Breast Cancer

A team at Lyon’s Cancer Research Center (CRCL) has revealed the role of an enzyme, PRMT5, in the response to tamoxifen, a drug used to prevent relapse in premenopausal women with breast cancer. The protein could become the first predictive marker of response to tamoxifen.

Muriel Le Romancer, MD, director of research at France’s Institute of Health and Medical Research, explained the issues involved in this discovery in an interview. She jointly led this research along with Olivier Trédan, MD, PhD, oncologist at Lyon’s Léon Bérard Clinic. The research concluded with the publication of a study in EMBO Molecular Medicine. The researchers both head up the CRCL’s hormone resistance, methylation, and breast cancer team.

Although the enzyme’s involvement in the mode of action of tamoxifen has been observed in close to 900 patients with breast cancer, these results need to be validated in other at-risk patient cohorts before the biomarker can be considered for routine use, said Dr. Le Romancer. She estimated that 2 more years of research are needed.

Can you tell us which cases involve the use of tamoxifen and what its mode of action is?

Dr. Le Romancer: Tamoxifen is a hormone therapy used to reduce the risk of breast cancer relapse. It is prescribed to premenopausal women with hormone-sensitive cancer, which equates to roughly 25% of women with breast cancer: 15,000 women each year. The drug, which is taken every day via oral administration, is an estrogen antagonist. By binding to these receptors, it blocks estrogen from mediating its biological effect in the breasts. Aromatase inhibitors are the preferred choice in postmenopausal women, as they have been shown to be more effective. These also have an antiestrogenic effect, but by inhibiting estrogen production.

Tamoxifen therapy is prescribed for a minimum period of 5 years. Despite this, 25% of women treated with tamoxifen relapse. Tamoxifen resistance is unique in that it occurs very late on, generally 10-15 years after starting treatment. This means that it’s really important for us to identify predictive markers of the response to hormone therapy to adapt treatment as best we can. For the moment, the only criteria used to prescribe tamoxifen are patient age and the presence of estrogen receptors within the tumor.

Exactly how would treatment be improved if a decisive predictive marker of response to tamoxifen could be identified?

Dr. Le Romancer: Currently, when a patient’s breast cancer relapses after several years of treatment with tamoxifen, we don’t know if the relapse is linked to tamoxifen resistance or not. This makes it difficult to choose the right treatment to manage such relapses, which remain complicated to treat. Lots of patients die because of metastases.

By predicting the response to tamoxifen using a marker, we will be able to either use another hormone therapy to prevent the relapse or prescribe tamoxifen alongside a molecule that stops resistance from developing. We hope that this will significantly reduce the rate of relapse.

You put forward PRMT5 as a potential predictive marker of response to tamoxifen. What makes you think it could be used in this way?

Dr. Le Romancer: Our research has allowed us to demonstrate that PRMT5, when present in the nuclei of tumor cells, is involved in the mechanisms of action of tamoxifen. Remember that estrogen receptors are located in cell nuclei. For tamoxifen to exert its antitumoral action, PRMT5, an enzyme, needs to enter the nucleus to modify the estrogen receptor. It’s this modification that allows tamoxifen to inhibit tumor growth. The proliferative effect induced by the estrogens is also blocked.

The results of our study showed that high nuclear expression of PRMT5, specifically in the nuclei of breast cancer cells, is associated with a prolonged survival of tamoxifen-treated patients. Until now, we thought this enzyme had an oncogenic role when present in the cytoplasm. It turns out that it also has the opposite effect when acting within the nucleus, at least in this patient cohort: women with hormone-sensitive breast cancer treated with tamoxifen.

What are the next steps in your research before we can begin to think about its use in clinical practice?

Dr. Le Romancer: Our next research will focus on understanding the circumstances surrounding PRMT5 entering and leaving the nucleus. We have also shown that in some patients, tamoxifen causes PRMT5 to enter the cell nucleus. This translocation is only seen in women who respond to tamoxifen, not in those who are resistant to treatment with the drug. All that remains is for us to work out how tamoxifen facilitates this translocation.

Once the elements promoting this translocation have been identified, we will be able to propose a treatment aimed at forcing the enzyme to enter the nucleus and stay there. Eventually, the idea is to combine treatment with antiestrogens with a medicinal product that promotes localization of PRMT5 in the nucleus to guarantee response to tamoxifen. It will be a few years of research before we can apply our findings to clinical practice.

Could we use this biomarker as is just to identify tamoxifen resistance?

Dr. Le Romancer: In the short term, yes, we could use this biomarker to better guide treatment choices at time of diagnosis. We have demonstrated the role of PRMT5 in response to tamoxifen by studying two cohorts of 900 patients with breast cancer receiving treatment at the Léon Bérard Center, Lyon. Before moving on to routine testing, we need to replicate these results in other cohorts, especially in high-risk patients with, for example, greater cell proliferation or those who experience relapse.

The use of this biomarker is based on histological examination of cancer tissue. Single antibody tissue staining targeting PRMT5 reveals the localization of the enzyme in the cells and provides a score evaluating its presence in the nucleus. Using this score, it would be possible to determine the level of response to tamoxifen and decide whether the treatment should be used. This biomarker is the first of its kind undergoing validation as part of the examination of resistance to hormone therapy. We should be able to confirm the findings within the next 2 years.

If clinical tests using this biomarker predict tamoxifen resistance, what alternative treatments are available to these patients?

Dr. Le Romancer: We could give them an aromatase inhibitor or one of the new estrogen antagonists that are currently in development. In a phase 3 study, fulvestrant (Faslodex), for example, demonstrated a significant benefit in treating women with hormone-sensitive advanced breast cancer when administered via injection. The same goes for oral treatment, elacestrant (Orserdu), which has recently been approved by the Food and Drug Administration. These treatments are usually deemed second line after tamoxifen, but they could certainly be used as first-line therapy in resistant patients.

The results obtained from research into novel estrogen antagonists are certainly encouraging. Can tamoxifen retain its prominent position while still ensuring its efficacy?

Dr. Le Romancer: Keeping in mind the current trend for personalized medicine, we should keep as many treatment options open as possible. When a patient relapses, there need to be other treatments available to them. Tamoxifen has been ousted in favor of aromatase inhibitors for postmenopausal women, but it’s still the gold standard for premenopausal women and has been for over 20 years. Despite having been replaced by a novel estrogen antagonist, it will still have a prominent place in the therapeutic arsenal of premenopausal women with breast cancer.

With the development of PRMT5 as a predictive biomarker, we could even see tamoxifen being proposed as first-line therapy for postmenopausal women in whom high levels of PRMT5 are found in the nuclei of their cancer cells. By predicting their response, we could achieve greater efficacy of tamoxifen, compared with aromatase inhibitors. For now, this remains a hypothesis and must be verified in further clinical studies.

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

A team at Lyon’s Cancer Research Center (CRCL) has revealed the role of an enzyme, PRMT5, in the response to tamoxifen, a drug used to prevent relapse in premenopausal women with breast cancer. The protein could become the first predictive marker of response to tamoxifen.

Muriel Le Romancer, MD, director of research at France’s Institute of Health and Medical Research, explained the issues involved in this discovery in an interview. She jointly led this research along with Olivier Trédan, MD, PhD, oncologist at Lyon’s Léon Bérard Clinic. The research concluded with the publication of a study in EMBO Molecular Medicine. The researchers both head up the CRCL’s hormone resistance, methylation, and breast cancer team.

Although the enzyme’s involvement in the mode of action of tamoxifen has been observed in close to 900 patients with breast cancer, these results need to be validated in other at-risk patient cohorts before the biomarker can be considered for routine use, said Dr. Le Romancer. She estimated that 2 more years of research are needed.

Can you tell us which cases involve the use of tamoxifen and what its mode of action is?

Dr. Le Romancer: Tamoxifen is a hormone therapy used to reduce the risk of breast cancer relapse. It is prescribed to premenopausal women with hormone-sensitive cancer, which equates to roughly 25% of women with breast cancer: 15,000 women each year. The drug, which is taken every day via oral administration, is an estrogen antagonist. By binding to these receptors, it blocks estrogen from mediating its biological effect in the breasts. Aromatase inhibitors are the preferred choice in postmenopausal women, as they have been shown to be more effective. These also have an antiestrogenic effect, but by inhibiting estrogen production.

Tamoxifen therapy is prescribed for a minimum period of 5 years. Despite this, 25% of women treated with tamoxifen relapse. Tamoxifen resistance is unique in that it occurs very late on, generally 10-15 years after starting treatment. This means that it’s really important for us to identify predictive markers of the response to hormone therapy to adapt treatment as best we can. For the moment, the only criteria used to prescribe tamoxifen are patient age and the presence of estrogen receptors within the tumor.

Exactly how would treatment be improved if a decisive predictive marker of response to tamoxifen could be identified?

Dr. Le Romancer: Currently, when a patient’s breast cancer relapses after several years of treatment with tamoxifen, we don’t know if the relapse is linked to tamoxifen resistance or not. This makes it difficult to choose the right treatment to manage such relapses, which remain complicated to treat. Lots of patients die because of metastases.

By predicting the response to tamoxifen using a marker, we will be able to either use another hormone therapy to prevent the relapse or prescribe tamoxifen alongside a molecule that stops resistance from developing. We hope that this will significantly reduce the rate of relapse.

You put forward PRMT5 as a potential predictive marker of response to tamoxifen. What makes you think it could be used in this way?

Dr. Le Romancer: Our research has allowed us to demonstrate that PRMT5, when present in the nuclei of tumor cells, is involved in the mechanisms of action of tamoxifen. Remember that estrogen receptors are located in cell nuclei. For tamoxifen to exert its antitumoral action, PRMT5, an enzyme, needs to enter the nucleus to modify the estrogen receptor. It’s this modification that allows tamoxifen to inhibit tumor growth. The proliferative effect induced by the estrogens is also blocked.

The results of our study showed that high nuclear expression of PRMT5, specifically in the nuclei of breast cancer cells, is associated with a prolonged survival of tamoxifen-treated patients. Until now, we thought this enzyme had an oncogenic role when present in the cytoplasm. It turns out that it also has the opposite effect when acting within the nucleus, at least in this patient cohort: women with hormone-sensitive breast cancer treated with tamoxifen.

What are the next steps in your research before we can begin to think about its use in clinical practice?

Dr. Le Romancer: Our next research will focus on understanding the circumstances surrounding PRMT5 entering and leaving the nucleus. We have also shown that in some patients, tamoxifen causes PRMT5 to enter the cell nucleus. This translocation is only seen in women who respond to tamoxifen, not in those who are resistant to treatment with the drug. All that remains is for us to work out how tamoxifen facilitates this translocation.

Once the elements promoting this translocation have been identified, we will be able to propose a treatment aimed at forcing the enzyme to enter the nucleus and stay there. Eventually, the idea is to combine treatment with antiestrogens with a medicinal product that promotes localization of PRMT5 in the nucleus to guarantee response to tamoxifen. It will be a few years of research before we can apply our findings to clinical practice.

Could we use this biomarker as is just to identify tamoxifen resistance?

Dr. Le Romancer: In the short term, yes, we could use this biomarker to better guide treatment choices at time of diagnosis. We have demonstrated the role of PRMT5 in response to tamoxifen by studying two cohorts of 900 patients with breast cancer receiving treatment at the Léon Bérard Center, Lyon. Before moving on to routine testing, we need to replicate these results in other cohorts, especially in high-risk patients with, for example, greater cell proliferation or those who experience relapse.

The use of this biomarker is based on histological examination of cancer tissue. Single antibody tissue staining targeting PRMT5 reveals the localization of the enzyme in the cells and provides a score evaluating its presence in the nucleus. Using this score, it would be possible to determine the level of response to tamoxifen and decide whether the treatment should be used. This biomarker is the first of its kind undergoing validation as part of the examination of resistance to hormone therapy. We should be able to confirm the findings within the next 2 years.

If clinical tests using this biomarker predict tamoxifen resistance, what alternative treatments are available to these patients?

Dr. Le Romancer: We could give them an aromatase inhibitor or one of the new estrogen antagonists that are currently in development. In a phase 3 study, fulvestrant (Faslodex), for example, demonstrated a significant benefit in treating women with hormone-sensitive advanced breast cancer when administered via injection. The same goes for oral treatment, elacestrant (Orserdu), which has recently been approved by the Food and Drug Administration. These treatments are usually deemed second line after tamoxifen, but they could certainly be used as first-line therapy in resistant patients.

The results obtained from research into novel estrogen antagonists are certainly encouraging. Can tamoxifen retain its prominent position while still ensuring its efficacy?

Dr. Le Romancer: Keeping in mind the current trend for personalized medicine, we should keep as many treatment options open as possible. When a patient relapses, there need to be other treatments available to them. Tamoxifen has been ousted in favor of aromatase inhibitors for postmenopausal women, but it’s still the gold standard for premenopausal women and has been for over 20 years. Despite having been replaced by a novel estrogen antagonist, it will still have a prominent place in the therapeutic arsenal of premenopausal women with breast cancer.

With the development of PRMT5 as a predictive biomarker, we could even see tamoxifen being proposed as first-line therapy for postmenopausal women in whom high levels of PRMT5 are found in the nuclei of their cancer cells. By predicting their response, we could achieve greater efficacy of tamoxifen, compared with aromatase inhibitors. For now, this remains a hypothesis and must be verified in further clinical studies.

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

A team at Lyon’s Cancer Research Center (CRCL) has revealed the role of an enzyme, PRMT5, in the response to tamoxifen, a drug used to prevent relapse in premenopausal women with breast cancer. The protein could become the first predictive marker of response to tamoxifen.

Muriel Le Romancer, MD, director of research at France’s Institute of Health and Medical Research, explained the issues involved in this discovery in an interview. She jointly led this research along with Olivier Trédan, MD, PhD, oncologist at Lyon’s Léon Bérard Clinic. The research concluded with the publication of a study in EMBO Molecular Medicine. The researchers both head up the CRCL’s hormone resistance, methylation, and breast cancer team.

Although the enzyme’s involvement in the mode of action of tamoxifen has been observed in close to 900 patients with breast cancer, these results need to be validated in other at-risk patient cohorts before the biomarker can be considered for routine use, said Dr. Le Romancer. She estimated that 2 more years of research are needed.

Can you tell us which cases involve the use of tamoxifen and what its mode of action is?

Dr. Le Romancer: Tamoxifen is a hormone therapy used to reduce the risk of breast cancer relapse. It is prescribed to premenopausal women with hormone-sensitive cancer, which equates to roughly 25% of women with breast cancer: 15,000 women each year. The drug, which is taken every day via oral administration, is an estrogen antagonist. By binding to these receptors, it blocks estrogen from mediating its biological effect in the breasts. Aromatase inhibitors are the preferred choice in postmenopausal women, as they have been shown to be more effective. These also have an antiestrogenic effect, but by inhibiting estrogen production.

Tamoxifen therapy is prescribed for a minimum period of 5 years. Despite this, 25% of women treated with tamoxifen relapse. Tamoxifen resistance is unique in that it occurs very late on, generally 10-15 years after starting treatment. This means that it’s really important for us to identify predictive markers of the response to hormone therapy to adapt treatment as best we can. For the moment, the only criteria used to prescribe tamoxifen are patient age and the presence of estrogen receptors within the tumor.

Exactly how would treatment be improved if a decisive predictive marker of response to tamoxifen could be identified?

Dr. Le Romancer: Currently, when a patient’s breast cancer relapses after several years of treatment with tamoxifen, we don’t know if the relapse is linked to tamoxifen resistance or not. This makes it difficult to choose the right treatment to manage such relapses, which remain complicated to treat. Lots of patients die because of metastases.

By predicting the response to tamoxifen using a marker, we will be able to either use another hormone therapy to prevent the relapse or prescribe tamoxifen alongside a molecule that stops resistance from developing. We hope that this will significantly reduce the rate of relapse.

You put forward PRMT5 as a potential predictive marker of response to tamoxifen. What makes you think it could be used in this way?

Dr. Le Romancer: Our research has allowed us to demonstrate that PRMT5, when present in the nuclei of tumor cells, is involved in the mechanisms of action of tamoxifen. Remember that estrogen receptors are located in cell nuclei. For tamoxifen to exert its antitumoral action, PRMT5, an enzyme, needs to enter the nucleus to modify the estrogen receptor. It’s this modification that allows tamoxifen to inhibit tumor growth. The proliferative effect induced by the estrogens is also blocked.

The results of our study showed that high nuclear expression of PRMT5, specifically in the nuclei of breast cancer cells, is associated with a prolonged survival of tamoxifen-treated patients. Until now, we thought this enzyme had an oncogenic role when present in the cytoplasm. It turns out that it also has the opposite effect when acting within the nucleus, at least in this patient cohort: women with hormone-sensitive breast cancer treated with tamoxifen.

What are the next steps in your research before we can begin to think about its use in clinical practice?

Dr. Le Romancer: Our next research will focus on understanding the circumstances surrounding PRMT5 entering and leaving the nucleus. We have also shown that in some patients, tamoxifen causes PRMT5 to enter the cell nucleus. This translocation is only seen in women who respond to tamoxifen, not in those who are resistant to treatment with the drug. All that remains is for us to work out how tamoxifen facilitates this translocation.

Once the elements promoting this translocation have been identified, we will be able to propose a treatment aimed at forcing the enzyme to enter the nucleus and stay there. Eventually, the idea is to combine treatment with antiestrogens with a medicinal product that promotes localization of PRMT5 in the nucleus to guarantee response to tamoxifen. It will be a few years of research before we can apply our findings to clinical practice.

Could we use this biomarker as is just to identify tamoxifen resistance?

Dr. Le Romancer: In the short term, yes, we could use this biomarker to better guide treatment choices at time of diagnosis. We have demonstrated the role of PRMT5 in response to tamoxifen by studying two cohorts of 900 patients with breast cancer receiving treatment at the Léon Bérard Center, Lyon. Before moving on to routine testing, we need to replicate these results in other cohorts, especially in high-risk patients with, for example, greater cell proliferation or those who experience relapse.

The use of this biomarker is based on histological examination of cancer tissue. Single antibody tissue staining targeting PRMT5 reveals the localization of the enzyme in the cells and provides a score evaluating its presence in the nucleus. Using this score, it would be possible to determine the level of response to tamoxifen and decide whether the treatment should be used. This biomarker is the first of its kind undergoing validation as part of the examination of resistance to hormone therapy. We should be able to confirm the findings within the next 2 years.

If clinical tests using this biomarker predict tamoxifen resistance, what alternative treatments are available to these patients?

Dr. Le Romancer: We could give them an aromatase inhibitor or one of the new estrogen antagonists that are currently in development. In a phase 3 study, fulvestrant (Faslodex), for example, demonstrated a significant benefit in treating women with hormone-sensitive advanced breast cancer when administered via injection. The same goes for oral treatment, elacestrant (Orserdu), which has recently been approved by the Food and Drug Administration. These treatments are usually deemed second line after tamoxifen, but they could certainly be used as first-line therapy in resistant patients.

The results obtained from research into novel estrogen antagonists are certainly encouraging. Can tamoxifen retain its prominent position while still ensuring its efficacy?

Dr. Le Romancer: Keeping in mind the current trend for personalized medicine, we should keep as many treatment options open as possible. When a patient relapses, there need to be other treatments available to them. Tamoxifen has been ousted in favor of aromatase inhibitors for postmenopausal women, but it’s still the gold standard for premenopausal women and has been for over 20 years. Despite having been replaced by a novel estrogen antagonist, it will still have a prominent place in the therapeutic arsenal of premenopausal women with breast cancer.

With the development of PRMT5 as a predictive biomarker, we could even see tamoxifen being proposed as first-line therapy for postmenopausal women in whom high levels of PRMT5 are found in the nuclei of their cancer cells. By predicting their response, we could achieve greater efficacy of tamoxifen, compared with aromatase inhibitors. For now, this remains a hypothesis and must be verified in further clinical studies.

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

Studies have shown that breast cancer survivors have increased rates of age-related conditions, including cardiovascular disease and osteoporosis among others, therefore postulating that the biological aging process may be accelerated in this population.² Among 417 women enrolled in the prospective Sister Study cohort, paired blood samples collected an average of 7.7 years apart compared three epigenetic metrics of biological aging (calculated on the basis of DNA methylation data) between women who were diagnosed and treated for breast cancer (n = 190) vs those who remained breast cancer–free (n = 227) (Kresovich et al). Women diagnosed and treated for breast cancer had higher biological aging metrics than women who were cancer-free at the time of follow-up: PhenoAgeAccel³ (standardized mean difference [β] = 0.13; P = .04), GrimAgeAccel⁴ (β = 0.14; P = .01), and DunedinPACE⁵ (β = 0.37; P < .001). Regarding breast cancer therapies received, the increases in biological aging were most striking for those women who underwent radiation. The effect of cancer treatments, specifically chemotherapy and radiation, on DNA methylation profiles and accelerating the aging process has been demonstrated in prior studies as well.⁶ Future research should strive to improve our understanding of the specific mechanisms underlying these age-related changes, identify ways to affect those which are modifiable, and positively influence long-term cognitive and functional consequences.

The association between cardiometabolic abnormalities, including obesity, hyperinsulinemia, diabetes, hypertension, and dyslipidemia, and an elevated breast cancer risk has been demonstrated in various studies.⁷ Furthermore, dysregulation of obesity-related proteins plays a role in breast cancer development and progression. A study by Xu and colleagues evaluated the temporal relationships and longitudinal associations of body mass index (BMI), cardiometabolic risk score (CRS), and obesity-related protein score (OPS) among 444 healthy women in a breast cancer screening cohort. After adjustment for demographics, lifestyle, and reproductive factors, a 1-kg/m² increase in BMI per year increased CRS in both premenopausal (0.057 unit; P = .025) and postmenopausal women (0.054 unit; P = .033) and increased OPS by 0.588 unit (P = .001) in postmenopausal women. A significant association was also observed between CRS and OPS in postmenopausal women (β = 0.281; P = .034). These results support the importance of weight management and its effect on cardiometabolic and obesity-related parameters in breast cancer prevention. Research focused on lifestyle interventions to modify risk factors and effective implementation of these techniques will contribute to further reducing breast cancer risk.

Additional References

1. García-Albéniz X, Hernán MA, Logan RW, et al. Continuation of annual screening mammography and breast cancer mortality in women older than 70 years. Ann Intern Med. 2020;172(6):381-389. doi: 10.7326/M18-1199
2. Greenlee H, Iribarren C, Rana JS, et al. Risk of cardiovascular disease in women with and without breast cancer: The Pathways Heart Study. J Clin Oncol. 2022;40(15):1647-1658. doi: 10.1200/JCO.21.01736
3. Levine ME, Lu AT, Quach A, et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY). 2018;10(4):573-591. doi: 10.18632/aging.101414
4. Lu AT, Quach A, Wilson JG, et al. DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging (Albany NY). 2019;11(2):303-327. doi: 10.18632/aging.101684
5. Belsky DW, Caspi A, Corcoran DL, et al. DunedinPACE, a DNA methylation biomarker of the pace of aging. eLife. 2022:11:e73420. doi: 10.7554/eLife.73420
6. Sehl ME, Carroll JE, Horvath S, Bower JE. The acute effects of adjuvant radiation and chemotherapy on peripheral blood epigenetic age in early stage breast cancer patients. NPJ Breast Cancer. 2020;6:23. doi: 10.1038/s41523-020-0161-3
7. Nouri M, Mohsenpour MA, Katsiki N, et al. Effect of serum lipid profile on the risk of breast cancer: Systematic review and meta-analysis of 1,628,871 women. J Clin Med. 2022;11(15):4503. doi: 10.3390/jcm11154503

Studies have shown that breast cancer survivors have increased rates of age-related conditions, including cardiovascular disease and osteoporosis among others, therefore postulating that the biological aging process may be accelerated in this population.² Among 417 women enrolled in the prospective Sister Study cohort, paired blood samples collected an average of 7.7 years apart compared three epigenetic metrics of biological aging (calculated on the basis of DNA methylation data) between women who were diagnosed and treated for breast cancer (n = 190) vs those who remained breast cancer–free (n = 227) (Kresovich et al). Women diagnosed and treated for breast cancer had higher biological aging metrics than women who were cancer-free at the time of follow-up: PhenoAgeAccel³ (standardized mean difference [β] = 0.13; P = .04), GrimAgeAccel⁴ (β = 0.14; P = .01), and DunedinPACE⁵ (β = 0.37; P < .001). Regarding breast cancer therapies received, the increases in biological aging were most striking for those women who underwent radiation. The effect of cancer treatments, specifically chemotherapy and radiation, on DNA methylation profiles and accelerating the aging process has been demonstrated in prior studies as well.⁶ Future research should strive to improve our understanding of the specific mechanisms underlying these age-related changes, identify ways to affect those which are modifiable, and positively influence long-term cognitive and functional consequences.

The association between cardiometabolic abnormalities, including obesity, hyperinsulinemia, diabetes, hypertension, and dyslipidemia, and an elevated breast cancer risk has been demonstrated in various studies.⁷ Furthermore, dysregulation of obesity-related proteins plays a role in breast cancer development and progression. A study by Xu and colleagues evaluated the temporal relationships and longitudinal associations of body mass index (BMI), cardiometabolic risk score (CRS), and obesity-related protein score (OPS) among 444 healthy women in a breast cancer screening cohort. After adjustment for demographics, lifestyle, and reproductive factors, a 1-kg/m² increase in BMI per year increased CRS in both premenopausal (0.057 unit; P = .025) and postmenopausal women (0.054 unit; P = .033) and increased OPS by 0.588 unit (P = .001) in postmenopausal women. A significant association was also observed between CRS and OPS in postmenopausal women (β = 0.281; P = .034). These results support the importance of weight management and its effect on cardiometabolic and obesity-related parameters in breast cancer prevention. Research focused on lifestyle interventions to modify risk factors and effective implementation of these techniques will contribute to further reducing breast cancer risk.

Additional References

1. García-Albéniz X, Hernán MA, Logan RW, et al. Continuation of annual screening mammography and breast cancer mortality in women older than 70 years. Ann Intern Med. 2020;172(6):381-389. doi: 10.7326/M18-1199
2. Greenlee H, Iribarren C, Rana JS, et al. Risk of cardiovascular disease in women with and without breast cancer: The Pathways Heart Study. J Clin Oncol. 2022;40(15):1647-1658. doi: 10.1200/JCO.21.01736
3. Levine ME, Lu AT, Quach A, et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY). 2018;10(4):573-591. doi: 10.18632/aging.101414
4. Lu AT, Quach A, Wilson JG, et al. DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging (Albany NY). 2019;11(2):303-327. doi: 10.18632/aging.101684
5. Belsky DW, Caspi A, Corcoran DL, et al. DunedinPACE, a DNA methylation biomarker of the pace of aging. eLife. 2022:11:e73420. doi: 10.7554/eLife.73420
6. Sehl ME, Carroll JE, Horvath S, Bower JE. The acute effects of adjuvant radiation and chemotherapy on peripheral blood epigenetic age in early stage breast cancer patients. NPJ Breast Cancer. 2020;6:23. doi: 10.1038/s41523-020-0161-3
7. Nouri M, Mohsenpour MA, Katsiki N, et al. Effect of serum lipid profile on the risk of breast cancer: Systematic review and meta-analysis of 1,628,871 women. J Clin Med. 2022;11(15):4503. doi: 10.3390/jcm11154503

Studies have shown that breast cancer survivors have increased rates of age-related conditions, including cardiovascular disease and osteoporosis among others, therefore postulating that the biological aging process may be accelerated in this population.² Among 417 women enrolled in the prospective Sister Study cohort, paired blood samples collected an average of 7.7 years apart compared three epigenetic metrics of biological aging (calculated on the basis of DNA methylation data) between women who were diagnosed and treated for breast cancer (n = 190) vs those who remained breast cancer–free (n = 227) (Kresovich et al). Women diagnosed and treated for breast cancer had higher biological aging metrics than women who were cancer-free at the time of follow-up: PhenoAgeAccel³ (standardized mean difference [β] = 0.13; P = .04), GrimAgeAccel⁴ (β = 0.14; P = .01), and DunedinPACE⁵ (β = 0.37; P < .001). Regarding breast cancer therapies received, the increases in biological aging were most striking for those women who underwent radiation. The effect of cancer treatments, specifically chemotherapy and radiation, on DNA methylation profiles and accelerating the aging process has been demonstrated in prior studies as well.⁶ Future research should strive to improve our understanding of the specific mechanisms underlying these age-related changes, identify ways to affect those which are modifiable, and positively influence long-term cognitive and functional consequences.

The association between cardiometabolic abnormalities, including obesity, hyperinsulinemia, diabetes, hypertension, and dyslipidemia, and an elevated breast cancer risk has been demonstrated in various studies.⁷ Furthermore, dysregulation of obesity-related proteins plays a role in breast cancer development and progression. A study by Xu and colleagues evaluated the temporal relationships and longitudinal associations of body mass index (BMI), cardiometabolic risk score (CRS), and obesity-related protein score (OPS) among 444 healthy women in a breast cancer screening cohort. After adjustment for demographics, lifestyle, and reproductive factors, a 1-kg/m² increase in BMI per year increased CRS in both premenopausal (0.057 unit; P = .025) and postmenopausal women (0.054 unit; P = .033) and increased OPS by 0.588 unit (P = .001) in postmenopausal women. A significant association was also observed between CRS and OPS in postmenopausal women (β = 0.281; P = .034). These results support the importance of weight management and its effect on cardiometabolic and obesity-related parameters in breast cancer prevention. Research focused on lifestyle interventions to modify risk factors and effective implementation of these techniques will contribute to further reducing breast cancer risk.

Additional References

1. García-Albéniz X, Hernán MA, Logan RW, et al. Continuation of annual screening mammography and breast cancer mortality in women older than 70 years. Ann Intern Med. 2020;172(6):381-389. doi: 10.7326/M18-1199
2. Greenlee H, Iribarren C, Rana JS, et al. Risk of cardiovascular disease in women with and without breast cancer: The Pathways Heart Study. J Clin Oncol. 2022;40(15):1647-1658. doi: 10.1200/JCO.21.01736
3. Levine ME, Lu AT, Quach A, et al. An epigenetic biomarker of aging for lifespan and healthspan. Aging (Albany NY). 2018;10(4):573-591. doi: 10.18632/aging.101414
4. Lu AT, Quach A, Wilson JG, et al. DNA methylation GrimAge strongly predicts lifespan and healthspan. Aging (Albany NY). 2019;11(2):303-327. doi: 10.18632/aging.101684
5. Belsky DW, Caspi A, Corcoran DL, et al. DunedinPACE, a DNA methylation biomarker of the pace of aging. eLife. 2022:11:e73420. doi: 10.7554/eLife.73420
6. Sehl ME, Carroll JE, Horvath S, Bower JE. The acute effects of adjuvant radiation and chemotherapy on peripheral blood epigenetic age in early stage breast cancer patients. NPJ Breast Cancer. 2020;6:23. doi: 10.1038/s41523-020-0161-3
7. Nouri M, Mohsenpour MA, Katsiki N, et al. Effect of serum lipid profile on the risk of breast cancer: Systematic review and meta-analysis of 1,628,871 women. J Clin Med. 2022;11(15):4503. doi: 10.3390/jcm11154503

People under the age of 50 are becoming more likely to be diagnosed with cancer, according to comprehensive new data.

From 2010 to 2019, the rate of cancer diagnoses rose from 100 to 103 cases per 100,000 people, according to the study, published in JAMA Network Open. The increases were driven by jumps in certain types of cancer and within specific age, racial, and ethnic groups. Researchers analyzed data for more than 560,000 people under age 50 who were diagnosed with cancer during the 9-year period.

Breast cancer remained the most common type of cancer to affect younger people, while the most striking increase was seen in gastrointestinal cancers. The rate of people with GI cancers rose 15%.

Women were more likely to be diagnosed with cancer, whereas the rate of cancer among men under age 50 declined by 5%. When the researchers analyzed the data based on a person’s race or ethnicity, they found that cancer rates were increasing among people who are Asian, Pacific Islander, Hispanic, American Indian, or Alaska Native. The rate of cancer among Black people declined and was steady among White people.

The only age group that saw cancer rates increase was 30- to 39-year-olds. One of the top concerns for younger people with cancer is that there is a greater risk for the cancer to spread.

The cancer rate has been declining among older people, the researchers noted. One doctor told The Washington Post that it’s urgent that the reasons for the increases among young people be understood.

“If we don’t understand what’s causing this risk and we can’t do something to change it, we’re afraid that as time goes on, it’s going to become a bigger and bigger challenge,” said Paul Oberstein, MD, director of the gastrointestinal medical oncology program at NYU Langone’s Perlmutter Cancer Center, New York. He was not involved in the study.

It’s unclear why cancer rates are rising among young people, but some possible reasons are obesity, alcohol use, smoking, poor sleep, sedentary lifestyle, and things in the environment like pollution and carcinogens, the Post reported.

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

People under the age of 50 are becoming more likely to be diagnosed with cancer, according to comprehensive new data.

From 2010 to 2019, the rate of cancer diagnoses rose from 100 to 103 cases per 100,000 people, according to the study, published in JAMA Network Open. The increases were driven by jumps in certain types of cancer and within specific age, racial, and ethnic groups. Researchers analyzed data for more than 560,000 people under age 50 who were diagnosed with cancer during the 9-year period.

Breast cancer remained the most common type of cancer to affect younger people, while the most striking increase was seen in gastrointestinal cancers. The rate of people with GI cancers rose 15%.

Women were more likely to be diagnosed with cancer, whereas the rate of cancer among men under age 50 declined by 5%. When the researchers analyzed the data based on a person’s race or ethnicity, they found that cancer rates were increasing among people who are Asian, Pacific Islander, Hispanic, American Indian, or Alaska Native. The rate of cancer among Black people declined and was steady among White people.

The only age group that saw cancer rates increase was 30- to 39-year-olds. One of the top concerns for younger people with cancer is that there is a greater risk for the cancer to spread.

The cancer rate has been declining among older people, the researchers noted. One doctor told The Washington Post that it’s urgent that the reasons for the increases among young people be understood.

“If we don’t understand what’s causing this risk and we can’t do something to change it, we’re afraid that as time goes on, it’s going to become a bigger and bigger challenge,” said Paul Oberstein, MD, director of the gastrointestinal medical oncology program at NYU Langone’s Perlmutter Cancer Center, New York. He was not involved in the study.

It’s unclear why cancer rates are rising among young people, but some possible reasons are obesity, alcohol use, smoking, poor sleep, sedentary lifestyle, and things in the environment like pollution and carcinogens, the Post reported.

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

People under the age of 50 are becoming more likely to be diagnosed with cancer, according to comprehensive new data.

From 2010 to 2019, the rate of cancer diagnoses rose from 100 to 103 cases per 100,000 people, according to the study, published in JAMA Network Open. The increases were driven by jumps in certain types of cancer and within specific age, racial, and ethnic groups. Researchers analyzed data for more than 560,000 people under age 50 who were diagnosed with cancer during the 9-year period.

Breast cancer remained the most common type of cancer to affect younger people, while the most striking increase was seen in gastrointestinal cancers. The rate of people with GI cancers rose 15%.

Women were more likely to be diagnosed with cancer, whereas the rate of cancer among men under age 50 declined by 5%. When the researchers analyzed the data based on a person’s race or ethnicity, they found that cancer rates were increasing among people who are Asian, Pacific Islander, Hispanic, American Indian, or Alaska Native. The rate of cancer among Black people declined and was steady among White people.

The only age group that saw cancer rates increase was 30- to 39-year-olds. One of the top concerns for younger people with cancer is that there is a greater risk for the cancer to spread.

The cancer rate has been declining among older people, the researchers noted. One doctor told The Washington Post that it’s urgent that the reasons for the increases among young people be understood.

“If we don’t understand what’s causing this risk and we can’t do something to change it, we’re afraid that as time goes on, it’s going to become a bigger and bigger challenge,” said Paul Oberstein, MD, director of the gastrointestinal medical oncology program at NYU Langone’s Perlmutter Cancer Center, New York. He was not involved in the study.

It’s unclear why cancer rates are rising among young people, but some possible reasons are obesity, alcohol use, smoking, poor sleep, sedentary lifestyle, and things in the environment like pollution and carcinogens, the Post reported.

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

Key clinical point: Association of body mass index (BMI) with cardiometabolic risk score (CRS) and obesity-related protein score (OPS) and the relation between CRS and OPS in postmenopausal women indicated that weight control for the reduction of cardiometabolic risks may also help prevent breast cancer (BC).

Major finding: A 1-kg/m² increase in BMI per year increased CRS in both premenopausal (0.057 units; P = .025) and postmenopausal women (0.054 units; P = .033) and increased OPS by 0.588 units (P = .001) in postmenopausal women. A significant association was also observed between CRS and OPS in post-menopausal women (β 0.281, P = .034).

Study details: This longitudinal study included 444 healthy women age 35-64 years.

Disclosures: This study was funded by the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Xu B et al. Temporal relationships between BMI and obesity-related predictors of cardiometabolic and breast cancer risk in a longitudinal cohort. Sci Rep. 2023;13:12361 (Jul 31). doi: 10.1038/s41598-023-39387-w

Key clinical point: Association of body mass index (BMI) with cardiometabolic risk score (CRS) and obesity-related protein score (OPS) and the relation between CRS and OPS in postmenopausal women indicated that weight control for the reduction of cardiometabolic risks may also help prevent breast cancer (BC).

Major finding: A 1-kg/m² increase in BMI per year increased CRS in both premenopausal (0.057 units; P = .025) and postmenopausal women (0.054 units; P = .033) and increased OPS by 0.588 units (P = .001) in postmenopausal women. A significant association was also observed between CRS and OPS in post-menopausal women (β 0.281, P = .034).

Study details: This longitudinal study included 444 healthy women age 35-64 years.

Disclosures: This study was funded by the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Xu B et al. Temporal relationships between BMI and obesity-related predictors of cardiometabolic and breast cancer risk in a longitudinal cohort. Sci Rep. 2023;13:12361 (Jul 31). doi: 10.1038/s41598-023-39387-w

Key clinical point: Association of body mass index (BMI) with cardiometabolic risk score (CRS) and obesity-related protein score (OPS) and the relation between CRS and OPS in postmenopausal women indicated that weight control for the reduction of cardiometabolic risks may also help prevent breast cancer (BC).

Major finding: A 1-kg/m² increase in BMI per year increased CRS in both premenopausal (0.057 units; P = .025) and postmenopausal women (0.054 units; P = .033) and increased OPS by 0.588 units (P = .001) in postmenopausal women. A significant association was also observed between CRS and OPS in post-menopausal women (β 0.281, P = .034).

Study details: This longitudinal study included 444 healthy women age 35-64 years.

Disclosures: This study was funded by the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Xu B et al. Temporal relationships between BMI and obesity-related predictors of cardiometabolic and breast cancer risk in a longitudinal cohort. Sci Rep. 2023;13:12361 (Jul 31). doi: 10.1038/s41598-023-39387-w

Key clinical point: Women, particularly post-menopausal women, with diabetes mellitus (DM) faced a higher risk of developing different subtypes of breast cancer (BC).

Major finding: Women with DM had a 20% greater risk of developing BC (risk ratio [RR] 1.20; 95% CI 1.11-1.29), with the risk persisting only in postmenopausal women (RR 1.12; 95% CI 1.07-1.17). The risk of estrogen receptor-negative BC (RR 1.16; 95% CI 1.04-1.30) and triple-negative BC (RR 1.41; 95% CI 1.01-1.96) subtypes increased in patients with DM.

Study details: This meta-analysis of 70 cohort and case-control studies included premenopausal and postmenopausal women with or without DM who developed BC.

Disclosures: JM Chan received funding from the Cancer League Foundation. RE Graff, the corresponding author, declared being supported by a Young Investigator Award from the Prostate Cancer Foundation.

Source: Xiong F et al. Diabetes and incidence of breast cancer and its molecular subtypes: A systematic review and meta-analysis. Diabetes Metab Res Rev. 2023;e3709 (Aug 7). doi: 10.1002/dmrr.3709

Key clinical point: Women, particularly post-menopausal women, with diabetes mellitus (DM) faced a higher risk of developing different subtypes of breast cancer (BC).

Major finding: Women with DM had a 20% greater risk of developing BC (risk ratio [RR] 1.20; 95% CI 1.11-1.29), with the risk persisting only in postmenopausal women (RR 1.12; 95% CI 1.07-1.17). The risk of estrogen receptor-negative BC (RR 1.16; 95% CI 1.04-1.30) and triple-negative BC (RR 1.41; 95% CI 1.01-1.96) subtypes increased in patients with DM.

Study details: This meta-analysis of 70 cohort and case-control studies included premenopausal and postmenopausal women with or without DM who developed BC.

Disclosures: JM Chan received funding from the Cancer League Foundation. RE Graff, the corresponding author, declared being supported by a Young Investigator Award from the Prostate Cancer Foundation.

Source: Xiong F et al. Diabetes and incidence of breast cancer and its molecular subtypes: A systematic review and meta-analysis. Diabetes Metab Res Rev. 2023;e3709 (Aug 7). doi: 10.1002/dmrr.3709

Key clinical point: Women, particularly post-menopausal women, with diabetes mellitus (DM) faced a higher risk of developing different subtypes of breast cancer (BC).

Major finding: Women with DM had a 20% greater risk of developing BC (risk ratio [RR] 1.20; 95% CI 1.11-1.29), with the risk persisting only in postmenopausal women (RR 1.12; 95% CI 1.07-1.17). The risk of estrogen receptor-negative BC (RR 1.16; 95% CI 1.04-1.30) and triple-negative BC (RR 1.41; 95% CI 1.01-1.96) subtypes increased in patients with DM.

Study details: This meta-analysis of 70 cohort and case-control studies included premenopausal and postmenopausal women with or without DM who developed BC.

Disclosures: JM Chan received funding from the Cancer League Foundation. RE Graff, the corresponding author, declared being supported by a Young Investigator Award from the Prostate Cancer Foundation.

Source: Xiong F et al. Diabetes and incidence of breast cancer and its molecular subtypes: A systematic review and meta-analysis. Diabetes Metab Res Rev. 2023;e3709 (Aug 7). doi: 10.1002/dmrr.3709

Key clinical point: Use of metformin reduced the incidence of paclitaxel-induced peripheral neuropathy in patients with breast cancer (BC).

Major finding: A significantly lower proportion of patients receiving metformin vs placebo had grade 2 paclitaxel-induced peripheral neuropathy (36.1% vs 67.6%; P = .007).

Study details: This parallel-group trial included 73 patients with BC who were randomly assigned to receive either metformin or placebo 1 week before initiating treatment with paclitaxel.

Disclosures: This study did not disclose any funding source. The authors declared no conflicts of interest.

Source: Bakry HM et al. Efficacy of metformin in prevention of paclitaxel-induced peripheral neuropathy in breast cancer patients: A randomized controlled trial. Front Pharmacol. 2023;14:1181312 (Jul 31). doi: 10.3389/fphar.2023.1181312

Key clinical point: Use of metformin reduced the incidence of paclitaxel-induced peripheral neuropathy in patients with breast cancer (BC).

Major finding: A significantly lower proportion of patients receiving metformin vs placebo had grade 2 paclitaxel-induced peripheral neuropathy (36.1% vs 67.6%; P = .007).

Study details: This parallel-group trial included 73 patients with BC who were randomly assigned to receive either metformin or placebo 1 week before initiating treatment with paclitaxel.

Disclosures: This study did not disclose any funding source. The authors declared no conflicts of interest.

Source: Bakry HM et al. Efficacy of metformin in prevention of paclitaxel-induced peripheral neuropathy in breast cancer patients: A randomized controlled trial. Front Pharmacol. 2023;14:1181312 (Jul 31). doi: 10.3389/fphar.2023.1181312

Key clinical point: Use of metformin reduced the incidence of paclitaxel-induced peripheral neuropathy in patients with breast cancer (BC).

Major finding: A significantly lower proportion of patients receiving metformin vs placebo had grade 2 paclitaxel-induced peripheral neuropathy (36.1% vs 67.6%; P = .007).

Study details: This parallel-group trial included 73 patients with BC who were randomly assigned to receive either metformin or placebo 1 week before initiating treatment with paclitaxel.

Disclosures: This study did not disclose any funding source. The authors declared no conflicts of interest.

Source: Bakry HM et al. Efficacy of metformin in prevention of paclitaxel-induced peripheral neuropathy in breast cancer patients: A randomized controlled trial. Front Pharmacol. 2023;14:1181312 (Jul 31). doi: 10.3389/fphar.2023.1181312

Key clinical point: In postmenopausal women with estrogen receptor-positive (ER+) human epidermal growth factor receptor 2-positive (HER2+) advanced or metastatic breast cancer (BC), 500 mg fulvestrant (F500) with or without anti-HER2 therapy prolonged the time to treatment failure (TTF) in first- and second-line settings and improved the overall survival (OS) outcomes in those who received chemotherapy-free initial systemic therapy and required longer time to chemotherapy (TTC).

Major finding: F500 improved TTF in the first- and second-line vs third- or later-lines of therapy (6.6 vs 3.7 months; P = .014) and OS in patients who received chemotherapy-free initial systemic therapy and had TTC ≥ 3 years vs < 3 years (hazard ratio 0.32; P = .001).

Study details: This study analyzed 94 postmenopausal women with ER+/HER2+ advanced or metastatic BC from the SAFARI study who received F500 with or without anti-HER2 therapy.

Disclosures: This study was sponsored by Japan Breast Cancer Research Group and AstraZeneca. Several authors declared ties with various sources, including the funding agencies.

Source: Masuyama M et al. Fulvestrant with or without anti-HER2 therapy in patients in a postmenopausal hormonal state and with ER-positive HER2-positive advanced or metastatic breast cancer: A subgroup analysis of data from the Safari study (JBCRG-C06). Cancer Med. 2023 (Aug 1). doi: 10.1002/cam4.6390

Key clinical point: In postmenopausal women with estrogen receptor-positive (ER+) human epidermal growth factor receptor 2-positive (HER2+) advanced or metastatic breast cancer (BC), 500 mg fulvestrant (F500) with or without anti-HER2 therapy prolonged the time to treatment failure (TTF) in first- and second-line settings and improved the overall survival (OS) outcomes in those who received chemotherapy-free initial systemic therapy and required longer time to chemotherapy (TTC).

Major finding: F500 improved TTF in the first- and second-line vs third- or later-lines of therapy (6.6 vs 3.7 months; P = .014) and OS in patients who received chemotherapy-free initial systemic therapy and had TTC ≥ 3 years vs < 3 years (hazard ratio 0.32; P = .001).

Study details: This study analyzed 94 postmenopausal women with ER+/HER2+ advanced or metastatic BC from the SAFARI study who received F500 with or without anti-HER2 therapy.

Disclosures: This study was sponsored by Japan Breast Cancer Research Group and AstraZeneca. Several authors declared ties with various sources, including the funding agencies.

Source: Masuyama M et al. Fulvestrant with or without anti-HER2 therapy in patients in a postmenopausal hormonal state and with ER-positive HER2-positive advanced or metastatic breast cancer: A subgroup analysis of data from the Safari study (JBCRG-C06). Cancer Med. 2023 (Aug 1). doi: 10.1002/cam4.6390

Key clinical point: In postmenopausal women with estrogen receptor-positive (ER+) human epidermal growth factor receptor 2-positive (HER2+) advanced or metastatic breast cancer (BC), 500 mg fulvestrant (F500) with or without anti-HER2 therapy prolonged the time to treatment failure (TTF) in first- and second-line settings and improved the overall survival (OS) outcomes in those who received chemotherapy-free initial systemic therapy and required longer time to chemotherapy (TTC).

Major finding: F500 improved TTF in the first- and second-line vs third- or later-lines of therapy (6.6 vs 3.7 months; P = .014) and OS in patients who received chemotherapy-free initial systemic therapy and had TTC ≥ 3 years vs < 3 years (hazard ratio 0.32; P = .001).

Study details: This study analyzed 94 postmenopausal women with ER+/HER2+ advanced or metastatic BC from the SAFARI study who received F500 with or without anti-HER2 therapy.

Disclosures: This study was sponsored by Japan Breast Cancer Research Group and AstraZeneca. Several authors declared ties with various sources, including the funding agencies.

Source: Masuyama M et al. Fulvestrant with or without anti-HER2 therapy in patients in a postmenopausal hormonal state and with ER-positive HER2-positive advanced or metastatic breast cancer: A subgroup analysis of data from the Safari study (JBCRG-C06). Cancer Med. 2023 (Aug 1). doi: 10.1002/cam4.6390

Key clinical point: Adjuvant radiotherapy (RT) following breast-conserving surgery (BCS) improved survival outcomes in women age ≥ 70 years with T1-2N0 estrogen receptor-negative (ER−) breast cancer (BC); however, patients age ≥ 80 years or those with T1mic+T1a, T1b tumors did not benefit from it.

Major finding: Overall survival (hazard ratio [HR] 0.62; P < .001) and BC-specific survival (HR 0.71; P = .002) improved significantly in patients who received vs did not receive adjuvant RT. Patients age ≥ 80 years (P = .056) or with clinical stage T1mic+T1a (P = .543) or T1b (P = .329) tumors did not show improvement in OS after receiving RT.

Study details: This study included 4201 women with T1-2N0 ER− BC (from the Surveillance, Epidemiology, and End Results [SEER] study) who were age ≥ 70 years and underwent BCS, of which 2811 women received adjuvant RT.

Disclosures: This study was supported by the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Chen C et al. The effect of adjuvant radiotherapy after breast-conserving surgery in elderly women with T1-2N0 estrogen receptor-negative breast cancer. PLoS One. 2023;18(8):e0288078 (Aug 3). doi: 10.1371/journal.pone.0288078

Key clinical point: Adjuvant radiotherapy (RT) following breast-conserving surgery (BCS) improved survival outcomes in women age ≥ 70 years with T1-2N0 estrogen receptor-negative (ER−) breast cancer (BC); however, patients age ≥ 80 years or those with T1mic+T1a, T1b tumors did not benefit from it.

Major finding: Overall survival (hazard ratio [HR] 0.62; P < .001) and BC-specific survival (HR 0.71; P = .002) improved significantly in patients who received vs did not receive adjuvant RT. Patients age ≥ 80 years (P = .056) or with clinical stage T1mic+T1a (P = .543) or T1b (P = .329) tumors did not show improvement in OS after receiving RT.

Study details: This study included 4201 women with T1-2N0 ER− BC (from the Surveillance, Epidemiology, and End Results [SEER] study) who were age ≥ 70 years and underwent BCS, of which 2811 women received adjuvant RT.

Disclosures: This study was supported by the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Chen C et al. The effect of adjuvant radiotherapy after breast-conserving surgery in elderly women with T1-2N0 estrogen receptor-negative breast cancer. PLoS One. 2023;18(8):e0288078 (Aug 3). doi: 10.1371/journal.pone.0288078

Key clinical point: Adjuvant radiotherapy (RT) following breast-conserving surgery (BCS) improved survival outcomes in women age ≥ 70 years with T1-2N0 estrogen receptor-negative (ER−) breast cancer (BC); however, patients age ≥ 80 years or those with T1mic+T1a, T1b tumors did not benefit from it.

Major finding: Overall survival (hazard ratio [HR] 0.62; P < .001) and BC-specific survival (HR 0.71; P = .002) improved significantly in patients who received vs did not receive adjuvant RT. Patients age ≥ 80 years (P = .056) or with clinical stage T1mic+T1a (P = .543) or T1b (P = .329) tumors did not show improvement in OS after receiving RT.

Study details: This study included 4201 women with T1-2N0 ER− BC (from the Surveillance, Epidemiology, and End Results [SEER] study) who were age ≥ 70 years and underwent BCS, of which 2811 women received adjuvant RT.

Disclosures: This study was supported by the National Natural Science Foundation of China and other sources. The authors declared no conflicts of interest.

Source: Chen C et al. The effect of adjuvant radiotherapy after breast-conserving surgery in elderly women with T1-2N0 estrogen receptor-negative breast cancer. PLoS One. 2023;18(8):e0288078 (Aug 3). doi: 10.1371/journal.pone.0288078

Key clinical point: Decreased levels of plasma apolipoprotein M (APOM) were associated with worsened mortality outcomes in patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor-2 negative (HER2−) metastatic breast cancer (BC).

Major finding: Mean baseline plasma APOM levels were significantly lower in patients who had deceased vs survived during the 24-month follow-up period (42.7 vs 52.2 µg/mL; P = .003), and the doubling of plasma APOM levels was associated with an improvement in the overall survival outcomes (adjusted hazard ratio 0.23; P = .001).

Study details: This study measured APOM plasma levels in 75 patients with ER+/HER2− metastatic BC.

Disclosures: This study was partly sponsored by the European Regional Development fund. The authors declared no conflicts of interest.

Source: Muendlein A et al. Plasma apolipoprotein M predicts overall survival in metastatic breast cancer patients. Breast Cancer Res Treat. 2023 (Jul 25). doi: 10.1007/s10549-023-07045-4

Key clinical point: Decreased levels of plasma apolipoprotein M (APOM) were associated with worsened mortality outcomes in patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor-2 negative (HER2−) metastatic breast cancer (BC).

Major finding: Mean baseline plasma APOM levels were significantly lower in patients who had deceased vs survived during the 24-month follow-up period (42.7 vs 52.2 µg/mL; P = .003), and the doubling of plasma APOM levels was associated with an improvement in the overall survival outcomes (adjusted hazard ratio 0.23; P = .001).

Study details: This study measured APOM plasma levels in 75 patients with ER+/HER2− metastatic BC.

Disclosures: This study was partly sponsored by the European Regional Development fund. The authors declared no conflicts of interest.

Source: Muendlein A et al. Plasma apolipoprotein M predicts overall survival in metastatic breast cancer patients. Breast Cancer Res Treat. 2023 (Jul 25). doi: 10.1007/s10549-023-07045-4

Key clinical point: Decreased levels of plasma apolipoprotein M (APOM) were associated with worsened mortality outcomes in patients with estrogen receptor-positive (ER+), human epidermal growth factor receptor-2 negative (HER2−) metastatic breast cancer (BC).

Major finding: Mean baseline plasma APOM levels were significantly lower in patients who had deceased vs survived during the 24-month follow-up period (42.7 vs 52.2 µg/mL; P = .003), and the doubling of plasma APOM levels was associated with an improvement in the overall survival outcomes (adjusted hazard ratio 0.23; P = .001).

Study details: This study measured APOM plasma levels in 75 patients with ER+/HER2− metastatic BC.

Disclosures: This study was partly sponsored by the European Regional Development fund. The authors declared no conflicts of interest.

Source: Muendlein A et al. Plasma apolipoprotein M predicts overall survival in metastatic breast cancer patients. Breast Cancer Res Treat. 2023 (Jul 25). doi: 10.1007/s10549-023-07045-4

Key clinical point: Omission of axillary lymph node dissection (ALND) was associated with lymph node understaging but had no impact on systemic therapy recommendations in patients with clinically node-positive breast cancer (cN+ BC).

Major finding: A higher proportion of patients undergoing ALND vs receiving axillary radiotherapy (ART) were detected with ≥ 4 positive nodes (58.9% vs 33.8%). ALND was not associated with the proportion of patients receiving adjuvant chemotherapy after upfront surgery (adjusted odds ratio [aOR] 0.72; 95% CI 0.19-2.67) or systemic therapy after neoadjuvant chemotherapy (aOR 0.86; 95% CI 0.43-1.70).

Study details: Findings are from a prospective, observational cohort study including 500 patients with cN+ BC who underwent tailored axillary surgery and were randomly assigned to undergo ALND or receive ART.

Disclosures: This study was supported by the Swiss State Secretariat for Education, Research and Innovation, and other sources. Some authors declared receiving grants, personal fees, speaker fees, patient fees or having other ties with various sources including the funding source.

Source: Weber WP et al and the TAXIS Study Writing Group . Association of axillary dissection with systemic therapy in patients with clinically node-positive breast cancer. JAMA Surg. 2023 (Jul 19). doi: 10.1001/jamasurg.2023.2840

Key clinical point: Omission of axillary lymph node dissection (ALND) was associated with lymph node understaging but had no impact on systemic therapy recommendations in patients with clinically node-positive breast cancer (cN+ BC).

Major finding: A higher proportion of patients undergoing ALND vs receiving axillary radiotherapy (ART) were detected with ≥ 4 positive nodes (58.9% vs 33.8%). ALND was not associated with the proportion of patients receiving adjuvant chemotherapy after upfront surgery (adjusted odds ratio [aOR] 0.72; 95% CI 0.19-2.67) or systemic therapy after neoadjuvant chemotherapy (aOR 0.86; 95% CI 0.43-1.70).

Study details: Findings are from a prospective, observational cohort study including 500 patients with cN+ BC who underwent tailored axillary surgery and were randomly assigned to undergo ALND or receive ART.

Disclosures: This study was supported by the Swiss State Secretariat for Education, Research and Innovation, and other sources. Some authors declared receiving grants, personal fees, speaker fees, patient fees or having other ties with various sources including the funding source.

Source: Weber WP et al and the TAXIS Study Writing Group . Association of axillary dissection with systemic therapy in patients with clinically node-positive breast cancer. JAMA Surg. 2023 (Jul 19). doi: 10.1001/jamasurg.2023.2840

Key clinical point: Omission of axillary lymph node dissection (ALND) was associated with lymph node understaging but had no impact on systemic therapy recommendations in patients with clinically node-positive breast cancer (cN+ BC).

Major finding: A higher proportion of patients undergoing ALND vs receiving axillary radiotherapy (ART) were detected with ≥ 4 positive nodes (58.9% vs 33.8%). ALND was not associated with the proportion of patients receiving adjuvant chemotherapy after upfront surgery (adjusted odds ratio [aOR] 0.72; 95% CI 0.19-2.67) or systemic therapy after neoadjuvant chemotherapy (aOR 0.86; 95% CI 0.43-1.70).

Study details: Findings are from a prospective, observational cohort study including 500 patients with cN+ BC who underwent tailored axillary surgery and were randomly assigned to undergo ALND or receive ART.

Disclosures: This study was supported by the Swiss State Secretariat for Education, Research and Innovation, and other sources. Some authors declared receiving grants, personal fees, speaker fees, patient fees or having other ties with various sources including the funding source.

Source: Weber WP et al and the TAXIS Study Writing Group . Association of axillary dissection with systemic therapy in patients with clinically node-positive breast cancer. JAMA Surg. 2023 (Jul 19). doi: 10.1001/jamasurg.2023.2840