patients with HR+/HER2+ breast cancer, especially in premenopausal patients.

 

Contralateral Prophylactic Mastectomy Offers No Survival Advantage in Triple-Negative Breast Cancer

There is insufficient evidence that contralateral prophylactic mastectomy (CPM) improves survival in patients with unilateral triple-negative breast cancer (TNBC). A multi-institutional database study, including 796 patients with TNBC, of which 15.5% underwent CPM, showed that CPM did not offer survival benefit to patients with unilateral TNBC. Women who underwent CPM were more likely to be White (P < .001), younger (P < .001), and had had genetic testing performed (P < .001). While there was a borderline improvement in 5-year unadjusted overall survival for patients undergoing CPM compared with no CPM overall (95.1% vs 85.0%; P = .05), no significant improvement was observed for local recurrence-free survival (P = .40) or distant recurrence-free survival (P = .37). Very few (n= 15/673, 2.2%) of the no-CPM patients developed a new primary breast cancer; 3 of the 15 patients were known BRCA1 or BRCA2 mutation carriers. Among the genetic mutation carriers, 5-year overall survival was 97.2% for CPM vs 84.1% for no CPM (P = .35). This study did not demonstrate any statistically significant survival difference between CPM compared with no CPM, regardless of the presence of a BRCA mutation, although prior studies have shown improved outcomes for CPM in BRCA mutation carriers.[2] Larger prospective studies are needed to evaluate the potential benefit of CPM among patients with TNBC, especially patients with BRCA1/2 mutations.

 

Adding Endocrine Therapy to Dual Anti-HER2 Targeted Therapy Beneficial in HER2+/HR+ Metastatic Breast Cancer

The current first-line standard of care for HER2+ metastatic breast cancer is dual anti-HER2 targeted therapy plus chemotherapy, with consideration for maintenance treatment with anti-HER2 therapy and ET for patients with HR+ and HER2+ metastatic breast cancer. The potential benefit of adding ET for patients with HR+/HER2+ metastatic breast cancer has been reported previously, but data overall are limited. This study analyzed the real-world data of 147 patients with HR+/HER2+ metastatic breast cancer from a prospective registry and who received first-line chemotherapy plus trastuzumab and pertuzumab with (n = 91) or without (n = 56) concurrent ET. The findings showed that adding ET resulted in a significant improvement in 5-year progression-free survival (PFS) (hazard ratio 0.59; P = .031) and overall survival (hazard ratio 0.52; P = .018) compared with not adding ET. No new safety concerns were identified when combining HER2+ targeted therapy and ET. While this is a small retrospective analysis, results are certainly encouraging and support the addition of ET to dual anti-HER2 therapy as maintenance therapy post chemotherapy in this subset of patients.

 

High PD-L2 Levels May Predict Worse Clinical Outcomes in ER+ Breast Cancer

Programmed cell death-1 ligand-2 (PD-L2) is a second ligand for programmed cell death-1 (PD-1) and inhibits T-cell activation. A retrospective study including patients with estrogen receptor–positive (ER+) breast cancer looked at PD-L2 protein levels in cancer cells and stromal cells of therapy-naive, locoregional ER+ breast cancer in the main study cohort (n = 684) and in an independent validation cohort (n = 273), and correlated findings with PFS. High levels of PD-L2 protein were present in up to one third (33%) of ER+ tumors and were associated with shorter PFS in the entire cohort of patients with ER+ breast cancer (hazard ratio 2.0; P < .001) and in the subgroup of patients treated with adjuvant chemotherapy (hazard ratio 3.4; P < .001). A multivariable analysis showed that high levels of PD-L2 were an independent prognostic marker in ER+ patients. These findings suggest that high PD-L2 is associated with unfavorable prognosis in ER+ breast cancer and may be a potential biomarker of response to checkpoint inhibitors.

 

Additional References

  1. Francis PA, Pagani O, Fleming GF, et al for the SOFT and TEXT Investigators and the International Breast Cancer Study Group. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med. 2018;379:122-137. Doi: 10.1056/NEJMoa1803164
  2. Li X, You R, Wang X, et al. Effectiveness of prophylactic surgeries in BRCA1 or BRCA2 mutation carriers: A meta-analysis and systematic review. Clin Cancer Res. 2016;22:3971-3981. Doi: 10.1158/1078-0432.CCR-15-1465

Yara Abdou, MD
Adjuvant Aromatase Inhibitor Yields Better Survival Outcomes Than Tamoxifen or Tamoxifen and Aromatase Inhibitor in HR+/HER2+ Breast Cancer

A post hoc analysis of the ShortHER trial, including 784 patients with hormone-positive (HR+) and human epidermal growth factor receptor 2–positive (HER2+) early breast cancer who received adjuvant trastuzumab plus chemotherapy, showed that adjuvant endocrine therapy (ET) with an aromatase inhibitor (AI) was associated with better outcomes than tamoxifen (TAM) or TAM and AI (TAM-AI) in this population. Disease-free survival rates at 8 years were 86.4% for AI vs 79.7% for the TAM/TAM-AI groups, with an absolute difference of 6.7% (log-rank P = .013). This effect was seen independently of menopausal status in a multivariate analysis.

In the exploratory analysis focusing on the premenopausal patients, the addition of gonadotropin-releasing hormone to ET was associated with a significantly better disease-free survival. This was also noted in an exploratory subgroup analysis of the SOFT trial,[1] which showed greater benefit from the addition of ovarian suppression to TAM, as compared with TAM alone, among women with HER2+ disease (hazard ratio 0.41; 95% CI 0.22-0.75).

It is important to note that not all patients in the ShortHER trial received the standard-of-care duration of adjuvant trastuzumab; half of them received only 9-week treatment as opposed to the standard 12 months of adjuvant therapy. It is unclear whether this difference in adjuvant therapy could have affected the results, although the disease-free survival multivariate analysis showed no significant effect of the treatment arm on the role of ET. More studies are needed to verify the optimal adjuvant ET for patients with HR+/HER2+ breast cancer, especially in premenopausal patients.

 

Contralateral Prophylactic Mastectomy Offers No Survival Advantage in Triple-Negative Breast Cancer

There is insufficient evidence that contralateral prophylactic mastectomy (CPM) improves survival in patients with unilateral triple-negative breast cancer (TNBC). A multi-institutional database study, including 796 patients with TNBC, of which 15.5% underwent CPM, showed that CPM did not offer survival benefit to patients with unilateral TNBC. Women who underwent CPM were more likely to be White (P < .001), younger (P < .001), and had had genetic testing performed (P < .001). While there was a borderline improvement in 5-year unadjusted overall survival for patients undergoing CPM compared with no CPM overall (95.1% vs 85.0%; P = .05), no significant improvement was observed for local recurrence-free survival (P = .40) or distant recurrence-free survival (P = .37). Very few (n= 15/673, 2.2%) of the no-CPM patients developed a new primary breast cancer; 3 of the 15 patients were known BRCA1 or BRCA2 mutation carriers. Among the genetic mutation carriers, 5-year overall survival was 97.2% for CPM vs 84.1% for no CPM (P = .35). This study did not demonstrate any statistically significant survival difference between CPM compared with no CPM, regardless of the presence of a BRCA mutation, although prior studies have shown improved outcomes for CPM in BRCA mutation carriers.[2] Larger prospective studies are needed to evaluate the potential benefit of CPM among patients with TNBC, especially patients with BRCA1/2 mutations.

 

Adding Endocrine Therapy to Dual Anti-HER2 Targeted Therapy Beneficial in HER2+/HR+ Metastatic Breast Cancer

The current first-line standard of care for HER2+ metastatic breast cancer is dual anti-HER2 targeted therapy plus chemotherapy, with consideration for maintenance treatment with anti-HER2 therapy and ET for patients with HR+ and HER2+ metastatic breast cancer. The potential benefit of adding ET for patients with HR+/HER2+ metastatic breast cancer has been reported previously, but data overall are limited. This study analyzed the real-world data of 147 patients with HR+/HER2+ metastatic breast cancer from a prospective registry and who received first-line chemotherapy plus trastuzumab and pertuzumab with (n = 91) or without (n = 56) concurrent ET. The findings showed that adding ET resulted in a significant improvement in 5-year progression-free survival (PFS) (hazard ratio 0.59; P = .031) and overall survival (hazard ratio 0.52; P = .018) compared with not adding ET. No new safety concerns were identified when combining HER2+ targeted therapy and ET. While this is a small retrospective analysis, results are certainly encouraging and support the addition of ET to dual anti-HER2 therapy as maintenance therapy post chemotherapy in this subset of patients.

 

High PD-L2 Levels May Predict Worse Clinical Outcomes in ER+ Breast Cancer

Programmed cell death-1 ligand-2 (PD-L2) is a second ligand for programmed cell death-1 (PD-1) and inhibits T-cell activation. A retrospective study including patients with estrogen receptor–positive (ER+) breast cancer looked at PD-L2 protein levels in cancer cells and stromal cells of therapy-naive, locoregional ER+ breast cancer in the main study cohort (n = 684) and in an independent validation cohort (n = 273), and correlated findings with PFS. High levels of PD-L2 protein were present in up to one third (33%) of ER+ tumors and were associated with shorter PFS in the entire cohort of patients with ER+ breast cancer (hazard ratio 2.0; P < .001) and in the subgroup of patients treated with adjuvant chemotherapy (hazard ratio 3.4; P < .001). A multivariable analysis showed that high levels of PD-L2 were an independent prognostic marker in ER+ patients. These findings suggest that high PD-L2 is associated with unfavorable prognosis in ER+ breast cancer and may be a potential biomarker of response to checkpoint inhibitors.

 

Additional References

  1. Francis PA, Pagani O, Fleming GF, et al for the SOFT and TEXT Investigators and the International Breast Cancer Study Group. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Engl J Med. 2018;379:122-137. Doi: 10.1056/NEJMoa1803164
  2. Li X, You R, Wang X, et al. Effectiveness of prophylactic surgeries in BRCA1 or BRCA2 mutation carriers: A meta-analysis and systematic review. Clin Cancer Res. 2016;22:3971-3981. Doi: 10.1158/1078-0432.CCR-15-1465
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Who’s at higher risk for breast cancer recurrence?

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Wed, 03/01/2023 - 11:40

When it comes to a woman’s risk for a breast cancer recurrence, hormone status appears to matter.

New research shows that patients with ER-negative disease have a higher risk of a second breast cancer within a 5-year window post diagnosis, compared with patients with ER-positive disease.

“Our findings suggest that primary breast cancer ER status could be used to identify women at highest risk of second breast cancer events during the early post-treatment period and should be a consideration for guidelines and decision-making regarding surveillance imaging regimens for breast cancer survivors,” the study authors, led by Kathryn P. Lowry, MD, of Fred Hutchinson Cancer Center in Seattle, concluded.

The study was published online in Cancer.

Breast cancer survivors are at risk for a second breast cancer, making ongoing surveillance essential. Surveillance could be informed by better understanding an individual’s recurrence risk, but whether differences exist for women with ER‐positive vs. ER‐negative cancers remains unclear.

Dr. Lowry and colleagues analyzed women diagnosed with stage I-III breast cancer between 2000 and 2017, drawing from six Breast Cancer Surveillance Consortium registries. The team collected information on patients’ ER status as well as second breast cancer events detectable by surveillance imaging. Second breast cancer rates were assessed 1-5 years and 6-10 years after diagnosis. The final study cohort included 23,139 women with ER-positive disease and 4,605 with ER-negative disease.

The researchers found that, at the 5-year mark, the cumulative breast cancer incidence was 7.1% for ER‐negative disease and 3.6% for ER‐positive disease. At the 10-year mark, the cumulative breast cancer incidence was still higher for women with ER-negative disease – 11.8% vs. 7.5% among those with ER-positive disease. 

Patients with ER-negative disease also had higher rates of second breast cancers within the first 5 years of follow-ups – 16.0 per 1,000 person‐years vs. 7.8 per 1,000 person‐years for those with ER‐positive breast cancer – though after 5 years, the rates by ER status were similar among the two groups (12.1 per 1,000 vs. 9.3 per 1,000 person‐years, respectively).

Overall, the findings indicate that the “ER status of the primary invasive cancer was an important prognostic factor for both the magnitude and the timing of second breast cancer events,” the authors concluded.

The team noted several limitations to their study, including that information on the presence of pathogenic variants, such as BRCA1 and BRCA2, were not available. Given that these variants tend to be more common among women with ER-negative breast cancers, this could represent a confounder.

Marisa C. Weiss, MD, chief medical officer and founder of Breastcancer.org, who was not involved in the research, highlighted two important details to keep in mind.

“We do know that triple negative breast cancers are associated with a higher risk of having an inherited genetic abnormality like BRCA1, which predicts a higher risk of second malignancies,” said Dr. Weiss, a breast oncologist at Lankenau Medical Center in Wynnewood, Pa. “Also, it should be noted that patients with HR-positive breast cancer have a higher incidence of local recurrence spread out over 10-plus years.”

What might these results mean for practice and following patients over the long term?

According to the researchers, “further study is needed to evaluate whether women with ER‐negative primary cancers may potentially benefit from more intensive surveillance in the early postdiagnosis period.”

Dr. Weiss noted as well that “each person’s situation is unique,” and it is “very important to develop a customized survivorship care plan with close surveillance,” which includes genetic testing.

Dr. Lowry reported grants from the American Cancer Society and personal fees from the Radiological Society of North America outside the submitted work. Several coauthors also reported disclosures. Dr. Weiss reported no relevant financial relationships.

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

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When it comes to a woman’s risk for a breast cancer recurrence, hormone status appears to matter.

New research shows that patients with ER-negative disease have a higher risk of a second breast cancer within a 5-year window post diagnosis, compared with patients with ER-positive disease.

“Our findings suggest that primary breast cancer ER status could be used to identify women at highest risk of second breast cancer events during the early post-treatment period and should be a consideration for guidelines and decision-making regarding surveillance imaging regimens for breast cancer survivors,” the study authors, led by Kathryn P. Lowry, MD, of Fred Hutchinson Cancer Center in Seattle, concluded.

The study was published online in Cancer.

Breast cancer survivors are at risk for a second breast cancer, making ongoing surveillance essential. Surveillance could be informed by better understanding an individual’s recurrence risk, but whether differences exist for women with ER‐positive vs. ER‐negative cancers remains unclear.

Dr. Lowry and colleagues analyzed women diagnosed with stage I-III breast cancer between 2000 and 2017, drawing from six Breast Cancer Surveillance Consortium registries. The team collected information on patients’ ER status as well as second breast cancer events detectable by surveillance imaging. Second breast cancer rates were assessed 1-5 years and 6-10 years after diagnosis. The final study cohort included 23,139 women with ER-positive disease and 4,605 with ER-negative disease.

The researchers found that, at the 5-year mark, the cumulative breast cancer incidence was 7.1% for ER‐negative disease and 3.6% for ER‐positive disease. At the 10-year mark, the cumulative breast cancer incidence was still higher for women with ER-negative disease – 11.8% vs. 7.5% among those with ER-positive disease. 

Patients with ER-negative disease also had higher rates of second breast cancers within the first 5 years of follow-ups – 16.0 per 1,000 person‐years vs. 7.8 per 1,000 person‐years for those with ER‐positive breast cancer – though after 5 years, the rates by ER status were similar among the two groups (12.1 per 1,000 vs. 9.3 per 1,000 person‐years, respectively).

Overall, the findings indicate that the “ER status of the primary invasive cancer was an important prognostic factor for both the magnitude and the timing of second breast cancer events,” the authors concluded.

The team noted several limitations to their study, including that information on the presence of pathogenic variants, such as BRCA1 and BRCA2, were not available. Given that these variants tend to be more common among women with ER-negative breast cancers, this could represent a confounder.

Marisa C. Weiss, MD, chief medical officer and founder of Breastcancer.org, who was not involved in the research, highlighted two important details to keep in mind.

“We do know that triple negative breast cancers are associated with a higher risk of having an inherited genetic abnormality like BRCA1, which predicts a higher risk of second malignancies,” said Dr. Weiss, a breast oncologist at Lankenau Medical Center in Wynnewood, Pa. “Also, it should be noted that patients with HR-positive breast cancer have a higher incidence of local recurrence spread out over 10-plus years.”

What might these results mean for practice and following patients over the long term?

According to the researchers, “further study is needed to evaluate whether women with ER‐negative primary cancers may potentially benefit from more intensive surveillance in the early postdiagnosis period.”

Dr. Weiss noted as well that “each person’s situation is unique,” and it is “very important to develop a customized survivorship care plan with close surveillance,” which includes genetic testing.

Dr. Lowry reported grants from the American Cancer Society and personal fees from the Radiological Society of North America outside the submitted work. Several coauthors also reported disclosures. Dr. Weiss reported no relevant financial relationships.

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

When it comes to a woman’s risk for a breast cancer recurrence, hormone status appears to matter.

New research shows that patients with ER-negative disease have a higher risk of a second breast cancer within a 5-year window post diagnosis, compared with patients with ER-positive disease.

“Our findings suggest that primary breast cancer ER status could be used to identify women at highest risk of second breast cancer events during the early post-treatment period and should be a consideration for guidelines and decision-making regarding surveillance imaging regimens for breast cancer survivors,” the study authors, led by Kathryn P. Lowry, MD, of Fred Hutchinson Cancer Center in Seattle, concluded.

The study was published online in Cancer.

Breast cancer survivors are at risk for a second breast cancer, making ongoing surveillance essential. Surveillance could be informed by better understanding an individual’s recurrence risk, but whether differences exist for women with ER‐positive vs. ER‐negative cancers remains unclear.

Dr. Lowry and colleagues analyzed women diagnosed with stage I-III breast cancer between 2000 and 2017, drawing from six Breast Cancer Surveillance Consortium registries. The team collected information on patients’ ER status as well as second breast cancer events detectable by surveillance imaging. Second breast cancer rates were assessed 1-5 years and 6-10 years after diagnosis. The final study cohort included 23,139 women with ER-positive disease and 4,605 with ER-negative disease.

The researchers found that, at the 5-year mark, the cumulative breast cancer incidence was 7.1% for ER‐negative disease and 3.6% for ER‐positive disease. At the 10-year mark, the cumulative breast cancer incidence was still higher for women with ER-negative disease – 11.8% vs. 7.5% among those with ER-positive disease. 

Patients with ER-negative disease also had higher rates of second breast cancers within the first 5 years of follow-ups – 16.0 per 1,000 person‐years vs. 7.8 per 1,000 person‐years for those with ER‐positive breast cancer – though after 5 years, the rates by ER status were similar among the two groups (12.1 per 1,000 vs. 9.3 per 1,000 person‐years, respectively).

Overall, the findings indicate that the “ER status of the primary invasive cancer was an important prognostic factor for both the magnitude and the timing of second breast cancer events,” the authors concluded.

The team noted several limitations to their study, including that information on the presence of pathogenic variants, such as BRCA1 and BRCA2, were not available. Given that these variants tend to be more common among women with ER-negative breast cancers, this could represent a confounder.

Marisa C. Weiss, MD, chief medical officer and founder of Breastcancer.org, who was not involved in the research, highlighted two important details to keep in mind.

“We do know that triple negative breast cancers are associated with a higher risk of having an inherited genetic abnormality like BRCA1, which predicts a higher risk of second malignancies,” said Dr. Weiss, a breast oncologist at Lankenau Medical Center in Wynnewood, Pa. “Also, it should be noted that patients with HR-positive breast cancer have a higher incidence of local recurrence spread out over 10-plus years.”

What might these results mean for practice and following patients over the long term?

According to the researchers, “further study is needed to evaluate whether women with ER‐negative primary cancers may potentially benefit from more intensive surveillance in the early postdiagnosis period.”

Dr. Weiss noted as well that “each person’s situation is unique,” and it is “very important to develop a customized survivorship care plan with close surveillance,” which includes genetic testing.

Dr. Lowry reported grants from the American Cancer Society and personal fees from the Radiological Society of North America outside the submitted work. Several coauthors also reported disclosures. Dr. Weiss reported no relevant financial relationships.

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

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Myths about smoking, diet, alcohol, and cancer persist

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Tue, 02/28/2023 - 15:35

– Conducted every 5 years since 2005, the Cancer Survey documents the knowledge, perceptions, and way of life of the French people in relation to cancer. The French National Cancer Institute (InCA), in partnership with Public Health France (SPF), has published the results of its 2021 survey. The researchers analyzed responses to telephone interviews of a representative sample of almost 5,000 individuals aged 15-85 years.

This study shows how thinking has changed over time and how difficult it is to alter preconceived notions.
 

Is cancer hereditary?

The report shows that 67.7% of respondents believe that cancer is a hereditary disease. Respondents were asked to explain their answer. “Data show that medical practices for cancer treatment substantiate this belief [that cancer is hereditary],” wrote the authors of the report.

“Indeed, health care professionals almost systematically ask questions about family history of breast cancer and, when a family member has been diagnosed with cancer, medical monitoring of other family members is often sought out, thus reinforcing the belief that cancer is hereditary,” they said.

Furthermore, there seems to be confusion regarding the role of genes in the development of cancer. A person can inherit cancer-predisposing genes, not cancer itself. The authors highlighted their concern that this confusion may “lead people to think that prevention measures are unnecessary because cancer is inherited.”
 

Misconceptions about smoking

About 41% of smokers think that the length of time one has been smoking is the biggest determining factor for developing cancer; 58.1% think the number of cigarettes smoked per day has a bigger impact.

Experts at InCA and SPF put the debate to rest, stating that prolonged exposure to carcinogenic substances is far more toxic. As for the danger threshold concerning the number of cigarettes smoked per day, respondents believed this to be 9.2 cigarettes per day, on average. They believed that the danger threshold for the number of years as an active smoker is 13.4, on average.

“The [survey] respondents clearly understand that smoking carries a risk, but many smokers think that light smoking or smoking for a short period of time doesn’t carry any risks.” Yet it is understood that even occasional tobacco consumption increases mortality.

This was not the only misconception regarding smoking and its relationship with cancer. About 34% of survey respondents agreed with the following statement: “Smoking doesn’t cause cancer unless you’re a heavy smoker and have smoked for a long time.” Furthermore, 43.3% agreed with the statement, “Pollution is more likely to cause cancer than smoking,” 54.6% think that “exercising cleans your lungs of tobacco,” and 61.6% think that “a smoker can prevent developing cancer caused by smoking if they know to quit on time.”
 

Overweight and obesity

Although diet and excess weight represent the third and fourth biggest avoidable cancer risk factors, after smoking and alcohol, only 30% of survey respondents knew of this link.

“Among the causes of cancer known and cited by respondents without prompting, excessive weight and obesity were mentioned only 100 times out of 12,558 responses,” highlighted the authors of the report. The explanation put forward by the authors is that discourse about diet has been more focused on diet as a protective health factor, especially in preventing cardiovascular diseases. “The link between cancer and diet is less prominent in the public space,” they noted.
 

 

 

Breastfeeding and cancer

About 63% of survey respondents, which for the first time included both women and men, believe that breastfeeding does not affect mothers’ risk of breast cancer, but this is a misconception. And almost 1 in 3 respondents said that breastfeeding provides health benefits for the mother.

Artificial UV rays

Exposure to UV rays, whether of natural or artificial origin, is a major risk factor for skin cancer. However, 1 in 5 people (20.9%) think that a session in a tanning bed is less harmful than sun exposure.

Daily stress

Regarding psychological factors linked to cancer, the authors noted that risk factors not supported by scientific evidence were, ironically, cited more often by respondents than proven risk factors. There is a real knowledge gap between scientific data and the beliefs of the French people. For example, “working at night” is largely not seen as a risk factor, but data show that it presents a clear risk. However, “not being able to express one’s feelings,” “having been weakened by traumatic experiences,” and “being exposed to the stress of modern life” are seen as risk factors of cancer, without any scientific evidence.

Cigarettes and e-cigarettes

About 53% of respondents agreed that “e-cigarettes are just as harmful or more harmful than traditional cigarettes.” Nicotine and the flavors in e-cigarettes are largely perceived as “very” or “extremely” harmful to the health of a person. However, the authors note that “no published study on nicotine substitutes has shown harmful effects on the health of a person, let alone determined it a risk factor for cancer. The nicotine doses in e-cigarettes are similar to traditional nicotine substitutes, and no cytotoxic effect of nicotine in its inhaled form has been found.” There seems to be confusion between dependence and risk of cancer.

Alcohol consumption

Eight of 10 respondents believe that “some people can drink a lot of alcohol all their life without ever getting cancer,” which goes against the scientific literature. The authors of the report state that the negative effects of alcohol on health seem poorly understood. Although alcohol is the second biggest cause of cancer, only a third of survey respondents cited it without having been prompted as one of the main causes of cancer. And 23.5% even think that “in terms of decreasing your risk of cancer, it’s better to drink a little wine than to drink no wine at all.”

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

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– Conducted every 5 years since 2005, the Cancer Survey documents the knowledge, perceptions, and way of life of the French people in relation to cancer. The French National Cancer Institute (InCA), in partnership with Public Health France (SPF), has published the results of its 2021 survey. The researchers analyzed responses to telephone interviews of a representative sample of almost 5,000 individuals aged 15-85 years.

This study shows how thinking has changed over time and how difficult it is to alter preconceived notions.
 

Is cancer hereditary?

The report shows that 67.7% of respondents believe that cancer is a hereditary disease. Respondents were asked to explain their answer. “Data show that medical practices for cancer treatment substantiate this belief [that cancer is hereditary],” wrote the authors of the report.

“Indeed, health care professionals almost systematically ask questions about family history of breast cancer and, when a family member has been diagnosed with cancer, medical monitoring of other family members is often sought out, thus reinforcing the belief that cancer is hereditary,” they said.

Furthermore, there seems to be confusion regarding the role of genes in the development of cancer. A person can inherit cancer-predisposing genes, not cancer itself. The authors highlighted their concern that this confusion may “lead people to think that prevention measures are unnecessary because cancer is inherited.”
 

Misconceptions about smoking

About 41% of smokers think that the length of time one has been smoking is the biggest determining factor for developing cancer; 58.1% think the number of cigarettes smoked per day has a bigger impact.

Experts at InCA and SPF put the debate to rest, stating that prolonged exposure to carcinogenic substances is far more toxic. As for the danger threshold concerning the number of cigarettes smoked per day, respondents believed this to be 9.2 cigarettes per day, on average. They believed that the danger threshold for the number of years as an active smoker is 13.4, on average.

“The [survey] respondents clearly understand that smoking carries a risk, but many smokers think that light smoking or smoking for a short period of time doesn’t carry any risks.” Yet it is understood that even occasional tobacco consumption increases mortality.

This was not the only misconception regarding smoking and its relationship with cancer. About 34% of survey respondents agreed with the following statement: “Smoking doesn’t cause cancer unless you’re a heavy smoker and have smoked for a long time.” Furthermore, 43.3% agreed with the statement, “Pollution is more likely to cause cancer than smoking,” 54.6% think that “exercising cleans your lungs of tobacco,” and 61.6% think that “a smoker can prevent developing cancer caused by smoking if they know to quit on time.”
 

Overweight and obesity

Although diet and excess weight represent the third and fourth biggest avoidable cancer risk factors, after smoking and alcohol, only 30% of survey respondents knew of this link.

“Among the causes of cancer known and cited by respondents without prompting, excessive weight and obesity were mentioned only 100 times out of 12,558 responses,” highlighted the authors of the report. The explanation put forward by the authors is that discourse about diet has been more focused on diet as a protective health factor, especially in preventing cardiovascular diseases. “The link between cancer and diet is less prominent in the public space,” they noted.
 

 

 

Breastfeeding and cancer

About 63% of survey respondents, which for the first time included both women and men, believe that breastfeeding does not affect mothers’ risk of breast cancer, but this is a misconception. And almost 1 in 3 respondents said that breastfeeding provides health benefits for the mother.

Artificial UV rays

Exposure to UV rays, whether of natural or artificial origin, is a major risk factor for skin cancer. However, 1 in 5 people (20.9%) think that a session in a tanning bed is less harmful than sun exposure.

Daily stress

Regarding psychological factors linked to cancer, the authors noted that risk factors not supported by scientific evidence were, ironically, cited more often by respondents than proven risk factors. There is a real knowledge gap between scientific data and the beliefs of the French people. For example, “working at night” is largely not seen as a risk factor, but data show that it presents a clear risk. However, “not being able to express one’s feelings,” “having been weakened by traumatic experiences,” and “being exposed to the stress of modern life” are seen as risk factors of cancer, without any scientific evidence.

Cigarettes and e-cigarettes

About 53% of respondents agreed that “e-cigarettes are just as harmful or more harmful than traditional cigarettes.” Nicotine and the flavors in e-cigarettes are largely perceived as “very” or “extremely” harmful to the health of a person. However, the authors note that “no published study on nicotine substitutes has shown harmful effects on the health of a person, let alone determined it a risk factor for cancer. The nicotine doses in e-cigarettes are similar to traditional nicotine substitutes, and no cytotoxic effect of nicotine in its inhaled form has been found.” There seems to be confusion between dependence and risk of cancer.

Alcohol consumption

Eight of 10 respondents believe that “some people can drink a lot of alcohol all their life without ever getting cancer,” which goes against the scientific literature. The authors of the report state that the negative effects of alcohol on health seem poorly understood. Although alcohol is the second biggest cause of cancer, only a third of survey respondents cited it without having been prompted as one of the main causes of cancer. And 23.5% even think that “in terms of decreasing your risk of cancer, it’s better to drink a little wine than to drink no wine at all.”

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

– Conducted every 5 years since 2005, the Cancer Survey documents the knowledge, perceptions, and way of life of the French people in relation to cancer. The French National Cancer Institute (InCA), in partnership with Public Health France (SPF), has published the results of its 2021 survey. The researchers analyzed responses to telephone interviews of a representative sample of almost 5,000 individuals aged 15-85 years.

This study shows how thinking has changed over time and how difficult it is to alter preconceived notions.
 

Is cancer hereditary?

The report shows that 67.7% of respondents believe that cancer is a hereditary disease. Respondents were asked to explain their answer. “Data show that medical practices for cancer treatment substantiate this belief [that cancer is hereditary],” wrote the authors of the report.

“Indeed, health care professionals almost systematically ask questions about family history of breast cancer and, when a family member has been diagnosed with cancer, medical monitoring of other family members is often sought out, thus reinforcing the belief that cancer is hereditary,” they said.

Furthermore, there seems to be confusion regarding the role of genes in the development of cancer. A person can inherit cancer-predisposing genes, not cancer itself. The authors highlighted their concern that this confusion may “lead people to think that prevention measures are unnecessary because cancer is inherited.”
 

Misconceptions about smoking

About 41% of smokers think that the length of time one has been smoking is the biggest determining factor for developing cancer; 58.1% think the number of cigarettes smoked per day has a bigger impact.

Experts at InCA and SPF put the debate to rest, stating that prolonged exposure to carcinogenic substances is far more toxic. As for the danger threshold concerning the number of cigarettes smoked per day, respondents believed this to be 9.2 cigarettes per day, on average. They believed that the danger threshold for the number of years as an active smoker is 13.4, on average.

“The [survey] respondents clearly understand that smoking carries a risk, but many smokers think that light smoking or smoking for a short period of time doesn’t carry any risks.” Yet it is understood that even occasional tobacco consumption increases mortality.

This was not the only misconception regarding smoking and its relationship with cancer. About 34% of survey respondents agreed with the following statement: “Smoking doesn’t cause cancer unless you’re a heavy smoker and have smoked for a long time.” Furthermore, 43.3% agreed with the statement, “Pollution is more likely to cause cancer than smoking,” 54.6% think that “exercising cleans your lungs of tobacco,” and 61.6% think that “a smoker can prevent developing cancer caused by smoking if they know to quit on time.”
 

Overweight and obesity

Although diet and excess weight represent the third and fourth biggest avoidable cancer risk factors, after smoking and alcohol, only 30% of survey respondents knew of this link.

“Among the causes of cancer known and cited by respondents without prompting, excessive weight and obesity were mentioned only 100 times out of 12,558 responses,” highlighted the authors of the report. The explanation put forward by the authors is that discourse about diet has been more focused on diet as a protective health factor, especially in preventing cardiovascular diseases. “The link between cancer and diet is less prominent in the public space,” they noted.
 

 

 

Breastfeeding and cancer

About 63% of survey respondents, which for the first time included both women and men, believe that breastfeeding does not affect mothers’ risk of breast cancer, but this is a misconception. And almost 1 in 3 respondents said that breastfeeding provides health benefits for the mother.

Artificial UV rays

Exposure to UV rays, whether of natural or artificial origin, is a major risk factor for skin cancer. However, 1 in 5 people (20.9%) think that a session in a tanning bed is less harmful than sun exposure.

Daily stress

Regarding psychological factors linked to cancer, the authors noted that risk factors not supported by scientific evidence were, ironically, cited more often by respondents than proven risk factors. There is a real knowledge gap between scientific data and the beliefs of the French people. For example, “working at night” is largely not seen as a risk factor, but data show that it presents a clear risk. However, “not being able to express one’s feelings,” “having been weakened by traumatic experiences,” and “being exposed to the stress of modern life” are seen as risk factors of cancer, without any scientific evidence.

Cigarettes and e-cigarettes

About 53% of respondents agreed that “e-cigarettes are just as harmful or more harmful than traditional cigarettes.” Nicotine and the flavors in e-cigarettes are largely perceived as “very” or “extremely” harmful to the health of a person. However, the authors note that “no published study on nicotine substitutes has shown harmful effects on the health of a person, let alone determined it a risk factor for cancer. The nicotine doses in e-cigarettes are similar to traditional nicotine substitutes, and no cytotoxic effect of nicotine in its inhaled form has been found.” There seems to be confusion between dependence and risk of cancer.

Alcohol consumption

Eight of 10 respondents believe that “some people can drink a lot of alcohol all their life without ever getting cancer,” which goes against the scientific literature. The authors of the report state that the negative effects of alcohol on health seem poorly understood. Although alcohol is the second biggest cause of cancer, only a third of survey respondents cited it without having been prompted as one of the main causes of cancer. And 23.5% even think that “in terms of decreasing your risk of cancer, it’s better to drink a little wine than to drink no wine at all.”

This article was translated from the Medscape French edition. A version of this article appeared on Medscape.com.

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Ethylene oxide emissions increase risk for ductal carcinoma in situ of the breast

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Wed, 03/01/2023 - 13:47

Key clinical point: Exposure to ethylene oxide (EtO) emissions (proximity range 10 km) may increase the risk for ductal carcinoma in situ (DCIS) of the breast.

Major finding: The presence of EtO-emitting facilities within 10 km was associated with a significant increase in the risk for DCIS (hazard ratio [HR] 1.13; 95% CI 1.01-1.27); however, there was no increase in the risk for invasive breast cancers (HR 1.03; 95% CI 0.97-1.09).

Study details: This study evaluated the data of the US National Institutes of Health-AARP Diet and Health Study cohort including 12,222 cases of breast cancer diagnosed in 173,648 postmenopausal women over a median follow-up of 16 years.

Disclosures: This study was supported by the Intramural Research Program of the National Cancer Institute. The authors declared no conflicts of interest.

Source: Jones RR et al. Ethylene oxide emissions and incident breast cancer and non-Hodgkin lymphoma in a U.S. cohort. J Natl Cancer Inst. 2023 (Jan 12). Doi: 10.1093/jnci/djad004

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Key clinical point: Exposure to ethylene oxide (EtO) emissions (proximity range 10 km) may increase the risk for ductal carcinoma in situ (DCIS) of the breast.

Major finding: The presence of EtO-emitting facilities within 10 km was associated with a significant increase in the risk for DCIS (hazard ratio [HR] 1.13; 95% CI 1.01-1.27); however, there was no increase in the risk for invasive breast cancers (HR 1.03; 95% CI 0.97-1.09).

Study details: This study evaluated the data of the US National Institutes of Health-AARP Diet and Health Study cohort including 12,222 cases of breast cancer diagnosed in 173,648 postmenopausal women over a median follow-up of 16 years.

Disclosures: This study was supported by the Intramural Research Program of the National Cancer Institute. The authors declared no conflicts of interest.

Source: Jones RR et al. Ethylene oxide emissions and incident breast cancer and non-Hodgkin lymphoma in a U.S. cohort. J Natl Cancer Inst. 2023 (Jan 12). Doi: 10.1093/jnci/djad004

Key clinical point: Exposure to ethylene oxide (EtO) emissions (proximity range 10 km) may increase the risk for ductal carcinoma in situ (DCIS) of the breast.

Major finding: The presence of EtO-emitting facilities within 10 km was associated with a significant increase in the risk for DCIS (hazard ratio [HR] 1.13; 95% CI 1.01-1.27); however, there was no increase in the risk for invasive breast cancers (HR 1.03; 95% CI 0.97-1.09).

Study details: This study evaluated the data of the US National Institutes of Health-AARP Diet and Health Study cohort including 12,222 cases of breast cancer diagnosed in 173,648 postmenopausal women over a median follow-up of 16 years.

Disclosures: This study was supported by the Intramural Research Program of the National Cancer Institute. The authors declared no conflicts of interest.

Source: Jones RR et al. Ethylene oxide emissions and incident breast cancer and non-Hodgkin lymphoma in a U.S. cohort. J Natl Cancer Inst. 2023 (Jan 12). Doi: 10.1093/jnci/djad004

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