Diana Kwon

Racial differences in cancer outcomes are widespread. Studies indicate that Black people face higher rates of mortality for most cancers than their White counterparts. To bridge this racial gap, researchers need to investigate the biological effects of structural racism and discrimination on cancer outcomes, experts say.

“As a physician, I always like to think that I can influence care in that if I just find the right drugs, help patients understand what their options are, it will help them,” said Ruth Carlos, MD, a radiologist with the University of Michigan Hospital, Ann Arbor. But these things alone are often not enough, because a large proportion of the variation in cancer outcomes is attributable to neighborhood social conditions and the physical environment. “It is incredibly important for us to start to understand just how the neighborhood exerts this effect.”

In a commentary published in the Journal of Clinical Oncology, Dr. Carlos and colleagues highlighted the limitations of previous studies aimed at identifying the causes of racial differences in cancer outcomes. They call upon researchers to turn instead to the long-underexamined biological effects of structural racism and discrimination that contribute to these differences.

In the past, studies on the role of race in health outcomes largely looked at race as a proxy for genetic predisposition. But such an interpretation is flawed, because no genes are specific for a racial or ethnic group, Dr. Carlos and coauthors wrote. Researchers have shown that the vast majority of genetic variation occurs within, rather than between groups.

In an analysis published in Science, researchers reported that within-group differences account for more than 90% of genetic variation.

“Using race in these analyses was not necessarily wrong, but the inferences may have been flawed or incomplete,” Dr. Carlos said. On one hand, looking at genetic predisposition has led to important insights, such as the link between mutations in the BRCA gene and increased risk for breast and ovarian cancer.

However, genetic variation alone is not enough to explain the disparities in cancer outcomes between racial and ethnic groups. The fact that breast cancer can be more aggressive in Black women raises several questions, Dr. Carlos said. Is the cancer worse because Black women have a specific genetic predisposition? Is it worse because Black women exist in a society that marginalizes them and exposes them to increased stress, which in turn produces bad outcomes? Or, could it be both?

Despite progress in the screening, diagnosis and treatment of breast cancer, Black women are 40% more likely to die from the disease than White women. At the time of diagnosis, Black women are more likely to have high-grade, more aggressive breast cancer molecular subtypes, and to have had their cancer spread to the lymph nodes. They also tend to be diagnosed at more advanced stages of breast cancer while at the same time, experience higher rates of false-positive screening results.

Although researchers have hypothesized that genetic differences related to African or European ancestry might contribute, studies have not turned up any differences in cancer susceptibility genes by race. Other factors, such as racial differences in the stage of presentation, molecular subtypes, and disparities in treatment, have also emerged as potential culprits.

In her commentary, Dr. Carlos and colleagues wrote that disparities in breast cancer outcomes previously attributed to race need to be examined from multiple angles. This means looking at both the complex interactions between social conditions and policies, which encompass racism both at the individual and structural level, and stressors such as the experience of discrimination in addition to potential biological and genetic contributions.

Many studies now provide evidence for the harmful effects of racism on health. For breast cancer, specifically, studies also suggest that factors such as racial segregation can influence the stage at which Black women get diagnosed and their likelihood of dying from the disease.

However, an important question that remains is what biological changes occur in women exposed to the kind of persistent low-level stress that is associated with structural racism and discrimination, Dr. Carlos said. “We don’t know what stress pathways actually manifest in the body and how they eventually produce the disease.” Studies to address this issue are important, “especially if you would like to develop interventions to prevent or mitigate disease.”

To address this issue, Dr. Carlos and colleagues called upon the research community to conduct both studies that delineate the underlying biology as well as those that test potential interventions – particularly those associated with breast cancer screening outcomes – to try to shed light on why Black women receive more false positives and diagnoses of more aggressive cancer.

Interventions that can target these specific biological pathways could potentially reduce the negative effects of structural racism and discrimination as well as the effects of other social factors that contribute to breast cancer outcomes, “to ultimately help enhance clinical outcomes and close persistent disparities gaps,” the authors wrote.

Racial differences in cancer outcomes are widespread. Studies indicate that Black people face higher rates of mortality for most cancers than their White counterparts. To bridge this racial gap, researchers need to investigate the biological effects of structural racism and discrimination on cancer outcomes, experts say.

“As a physician, I always like to think that I can influence care in that if I just find the right drugs, help patients understand what their options are, it will help them,” said Ruth Carlos, MD, a radiologist with the University of Michigan Hospital, Ann Arbor. But these things alone are often not enough, because a large proportion of the variation in cancer outcomes is attributable to neighborhood social conditions and the physical environment. “It is incredibly important for us to start to understand just how the neighborhood exerts this effect.”

In a commentary published in the Journal of Clinical Oncology, Dr. Carlos and colleagues highlighted the limitations of previous studies aimed at identifying the causes of racial differences in cancer outcomes. They call upon researchers to turn instead to the long-underexamined biological effects of structural racism and discrimination that contribute to these differences.

In the past, studies on the role of race in health outcomes largely looked at race as a proxy for genetic predisposition. But such an interpretation is flawed, because no genes are specific for a racial or ethnic group, Dr. Carlos and coauthors wrote. Researchers have shown that the vast majority of genetic variation occurs within, rather than between groups.

In an analysis published in Science, researchers reported that within-group differences account for more than 90% of genetic variation.

“Using race in these analyses was not necessarily wrong, but the inferences may have been flawed or incomplete,” Dr. Carlos said. On one hand, looking at genetic predisposition has led to important insights, such as the link between mutations in the BRCA gene and increased risk for breast and ovarian cancer.

However, genetic variation alone is not enough to explain the disparities in cancer outcomes between racial and ethnic groups. The fact that breast cancer can be more aggressive in Black women raises several questions, Dr. Carlos said. Is the cancer worse because Black women have a specific genetic predisposition? Is it worse because Black women exist in a society that marginalizes them and exposes them to increased stress, which in turn produces bad outcomes? Or, could it be both?

Despite progress in the screening, diagnosis and treatment of breast cancer, Black women are 40% more likely to die from the disease than White women. At the time of diagnosis, Black women are more likely to have high-grade, more aggressive breast cancer molecular subtypes, and to have had their cancer spread to the lymph nodes. They also tend to be diagnosed at more advanced stages of breast cancer while at the same time, experience higher rates of false-positive screening results.

Although researchers have hypothesized that genetic differences related to African or European ancestry might contribute, studies have not turned up any differences in cancer susceptibility genes by race. Other factors, such as racial differences in the stage of presentation, molecular subtypes, and disparities in treatment, have also emerged as potential culprits.

In her commentary, Dr. Carlos and colleagues wrote that disparities in breast cancer outcomes previously attributed to race need to be examined from multiple angles. This means looking at both the complex interactions between social conditions and policies, which encompass racism both at the individual and structural level, and stressors such as the experience of discrimination in addition to potential biological and genetic contributions.

Many studies now provide evidence for the harmful effects of racism on health. For breast cancer, specifically, studies also suggest that factors such as racial segregation can influence the stage at which Black women get diagnosed and their likelihood of dying from the disease.

However, an important question that remains is what biological changes occur in women exposed to the kind of persistent low-level stress that is associated with structural racism and discrimination, Dr. Carlos said. “We don’t know what stress pathways actually manifest in the body and how they eventually produce the disease.” Studies to address this issue are important, “especially if you would like to develop interventions to prevent or mitigate disease.”

To address this issue, Dr. Carlos and colleagues called upon the research community to conduct both studies that delineate the underlying biology as well as those that test potential interventions – particularly those associated with breast cancer screening outcomes – to try to shed light on why Black women receive more false positives and diagnoses of more aggressive cancer.

Interventions that can target these specific biological pathways could potentially reduce the negative effects of structural racism and discrimination as well as the effects of other social factors that contribute to breast cancer outcomes, “to ultimately help enhance clinical outcomes and close persistent disparities gaps,” the authors wrote.

Racial differences in cancer outcomes are widespread. Studies indicate that Black people face higher rates of mortality for most cancers than their White counterparts. To bridge this racial gap, researchers need to investigate the biological effects of structural racism and discrimination on cancer outcomes, experts say.

“As a physician, I always like to think that I can influence care in that if I just find the right drugs, help patients understand what their options are, it will help them,” said Ruth Carlos, MD, a radiologist with the University of Michigan Hospital, Ann Arbor. But these things alone are often not enough, because a large proportion of the variation in cancer outcomes is attributable to neighborhood social conditions and the physical environment. “It is incredibly important for us to start to understand just how the neighborhood exerts this effect.”

In a commentary published in the Journal of Clinical Oncology, Dr. Carlos and colleagues highlighted the limitations of previous studies aimed at identifying the causes of racial differences in cancer outcomes. They call upon researchers to turn instead to the long-underexamined biological effects of structural racism and discrimination that contribute to these differences.

In the past, studies on the role of race in health outcomes largely looked at race as a proxy for genetic predisposition. But such an interpretation is flawed, because no genes are specific for a racial or ethnic group, Dr. Carlos and coauthors wrote. Researchers have shown that the vast majority of genetic variation occurs within, rather than between groups.

In an analysis published in Science, researchers reported that within-group differences account for more than 90% of genetic variation.

“Using race in these analyses was not necessarily wrong, but the inferences may have been flawed or incomplete,” Dr. Carlos said. On one hand, looking at genetic predisposition has led to important insights, such as the link between mutations in the BRCA gene and increased risk for breast and ovarian cancer.

However, genetic variation alone is not enough to explain the disparities in cancer outcomes between racial and ethnic groups. The fact that breast cancer can be more aggressive in Black women raises several questions, Dr. Carlos said. Is the cancer worse because Black women have a specific genetic predisposition? Is it worse because Black women exist in a society that marginalizes them and exposes them to increased stress, which in turn produces bad outcomes? Or, could it be both?

Despite progress in the screening, diagnosis and treatment of breast cancer, Black women are 40% more likely to die from the disease than White women. At the time of diagnosis, Black women are more likely to have high-grade, more aggressive breast cancer molecular subtypes, and to have had their cancer spread to the lymph nodes. They also tend to be diagnosed at more advanced stages of breast cancer while at the same time, experience higher rates of false-positive screening results.

Although researchers have hypothesized that genetic differences related to African or European ancestry might contribute, studies have not turned up any differences in cancer susceptibility genes by race. Other factors, such as racial differences in the stage of presentation, molecular subtypes, and disparities in treatment, have also emerged as potential culprits.

In her commentary, Dr. Carlos and colleagues wrote that disparities in breast cancer outcomes previously attributed to race need to be examined from multiple angles. This means looking at both the complex interactions between social conditions and policies, which encompass racism both at the individual and structural level, and stressors such as the experience of discrimination in addition to potential biological and genetic contributions.

Many studies now provide evidence for the harmful effects of racism on health. For breast cancer, specifically, studies also suggest that factors such as racial segregation can influence the stage at which Black women get diagnosed and their likelihood of dying from the disease.

However, an important question that remains is what biological changes occur in women exposed to the kind of persistent low-level stress that is associated with structural racism and discrimination, Dr. Carlos said. “We don’t know what stress pathways actually manifest in the body and how they eventually produce the disease.” Studies to address this issue are important, “especially if you would like to develop interventions to prevent or mitigate disease.”

To address this issue, Dr. Carlos and colleagues called upon the research community to conduct both studies that delineate the underlying biology as well as those that test potential interventions – particularly those associated with breast cancer screening outcomes – to try to shed light on why Black women receive more false positives and diagnoses of more aggressive cancer.

Interventions that can target these specific biological pathways could potentially reduce the negative effects of structural racism and discrimination as well as the effects of other social factors that contribute to breast cancer outcomes, “to ultimately help enhance clinical outcomes and close persistent disparities gaps,” the authors wrote.

Patients with nonmetastatic triple-negative breast cancer lacking progressive death–ligand 1 expression are less responsive to neoadjuvant chemotherapy and face a poorer prognosis than patients with PD-L1–positive tumors, according to a study presented at ESMO Breast Cancer 2022, a meeting of the European Society for Medical Oncology.

“The newly distinct quadruple negative breast cancer subtype could be considered the breast cancer subtype with the poorest outcome,” wrote the authors, who were led by Loay Kassem, MD, a clinical oncology consultant at Cairo (Egypt) University.

Triple-negative breast cancer (TNBC) accounts for 15%-20% of all breast cancers. It tends to be more aggressive and difficult to treat than other subtypes.

Prior research has shown the expression of PD-L1 in tumors is predictive of immunotherapy response in patients with metastatic TNBC. The checkpoint inhibitor pembrolizumab (Keytruda, Merck) was approved by the Food and Drug Administration in 2021 for high-risk, early-stage, triple-negative breast cancer in combination with neoadjuvant chemotherapy, and then continued as a single treatment after surgery.

To determine whether PD-L1 expression could also predict response to chemotherapy in with nonmetastatic TNBC, the researchers conducted a systematic review and meta-analysis of 19 studies that included a total of 2,319 patients with nonmetastatic TBNC. The team examined whether PD-L1 expression could predict pathological complete response to neoadjuvant chemotherapy. PD-L1–positive TNBC were found to be significantly associated with a higher probability of achieving a pathological complete response with neoadjuvant chemotherapy. Long-term studies have shown that PD-L1 positivity was associated with better disease-free survival and overall survival than PD-L1–negative patients.

The researchers also examined RNA sequence data, which showed that PD-L1 expression was indicative of higher levels of expression of key immune-related genes that mediate response to chemotherapy in TNBC.

Dr. Kassem and colleagues suggest that quadruple-negative breast cancer defined by a lack of PD-L1 expression is a distinct subtype of breast cancer associated with the poorest outcomes. Another quadruple-negative breast cancer – a subtype of TNBC where patients lack expression of the androgen receptor, has also been associated with more aggressive disease and poorer response to treatment.

The authors report no funding or conflicts of interest.

Patients with nonmetastatic triple-negative breast cancer lacking progressive death–ligand 1 expression are less responsive to neoadjuvant chemotherapy and face a poorer prognosis than patients with PD-L1–positive tumors, according to a study presented at ESMO Breast Cancer 2022, a meeting of the European Society for Medical Oncology.

“The newly distinct quadruple negative breast cancer subtype could be considered the breast cancer subtype with the poorest outcome,” wrote the authors, who were led by Loay Kassem, MD, a clinical oncology consultant at Cairo (Egypt) University.

Triple-negative breast cancer (TNBC) accounts for 15%-20% of all breast cancers. It tends to be more aggressive and difficult to treat than other subtypes.

Prior research has shown the expression of PD-L1 in tumors is predictive of immunotherapy response in patients with metastatic TNBC. The checkpoint inhibitor pembrolizumab (Keytruda, Merck) was approved by the Food and Drug Administration in 2021 for high-risk, early-stage, triple-negative breast cancer in combination with neoadjuvant chemotherapy, and then continued as a single treatment after surgery.

To determine whether PD-L1 expression could also predict response to chemotherapy in with nonmetastatic TNBC, the researchers conducted a systematic review and meta-analysis of 19 studies that included a total of 2,319 patients with nonmetastatic TBNC. The team examined whether PD-L1 expression could predict pathological complete response to neoadjuvant chemotherapy. PD-L1–positive TNBC were found to be significantly associated with a higher probability of achieving a pathological complete response with neoadjuvant chemotherapy. Long-term studies have shown that PD-L1 positivity was associated with better disease-free survival and overall survival than PD-L1–negative patients.

The researchers also examined RNA sequence data, which showed that PD-L1 expression was indicative of higher levels of expression of key immune-related genes that mediate response to chemotherapy in TNBC.

Dr. Kassem and colleagues suggest that quadruple-negative breast cancer defined by a lack of PD-L1 expression is a distinct subtype of breast cancer associated with the poorest outcomes. Another quadruple-negative breast cancer – a subtype of TNBC where patients lack expression of the androgen receptor, has also been associated with more aggressive disease and poorer response to treatment.

The authors report no funding or conflicts of interest.

Patients with nonmetastatic triple-negative breast cancer lacking progressive death–ligand 1 expression are less responsive to neoadjuvant chemotherapy and face a poorer prognosis than patients with PD-L1–positive tumors, according to a study presented at ESMO Breast Cancer 2022, a meeting of the European Society for Medical Oncology.

“The newly distinct quadruple negative breast cancer subtype could be considered the breast cancer subtype with the poorest outcome,” wrote the authors, who were led by Loay Kassem, MD, a clinical oncology consultant at Cairo (Egypt) University.

Triple-negative breast cancer (TNBC) accounts for 15%-20% of all breast cancers. It tends to be more aggressive and difficult to treat than other subtypes.

Prior research has shown the expression of PD-L1 in tumors is predictive of immunotherapy response in patients with metastatic TNBC. The checkpoint inhibitor pembrolizumab (Keytruda, Merck) was approved by the Food and Drug Administration in 2021 for high-risk, early-stage, triple-negative breast cancer in combination with neoadjuvant chemotherapy, and then continued as a single treatment after surgery.

To determine whether PD-L1 expression could also predict response to chemotherapy in with nonmetastatic TNBC, the researchers conducted a systematic review and meta-analysis of 19 studies that included a total of 2,319 patients with nonmetastatic TBNC. The team examined whether PD-L1 expression could predict pathological complete response to neoadjuvant chemotherapy. PD-L1–positive TNBC were found to be significantly associated with a higher probability of achieving a pathological complete response with neoadjuvant chemotherapy. Long-term studies have shown that PD-L1 positivity was associated with better disease-free survival and overall survival than PD-L1–negative patients.

The researchers also examined RNA sequence data, which showed that PD-L1 expression was indicative of higher levels of expression of key immune-related genes that mediate response to chemotherapy in TNBC.

Dr. Kassem and colleagues suggest that quadruple-negative breast cancer defined by a lack of PD-L1 expression is a distinct subtype of breast cancer associated with the poorest outcomes. Another quadruple-negative breast cancer – a subtype of TNBC where patients lack expression of the androgen receptor, has also been associated with more aggressive disease and poorer response to treatment.

The authors report no funding or conflicts of interest.

A study presented at ESMO Breast Cancer 2022 documents a “significant long-term benefit” among women with breast cancer who were treated with tamoxifen.

The study was a secondary analysis of women with estrogen receptor (ER)-positive HER2-negative breast cancer who were treated between 1976 and 1996 in Sweden.

“Our findings suggest a significant long-term tamoxifen treatment benefit among patients with larger tumors, lymph node-negative tumors, PR-positive tumors, and Ki-67 low tumors,” according to Huma Dar, a doctoral candidate at Karolinska Institute, Stockholm, who authored the study.

The analysis found that patients with tumor size T1c, grade 2, lymph node-negative, PR-positive, and Ki-67-low tumors significantly benefited from treatment with tamoxifen for 20 years. And, for patients with tumor size T2-3, benefited significantly after 10 years of treatment with tamoxifen.

It is known that breast cancer patients with ER-positive tumors have a greater risk of distant recurrence – cancer spreading to tissues and organs far from the original tumor site. The selective estrogen receptor modulator tamoxifen, when used as an adjuvant therapy, has been shown to reduce the risk of tumor recurrence and increase survival in patients with ER-positive breast cancer, but not all patients benefit from this therapy.

To examine the long-term benefit of tamoxifen, Ms. Dar and colleagues analyzed data from randomized clinical trials of tamoxifen that took place in Stockholm between 1976 and 1997. The study included 1,242 patients with ER-positive/HER2-negative breast cancer and included a 20-year follow-up. Researchers looked at the relationship between tumor characteristics – including size, grade, lymph node status, the presence of progesterone receptor (PR), and levels of Ki-67, a protein linked with cell proliferation – and patient outcomes. 

In a related study published last year in JAMA Network Open, Ms. Dar and colleagues examined the long-term effects of tamoxifen in patients with low risk, postmenopausal, and lymph-node negative cancer. They found that patients with larger tumors, lower tumor grade and PR-positive tumors appeared to significantly benefit from tamoxifen treatment for up to 25 years. The team has since extended that work by looking at pre- and postmenopausal as well as low- and high-risk patients, Ms. Dar said. 

“We believe that our findings together with other study findings are important to understand the lifetime risk for patients diagnosed with breast cancer,” Ms. Dar said. “One potential clinical implication is related to tamoxifen benefit, which in our study we don’t see for patients with the smallest tumors.” She said that more studies are needed to confirm this result.

A limitation of this study is that clinical recommendations for disease management and treatment have changed since the initiation of the clinical trials. “The STO-trials were performed before aromatase inhibitors or ovarian function suppression became one of the recommended treatment options for ER-positive breast cancer, and when the duration of tamoxifen therapy was shorter than current recommendations,” Ms. Dar said.

The study was funded by the Swedish Research Council, Swedish Research Council for Health, Working life and Welfare, The Gösta Milton Donation Fund, and Swedish Cancer Society. The authors had no relevant disclosures.

A study presented at ESMO Breast Cancer 2022 documents a “significant long-term benefit” among women with breast cancer who were treated with tamoxifen.

The study was a secondary analysis of women with estrogen receptor (ER)-positive HER2-negative breast cancer who were treated between 1976 and 1996 in Sweden.

“Our findings suggest a significant long-term tamoxifen treatment benefit among patients with larger tumors, lymph node-negative tumors, PR-positive tumors, and Ki-67 low tumors,” according to Huma Dar, a doctoral candidate at Karolinska Institute, Stockholm, who authored the study.

The analysis found that patients with tumor size T1c, grade 2, lymph node-negative, PR-positive, and Ki-67-low tumors significantly benefited from treatment with tamoxifen for 20 years. And, for patients with tumor size T2-3, benefited significantly after 10 years of treatment with tamoxifen.

It is known that breast cancer patients with ER-positive tumors have a greater risk of distant recurrence – cancer spreading to tissues and organs far from the original tumor site. The selective estrogen receptor modulator tamoxifen, when used as an adjuvant therapy, has been shown to reduce the risk of tumor recurrence and increase survival in patients with ER-positive breast cancer, but not all patients benefit from this therapy.

To examine the long-term benefit of tamoxifen, Ms. Dar and colleagues analyzed data from randomized clinical trials of tamoxifen that took place in Stockholm between 1976 and 1997. The study included 1,242 patients with ER-positive/HER2-negative breast cancer and included a 20-year follow-up. Researchers looked at the relationship between tumor characteristics – including size, grade, lymph node status, the presence of progesterone receptor (PR), and levels of Ki-67, a protein linked with cell proliferation – and patient outcomes. 

In a related study published last year in JAMA Network Open, Ms. Dar and colleagues examined the long-term effects of tamoxifen in patients with low risk, postmenopausal, and lymph-node negative cancer. They found that patients with larger tumors, lower tumor grade and PR-positive tumors appeared to significantly benefit from tamoxifen treatment for up to 25 years. The team has since extended that work by looking at pre- and postmenopausal as well as low- and high-risk patients, Ms. Dar said. 

“We believe that our findings together with other study findings are important to understand the lifetime risk for patients diagnosed with breast cancer,” Ms. Dar said. “One potential clinical implication is related to tamoxifen benefit, which in our study we don’t see for patients with the smallest tumors.” She said that more studies are needed to confirm this result.

A limitation of this study is that clinical recommendations for disease management and treatment have changed since the initiation of the clinical trials. “The STO-trials were performed before aromatase inhibitors or ovarian function suppression became one of the recommended treatment options for ER-positive breast cancer, and when the duration of tamoxifen therapy was shorter than current recommendations,” Ms. Dar said.

The study was funded by the Swedish Research Council, Swedish Research Council for Health, Working life and Welfare, The Gösta Milton Donation Fund, and Swedish Cancer Society. The authors had no relevant disclosures.

A study presented at ESMO Breast Cancer 2022 documents a “significant long-term benefit” among women with breast cancer who were treated with tamoxifen.

The study was a secondary analysis of women with estrogen receptor (ER)-positive HER2-negative breast cancer who were treated between 1976 and 1996 in Sweden.

“Our findings suggest a significant long-term tamoxifen treatment benefit among patients with larger tumors, lymph node-negative tumors, PR-positive tumors, and Ki-67 low tumors,” according to Huma Dar, a doctoral candidate at Karolinska Institute, Stockholm, who authored the study.

The analysis found that patients with tumor size T1c, grade 2, lymph node-negative, PR-positive, and Ki-67-low tumors significantly benefited from treatment with tamoxifen for 20 years. And, for patients with tumor size T2-3, benefited significantly after 10 years of treatment with tamoxifen.

It is known that breast cancer patients with ER-positive tumors have a greater risk of distant recurrence – cancer spreading to tissues and organs far from the original tumor site. The selective estrogen receptor modulator tamoxifen, when used as an adjuvant therapy, has been shown to reduce the risk of tumor recurrence and increase survival in patients with ER-positive breast cancer, but not all patients benefit from this therapy.

To examine the long-term benefit of tamoxifen, Ms. Dar and colleagues analyzed data from randomized clinical trials of tamoxifen that took place in Stockholm between 1976 and 1997. The study included 1,242 patients with ER-positive/HER2-negative breast cancer and included a 20-year follow-up. Researchers looked at the relationship between tumor characteristics – including size, grade, lymph node status, the presence of progesterone receptor (PR), and levels of Ki-67, a protein linked with cell proliferation – and patient outcomes. 

In a related study published last year in JAMA Network Open, Ms. Dar and colleagues examined the long-term effects of tamoxifen in patients with low risk, postmenopausal, and lymph-node negative cancer. They found that patients with larger tumors, lower tumor grade and PR-positive tumors appeared to significantly benefit from tamoxifen treatment for up to 25 years. The team has since extended that work by looking at pre- and postmenopausal as well as low- and high-risk patients, Ms. Dar said. 

“We believe that our findings together with other study findings are important to understand the lifetime risk for patients diagnosed with breast cancer,” Ms. Dar said. “One potential clinical implication is related to tamoxifen benefit, which in our study we don’t see for patients with the smallest tumors.” She said that more studies are needed to confirm this result.

A limitation of this study is that clinical recommendations for disease management and treatment have changed since the initiation of the clinical trials. “The STO-trials were performed before aromatase inhibitors or ovarian function suppression became one of the recommended treatment options for ER-positive breast cancer, and when the duration of tamoxifen therapy was shorter than current recommendations,” Ms. Dar said.

The study was funded by the Swedish Research Council, Swedish Research Council for Health, Working life and Welfare, The Gösta Milton Donation Fund, and Swedish Cancer Society. The authors had no relevant disclosures.

Women with ductal carcinoma in situ (DCIS) breast cancer are generally uninformed about their diagnosis and are making uninformed treatment decisions, according to results of a study presented this month at ESMO Breast Cancer 2022, an annual meeting of the European Society for Medical Oncology.

The standard of care for women diagnosed with DCIS includes surgery with or without radiotherapy – even low-risk patients who are increasingly being steered toward active surveillance with annual mammograms. But few patients understand their diagnosis well enough to make informed decisions about treatment, according to a study led by Ellen Engelhardt, PhD, a postdoctoral fellow at The Netherlands Cancer Institute, Amsterdam.

“You’re not able to really have an informed preference until you understand the choices,” she said.

Dr. Engelhardt and colleagues surveyed 200 patients (mean age 59 years) from the LORD study, which is currently underway at The Netherlands Cancer Institute. The women were asked to complete a survey before treatment decisions were made. Their objective was to determine how knowledgeable patients were about DCIS. They found that only 34% of women answered four out of seven questions correctly: 19% of patients believed that DCIS could metastasize to organs other than the breast; 31% did not realize DCIS could progress to invasive breast cancer if left untreated; 79% thought DCIS could always be seen on mammograms; and, 93% said that progression could always be detected before it becomes “too extensive.” Knowledge of DCIS was found not to be associated with patient education level.

Susie X. Sun, MD, FACS, a breast surgeon at the University of Texas MD Anderson Cancer Center, Houston, said the findings clearly highlight a disconnect in communication between doctor and patient.

“I was surprised, because this clearly demonstrates there is a disconnect between what patients are being told by their providers and what is being perceived. It really shows us that we need to do a better job of making sure that our patients understand the information they’re given,” she said.

Dr. Sun, who was not involved in the study, said that DCIS needs to be explained well to patients. When they receive a diagnosis, often all they hear is, “I have breast cancer. It is really important for us to stress to patients how DCIS is different from invasive breast cancer,” she said.

The “Management of Low-risk (grade I and II) DCIS (LORD)” study is one of three studies comparing active surveillance to surgery (with or without radiotherapy).

A limitation of the study presented at ESMO Breast Cancer is that it remains unclear why patients answered questions incorrectly. Was information never communicated to them? Or, did they mishear or misunderstand the doctor? In future studies, Dr. Engelhardt and her colleagues plan to record and analyze audio tapes of consultations to determine where the communication disconnect lies.

Dr. Engelhardt did not disclose any conflicts associated with this work.

Women with ductal carcinoma in situ (DCIS) breast cancer are generally uninformed about their diagnosis and are making uninformed treatment decisions, according to results of a study presented this month at ESMO Breast Cancer 2022, an annual meeting of the European Society for Medical Oncology.

The standard of care for women diagnosed with DCIS includes surgery with or without radiotherapy – even low-risk patients who are increasingly being steered toward active surveillance with annual mammograms. But few patients understand their diagnosis well enough to make informed decisions about treatment, according to a study led by Ellen Engelhardt, PhD, a postdoctoral fellow at The Netherlands Cancer Institute, Amsterdam.

“You’re not able to really have an informed preference until you understand the choices,” she said.

Dr. Engelhardt and colleagues surveyed 200 patients (mean age 59 years) from the LORD study, which is currently underway at The Netherlands Cancer Institute. The women were asked to complete a survey before treatment decisions were made. Their objective was to determine how knowledgeable patients were about DCIS. They found that only 34% of women answered four out of seven questions correctly: 19% of patients believed that DCIS could metastasize to organs other than the breast; 31% did not realize DCIS could progress to invasive breast cancer if left untreated; 79% thought DCIS could always be seen on mammograms; and, 93% said that progression could always be detected before it becomes “too extensive.” Knowledge of DCIS was found not to be associated with patient education level.

Susie X. Sun, MD, FACS, a breast surgeon at the University of Texas MD Anderson Cancer Center, Houston, said the findings clearly highlight a disconnect in communication between doctor and patient.

“I was surprised, because this clearly demonstrates there is a disconnect between what patients are being told by their providers and what is being perceived. It really shows us that we need to do a better job of making sure that our patients understand the information they’re given,” she said.

Dr. Sun, who was not involved in the study, said that DCIS needs to be explained well to patients. When they receive a diagnosis, often all they hear is, “I have breast cancer. It is really important for us to stress to patients how DCIS is different from invasive breast cancer,” she said.

The “Management of Low-risk (grade I and II) DCIS (LORD)” study is one of three studies comparing active surveillance to surgery (with or without radiotherapy).

A limitation of the study presented at ESMO Breast Cancer is that it remains unclear why patients answered questions incorrectly. Was information never communicated to them? Or, did they mishear or misunderstand the doctor? In future studies, Dr. Engelhardt and her colleagues plan to record and analyze audio tapes of consultations to determine where the communication disconnect lies.

Dr. Engelhardt did not disclose any conflicts associated with this work.

Women with ductal carcinoma in situ (DCIS) breast cancer are generally uninformed about their diagnosis and are making uninformed treatment decisions, according to results of a study presented this month at ESMO Breast Cancer 2022, an annual meeting of the European Society for Medical Oncology.

The standard of care for women diagnosed with DCIS includes surgery with or without radiotherapy – even low-risk patients who are increasingly being steered toward active surveillance with annual mammograms. But few patients understand their diagnosis well enough to make informed decisions about treatment, according to a study led by Ellen Engelhardt, PhD, a postdoctoral fellow at The Netherlands Cancer Institute, Amsterdam.

“You’re not able to really have an informed preference until you understand the choices,” she said.

Dr. Engelhardt and colleagues surveyed 200 patients (mean age 59 years) from the LORD study, which is currently underway at The Netherlands Cancer Institute. The women were asked to complete a survey before treatment decisions were made. Their objective was to determine how knowledgeable patients were about DCIS. They found that only 34% of women answered four out of seven questions correctly: 19% of patients believed that DCIS could metastasize to organs other than the breast; 31% did not realize DCIS could progress to invasive breast cancer if left untreated; 79% thought DCIS could always be seen on mammograms; and, 93% said that progression could always be detected before it becomes “too extensive.” Knowledge of DCIS was found not to be associated with patient education level.

Susie X. Sun, MD, FACS, a breast surgeon at the University of Texas MD Anderson Cancer Center, Houston, said the findings clearly highlight a disconnect in communication between doctor and patient.

“I was surprised, because this clearly demonstrates there is a disconnect between what patients are being told by their providers and what is being perceived. It really shows us that we need to do a better job of making sure that our patients understand the information they’re given,” she said.

Dr. Sun, who was not involved in the study, said that DCIS needs to be explained well to patients. When they receive a diagnosis, often all they hear is, “I have breast cancer. It is really important for us to stress to patients how DCIS is different from invasive breast cancer,” she said.

The “Management of Low-risk (grade I and II) DCIS (LORD)” study is one of three studies comparing active surveillance to surgery (with or without radiotherapy).

A limitation of the study presented at ESMO Breast Cancer is that it remains unclear why patients answered questions incorrectly. Was information never communicated to them? Or, did they mishear or misunderstand the doctor? In future studies, Dr. Engelhardt and her colleagues plan to record and analyze audio tapes of consultations to determine where the communication disconnect lies.

Dr. Engelhardt did not disclose any conflicts associated with this work.

Even within the first year of implementation, the Research to Accelerate Cures and Equity (RACE) for Children Act has made an impact.

“In the year prior to RACE implementation, there were no approvals of therapeutics that required pediatric studies,” said Brittany Avin McKelvey, PhD, science policy analyst with Friends of Cancer Research and a childhood cancer survivor. “Within the first year of implementation, almost half of approved therapeutics required pediatric study.”

The legislation was passed by Congress in 2017 and took effect in August 2020. It requires that therapeutics that are approved for adult cancers be tested in pediatric cancers if those drugs are directed at molecular targets relevant for pediatric cancers.

The RACE Act also requires testing of therapeutics that are given an orphan drug designation. Such drugs were previously exempt from pediatric trials.

Dr. McKelvey presented the new findings at the annual meeting of the American Association for Cancer Research.

To evaluate the impact of the RACE Act during the first year of its implementation, her team assessed all the new cancer drugs approved between August 2019 and August 2021.

Nineteen drugs were identified; 63.2% were approved in the year before the RACE Act took effect, and 36.8% were approved after its implementation. The team suspects that the coronavirus pandemic may have contributed to the lower number of post-RACE approvals.

The researchers found that prior to implementation of the RACE Act, none of the approved adult cancer therapeutics were required to be studied in pediatric populations. But more than 90% of those had molecular targets that would have required that they be studied in pediatric cancers had the RACE Act been in place. The majority of these drugs were exempt because of their designation as orphan drugs.

In the post-RACE group, however, 42.9% of approved drugs are required to be studied in pediatric cancers. One example is infigratinib (Truseltiq), a drug for adult cholangiocarcinoma that targets the protein fibroblast growth factor receptor 2 (FGFR2). Truseltiq is an orphan drug – and thus would have been exempt prior to the RACE Act – but it will now be studied in pediatric patients with advanced or metastatic tumors harboring alterations in FGFR2.

“I find these results encouraging, but it is still very early,” said John Maris, MD, an attending physician and professor of pediatrics at the Children’s Hospital of Philadelphia, who was not involved in the study. “This is only 1 year into implementation, and this legislation will be around for a long time.”

In an interview, Dr. McKelvey noted that although a handful of clinical trials for pediatric cancers have been launched since implementation of RACE, many drugs are still being waived for pediatric study even when a relevant mechanism of action is present – largely because the extremely low incidence of many childhood cancers makes it impractical or, in some cases, impossible to conduct such studies. “This highlights the need for additional opportunities to help facilitate and encourage robust pediatric studies,” she said.

The main limitation of the study is that it examined data 1 year after the implementation of the RACE Act; further analysis is needed to determine the full extent of its impact, Dr. McKelvey said. “The true measure of success will be determined by whether increased pediatric studies actually translate to label expansions for pediatric patient populations and access to these therapies.”

The study was supported by funding from Friends of Cancer Research.

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

Even within the first year of implementation, the Research to Accelerate Cures and Equity (RACE) for Children Act has made an impact.

“In the year prior to RACE implementation, there were no approvals of therapeutics that required pediatric studies,” said Brittany Avin McKelvey, PhD, science policy analyst with Friends of Cancer Research and a childhood cancer survivor. “Within the first year of implementation, almost half of approved therapeutics required pediatric study.”

The legislation was passed by Congress in 2017 and took effect in August 2020. It requires that therapeutics that are approved for adult cancers be tested in pediatric cancers if those drugs are directed at molecular targets relevant for pediatric cancers.

The RACE Act also requires testing of therapeutics that are given an orphan drug designation. Such drugs were previously exempt from pediatric trials.

Dr. McKelvey presented the new findings at the annual meeting of the American Association for Cancer Research.

To evaluate the impact of the RACE Act during the first year of its implementation, her team assessed all the new cancer drugs approved between August 2019 and August 2021.

Nineteen drugs were identified; 63.2% were approved in the year before the RACE Act took effect, and 36.8% were approved after its implementation. The team suspects that the coronavirus pandemic may have contributed to the lower number of post-RACE approvals.

The researchers found that prior to implementation of the RACE Act, none of the approved adult cancer therapeutics were required to be studied in pediatric populations. But more than 90% of those had molecular targets that would have required that they be studied in pediatric cancers had the RACE Act been in place. The majority of these drugs were exempt because of their designation as orphan drugs.

In the post-RACE group, however, 42.9% of approved drugs are required to be studied in pediatric cancers. One example is infigratinib (Truseltiq), a drug for adult cholangiocarcinoma that targets the protein fibroblast growth factor receptor 2 (FGFR2). Truseltiq is an orphan drug – and thus would have been exempt prior to the RACE Act – but it will now be studied in pediatric patients with advanced or metastatic tumors harboring alterations in FGFR2.

“I find these results encouraging, but it is still very early,” said John Maris, MD, an attending physician and professor of pediatrics at the Children’s Hospital of Philadelphia, who was not involved in the study. “This is only 1 year into implementation, and this legislation will be around for a long time.”

In an interview, Dr. McKelvey noted that although a handful of clinical trials for pediatric cancers have been launched since implementation of RACE, many drugs are still being waived for pediatric study even when a relevant mechanism of action is present – largely because the extremely low incidence of many childhood cancers makes it impractical or, in some cases, impossible to conduct such studies. “This highlights the need for additional opportunities to help facilitate and encourage robust pediatric studies,” she said.

The main limitation of the study is that it examined data 1 year after the implementation of the RACE Act; further analysis is needed to determine the full extent of its impact, Dr. McKelvey said. “The true measure of success will be determined by whether increased pediatric studies actually translate to label expansions for pediatric patient populations and access to these therapies.”

The study was supported by funding from Friends of Cancer Research.

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

Even within the first year of implementation, the Research to Accelerate Cures and Equity (RACE) for Children Act has made an impact.

“In the year prior to RACE implementation, there were no approvals of therapeutics that required pediatric studies,” said Brittany Avin McKelvey, PhD, science policy analyst with Friends of Cancer Research and a childhood cancer survivor. “Within the first year of implementation, almost half of approved therapeutics required pediatric study.”

The legislation was passed by Congress in 2017 and took effect in August 2020. It requires that therapeutics that are approved for adult cancers be tested in pediatric cancers if those drugs are directed at molecular targets relevant for pediatric cancers.

The RACE Act also requires testing of therapeutics that are given an orphan drug designation. Such drugs were previously exempt from pediatric trials.

Dr. McKelvey presented the new findings at the annual meeting of the American Association for Cancer Research.

To evaluate the impact of the RACE Act during the first year of its implementation, her team assessed all the new cancer drugs approved between August 2019 and August 2021.

Nineteen drugs were identified; 63.2% were approved in the year before the RACE Act took effect, and 36.8% were approved after its implementation. The team suspects that the coronavirus pandemic may have contributed to the lower number of post-RACE approvals.

The researchers found that prior to implementation of the RACE Act, none of the approved adult cancer therapeutics were required to be studied in pediatric populations. But more than 90% of those had molecular targets that would have required that they be studied in pediatric cancers had the RACE Act been in place. The majority of these drugs were exempt because of their designation as orphan drugs.

In the post-RACE group, however, 42.9% of approved drugs are required to be studied in pediatric cancers. One example is infigratinib (Truseltiq), a drug for adult cholangiocarcinoma that targets the protein fibroblast growth factor receptor 2 (FGFR2). Truseltiq is an orphan drug – and thus would have been exempt prior to the RACE Act – but it will now be studied in pediatric patients with advanced or metastatic tumors harboring alterations in FGFR2.

“I find these results encouraging, but it is still very early,” said John Maris, MD, an attending physician and professor of pediatrics at the Children’s Hospital of Philadelphia, who was not involved in the study. “This is only 1 year into implementation, and this legislation will be around for a long time.”

In an interview, Dr. McKelvey noted that although a handful of clinical trials for pediatric cancers have been launched since implementation of RACE, many drugs are still being waived for pediatric study even when a relevant mechanism of action is present – largely because the extremely low incidence of many childhood cancers makes it impractical or, in some cases, impossible to conduct such studies. “This highlights the need for additional opportunities to help facilitate and encourage robust pediatric studies,” she said.

The main limitation of the study is that it examined data 1 year after the implementation of the RACE Act; further analysis is needed to determine the full extent of its impact, Dr. McKelvey said. “The true measure of success will be determined by whether increased pediatric studies actually translate to label expansions for pediatric patient populations and access to these therapies.”

The study was supported by funding from Friends of Cancer Research.

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

In more than 10% of cases in which ductal carcinoma in situ (DCIS) recurs in the same breast, the new lesion is genetically distinct from the original lesion, according to a study presented at the annual meeting of the American Association for Cancer Research.

If these findings of de novo tumor recurrences hold true, “it should change how you should treat the patients in the clinic,” commented lead author Tanjina Kader, PhD, a postdoctoral researcher in the department of oncology at the Peter MacCallum Cancer Centre in the University of Melbourne.

Up to a quarter of cases of DCIS recur, and half of those cases emerge in the form of invasive breast cancer. Currently, all recurrent tumor patients are provided the same treatment on the assumption that all recurrences arise from the primary lesion, Dr. Kader commented.

But the new findings could change this practice. If a patient with DCIS returns to the clinic with a tumor independent of the primary lesion, physicians should consider preventive therapies, such as mastectomy or genetic counseling, she said in an interview.

For their study, Dr. Kader and colleagues gathered patient samples and extracted 67 pairs of primary DCIS and their recurrences from the same breast. They also collected 32 samples from nonrecurrent cases of DCIS.

They then used advanced DNA sequencing methods to conduct detailed molecular analyses in order to determine whether the recurrences were genetically distinct from the original lesion.

The team found that 82% of cases appeared to be clonal – derived from the same ancestral cell as the original tumor – and 18% were nonclonal – arose independently of the original DCIS.

The researchers also identified specific genetic changes, including a mutation in the TP53 gene, that were present in recurrences of DCIS but not in nonrecurrent or nonclonal cases.

“It was surprising to see that nonclonal tumors have a similar genetic profile as nonrecurrent tumors,” Dr. Kader said. This means that, if these genetic changes are used as biomarkers to predict the recurrence of DCIS, they could lead to the undertreatment of patients who could develop nonclonal tumors, since these individuals may be categorized as having a low risk of recurrence, she explained.

“For the last 10 years, everyone has been trying their best to find a biomarker without actually taking into account that independent tumors can actually arise on the same breast independently,” Dr. Kader said.

The main limitation of this study was the lack of DNA from matched healthy cells to compare to the patient samples, said Dr. Kader. Because of the lack of these samples, the study focused only on chromosomal changes.

This study is “highly relevant, as it adds to our knowledge to what extent DCIS can be considered a precursor lesion as well as a risk lesion,” said Jelle Wesseling, MD, PhD, a breast pathologist at the Netherlands Cancer Institute. He was not involved in this research, but his team has also found that primary DCIS lesions and their subsequent events can be clonally unrelated.

Dr. Wesseling said there are still many questions, such as whether inherited genetic variants or the tumor microenvironment contribute to DCIS recurrences. “There is a lot more work to be done here to tease this out in more detail.”

The study was funded by grants from the National Breast Cancer Foundation, the Cancer Council Victoria, and the Victorian Cancer Agency.

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

In more than 10% of cases in which ductal carcinoma in situ (DCIS) recurs in the same breast, the new lesion is genetically distinct from the original lesion, according to a study presented at the annual meeting of the American Association for Cancer Research.

If these findings of de novo tumor recurrences hold true, “it should change how you should treat the patients in the clinic,” commented lead author Tanjina Kader, PhD, a postdoctoral researcher in the department of oncology at the Peter MacCallum Cancer Centre in the University of Melbourne.

Up to a quarter of cases of DCIS recur, and half of those cases emerge in the form of invasive breast cancer. Currently, all recurrent tumor patients are provided the same treatment on the assumption that all recurrences arise from the primary lesion, Dr. Kader commented.

But the new findings could change this practice. If a patient with DCIS returns to the clinic with a tumor independent of the primary lesion, physicians should consider preventive therapies, such as mastectomy or genetic counseling, she said in an interview.

For their study, Dr. Kader and colleagues gathered patient samples and extracted 67 pairs of primary DCIS and their recurrences from the same breast. They also collected 32 samples from nonrecurrent cases of DCIS.

They then used advanced DNA sequencing methods to conduct detailed molecular analyses in order to determine whether the recurrences were genetically distinct from the original lesion.

The team found that 82% of cases appeared to be clonal – derived from the same ancestral cell as the original tumor – and 18% were nonclonal – arose independently of the original DCIS.

The researchers also identified specific genetic changes, including a mutation in the TP53 gene, that were present in recurrences of DCIS but not in nonrecurrent or nonclonal cases.

“It was surprising to see that nonclonal tumors have a similar genetic profile as nonrecurrent tumors,” Dr. Kader said. This means that, if these genetic changes are used as biomarkers to predict the recurrence of DCIS, they could lead to the undertreatment of patients who could develop nonclonal tumors, since these individuals may be categorized as having a low risk of recurrence, she explained.

“For the last 10 years, everyone has been trying their best to find a biomarker without actually taking into account that independent tumors can actually arise on the same breast independently,” Dr. Kader said.

The main limitation of this study was the lack of DNA from matched healthy cells to compare to the patient samples, said Dr. Kader. Because of the lack of these samples, the study focused only on chromosomal changes.

This study is “highly relevant, as it adds to our knowledge to what extent DCIS can be considered a precursor lesion as well as a risk lesion,” said Jelle Wesseling, MD, PhD, a breast pathologist at the Netherlands Cancer Institute. He was not involved in this research, but his team has also found that primary DCIS lesions and their subsequent events can be clonally unrelated.

Dr. Wesseling said there are still many questions, such as whether inherited genetic variants or the tumor microenvironment contribute to DCIS recurrences. “There is a lot more work to be done here to tease this out in more detail.”

The study was funded by grants from the National Breast Cancer Foundation, the Cancer Council Victoria, and the Victorian Cancer Agency.

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

In more than 10% of cases in which ductal carcinoma in situ (DCIS) recurs in the same breast, the new lesion is genetically distinct from the original lesion, according to a study presented at the annual meeting of the American Association for Cancer Research.

If these findings of de novo tumor recurrences hold true, “it should change how you should treat the patients in the clinic,” commented lead author Tanjina Kader, PhD, a postdoctoral researcher in the department of oncology at the Peter MacCallum Cancer Centre in the University of Melbourne.

Up to a quarter of cases of DCIS recur, and half of those cases emerge in the form of invasive breast cancer. Currently, all recurrent tumor patients are provided the same treatment on the assumption that all recurrences arise from the primary lesion, Dr. Kader commented.

But the new findings could change this practice. If a patient with DCIS returns to the clinic with a tumor independent of the primary lesion, physicians should consider preventive therapies, such as mastectomy or genetic counseling, she said in an interview.

For their study, Dr. Kader and colleagues gathered patient samples and extracted 67 pairs of primary DCIS and their recurrences from the same breast. They also collected 32 samples from nonrecurrent cases of DCIS.

They then used advanced DNA sequencing methods to conduct detailed molecular analyses in order to determine whether the recurrences were genetically distinct from the original lesion.

The team found that 82% of cases appeared to be clonal – derived from the same ancestral cell as the original tumor – and 18% were nonclonal – arose independently of the original DCIS.

The researchers also identified specific genetic changes, including a mutation in the TP53 gene, that were present in recurrences of DCIS but not in nonrecurrent or nonclonal cases.

“It was surprising to see that nonclonal tumors have a similar genetic profile as nonrecurrent tumors,” Dr. Kader said. This means that, if these genetic changes are used as biomarkers to predict the recurrence of DCIS, they could lead to the undertreatment of patients who could develop nonclonal tumors, since these individuals may be categorized as having a low risk of recurrence, she explained.

“For the last 10 years, everyone has been trying their best to find a biomarker without actually taking into account that independent tumors can actually arise on the same breast independently,” Dr. Kader said.

The main limitation of this study was the lack of DNA from matched healthy cells to compare to the patient samples, said Dr. Kader. Because of the lack of these samples, the study focused only on chromosomal changes.

This study is “highly relevant, as it adds to our knowledge to what extent DCIS can be considered a precursor lesion as well as a risk lesion,” said Jelle Wesseling, MD, PhD, a breast pathologist at the Netherlands Cancer Institute. He was not involved in this research, but his team has also found that primary DCIS lesions and their subsequent events can be clonally unrelated.

Dr. Wesseling said there are still many questions, such as whether inherited genetic variants or the tumor microenvironment contribute to DCIS recurrences. “There is a lot more work to be done here to tease this out in more detail.”

The study was funded by grants from the National Breast Cancer Foundation, the Cancer Council Victoria, and the Victorian Cancer Agency.

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

People with cancer are often desperate to know what caused their disease. Was it something they did? Something they could have prevented?

vitanovski/Thinkstock.com

In a recent analysis, experts estimated that about 40% of cancers can be explained by known, often modifiable risk factors. Smoking and obesity represent the primary drivers, though a host of other factors – germline mutations, alcohol, infections, or environmental pollutants like asbestos – contribute to cancer risk as well.

But what about the remaining 60% of cancers?

The study suggests that, although many of these cases likely have an underlying lifestyle or environmental component, experts still do not fully understand their origin story. And a small but significant number may simply be caused by chance.

Here’s what experts suspect those missing causes might be, and why they can be so difficult to confirm.
 

Possibility 1: Known risk factors contribute more than we realize

For certain factors, a straight line can be drawn to cancer.

Take smoking, for instance. Decades of research have helped scientists clearly delineate tobacco’s carcinogenic effects. Researchers have pinpointed a unique set of mutations in the tumors of smokers that can be seen when cells grown in a dish are exposed to the carcinogens present in tobacco.

In addition, experts have been able to collect robust data from epidemiologic studies on smoking prevalence as well as associated cancer risks and deaths, in large part because an individual’s lifetime tobacco exposure is fairly easy to measure.

“The evidence for smoking is incredibly consistent,” Paul Brennan, PhD, a cancer epidemiologist at the World Health Organization’s International Agency for Research on Cancer, said in an interview.

For other known risk factors, such as obesity and air pollution, many more questions than answers remain.

Because of the limitations in how such factors are measured, we are likely downplaying their effects, said Richard Martin, PhD, a professor of clinical epidemiology at the University of Bristol (England).

Take obesity. Excess body weight is associated with an increased risk of at least 13 cancers. Although risk estimates vary by study and cancer type, according to a global snapshot from 2012, being overweight or obese accounted for about 4% of all cancers worldwide – 1% in low-income countries and as high as 8% in high-income countries.

However, Dr. Brennan believes “we have underestimated the effect of obesity [on cancer].”

A key reason, he said, is most studies use body mass index to determine whether someone is overweight or obese, but BMI is a poor measure of body fat. BMI does not differentiate between fat and muscle, which means two people with the same height and weight can have the same BMI, even if one is an athlete who eats lean meats and vegetables while the other lives a sedentary life and consumes large quantities of processed foods and alcohol.

On top of that, studies often only calculate a person’s BMI once, and a single measurement can’t tell you how a person’s weight has fluctuated in recent years or across different stages of their life. However, recent analyses suggest that obesity status over time may be more relevant to cancer risk than one-off measures.

In addition, many studies now suggest that alterations to our gut microbes and high blood insulin level – often seen in people who are overweight or obese – may increase the risk of cancer and speed the growth of tumors.

When these additional factors are considered, the impact of excess body fat may ultimately play a much more significant role in cancer risk. In fact, according to Dr. Brennan, “if we estimate [the effects of obesity] properly, it might at some point become the main cause of cancer.”
 

Possibility 2: Environmental or lifestyle factors remain under the radar

Researchers have linked many substances we consume or are exposed to in our daily lives – air pollution, toxins from industrial waste, and highly processed foods – to cancer. But the extent or contribution of potential carcinogens in our surroundings, particularly those found almost everywhere at low levels, is still largely unknown.

One simple reason is the effects of many of these substances remain difficult to assess. For instance, it is much harder to study the impact of pollutants found in food or water, in which a given population will share similar exposure levels versus tobacco, where it is possible to compare a person who smokes a pack of cigarettes a day with a person who does not smoke.

“If you’ve got exposures that are ubiquitous, it can be difficult to discern their [individual] roles,” Dr. Martin said. “There are many causes that we [likely] don’t really know because everyone has been exposed.”

On the flip side, some carcinogenic substances that people encounter for limited periods might be missed if studies are not performed at the time of exposure.

“What’s in the body at age 40 may not reflect what you were exposed at age 5-10 on the playground or soccer field,” said Graham Colditz, MD, PhD, an epidemiologist and public health expert at Washington University, St. Louis. “The technology keeps changing so we can get better measures of what you’ve got exposure to today, but how that relates to 5, 10, 15 years ago is probably very variable.”

In addition, researchers have found that many carcinogens do not cause specific mutations in a cell’s DNA; rather, studies suggest that most carcinogens lead to cancer-promoting changes in cells, such as inflammation.

“We need to think of how potential carcinogens are causing cancer,” Dr. Brennan said. Instead of provoking mutations, potential carcinogens may use a “whole other kind of pathway.” When, for instance, inflammation becomes chronic, it may spur a cascade of events that ultimately leads to cancer.

Finally, not much is known about what causes cancers in low- and middle-income countries. Most of the research to date has been in high-income countries, such the United States, Australia, and parts of Europe.

“There’s a real lack of robust epidemiological studies in other parts of the world, Latin America, Africa, parts of Asia,” Marc Gunter, PhD, a molecular epidemiologist at the IARC, told this news organization.
 

Possibility 3: Some cancers occur by chance

When it comes to cancer risk, an element of chance may be at play. Cancer can occur in individuals who have very little exposure to known carcinogens or have no family history of cancer.

“We all know there are people who get cancer who eat very healthy diets, are never overweight, and never smoke,” Dr. Gunter said. “Then there are people on the other end of the extreme who don’t get cancer.”

But what fraction of cancers are attributable to chance?

A controversial 2017 study published in Science suggested that, based on the rate of cell turnover in healthy tissues in the lung, pancreas, and other parts of the body, only about one-third of cancers could be linked to environmental or genetic factors. The rest, the authors claimed, occurred because of random mutations that accumulated in a person’s DNA – in other words, bad luck.

That study brought on a flood of criticism from scientists who pointed to serious flaws in the work that led the researchers to significantly overestimate the share of chance-related cancers.

The actual proportion of cancers that occur by chance is much lower, according to Dr. Brennan. “If you look at international comparisons [of cancer rates] and take a conservative estimate, you see that maybe 10% or 15% of cancers are really chance.”

Whether some cancers are caused by bad luck or undiscovered risk factors remains an open question.

But the bottom line is many unknown causes of cancer are likely environmental or lifestyle related, which means that, in theory, they can be altered, even prevented.

“There is always going to be some element of chance, but you can modify your chance, depending on your lifestyle and maybe other factors, which we don’t fully understand yet,” Dr. Gunter said.

The good news is that, when it comes to prevention, there are many ways to modify our behaviors – such as consuming fewer processed meats, going for a daily walk, or getting vaccinated against cancer-causing viruses – to improve our chances of living cancer free. And as scientists better understand more about what causes cancer, possibilities for prevention will only grow.

“There is a constant, slow growth [in knowledge] that is lowering the overall risk of cancer,” Dr. Brennan said. “We’re never going to eliminate cancer, but we will be able to control it as a disease.”

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

People with cancer are often desperate to know what caused their disease. Was it something they did? Something they could have prevented?

vitanovski/Thinkstock.com

In a recent analysis, experts estimated that about 40% of cancers can be explained by known, often modifiable risk factors. Smoking and obesity represent the primary drivers, though a host of other factors – germline mutations, alcohol, infections, or environmental pollutants like asbestos – contribute to cancer risk as well.

But what about the remaining 60% of cancers?

The study suggests that, although many of these cases likely have an underlying lifestyle or environmental component, experts still do not fully understand their origin story. And a small but significant number may simply be caused by chance.

Here’s what experts suspect those missing causes might be, and why they can be so difficult to confirm.
 

Possibility 1: Known risk factors contribute more than we realize

For certain factors, a straight line can be drawn to cancer.

Take smoking, for instance. Decades of research have helped scientists clearly delineate tobacco’s carcinogenic effects. Researchers have pinpointed a unique set of mutations in the tumors of smokers that can be seen when cells grown in a dish are exposed to the carcinogens present in tobacco.

In addition, experts have been able to collect robust data from epidemiologic studies on smoking prevalence as well as associated cancer risks and deaths, in large part because an individual’s lifetime tobacco exposure is fairly easy to measure.

“The evidence for smoking is incredibly consistent,” Paul Brennan, PhD, a cancer epidemiologist at the World Health Organization’s International Agency for Research on Cancer, said in an interview.

For other known risk factors, such as obesity and air pollution, many more questions than answers remain.

Because of the limitations in how such factors are measured, we are likely downplaying their effects, said Richard Martin, PhD, a professor of clinical epidemiology at the University of Bristol (England).

Take obesity. Excess body weight is associated with an increased risk of at least 13 cancers. Although risk estimates vary by study and cancer type, according to a global snapshot from 2012, being overweight or obese accounted for about 4% of all cancers worldwide – 1% in low-income countries and as high as 8% in high-income countries.

However, Dr. Brennan believes “we have underestimated the effect of obesity [on cancer].”

A key reason, he said, is most studies use body mass index to determine whether someone is overweight or obese, but BMI is a poor measure of body fat. BMI does not differentiate between fat and muscle, which means two people with the same height and weight can have the same BMI, even if one is an athlete who eats lean meats and vegetables while the other lives a sedentary life and consumes large quantities of processed foods and alcohol.

On top of that, studies often only calculate a person’s BMI once, and a single measurement can’t tell you how a person’s weight has fluctuated in recent years or across different stages of their life. However, recent analyses suggest that obesity status over time may be more relevant to cancer risk than one-off measures.

In addition, many studies now suggest that alterations to our gut microbes and high blood insulin level – often seen in people who are overweight or obese – may increase the risk of cancer and speed the growth of tumors.

When these additional factors are considered, the impact of excess body fat may ultimately play a much more significant role in cancer risk. In fact, according to Dr. Brennan, “if we estimate [the effects of obesity] properly, it might at some point become the main cause of cancer.”
 

Possibility 2: Environmental or lifestyle factors remain under the radar

Researchers have linked many substances we consume or are exposed to in our daily lives – air pollution, toxins from industrial waste, and highly processed foods – to cancer. But the extent or contribution of potential carcinogens in our surroundings, particularly those found almost everywhere at low levels, is still largely unknown.

One simple reason is the effects of many of these substances remain difficult to assess. For instance, it is much harder to study the impact of pollutants found in food or water, in which a given population will share similar exposure levels versus tobacco, where it is possible to compare a person who smokes a pack of cigarettes a day with a person who does not smoke.

“If you’ve got exposures that are ubiquitous, it can be difficult to discern their [individual] roles,” Dr. Martin said. “There are many causes that we [likely] don’t really know because everyone has been exposed.”

On the flip side, some carcinogenic substances that people encounter for limited periods might be missed if studies are not performed at the time of exposure.

“What’s in the body at age 40 may not reflect what you were exposed at age 5-10 on the playground or soccer field,” said Graham Colditz, MD, PhD, an epidemiologist and public health expert at Washington University, St. Louis. “The technology keeps changing so we can get better measures of what you’ve got exposure to today, but how that relates to 5, 10, 15 years ago is probably very variable.”

In addition, researchers have found that many carcinogens do not cause specific mutations in a cell’s DNA; rather, studies suggest that most carcinogens lead to cancer-promoting changes in cells, such as inflammation.

“We need to think of how potential carcinogens are causing cancer,” Dr. Brennan said. Instead of provoking mutations, potential carcinogens may use a “whole other kind of pathway.” When, for instance, inflammation becomes chronic, it may spur a cascade of events that ultimately leads to cancer.

Finally, not much is known about what causes cancers in low- and middle-income countries. Most of the research to date has been in high-income countries, such the United States, Australia, and parts of Europe.

“There’s a real lack of robust epidemiological studies in other parts of the world, Latin America, Africa, parts of Asia,” Marc Gunter, PhD, a molecular epidemiologist at the IARC, told this news organization.
 

Possibility 3: Some cancers occur by chance

When it comes to cancer risk, an element of chance may be at play. Cancer can occur in individuals who have very little exposure to known carcinogens or have no family history of cancer.

“We all know there are people who get cancer who eat very healthy diets, are never overweight, and never smoke,” Dr. Gunter said. “Then there are people on the other end of the extreme who don’t get cancer.”

But what fraction of cancers are attributable to chance?

A controversial 2017 study published in Science suggested that, based on the rate of cell turnover in healthy tissues in the lung, pancreas, and other parts of the body, only about one-third of cancers could be linked to environmental or genetic factors. The rest, the authors claimed, occurred because of random mutations that accumulated in a person’s DNA – in other words, bad luck.

That study brought on a flood of criticism from scientists who pointed to serious flaws in the work that led the researchers to significantly overestimate the share of chance-related cancers.

The actual proportion of cancers that occur by chance is much lower, according to Dr. Brennan. “If you look at international comparisons [of cancer rates] and take a conservative estimate, you see that maybe 10% or 15% of cancers are really chance.”

Whether some cancers are caused by bad luck or undiscovered risk factors remains an open question.

But the bottom line is many unknown causes of cancer are likely environmental or lifestyle related, which means that, in theory, they can be altered, even prevented.

“There is always going to be some element of chance, but you can modify your chance, depending on your lifestyle and maybe other factors, which we don’t fully understand yet,” Dr. Gunter said.

The good news is that, when it comes to prevention, there are many ways to modify our behaviors – such as consuming fewer processed meats, going for a daily walk, or getting vaccinated against cancer-causing viruses – to improve our chances of living cancer free. And as scientists better understand more about what causes cancer, possibilities for prevention will only grow.

“There is a constant, slow growth [in knowledge] that is lowering the overall risk of cancer,” Dr. Brennan said. “We’re never going to eliminate cancer, but we will be able to control it as a disease.”

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

People with cancer are often desperate to know what caused their disease. Was it something they did? Something they could have prevented?

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In a recent analysis, experts estimated that about 40% of cancers can be explained by known, often modifiable risk factors. Smoking and obesity represent the primary drivers, though a host of other factors – germline mutations, alcohol, infections, or environmental pollutants like asbestos – contribute to cancer risk as well.

But what about the remaining 60% of cancers?

The study suggests that, although many of these cases likely have an underlying lifestyle or environmental component, experts still do not fully understand their origin story. And a small but significant number may simply be caused by chance.

Here’s what experts suspect those missing causes might be, and why they can be so difficult to confirm.
 

Possibility 1: Known risk factors contribute more than we realize

For certain factors, a straight line can be drawn to cancer.

Take smoking, for instance. Decades of research have helped scientists clearly delineate tobacco’s carcinogenic effects. Researchers have pinpointed a unique set of mutations in the tumors of smokers that can be seen when cells grown in a dish are exposed to the carcinogens present in tobacco.

In addition, experts have been able to collect robust data from epidemiologic studies on smoking prevalence as well as associated cancer risks and deaths, in large part because an individual’s lifetime tobacco exposure is fairly easy to measure.

“The evidence for smoking is incredibly consistent,” Paul Brennan, PhD, a cancer epidemiologist at the World Health Organization’s International Agency for Research on Cancer, said in an interview.

For other known risk factors, such as obesity and air pollution, many more questions than answers remain.

Because of the limitations in how such factors are measured, we are likely downplaying their effects, said Richard Martin, PhD, a professor of clinical epidemiology at the University of Bristol (England).

Take obesity. Excess body weight is associated with an increased risk of at least 13 cancers. Although risk estimates vary by study and cancer type, according to a global snapshot from 2012, being overweight or obese accounted for about 4% of all cancers worldwide – 1% in low-income countries and as high as 8% in high-income countries.

However, Dr. Brennan believes “we have underestimated the effect of obesity [on cancer].”

A key reason, he said, is most studies use body mass index to determine whether someone is overweight or obese, but BMI is a poor measure of body fat. BMI does not differentiate between fat and muscle, which means two people with the same height and weight can have the same BMI, even if one is an athlete who eats lean meats and vegetables while the other lives a sedentary life and consumes large quantities of processed foods and alcohol.

On top of that, studies often only calculate a person’s BMI once, and a single measurement can’t tell you how a person’s weight has fluctuated in recent years or across different stages of their life. However, recent analyses suggest that obesity status over time may be more relevant to cancer risk than one-off measures.

In addition, many studies now suggest that alterations to our gut microbes and high blood insulin level – often seen in people who are overweight or obese – may increase the risk of cancer and speed the growth of tumors.

When these additional factors are considered, the impact of excess body fat may ultimately play a much more significant role in cancer risk. In fact, according to Dr. Brennan, “if we estimate [the effects of obesity] properly, it might at some point become the main cause of cancer.”
 

Possibility 2: Environmental or lifestyle factors remain under the radar

Researchers have linked many substances we consume or are exposed to in our daily lives – air pollution, toxins from industrial waste, and highly processed foods – to cancer. But the extent or contribution of potential carcinogens in our surroundings, particularly those found almost everywhere at low levels, is still largely unknown.

One simple reason is the effects of many of these substances remain difficult to assess. For instance, it is much harder to study the impact of pollutants found in food or water, in which a given population will share similar exposure levels versus tobacco, where it is possible to compare a person who smokes a pack of cigarettes a day with a person who does not smoke.

“If you’ve got exposures that are ubiquitous, it can be difficult to discern their [individual] roles,” Dr. Martin said. “There are many causes that we [likely] don’t really know because everyone has been exposed.”

On the flip side, some carcinogenic substances that people encounter for limited periods might be missed if studies are not performed at the time of exposure.

“What’s in the body at age 40 may not reflect what you were exposed at age 5-10 on the playground or soccer field,” said Graham Colditz, MD, PhD, an epidemiologist and public health expert at Washington University, St. Louis. “The technology keeps changing so we can get better measures of what you’ve got exposure to today, but how that relates to 5, 10, 15 years ago is probably very variable.”

In addition, researchers have found that many carcinogens do not cause specific mutations in a cell’s DNA; rather, studies suggest that most carcinogens lead to cancer-promoting changes in cells, such as inflammation.

“We need to think of how potential carcinogens are causing cancer,” Dr. Brennan said. Instead of provoking mutations, potential carcinogens may use a “whole other kind of pathway.” When, for instance, inflammation becomes chronic, it may spur a cascade of events that ultimately leads to cancer.

Finally, not much is known about what causes cancers in low- and middle-income countries. Most of the research to date has been in high-income countries, such the United States, Australia, and parts of Europe.

“There’s a real lack of robust epidemiological studies in other parts of the world, Latin America, Africa, parts of Asia,” Marc Gunter, PhD, a molecular epidemiologist at the IARC, told this news organization.
 

Possibility 3: Some cancers occur by chance

When it comes to cancer risk, an element of chance may be at play. Cancer can occur in individuals who have very little exposure to known carcinogens or have no family history of cancer.

“We all know there are people who get cancer who eat very healthy diets, are never overweight, and never smoke,” Dr. Gunter said. “Then there are people on the other end of the extreme who don’t get cancer.”

But what fraction of cancers are attributable to chance?

A controversial 2017 study published in Science suggested that, based on the rate of cell turnover in healthy tissues in the lung, pancreas, and other parts of the body, only about one-third of cancers could be linked to environmental or genetic factors. The rest, the authors claimed, occurred because of random mutations that accumulated in a person’s DNA – in other words, bad luck.

That study brought on a flood of criticism from scientists who pointed to serious flaws in the work that led the researchers to significantly overestimate the share of chance-related cancers.

The actual proportion of cancers that occur by chance is much lower, according to Dr. Brennan. “If you look at international comparisons [of cancer rates] and take a conservative estimate, you see that maybe 10% or 15% of cancers are really chance.”

Whether some cancers are caused by bad luck or undiscovered risk factors remains an open question.

But the bottom line is many unknown causes of cancer are likely environmental or lifestyle related, which means that, in theory, they can be altered, even prevented.

“There is always going to be some element of chance, but you can modify your chance, depending on your lifestyle and maybe other factors, which we don’t fully understand yet,” Dr. Gunter said.

The good news is that, when it comes to prevention, there are many ways to modify our behaviors – such as consuming fewer processed meats, going for a daily walk, or getting vaccinated against cancer-causing viruses – to improve our chances of living cancer free. And as scientists better understand more about what causes cancer, possibilities for prevention will only grow.

“There is a constant, slow growth [in knowledge] that is lowering the overall risk of cancer,” Dr. Brennan said. “We’re never going to eliminate cancer, but we will be able to control it as a disease.”

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