Breast Cancer

I’m often in the position of caring for patients after they’ve stopped active cancer treatments, but before they’ve made the decision to enroll in hospice. They remain under my care until they feel emotionally ready, or until their care needs have escalated to the point in which hospice is unavoidable.

Jenny, a mom in her 50s with metastatic pancreatic cancer, stopped coming to the clinic. She lived about 40 minutes away from the clinic and was no longer receiving treatment. The car rides were painful and difficult for her. I held weekly video visits with her for 2 months before she eventually went to hospice and passed away. Before she died, she shared with me her sadness that her oncologist – who had taken care of her for 3 years – had “washed his hands of [me].” She rarely heard from him after their final conversation in the clinic when he informed her that she was no longer a candidate for further therapy. The sense of abandonment Jenny described was visceral and devastating. With her permission, I let her oncology team know how she felt and they reached out to her just 1 week before her death. After she died, her husband told me how meaningful it had been for the whole family to hear from Jenny’s oncologist who told them that she had done everything possible to fight her cancer and that “no stone was left unturned.” Her husband felt this final conversation provided Jenny with the closure she needed to pass away peacefully.

Transitioning from active therapy to symptom management

Switching gears from an all-out pursuit of active therapy to focusing on cancer symptoms is often a scary transition for patients and their families. The transition is often viewed as a movement away from hope and optimism to “giving up the fight.” Whether you agree with the warrior language or not, many patients still describe their journey in these terms and thus, experience enrollment in hospice as a sense of having failed.

The sense of failure can be compounded by feelings of abandonment by oncology providers when they are referred without much guidance or continuity through the hospice enrollment process. Unfortunately, the consequences of suboptimal hospice transitions can be damaging, especially for the mental health and well-being of the patient and their surviving loved ones. Hospice transitions seem to reside in an area of clinical practice that is overlooked or, in my experience they are considered an afterthought by many oncologists.

When managed poorly, hospice transitions can easily lead to patient and family harm, which is a claim supported by research. A qualitative study published in 2019 included 92 caregivers of patients with terminal cancer. The authors found three common pathways for end-of-life transitions – a frictionless transition in which the patient and family are well prepared in advance by their oncologist; a more turbulent transition in which patient and family had direct conversations with their oncologist about the incurability of the disease and the lack of efficacy of further treatments, but were given no guidance on prognosis; and a third type of transition marked by abrupt shifts toward end-of-life care occurring in extremis and typically in the hospital.

In the latter two groups, caregivers felt their loved ones died very quickly after stopping treatment, taking them by surprise and leaving them rushing to put end-of-life care plans in place without much support from their oncologists. In the last group, caregivers shared they received their first prognostic information from the hospital or ICU doctor caring for their actively dying loved one, leaving them with a sense of anger and betrayal toward their oncologist for allowing them to be so ill-prepared.

A Japanese survey published in 2018 in The Oncologist of families of cancer patients who had passed away under hospice care over a 2-year period (2012-2014), found that about one-quarter felt abandoned by oncologists. Several factors that were associated with feeling either more or less abandonment. Spouses of patients, patients aged less than 60 years, and patients whose oncologists informed them that there was “nothing more to do” felt more abandoned by oncologists; whereas families for whom the oncologist provided reassurance about the trajectory of care, recommended hospice, and engaged with a palliative care team felt less abandoned by oncologists. Families who felt more abandoned had higher levels of depression and grief when measured with standardized instruments.
 

‘Don’t just put in the hospice order and walk away’

Fortunately, there are a few low-resource interventions that can improve the quality of care-to-hospice transitions and prevent the sense of abandonment felt by many patients and families.

First, don’t just put in the hospice order and walk away. Designate a staffer in your office to contact hospice directly, ensure all medical records are faxed and received, and update the patient and family on this progress throughout the transition. Taking care of details like these ensures the patient enrolls in hospice in a timely manner and reduces the chance the patient, who is likely to be quite sick at this point, will end up in the hospital despite your best efforts to get hospice involved.

Make sure the patient and family understand that you are still their oncologist and still available to them. If they want to continue care with you, have them name you as the “non–hospice-attending physician” so that you can continue to bill for telemedicine and office visits using the terminal diagnosis (with a billing modifier). This does not mean that you will be expected to manage the patient’s hospice problem list or respond to hospice nurse calls at 2 a.m. – the hospice doctor will still do this. It just ensures that patients do not receive a bill if you continue to see them.

If ongoing office or video visits are too much for the patient and family, consider assigning a member of your team to call the patient and family on a weekly basis to check in and offer support. A small 2018 pilot study aimed at improving communication found that when caregivers of advanced cancer patients transitioning to hospice received weekly supportive phone calls by a member of their oncology team (typically a nurse or nurse practitioner), they felt emotionally supported, had good continuity of care throughout the hospice enrollment, and appreciated the ability to have closure with their oncology team. In other words, a sense of abandonment was prevented and the patient-provider relationship was actually deepened through the transition.

These suggestions are not rocket science – they are simple, obvious ways to try to restore patient-centeredness to a transition that for providers can seem routine, but for patients and families is often the first time they have confronted the reality that death is approaching. That reality is terrifying and overwhelming. Patients and caregivers need our support more during hospice transitions than at any other point during their cancer journey – except perhaps at diagnosis.

As with Jenny, my patient who felt abandoned, all it took was a single call by her oncology team to restore the trust and heal the sense of feeling forsaken by the people who cared for her for years. Sometimes, even just one more phone call can feel like a lot to a chronically overburdened provider – but what a difference a simple call can make.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

I’m often in the position of caring for patients after they’ve stopped active cancer treatments, but before they’ve made the decision to enroll in hospice. They remain under my care until they feel emotionally ready, or until their care needs have escalated to the point in which hospice is unavoidable.

Jenny, a mom in her 50s with metastatic pancreatic cancer, stopped coming to the clinic. She lived about 40 minutes away from the clinic and was no longer receiving treatment. The car rides were painful and difficult for her. I held weekly video visits with her for 2 months before she eventually went to hospice and passed away. Before she died, she shared with me her sadness that her oncologist – who had taken care of her for 3 years – had “washed his hands of [me].” She rarely heard from him after their final conversation in the clinic when he informed her that she was no longer a candidate for further therapy. The sense of abandonment Jenny described was visceral and devastating. With her permission, I let her oncology team know how she felt and they reached out to her just 1 week before her death. After she died, her husband told me how meaningful it had been for the whole family to hear from Jenny’s oncologist who told them that she had done everything possible to fight her cancer and that “no stone was left unturned.” Her husband felt this final conversation provided Jenny with the closure she needed to pass away peacefully.

Transitioning from active therapy to symptom management

Switching gears from an all-out pursuit of active therapy to focusing on cancer symptoms is often a scary transition for patients and their families. The transition is often viewed as a movement away from hope and optimism to “giving up the fight.” Whether you agree with the warrior language or not, many patients still describe their journey in these terms and thus, experience enrollment in hospice as a sense of having failed.

The sense of failure can be compounded by feelings of abandonment by oncology providers when they are referred without much guidance or continuity through the hospice enrollment process. Unfortunately, the consequences of suboptimal hospice transitions can be damaging, especially for the mental health and well-being of the patient and their surviving loved ones. Hospice transitions seem to reside in an area of clinical practice that is overlooked or, in my experience they are considered an afterthought by many oncologists.

When managed poorly, hospice transitions can easily lead to patient and family harm, which is a claim supported by research. A qualitative study published in 2019 included 92 caregivers of patients with terminal cancer. The authors found three common pathways for end-of-life transitions – a frictionless transition in which the patient and family are well prepared in advance by their oncologist; a more turbulent transition in which patient and family had direct conversations with their oncologist about the incurability of the disease and the lack of efficacy of further treatments, but were given no guidance on prognosis; and a third type of transition marked by abrupt shifts toward end-of-life care occurring in extremis and typically in the hospital.

In the latter two groups, caregivers felt their loved ones died very quickly after stopping treatment, taking them by surprise and leaving them rushing to put end-of-life care plans in place without much support from their oncologists. In the last group, caregivers shared they received their first prognostic information from the hospital or ICU doctor caring for their actively dying loved one, leaving them with a sense of anger and betrayal toward their oncologist for allowing them to be so ill-prepared.

A Japanese survey published in 2018 in The Oncologist of families of cancer patients who had passed away under hospice care over a 2-year period (2012-2014), found that about one-quarter felt abandoned by oncologists. Several factors that were associated with feeling either more or less abandonment. Spouses of patients, patients aged less than 60 years, and patients whose oncologists informed them that there was “nothing more to do” felt more abandoned by oncologists; whereas families for whom the oncologist provided reassurance about the trajectory of care, recommended hospice, and engaged with a palliative care team felt less abandoned by oncologists. Families who felt more abandoned had higher levels of depression and grief when measured with standardized instruments.
 

‘Don’t just put in the hospice order and walk away’

Fortunately, there are a few low-resource interventions that can improve the quality of care-to-hospice transitions and prevent the sense of abandonment felt by many patients and families.

First, don’t just put in the hospice order and walk away. Designate a staffer in your office to contact hospice directly, ensure all medical records are faxed and received, and update the patient and family on this progress throughout the transition. Taking care of details like these ensures the patient enrolls in hospice in a timely manner and reduces the chance the patient, who is likely to be quite sick at this point, will end up in the hospital despite your best efforts to get hospice involved.

Make sure the patient and family understand that you are still their oncologist and still available to them. If they want to continue care with you, have them name you as the “non–hospice-attending physician” so that you can continue to bill for telemedicine and office visits using the terminal diagnosis (with a billing modifier). This does not mean that you will be expected to manage the patient’s hospice problem list or respond to hospice nurse calls at 2 a.m. – the hospice doctor will still do this. It just ensures that patients do not receive a bill if you continue to see them.

If ongoing office or video visits are too much for the patient and family, consider assigning a member of your team to call the patient and family on a weekly basis to check in and offer support. A small 2018 pilot study aimed at improving communication found that when caregivers of advanced cancer patients transitioning to hospice received weekly supportive phone calls by a member of their oncology team (typically a nurse or nurse practitioner), they felt emotionally supported, had good continuity of care throughout the hospice enrollment, and appreciated the ability to have closure with their oncology team. In other words, a sense of abandonment was prevented and the patient-provider relationship was actually deepened through the transition.

These suggestions are not rocket science – they are simple, obvious ways to try to restore patient-centeredness to a transition that for providers can seem routine, but for patients and families is often the first time they have confronted the reality that death is approaching. That reality is terrifying and overwhelming. Patients and caregivers need our support more during hospice transitions than at any other point during their cancer journey – except perhaps at diagnosis.

As with Jenny, my patient who felt abandoned, all it took was a single call by her oncology team to restore the trust and heal the sense of feeling forsaken by the people who cared for her for years. Sometimes, even just one more phone call can feel like a lot to a chronically overburdened provider – but what a difference a simple call can make.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

I’m often in the position of caring for patients after they’ve stopped active cancer treatments, but before they’ve made the decision to enroll in hospice. They remain under my care until they feel emotionally ready, or until their care needs have escalated to the point in which hospice is unavoidable.

Jenny, a mom in her 50s with metastatic pancreatic cancer, stopped coming to the clinic. She lived about 40 minutes away from the clinic and was no longer receiving treatment. The car rides were painful and difficult for her. I held weekly video visits with her for 2 months before she eventually went to hospice and passed away. Before she died, she shared with me her sadness that her oncologist – who had taken care of her for 3 years – had “washed his hands of [me].” She rarely heard from him after their final conversation in the clinic when he informed her that she was no longer a candidate for further therapy. The sense of abandonment Jenny described was visceral and devastating. With her permission, I let her oncology team know how she felt and they reached out to her just 1 week before her death. After she died, her husband told me how meaningful it had been for the whole family to hear from Jenny’s oncologist who told them that she had done everything possible to fight her cancer and that “no stone was left unturned.” Her husband felt this final conversation provided Jenny with the closure she needed to pass away peacefully.

Transitioning from active therapy to symptom management

Switching gears from an all-out pursuit of active therapy to focusing on cancer symptoms is often a scary transition for patients and their families. The transition is often viewed as a movement away from hope and optimism to “giving up the fight.” Whether you agree with the warrior language or not, many patients still describe their journey in these terms and thus, experience enrollment in hospice as a sense of having failed.

The sense of failure can be compounded by feelings of abandonment by oncology providers when they are referred without much guidance or continuity through the hospice enrollment process. Unfortunately, the consequences of suboptimal hospice transitions can be damaging, especially for the mental health and well-being of the patient and their surviving loved ones. Hospice transitions seem to reside in an area of clinical practice that is overlooked or, in my experience they are considered an afterthought by many oncologists.

When managed poorly, hospice transitions can easily lead to patient and family harm, which is a claim supported by research. A qualitative study published in 2019 included 92 caregivers of patients with terminal cancer. The authors found three common pathways for end-of-life transitions – a frictionless transition in which the patient and family are well prepared in advance by their oncologist; a more turbulent transition in which patient and family had direct conversations with their oncologist about the incurability of the disease and the lack of efficacy of further treatments, but were given no guidance on prognosis; and a third type of transition marked by abrupt shifts toward end-of-life care occurring in extremis and typically in the hospital.

In the latter two groups, caregivers felt their loved ones died very quickly after stopping treatment, taking them by surprise and leaving them rushing to put end-of-life care plans in place without much support from their oncologists. In the last group, caregivers shared they received their first prognostic information from the hospital or ICU doctor caring for their actively dying loved one, leaving them with a sense of anger and betrayal toward their oncologist for allowing them to be so ill-prepared.

A Japanese survey published in 2018 in The Oncologist of families of cancer patients who had passed away under hospice care over a 2-year period (2012-2014), found that about one-quarter felt abandoned by oncologists. Several factors that were associated with feeling either more or less abandonment. Spouses of patients, patients aged less than 60 years, and patients whose oncologists informed them that there was “nothing more to do” felt more abandoned by oncologists; whereas families for whom the oncologist provided reassurance about the trajectory of care, recommended hospice, and engaged with a palliative care team felt less abandoned by oncologists. Families who felt more abandoned had higher levels of depression and grief when measured with standardized instruments.
 

‘Don’t just put in the hospice order and walk away’

Fortunately, there are a few low-resource interventions that can improve the quality of care-to-hospice transitions and prevent the sense of abandonment felt by many patients and families.

First, don’t just put in the hospice order and walk away. Designate a staffer in your office to contact hospice directly, ensure all medical records are faxed and received, and update the patient and family on this progress throughout the transition. Taking care of details like these ensures the patient enrolls in hospice in a timely manner and reduces the chance the patient, who is likely to be quite sick at this point, will end up in the hospital despite your best efforts to get hospice involved.

Make sure the patient and family understand that you are still their oncologist and still available to them. If they want to continue care with you, have them name you as the “non–hospice-attending physician” so that you can continue to bill for telemedicine and office visits using the terminal diagnosis (with a billing modifier). This does not mean that you will be expected to manage the patient’s hospice problem list or respond to hospice nurse calls at 2 a.m. – the hospice doctor will still do this. It just ensures that patients do not receive a bill if you continue to see them.

If ongoing office or video visits are too much for the patient and family, consider assigning a member of your team to call the patient and family on a weekly basis to check in and offer support. A small 2018 pilot study aimed at improving communication found that when caregivers of advanced cancer patients transitioning to hospice received weekly supportive phone calls by a member of their oncology team (typically a nurse or nurse practitioner), they felt emotionally supported, had good continuity of care throughout the hospice enrollment, and appreciated the ability to have closure with their oncology team. In other words, a sense of abandonment was prevented and the patient-provider relationship was actually deepened through the transition.

These suggestions are not rocket science – they are simple, obvious ways to try to restore patient-centeredness to a transition that for providers can seem routine, but for patients and families is often the first time they have confronted the reality that death is approaching. That reality is terrifying and overwhelming. Patients and caregivers need our support more during hospice transitions than at any other point during their cancer journey – except perhaps at diagnosis.

As with Jenny, my patient who felt abandoned, all it took was a single call by her oncology team to restore the trust and heal the sense of feeling forsaken by the people who cared for her for years. Sometimes, even just one more phone call can feel like a lot to a chronically overburdened provider – but what a difference a simple call can make.

Ms. D’Ambruoso is a hospice and palliative care nurse practitioner for UCLA Health Cancer Care, Santa Monica, Calif.

BERLIN – Some breast cancer specialists still have misconceptions about the appropriate use of multigene signatures in making prognostic and treatment decisions in early-stage disease, a European survey suggests.

The authors found, for instance, that while most specialists agreed that molecular intrinsic subtypes had clinical utility for understanding prognosis in early-stage hormone receptor (HR)–positive disease and for identifying patients for whom chemotherapy could be safely avoided, about 1 in 4 experts either disagreed or felt neutral about the use of signatures in these settings.

Similarly, almost 75% of respondents felt that these signatures were not useful in the triple-negative or metastatic setting, but a small percentage believed they were, and about 10% were neutral.

“Considering that breast cancer multigene signatures were developed in the post menopausal HR+/HER2- early breast cancer setting, the fact that some experts consider [them] useful in triple-negative, HER2+ breast cancer or in the metastatic setting corroborates a misunderstanding on how to interpret the results,” study author Giuseppe Curigliano, MD, PhD, associate professor of medical oncology at the University of Milan, and colleagues wrote.

Dr. Curigliano, who is also head of the Division of Early Drug Development at the European Institute of Oncology, presented the survey findings on May 4 at the European Society for Medical Oncology (ESMO BCC) Breast Cancer Congress.

Although several breast cancer multigene signatures are available to profile early breast cancer, little information exists on how these signatures should be used in clinical practice.

To investigate, Dr. Curigliano and colleagues convened a scientific committee of eight breast cancer experts to develop a Delphi questionnaire to examine respondents’ opinions and uses of these signatures.

The questionnaire asked about the clinical utility of multigene signatures in breast cancer and recommendations for their use in clinical practice.

In all, 133 breast cancer specialists from 11 European countries completed the questionnaire. Respondents were about 49 years old on average, and most (86.5%) worked in a teaching hospital. More than 72% were medical oncologists; 12% were pathologists.

Consensus was considered to be reached when 70% or more of the respondents were in agreement on a topic.

Participants had “extensive experience in the management of breast cancer patients and have been using breast cancer multigene signatures in clinical practice,” Dr. Curigliano said.

Almost all respondents (93.6%) reported using breast cancer multigene signatures routinely or in selected patients, and 73.4% had more than 5 years of experience with them.

Overall, more than 70% of respondents agreed that identifying tumor intrinsic subtype via gene expression profiling was important in making prognostic and treatment decisions; however, a consensus was not reached on the use of immunohistochemistry.

In addition, most respondents (76%) agreed that identifying breast cancer molecular intrinsic subtypes had clinical utility for prognosis in early-stage HR-positive disease and for identifying patients for whom chemotherapy can be safely avoided (75%). However, in both cases, about one-quarter of respondents either disagreed or felt neutral.

No consensus was reached on the clinical utility of these subtypes for selecting the most appropriate chemotherapy treatment – two-thirds disagreed, while 13% agreed and 17% felt neutral.

When deciding on the use of chemotherapy in the adjuvant setting in early node-negative breast cancer, 88% of respondents felt that breast cancer multigene signatures were important. Moreover, 75% considered such signatures important when deciding whether to use chemotherapy in the adjuvant setting for patients with one to three positive lymph nodes. However, no consensus was reached on the utility of signatures for deciding whether to extend endocrine therapy in either setting.

When examining the usefulness of signatures in more special settings, the authors found that the vast majority (90%) of respondents believed that multigene signatures had clinical utility for postmenopausal early breast cancer patients, and 82% did not consider signatures clinically useful in the early-stage HER2-overexpressed setting.

In addition, 74% thought that breast cancer multigene signatures were not useful in triple-negative disease or in the metastatic setting.

Respondents did not reach a consensus on the clinical utility of multigene signatures in the neoadjuvant setting – only 27% considered them useful, and almost half did not.

The “low percentage” of respondents using the signatures in the neoadjuvant setting and the “misconception regarding the predictive value of these tests on chemotherapy benefits suggest there is still room for training on results interpretation [for breast cancer multigene signatures],” the authors write.

The study was sponsored by Veracyte. Dr. Curigliano has relationships with Pfizer, Novartis, Lilly, Roche, Seattle Genetics, Celltrion, and Veracyte. No other relevant financial relationships were disclosed.

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

This article was updated 5/9/22.

BERLIN – Some breast cancer specialists still have misconceptions about the appropriate use of multigene signatures in making prognostic and treatment decisions in early-stage disease, a European survey suggests.

The authors found, for instance, that while most specialists agreed that molecular intrinsic subtypes had clinical utility for understanding prognosis in early-stage hormone receptor (HR)–positive disease and for identifying patients for whom chemotherapy could be safely avoided, about 1 in 4 experts either disagreed or felt neutral about the use of signatures in these settings.

Similarly, almost 75% of respondents felt that these signatures were not useful in the triple-negative or metastatic setting, but a small percentage believed they were, and about 10% were neutral.

“Considering that breast cancer multigene signatures were developed in the post menopausal HR+/HER2- early breast cancer setting, the fact that some experts consider [them] useful in triple-negative, HER2+ breast cancer or in the metastatic setting corroborates a misunderstanding on how to interpret the results,” study author Giuseppe Curigliano, MD, PhD, associate professor of medical oncology at the University of Milan, and colleagues wrote.

Dr. Curigliano, who is also head of the Division of Early Drug Development at the European Institute of Oncology, presented the survey findings on May 4 at the European Society for Medical Oncology (ESMO BCC) Breast Cancer Congress.

Although several breast cancer multigene signatures are available to profile early breast cancer, little information exists on how these signatures should be used in clinical practice.

To investigate, Dr. Curigliano and colleagues convened a scientific committee of eight breast cancer experts to develop a Delphi questionnaire to examine respondents’ opinions and uses of these signatures.

The questionnaire asked about the clinical utility of multigene signatures in breast cancer and recommendations for their use in clinical practice.

In all, 133 breast cancer specialists from 11 European countries completed the questionnaire. Respondents were about 49 years old on average, and most (86.5%) worked in a teaching hospital. More than 72% were medical oncologists; 12% were pathologists.

Consensus was considered to be reached when 70% or more of the respondents were in agreement on a topic.

Participants had “extensive experience in the management of breast cancer patients and have been using breast cancer multigene signatures in clinical practice,” Dr. Curigliano said.

Almost all respondents (93.6%) reported using breast cancer multigene signatures routinely or in selected patients, and 73.4% had more than 5 years of experience with them.

Overall, more than 70% of respondents agreed that identifying tumor intrinsic subtype via gene expression profiling was important in making prognostic and treatment decisions; however, a consensus was not reached on the use of immunohistochemistry.

In addition, most respondents (76%) agreed that identifying breast cancer molecular intrinsic subtypes had clinical utility for prognosis in early-stage HR-positive disease and for identifying patients for whom chemotherapy can be safely avoided (75%). However, in both cases, about one-quarter of respondents either disagreed or felt neutral.

No consensus was reached on the clinical utility of these subtypes for selecting the most appropriate chemotherapy treatment – two-thirds disagreed, while 13% agreed and 17% felt neutral.

When deciding on the use of chemotherapy in the adjuvant setting in early node-negative breast cancer, 88% of respondents felt that breast cancer multigene signatures were important. Moreover, 75% considered such signatures important when deciding whether to use chemotherapy in the adjuvant setting for patients with one to three positive lymph nodes. However, no consensus was reached on the utility of signatures for deciding whether to extend endocrine therapy in either setting.

When examining the usefulness of signatures in more special settings, the authors found that the vast majority (90%) of respondents believed that multigene signatures had clinical utility for postmenopausal early breast cancer patients, and 82% did not consider signatures clinically useful in the early-stage HER2-overexpressed setting.

In addition, 74% thought that breast cancer multigene signatures were not useful in triple-negative disease or in the metastatic setting.

Respondents did not reach a consensus on the clinical utility of multigene signatures in the neoadjuvant setting – only 27% considered them useful, and almost half did not.

The “low percentage” of respondents using the signatures in the neoadjuvant setting and the “misconception regarding the predictive value of these tests on chemotherapy benefits suggest there is still room for training on results interpretation [for breast cancer multigene signatures],” the authors write.

The study was sponsored by Veracyte. Dr. Curigliano has relationships with Pfizer, Novartis, Lilly, Roche, Seattle Genetics, Celltrion, and Veracyte. No other relevant financial relationships were disclosed.

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

This article was updated 5/9/22.

BERLIN – Some breast cancer specialists still have misconceptions about the appropriate use of multigene signatures in making prognostic and treatment decisions in early-stage disease, a European survey suggests.

The authors found, for instance, that while most specialists agreed that molecular intrinsic subtypes had clinical utility for understanding prognosis in early-stage hormone receptor (HR)–positive disease and for identifying patients for whom chemotherapy could be safely avoided, about 1 in 4 experts either disagreed or felt neutral about the use of signatures in these settings.

Similarly, almost 75% of respondents felt that these signatures were not useful in the triple-negative or metastatic setting, but a small percentage believed they were, and about 10% were neutral.

“Considering that breast cancer multigene signatures were developed in the post menopausal HR+/HER2- early breast cancer setting, the fact that some experts consider [them] useful in triple-negative, HER2+ breast cancer or in the metastatic setting corroborates a misunderstanding on how to interpret the results,” study author Giuseppe Curigliano, MD, PhD, associate professor of medical oncology at the University of Milan, and colleagues wrote.

Dr. Curigliano, who is also head of the Division of Early Drug Development at the European Institute of Oncology, presented the survey findings on May 4 at the European Society for Medical Oncology (ESMO BCC) Breast Cancer Congress.

Although several breast cancer multigene signatures are available to profile early breast cancer, little information exists on how these signatures should be used in clinical practice.

To investigate, Dr. Curigliano and colleagues convened a scientific committee of eight breast cancer experts to develop a Delphi questionnaire to examine respondents’ opinions and uses of these signatures.

The questionnaire asked about the clinical utility of multigene signatures in breast cancer and recommendations for their use in clinical practice.

In all, 133 breast cancer specialists from 11 European countries completed the questionnaire. Respondents were about 49 years old on average, and most (86.5%) worked in a teaching hospital. More than 72% were medical oncologists; 12% were pathologists.

Consensus was considered to be reached when 70% or more of the respondents were in agreement on a topic.

Participants had “extensive experience in the management of breast cancer patients and have been using breast cancer multigene signatures in clinical practice,” Dr. Curigliano said.

Almost all respondents (93.6%) reported using breast cancer multigene signatures routinely or in selected patients, and 73.4% had more than 5 years of experience with them.

Overall, more than 70% of respondents agreed that identifying tumor intrinsic subtype via gene expression profiling was important in making prognostic and treatment decisions; however, a consensus was not reached on the use of immunohistochemistry.

In addition, most respondents (76%) agreed that identifying breast cancer molecular intrinsic subtypes had clinical utility for prognosis in early-stage HR-positive disease and for identifying patients for whom chemotherapy can be safely avoided (75%). However, in both cases, about one-quarter of respondents either disagreed or felt neutral.

No consensus was reached on the clinical utility of these subtypes for selecting the most appropriate chemotherapy treatment – two-thirds disagreed, while 13% agreed and 17% felt neutral.

When deciding on the use of chemotherapy in the adjuvant setting in early node-negative breast cancer, 88% of respondents felt that breast cancer multigene signatures were important. Moreover, 75% considered such signatures important when deciding whether to use chemotherapy in the adjuvant setting for patients with one to three positive lymph nodes. However, no consensus was reached on the utility of signatures for deciding whether to extend endocrine therapy in either setting.

When examining the usefulness of signatures in more special settings, the authors found that the vast majority (90%) of respondents believed that multigene signatures had clinical utility for postmenopausal early breast cancer patients, and 82% did not consider signatures clinically useful in the early-stage HER2-overexpressed setting.

In addition, 74% thought that breast cancer multigene signatures were not useful in triple-negative disease or in the metastatic setting.

Respondents did not reach a consensus on the clinical utility of multigene signatures in the neoadjuvant setting – only 27% considered them useful, and almost half did not.

The “low percentage” of respondents using the signatures in the neoadjuvant setting and the “misconception regarding the predictive value of these tests on chemotherapy benefits suggest there is still room for training on results interpretation [for breast cancer multigene signatures],” the authors write.

The study was sponsored by Veracyte. Dr. Curigliano has relationships with Pfizer, Novartis, Lilly, Roche, Seattle Genetics, Celltrion, and Veracyte. No other relevant financial relationships were disclosed.

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

This article was updated 5/9/22.

When it comes to mammography recommendations state comprehensive cancer control (CCC) plans vary considerably and don’t always closely match the U.S. Preventive Services Task Force (USPSTF) recommendations for mammography frequency in women at average risk for breast cancer, according to a new cross-sectional study of CCC plans in all 50 states and the District of Columbia. The recommended age for initiation varied widely among CCC plans, and nearly one in five bore little resemblance at all to the USPTF recommendations.

According to the authors of the study, the variation among suggested ages of initiation may indicate a lack of consensus among state agencies. “For a recommendation tied to service coverage, this is a serious gap in public health policy,” they wrote in the study published online in JAMA Network Open.

CCC plans include goals, measurable objectives, and evidence-based strategies to combat cancers that are both common and preventable. They include input from multiple groups, frequently take 4-6 years to create, and should be updated regularly. Funding from the Centers for Disease Control and Prevention requires that the plans include data cancer screening prevalence rates and specific objectives and strategies.

Breast cancer is the most common cancer in women in the United States, and the second highest cause of cancer death. Regular, high-quality screening reduces breast cancer mortality by 25%-31% among women aged 50-69. As a result, the American Cancer Society, the USPSTF, the American College of Physicians, and the American Academy of Family Physicians have produced guidelines for mammography screening in women at average risk of breast cancer.

Although the benefits of screening are widely accepted, there is disagreement about the ages it should be initiated and ended. These inconsistencies stem from different evidence used to support recommendations, as well as different standards for benefits and harms from screening. Common concerns include overdiagnosis, false-positive results, and radiation damage from mammography.

Because these benefits and harms can vary based on age and values, there is an emphasis on shared decision-making between clinicians and women, especially those aged 40-49.

The most recent USPTF recommendation, issued in 2016, states that women aged 50-74 with average risk should be screened with mammography every 2 years. The choice of mammography in average-risk women under 50 should be approached on an individual basis. USPTF defines average risk as having no signs, symptoms, or previous diagnosis of breast cancer, and no family history or genetic causes for concern.

In the new study, researchers conducted a point-in-time evaluation of CCC plans from 50 states and the District of Columbia, between Nov. 1, 2019, and June 30, 2021.

Thirty-one percent of the plans included the complete USPTF recommendations of biennial mammography between ages 50 and 74; 51% included some, but not all of the USPTF recommendations; and 18% were not consistent at all with USPTF recommendations.

Overall, 59% of plans recommended initiation at age 50 and 37% at age 40, which is consistent with the older 2009 USPSTF recommendation. Eight percent of plans recommended starting at both 40 and 50, and 20% of plans had no recommended age of initiation.

Among the plans that were partially consistent with USPTF, 73% recommended initiation of mammography at age 40 and 31% at age 50. Eighty-five percent did not include an age to stop mammography; 15% did not include a recommended frequency; and 15% had an initiation age other than 40 or 50. Eighty-five percent of plans partially consistent with USPSTF included a recommendation that mammography should be conducted biennially.

The authors state that CCC plans could be improved by a unified emphasis on biennial screening of the general population of women aged 50-74, as well as clear differentiation between women at average risk and those at high risk, who could be screened at ages younger than 50 in consultation with their physician.

The study is limited by the fact that plans were reviewed a single time, while state CCC plans are updated with varying periodicity. The authors agree that implementation of population-based screening should be tailored to individual states and health care systems.

When it comes to mammography recommendations state comprehensive cancer control (CCC) plans vary considerably and don’t always closely match the U.S. Preventive Services Task Force (USPSTF) recommendations for mammography frequency in women at average risk for breast cancer, according to a new cross-sectional study of CCC plans in all 50 states and the District of Columbia. The recommended age for initiation varied widely among CCC plans, and nearly one in five bore little resemblance at all to the USPTF recommendations.

According to the authors of the study, the variation among suggested ages of initiation may indicate a lack of consensus among state agencies. “For a recommendation tied to service coverage, this is a serious gap in public health policy,” they wrote in the study published online in JAMA Network Open.

CCC plans include goals, measurable objectives, and evidence-based strategies to combat cancers that are both common and preventable. They include input from multiple groups, frequently take 4-6 years to create, and should be updated regularly. Funding from the Centers for Disease Control and Prevention requires that the plans include data cancer screening prevalence rates and specific objectives and strategies.

Breast cancer is the most common cancer in women in the United States, and the second highest cause of cancer death. Regular, high-quality screening reduces breast cancer mortality by 25%-31% among women aged 50-69. As a result, the American Cancer Society, the USPSTF, the American College of Physicians, and the American Academy of Family Physicians have produced guidelines for mammography screening in women at average risk of breast cancer.

Although the benefits of screening are widely accepted, there is disagreement about the ages it should be initiated and ended. These inconsistencies stem from different evidence used to support recommendations, as well as different standards for benefits and harms from screening. Common concerns include overdiagnosis, false-positive results, and radiation damage from mammography.

Because these benefits and harms can vary based on age and values, there is an emphasis on shared decision-making between clinicians and women, especially those aged 40-49.

The most recent USPTF recommendation, issued in 2016, states that women aged 50-74 with average risk should be screened with mammography every 2 years. The choice of mammography in average-risk women under 50 should be approached on an individual basis. USPTF defines average risk as having no signs, symptoms, or previous diagnosis of breast cancer, and no family history or genetic causes for concern.

In the new study, researchers conducted a point-in-time evaluation of CCC plans from 50 states and the District of Columbia, between Nov. 1, 2019, and June 30, 2021.

Thirty-one percent of the plans included the complete USPTF recommendations of biennial mammography between ages 50 and 74; 51% included some, but not all of the USPTF recommendations; and 18% were not consistent at all with USPTF recommendations.

Overall, 59% of plans recommended initiation at age 50 and 37% at age 40, which is consistent with the older 2009 USPSTF recommendation. Eight percent of plans recommended starting at both 40 and 50, and 20% of plans had no recommended age of initiation.

Among the plans that were partially consistent with USPTF, 73% recommended initiation of mammography at age 40 and 31% at age 50. Eighty-five percent did not include an age to stop mammography; 15% did not include a recommended frequency; and 15% had an initiation age other than 40 or 50. Eighty-five percent of plans partially consistent with USPSTF included a recommendation that mammography should be conducted biennially.

The authors state that CCC plans could be improved by a unified emphasis on biennial screening of the general population of women aged 50-74, as well as clear differentiation between women at average risk and those at high risk, who could be screened at ages younger than 50 in consultation with their physician.

The study is limited by the fact that plans were reviewed a single time, while state CCC plans are updated with varying periodicity. The authors agree that implementation of population-based screening should be tailored to individual states and health care systems.

When it comes to mammography recommendations state comprehensive cancer control (CCC) plans vary considerably and don’t always closely match the U.S. Preventive Services Task Force (USPSTF) recommendations for mammography frequency in women at average risk for breast cancer, according to a new cross-sectional study of CCC plans in all 50 states and the District of Columbia. The recommended age for initiation varied widely among CCC plans, and nearly one in five bore little resemblance at all to the USPTF recommendations.

According to the authors of the study, the variation among suggested ages of initiation may indicate a lack of consensus among state agencies. “For a recommendation tied to service coverage, this is a serious gap in public health policy,” they wrote in the study published online in JAMA Network Open.

CCC plans include goals, measurable objectives, and evidence-based strategies to combat cancers that are both common and preventable. They include input from multiple groups, frequently take 4-6 years to create, and should be updated regularly. Funding from the Centers for Disease Control and Prevention requires that the plans include data cancer screening prevalence rates and specific objectives and strategies.

Breast cancer is the most common cancer in women in the United States, and the second highest cause of cancer death. Regular, high-quality screening reduces breast cancer mortality by 25%-31% among women aged 50-69. As a result, the American Cancer Society, the USPSTF, the American College of Physicians, and the American Academy of Family Physicians have produced guidelines for mammography screening in women at average risk of breast cancer.

Although the benefits of screening are widely accepted, there is disagreement about the ages it should be initiated and ended. These inconsistencies stem from different evidence used to support recommendations, as well as different standards for benefits and harms from screening. Common concerns include overdiagnosis, false-positive results, and radiation damage from mammography.

Because these benefits and harms can vary based on age and values, there is an emphasis on shared decision-making between clinicians and women, especially those aged 40-49.

The most recent USPTF recommendation, issued in 2016, states that women aged 50-74 with average risk should be screened with mammography every 2 years. The choice of mammography in average-risk women under 50 should be approached on an individual basis. USPTF defines average risk as having no signs, symptoms, or previous diagnosis of breast cancer, and no family history or genetic causes for concern.

In the new study, researchers conducted a point-in-time evaluation of CCC plans from 50 states and the District of Columbia, between Nov. 1, 2019, and June 30, 2021.

Thirty-one percent of the plans included the complete USPTF recommendations of biennial mammography between ages 50 and 74; 51% included some, but not all of the USPTF recommendations; and 18% were not consistent at all with USPTF recommendations.

Overall, 59% of plans recommended initiation at age 50 and 37% at age 40, which is consistent with the older 2009 USPSTF recommendation. Eight percent of plans recommended starting at both 40 and 50, and 20% of plans had no recommended age of initiation.

Among the plans that were partially consistent with USPTF, 73% recommended initiation of mammography at age 40 and 31% at age 50. Eighty-five percent did not include an age to stop mammography; 15% did not include a recommended frequency; and 15% had an initiation age other than 40 or 50. Eighty-five percent of plans partially consistent with USPSTF included a recommendation that mammography should be conducted biennially.

The authors state that CCC plans could be improved by a unified emphasis on biennial screening of the general population of women aged 50-74, as well as clear differentiation between women at average risk and those at high risk, who could be screened at ages younger than 50 in consultation with their physician.

The study is limited by the fact that plans were reviewed a single time, while state CCC plans are updated with varying periodicity. The authors agree that implementation of population-based screening should be tailored to individual states and health care systems.

A meta-analysis including over 5000 patients with metastatic hormone receptor–positive (HR+) and HER2- breast cancer showed a significant overall survival (OS) benefit with the addition of cyclin-dependent kinase (CDK) 4/6 inhibitors to endocrine therapy (hazard ratio 1.33; P < .001), albeit with higher rates of toxicities, including neutropenia, leukopenia, and diarrhea.³ The MONALEESA-2 study randomly assigned 668 postmenopausal women with metastatic HR+/HER2- breast cancer, treatment-naive in the advanced setting, to either ribociclib or placebo plus letrozole. Updated results with a median follow-up of 6.6 years demonstrated a significant OS benefit with ribociclib + letrozole compared with placebo + letrozole (median OS 63.9 months vs 51.4 months; hazard ratio 0.76; P = .008) (Hortobagyi and colleagues). An OS > 5 years with ribociclib plus endocrine therapy is certainly impressive, and efficacy as well as respective toxicities of the various CDK 4/6 inhibitors are factors taken into consideration when choosing the appropriate therapy for an individual patient.

The optimization of adjuvant endocrine therapy (ET) for HR+ early breast cancer, including use of ovarian suppression and extended adjuvant therapy, has improved outcomes for these women. However, there is a high-risk subset for whom the risk for distant recurrence persists. The phase 3 monarchE trial, which included 5637 patients with high-risk early breast cancer (≥ 4 positive nodes, or 1-3 nodes and either tumor size ≥ 5 cm, histologic grade 3, or central Ki-67 ≥ 20%), demonstrated benefits in invasive disease-free and distant-relapse-free survival with the addition of abemaciclib for 2 years to ET. A safety analysis of the monarchE study among patients who had received at least one dose of the study drug (n = 5591) demonstrated an overall manageable side-effect profile, with the majority of these toxicities addressed via dose holds/reductions or supportive medications (Rugo and colleagues). Abemaciclib + ET led to higher incidence of grade ≥ 3 adverse events vs ET alone (49.7% vs 16.3%), with neutropenia being the most frequent (grade 3 = 19.6%) although without significant clinical implications. Diarrhea was common (83.5%), although the majority was low grade (grade 1/2 = 75.7%), with grade 2/3 events characterized by early onset and short duration. Discontinuation of abemaciclib occurred in 18.5%, with two thirds due to grade 1/2 events and in over half without dose reduction.⁴ These findings show an acceptable safety profile with abemaciclib in the curative setting and highlight the importance of education, recognition, and early management of side effects to maintain patients on treatment.

The heterogeneity of tumor biology within the HR+ breast cancer subtype indicates the need to refine treatment regimens for an individual patient. Genomic assays (70-gene signature and 21-gene recurrence score) have helped tailor adjuvant systemic therapy and in many cases have identified women for whom chemotherapy can be omitted. CDK 4/6 inhibitors have shown impressive activity in the metastatic/advanced setting, although results from trials in the adjuvant setting have produced mixed results. The phase 2 NEOPAL trial evaluated the combination of letrozole + palbociclib vs chemotherapy (sequential anthracycline-taxane) among 106 postmenopausal women with high-risk, HR+/HER2- early breast cancer (luminal B or luminal A with nodal involvement). At a median follow-up of 40.4 months, 3-year PFS (hazard ratio 1.01; P = .98) and invasive disease-free survival (hazard ratio 0.83; P = .71) were similar in the letrozole + palbociclib and chemotherapy arms (Delaloge and colleagues). The phase 2 CORALLEEN trial,⁵  which investigated neoadjuvant letrozole + ribociclib vs chemotherapy in HR+/HER2- luminal B early breast cancer, demonstrated similar percentages of patients achieving downstaging via molecular assessment at the time of surgery. The neoadjuvant space represents a valuable setting to further study CDK 4/6 inhibitors as well as other novel therapies; endpoints including pathologic complete response and residual cancer burden correlating with long-term outcomes can provide a more rapid means to identify effective therapies. Translational biomarkers can be gathered and adjuvant strategies can be tailored based on response.

Additional References

1. Modi S, Saura C, Yamashita T, et al; DESTINY-Breast01 Investigators. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med. 2020;382:610-621. Doi:  10.1056/NEJMoa1914510 Source
2. Hurvitz S, Kim S-B, Chung W-P, et al. Trastuzumab deruxtecan (T-DXd; DS-8201a) versus trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (mBC): Subgroup analyses from the randomized phase 3 study DESTINY-Breast03. Presented at 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021;General Session, GS3-01. Source
3. Li J, Huo X, Zhao F, et al. Association of cyclin-dependent kinases 4 and 6 inhibitors with survival in patients with hormone receptor-positive metastatic breast cancer: A systematic review and meta-analysis. JAMA Netw Open. 2020;3:e2020312. Doi: 10.1001/jamanetworkopen.2020.20312 Source
4. Harbeck N, Rastogi P, Martin M, et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: Updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32:1571-1581. Doi: 10.1016/j.annonc.2021.09.015 Source
5. Prat A, Saura C, Pascual T, et al. Ribociclib plus letrozole versus chemotherapy for postmenopausal women with hormone receptor-positive, HER2- negative, luminal B breast cancer (CORALLEEN): An open-label, multicentre, randomised, phase 2 trial. Lancet Oncol. 2020;21:33-43. Doi: 10.1016/S1470-2045(19)30786-7 Source

A meta-analysis including over 5000 patients with metastatic hormone receptor–positive (HR+) and HER2- breast cancer showed a significant overall survival (OS) benefit with the addition of cyclin-dependent kinase (CDK) 4/6 inhibitors to endocrine therapy (hazard ratio 1.33; P < .001), albeit with higher rates of toxicities, including neutropenia, leukopenia, and diarrhea.³ The MONALEESA-2 study randomly assigned 668 postmenopausal women with metastatic HR+/HER2- breast cancer, treatment-naive in the advanced setting, to either ribociclib or placebo plus letrozole. Updated results with a median follow-up of 6.6 years demonstrated a significant OS benefit with ribociclib + letrozole compared with placebo + letrozole (median OS 63.9 months vs 51.4 months; hazard ratio 0.76; P = .008) (Hortobagyi and colleagues). An OS > 5 years with ribociclib plus endocrine therapy is certainly impressive, and efficacy as well as respective toxicities of the various CDK 4/6 inhibitors are factors taken into consideration when choosing the appropriate therapy for an individual patient.

The optimization of adjuvant endocrine therapy (ET) for HR+ early breast cancer, including use of ovarian suppression and extended adjuvant therapy, has improved outcomes for these women. However, there is a high-risk subset for whom the risk for distant recurrence persists. The phase 3 monarchE trial, which included 5637 patients with high-risk early breast cancer (≥ 4 positive nodes, or 1-3 nodes and either tumor size ≥ 5 cm, histologic grade 3, or central Ki-67 ≥ 20%), demonstrated benefits in invasive disease-free and distant-relapse-free survival with the addition of abemaciclib for 2 years to ET. A safety analysis of the monarchE study among patients who had received at least one dose of the study drug (n = 5591) demonstrated an overall manageable side-effect profile, with the majority of these toxicities addressed via dose holds/reductions or supportive medications (Rugo and colleagues). Abemaciclib + ET led to higher incidence of grade ≥ 3 adverse events vs ET alone (49.7% vs 16.3%), with neutropenia being the most frequent (grade 3 = 19.6%) although without significant clinical implications. Diarrhea was common (83.5%), although the majority was low grade (grade 1/2 = 75.7%), with grade 2/3 events characterized by early onset and short duration. Discontinuation of abemaciclib occurred in 18.5%, with two thirds due to grade 1/2 events and in over half without dose reduction.⁴ These findings show an acceptable safety profile with abemaciclib in the curative setting and highlight the importance of education, recognition, and early management of side effects to maintain patients on treatment.

The heterogeneity of tumor biology within the HR+ breast cancer subtype indicates the need to refine treatment regimens for an individual patient. Genomic assays (70-gene signature and 21-gene recurrence score) have helped tailor adjuvant systemic therapy and in many cases have identified women for whom chemotherapy can be omitted. CDK 4/6 inhibitors have shown impressive activity in the metastatic/advanced setting, although results from trials in the adjuvant setting have produced mixed results. The phase 2 NEOPAL trial evaluated the combination of letrozole + palbociclib vs chemotherapy (sequential anthracycline-taxane) among 106 postmenopausal women with high-risk, HR+/HER2- early breast cancer (luminal B or luminal A with nodal involvement). At a median follow-up of 40.4 months, 3-year PFS (hazard ratio 1.01; P = .98) and invasive disease-free survival (hazard ratio 0.83; P = .71) were similar in the letrozole + palbociclib and chemotherapy arms (Delaloge and colleagues). The phase 2 CORALLEEN trial,⁵  which investigated neoadjuvant letrozole + ribociclib vs chemotherapy in HR+/HER2- luminal B early breast cancer, demonstrated similar percentages of patients achieving downstaging via molecular assessment at the time of surgery. The neoadjuvant space represents a valuable setting to further study CDK 4/6 inhibitors as well as other novel therapies; endpoints including pathologic complete response and residual cancer burden correlating with long-term outcomes can provide a more rapid means to identify effective therapies. Translational biomarkers can be gathered and adjuvant strategies can be tailored based on response.

Additional References

1. Modi S, Saura C, Yamashita T, et al; DESTINY-Breast01 Investigators. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med. 2020;382:610-621. Doi:  10.1056/NEJMoa1914510 Source
2. Hurvitz S, Kim S-B, Chung W-P, et al. Trastuzumab deruxtecan (T-DXd; DS-8201a) versus trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (mBC): Subgroup analyses from the randomized phase 3 study DESTINY-Breast03. Presented at 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021;General Session, GS3-01. Source
3. Li J, Huo X, Zhao F, et al. Association of cyclin-dependent kinases 4 and 6 inhibitors with survival in patients with hormone receptor-positive metastatic breast cancer: A systematic review and meta-analysis. JAMA Netw Open. 2020;3:e2020312. Doi: 10.1001/jamanetworkopen.2020.20312 Source
4. Harbeck N, Rastogi P, Martin M, et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: Updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32:1571-1581. Doi: 10.1016/j.annonc.2021.09.015 Source
5. Prat A, Saura C, Pascual T, et al. Ribociclib plus letrozole versus chemotherapy for postmenopausal women with hormone receptor-positive, HER2- negative, luminal B breast cancer (CORALLEEN): An open-label, multicentre, randomised, phase 2 trial. Lancet Oncol. 2020;21:33-43. Doi: 10.1016/S1470-2045(19)30786-7 Source

A meta-analysis including over 5000 patients with metastatic hormone receptor–positive (HR+) and HER2- breast cancer showed a significant overall survival (OS) benefit with the addition of cyclin-dependent kinase (CDK) 4/6 inhibitors to endocrine therapy (hazard ratio 1.33; P < .001), albeit with higher rates of toxicities, including neutropenia, leukopenia, and diarrhea.³ The MONALEESA-2 study randomly assigned 668 postmenopausal women with metastatic HR+/HER2- breast cancer, treatment-naive in the advanced setting, to either ribociclib or placebo plus letrozole. Updated results with a median follow-up of 6.6 years demonstrated a significant OS benefit with ribociclib + letrozole compared with placebo + letrozole (median OS 63.9 months vs 51.4 months; hazard ratio 0.76; P = .008) (Hortobagyi and colleagues). An OS > 5 years with ribociclib plus endocrine therapy is certainly impressive, and efficacy as well as respective toxicities of the various CDK 4/6 inhibitors are factors taken into consideration when choosing the appropriate therapy for an individual patient.

The optimization of adjuvant endocrine therapy (ET) for HR+ early breast cancer, including use of ovarian suppression and extended adjuvant therapy, has improved outcomes for these women. However, there is a high-risk subset for whom the risk for distant recurrence persists. The phase 3 monarchE trial, which included 5637 patients with high-risk early breast cancer (≥ 4 positive nodes, or 1-3 nodes and either tumor size ≥ 5 cm, histologic grade 3, or central Ki-67 ≥ 20%), demonstrated benefits in invasive disease-free and distant-relapse-free survival with the addition of abemaciclib for 2 years to ET. A safety analysis of the monarchE study among patients who had received at least one dose of the study drug (n = 5591) demonstrated an overall manageable side-effect profile, with the majority of these toxicities addressed via dose holds/reductions or supportive medications (Rugo and colleagues). Abemaciclib + ET led to higher incidence of grade ≥ 3 adverse events vs ET alone (49.7% vs 16.3%), with neutropenia being the most frequent (grade 3 = 19.6%) although without significant clinical implications. Diarrhea was common (83.5%), although the majority was low grade (grade 1/2 = 75.7%), with grade 2/3 events characterized by early onset and short duration. Discontinuation of abemaciclib occurred in 18.5%, with two thirds due to grade 1/2 events and in over half without dose reduction.⁴ These findings show an acceptable safety profile with abemaciclib in the curative setting and highlight the importance of education, recognition, and early management of side effects to maintain patients on treatment.

The heterogeneity of tumor biology within the HR+ breast cancer subtype indicates the need to refine treatment regimens for an individual patient. Genomic assays (70-gene signature and 21-gene recurrence score) have helped tailor adjuvant systemic therapy and in many cases have identified women for whom chemotherapy can be omitted. CDK 4/6 inhibitors have shown impressive activity in the metastatic/advanced setting, although results from trials in the adjuvant setting have produced mixed results. The phase 2 NEOPAL trial evaluated the combination of letrozole + palbociclib vs chemotherapy (sequential anthracycline-taxane) among 106 postmenopausal women with high-risk, HR+/HER2- early breast cancer (luminal B or luminal A with nodal involvement). At a median follow-up of 40.4 months, 3-year PFS (hazard ratio 1.01; P = .98) and invasive disease-free survival (hazard ratio 0.83; P = .71) were similar in the letrozole + palbociclib and chemotherapy arms (Delaloge and colleagues). The phase 2 CORALLEEN trial,⁵  which investigated neoadjuvant letrozole + ribociclib vs chemotherapy in HR+/HER2- luminal B early breast cancer, demonstrated similar percentages of patients achieving downstaging via molecular assessment at the time of surgery. The neoadjuvant space represents a valuable setting to further study CDK 4/6 inhibitors as well as other novel therapies; endpoints including pathologic complete response and residual cancer burden correlating with long-term outcomes can provide a more rapid means to identify effective therapies. Translational biomarkers can be gathered and adjuvant strategies can be tailored based on response.

Additional References

1. Modi S, Saura C, Yamashita T, et al; DESTINY-Breast01 Investigators. Trastuzumab deruxtecan in previously treated HER2-positive breast cancer. N Engl J Med. 2020;382:610-621. Doi:  10.1056/NEJMoa1914510 Source
2. Hurvitz S, Kim S-B, Chung W-P, et al. Trastuzumab deruxtecan (T-DXd; DS-8201a) versus trastuzumab emtansine (T-DM1) in patients (pts) with HER2+ metastatic breast cancer (mBC): Subgroup analyses from the randomized phase 3 study DESTINY-Breast03. Presented at 2021 San Antonio Breast Cancer Symposium; December 7-10, 2021;General Session, GS3-01. Source
3. Li J, Huo X, Zhao F, et al. Association of cyclin-dependent kinases 4 and 6 inhibitors with survival in patients with hormone receptor-positive metastatic breast cancer: A systematic review and meta-analysis. JAMA Netw Open. 2020;3:e2020312. Doi: 10.1001/jamanetworkopen.2020.20312 Source
4. Harbeck N, Rastogi P, Martin M, et al. Adjuvant abemaciclib combined with endocrine therapy for high-risk early breast cancer: Updated efficacy and Ki-67 analysis from the monarchE study. Ann Oncol. 2021;32:1571-1581. Doi: 10.1016/j.annonc.2021.09.015 Source
5. Prat A, Saura C, Pascual T, et al. Ribociclib plus letrozole versus chemotherapy for postmenopausal women with hormone receptor-positive, HER2- negative, luminal B breast cancer (CORALLEEN): An open-label, multicentre, randomised, phase 2 trial. Lancet Oncol. 2020;21:33-43. Doi: 10.1016/S1470-2045(19)30786-7 Source

Based on the work you do at the Cleveland Clinic Taussig Cancer Institute, what is your standard approach to managing  early stage cancer patients?

Dr. Roesch: The approach to managing patients with early stage breast cancer very much depends on the subtype of breast cancer. Clinical stage at presentation and patient factors are considered here. For example, patients with small hormone receptor-positive tumors will often have surgery first, while patients with triple-negative or HER2-positive tumors will often receive preoperative or neoadjuvant chemotherapy.

In situations where there is a need or a desire for downstaging or shrinking of the primary tumor or lymph nodes in the axilla, we will also discuss neoadjuvant systemic therapy. For hormone receptor-positive tumors, endocrine or anti-estrogen therapy will be incorporated into their treatment regimen at some point in the future.

The role of chemotherapy for hormone receptor-positive breast cancer depends on a variety of factors, including pathologic staging, which we obtain at the time of surgery. Exceptions may include very small tumors or patients who have medical comorbidities that affect their candidacy for chemotherapy where the risk may outweigh the benefit.

Are there specific steps you take in managing and treating early stage triple-negative breast cancer?

Dr. Roesch: Most patients with early stage triple-negative breast cancer receive neoadjuvant or preoperative chemotherapy. As I mentioned above, this has the benefits of downstaging the primary tumor itself and the lymph nodes in the axilla as well as providing prognostic information. This approach can also help guide adjuvant therapy recommendations. Additionally, we often discuss the role of genetic counseling for these patients.

Are there targeted therapies you rely upon?

Dr. Roesch: This has been an evolving field with dramatic advances in the past couple of years. One is immunotherapy. There was a phase III study called the KEYONTE-522 trial, which demonstrated improvements in pathologic response rate and event-free survival with a regimen of neoadjuvant pembrolizumab plus chemotherapy followed by the pembrolizumab given in the adjuvant setting, compared to chemotherapy approach alone (1).

For patients who meet criteria for this study, which is essentially stage II/III triple-negative breast cancer, we have adopted this regimen in the neoadjuvant setting. Additionally, we consider adjuvant capecitabine for patients who have received neoadjuvant chemotherapy with an anthracycline, taxane or both and who have residual disease at the time of surgery. This is based on the CREATE-X trial, which showed a survival benefit for patients with triple-negative breast cancer in this situation (2).

Lastly, the PARP inhibitor, olaparib, was recently approved by the FDA in the adjuvant setting for BRCA mutation carriers diagnosed with HER-2-negative high-risk early breast cancer who have received neoadjuvant or adjuvant chemotherapy. This treatment also demonstrated survival benefit and is an exciting new option for these patients (3).

A critical question in my mind that has arisen out of these new developments is sequencing of these therapies. For example, if I have a patient who received the KEYNOTE-522 regimen with the immunotherapy agent, pembrolizumab, and has residual disease after surgery, how do we administer the capecitabine with the pembrolizumab? And what about radiation? What if a patient is a BRCA mutation carrier? These are all very relevant questions, which we are encountering every day, and the approach we take is often individualized.

This sounds very exciting. Can you talk about the research on managing early triple-negative breast cancer and what the future might hold?

Dr. Roesch: This is a very exciting time for both us as oncologists and our patients as there is a very rapid pace of new therapies being explored in the context of clinical trials. First, I'd like to mention the adjuvant vaccine trial we have at Cleveland Clinic for patients diagnosed with early stage triple-negative breast cancer at high risk of recurrence. This trial is investigating an alpha lactalbumin vaccine, which has been selected as a vaccine target because it is a breast-specific differentiation protein expressed at high levels in many human breast cancers, particularly in triple-negative breast cancer. The current trial's main objective is to determine the maximum tolerated dose of the vaccine, and other endpoints include looking at biomarkers of immune responses (4).

The I-SPY2 trial is another very exciting study we have open at Cleveland Clinic. This is a multicenter phase II trial using response adaptive randomization within molecular subtypes, which is defined by the receptor status and MammaPrint risk, which is a genomic assay, to evaluate novel agents as neoadjuvant therapy for women with high-risk breast cancer. Patients undergo serial MRIs and biopsies with information on the likelihood of them achieving a pathologic complete response (pCR) provided back in real time, which will then allow for therapy escalation or de-escalation. The goal here is individualized precision therapy based on the specific intrinsic subtype of the tumor itself and response with the ultimate goal being to achieve a pCR (5).

Again, this is a very exciting time for us as medical providers and our patients because new therapies are being developed and studied in clinical trials every day.

Based on the work you do at the Cleveland Clinic Taussig Cancer Institute, what is your standard approach to managing  early stage cancer patients?

Dr. Roesch: The approach to managing patients with early stage breast cancer very much depends on the subtype of breast cancer. Clinical stage at presentation and patient factors are considered here. For example, patients with small hormone receptor-positive tumors will often have surgery first, while patients with triple-negative or HER2-positive tumors will often receive preoperative or neoadjuvant chemotherapy.

In situations where there is a need or a desire for downstaging or shrinking of the primary tumor or lymph nodes in the axilla, we will also discuss neoadjuvant systemic therapy. For hormone receptor-positive tumors, endocrine or anti-estrogen therapy will be incorporated into their treatment regimen at some point in the future.

The role of chemotherapy for hormone receptor-positive breast cancer depends on a variety of factors, including pathologic staging, which we obtain at the time of surgery. Exceptions may include very small tumors or patients who have medical comorbidities that affect their candidacy for chemotherapy where the risk may outweigh the benefit.

Are there specific steps you take in managing and treating early stage triple-negative breast cancer?

Dr. Roesch: Most patients with early stage triple-negative breast cancer receive neoadjuvant or preoperative chemotherapy. As I mentioned above, this has the benefits of downstaging the primary tumor itself and the lymph nodes in the axilla as well as providing prognostic information. This approach can also help guide adjuvant therapy recommendations. Additionally, we often discuss the role of genetic counseling for these patients.

Are there targeted therapies you rely upon?

Dr. Roesch: This has been an evolving field with dramatic advances in the past couple of years. One is immunotherapy. There was a phase III study called the KEYONTE-522 trial, which demonstrated improvements in pathologic response rate and event-free survival with a regimen of neoadjuvant pembrolizumab plus chemotherapy followed by the pembrolizumab given in the adjuvant setting, compared to chemotherapy approach alone (1).

For patients who meet criteria for this study, which is essentially stage II/III triple-negative breast cancer, we have adopted this regimen in the neoadjuvant setting. Additionally, we consider adjuvant capecitabine for patients who have received neoadjuvant chemotherapy with an anthracycline, taxane or both and who have residual disease at the time of surgery. This is based on the CREATE-X trial, which showed a survival benefit for patients with triple-negative breast cancer in this situation (2).

Lastly, the PARP inhibitor, olaparib, was recently approved by the FDA in the adjuvant setting for BRCA mutation carriers diagnosed with HER-2-negative high-risk early breast cancer who have received neoadjuvant or adjuvant chemotherapy. This treatment also demonstrated survival benefit and is an exciting new option for these patients (3).

A critical question in my mind that has arisen out of these new developments is sequencing of these therapies. For example, if I have a patient who received the KEYNOTE-522 regimen with the immunotherapy agent, pembrolizumab, and has residual disease after surgery, how do we administer the capecitabine with the pembrolizumab? And what about radiation? What if a patient is a BRCA mutation carrier? These are all very relevant questions, which we are encountering every day, and the approach we take is often individualized.

This sounds very exciting. Can you talk about the research on managing early triple-negative breast cancer and what the future might hold?

Dr. Roesch: This is a very exciting time for both us as oncologists and our patients as there is a very rapid pace of new therapies being explored in the context of clinical trials. First, I'd like to mention the adjuvant vaccine trial we have at Cleveland Clinic for patients diagnosed with early stage triple-negative breast cancer at high risk of recurrence. This trial is investigating an alpha lactalbumin vaccine, which has been selected as a vaccine target because it is a breast-specific differentiation protein expressed at high levels in many human breast cancers, particularly in triple-negative breast cancer. The current trial's main objective is to determine the maximum tolerated dose of the vaccine, and other endpoints include looking at biomarkers of immune responses (4).

The I-SPY2 trial is another very exciting study we have open at Cleveland Clinic. This is a multicenter phase II trial using response adaptive randomization within molecular subtypes, which is defined by the receptor status and MammaPrint risk, which is a genomic assay, to evaluate novel agents as neoadjuvant therapy for women with high-risk breast cancer. Patients undergo serial MRIs and biopsies with information on the likelihood of them achieving a pathologic complete response (pCR) provided back in real time, which will then allow for therapy escalation or de-escalation. The goal here is individualized precision therapy based on the specific intrinsic subtype of the tumor itself and response with the ultimate goal being to achieve a pCR (5).

Again, this is a very exciting time for us as medical providers and our patients because new therapies are being developed and studied in clinical trials every day.

Based on the work you do at the Cleveland Clinic Taussig Cancer Institute, what is your standard approach to managing  early stage cancer patients?

Dr. Roesch: The approach to managing patients with early stage breast cancer very much depends on the subtype of breast cancer. Clinical stage at presentation and patient factors are considered here. For example, patients with small hormone receptor-positive tumors will often have surgery first, while patients with triple-negative or HER2-positive tumors will often receive preoperative or neoadjuvant chemotherapy.

In situations where there is a need or a desire for downstaging or shrinking of the primary tumor or lymph nodes in the axilla, we will also discuss neoadjuvant systemic therapy. For hormone receptor-positive tumors, endocrine or anti-estrogen therapy will be incorporated into their treatment regimen at some point in the future.

The role of chemotherapy for hormone receptor-positive breast cancer depends on a variety of factors, including pathologic staging, which we obtain at the time of surgery. Exceptions may include very small tumors or patients who have medical comorbidities that affect their candidacy for chemotherapy where the risk may outweigh the benefit.

Are there specific steps you take in managing and treating early stage triple-negative breast cancer?

Dr. Roesch: Most patients with early stage triple-negative breast cancer receive neoadjuvant or preoperative chemotherapy. As I mentioned above, this has the benefits of downstaging the primary tumor itself and the lymph nodes in the axilla as well as providing prognostic information. This approach can also help guide adjuvant therapy recommendations. Additionally, we often discuss the role of genetic counseling for these patients.

Are there targeted therapies you rely upon?

Dr. Roesch: This has been an evolving field with dramatic advances in the past couple of years. One is immunotherapy. There was a phase III study called the KEYONTE-522 trial, which demonstrated improvements in pathologic response rate and event-free survival with a regimen of neoadjuvant pembrolizumab plus chemotherapy followed by the pembrolizumab given in the adjuvant setting, compared to chemotherapy approach alone (1).

For patients who meet criteria for this study, which is essentially stage II/III triple-negative breast cancer, we have adopted this regimen in the neoadjuvant setting. Additionally, we consider adjuvant capecitabine for patients who have received neoadjuvant chemotherapy with an anthracycline, taxane or both and who have residual disease at the time of surgery. This is based on the CREATE-X trial, which showed a survival benefit for patients with triple-negative breast cancer in this situation (2).

Lastly, the PARP inhibitor, olaparib, was recently approved by the FDA in the adjuvant setting for BRCA mutation carriers diagnosed with HER-2-negative high-risk early breast cancer who have received neoadjuvant or adjuvant chemotherapy. This treatment also demonstrated survival benefit and is an exciting new option for these patients (3).

A critical question in my mind that has arisen out of these new developments is sequencing of these therapies. For example, if I have a patient who received the KEYNOTE-522 regimen with the immunotherapy agent, pembrolizumab, and has residual disease after surgery, how do we administer the capecitabine with the pembrolizumab? And what about radiation? What if a patient is a BRCA mutation carrier? These are all very relevant questions, which we are encountering every day, and the approach we take is often individualized.

This sounds very exciting. Can you talk about the research on managing early triple-negative breast cancer and what the future might hold?

Dr. Roesch: This is a very exciting time for both us as oncologists and our patients as there is a very rapid pace of new therapies being explored in the context of clinical trials. First, I'd like to mention the adjuvant vaccine trial we have at Cleveland Clinic for patients diagnosed with early stage triple-negative breast cancer at high risk of recurrence. This trial is investigating an alpha lactalbumin vaccine, which has been selected as a vaccine target because it is a breast-specific differentiation protein expressed at high levels in many human breast cancers, particularly in triple-negative breast cancer. The current trial's main objective is to determine the maximum tolerated dose of the vaccine, and other endpoints include looking at biomarkers of immune responses (4).

The I-SPY2 trial is another very exciting study we have open at Cleveland Clinic. This is a multicenter phase II trial using response adaptive randomization within molecular subtypes, which is defined by the receptor status and MammaPrint risk, which is a genomic assay, to evaluate novel agents as neoadjuvant therapy for women with high-risk breast cancer. Patients undergo serial MRIs and biopsies with information on the likelihood of them achieving a pathologic complete response (pCR) provided back in real time, which will then allow for therapy escalation or de-escalation. The goal here is individualized precision therapy based on the specific intrinsic subtype of the tumor itself and response with the ultimate goal being to achieve a pCR (5).

Again, this is a very exciting time for us as medical providers and our patients because new therapies are being developed and studied in clinical trials every day.

Many patients with early-stage HR+/HER2- breast cancer are at high risk for disease recurrence within just a few years of first-line treatment. In this ReCAP, Michelle Melisko, MD, of the University of San Francisco Medical Center, discusses strategies for reducing recurrence rates in these patients.

Dr Melisko begins by identifying the traditional criteria for selecting treatment, including age, comorbidities, tumor size, and nodal status, along with proper utilization of genomic assays. She notes that the RxPONDER and TAILORx trials have demonstrated benefits of chemotherapy plus endocrine therapy in premenopausal patients on the basis of Oncotype DX recurrence scores between 0 and 25.

Next, Dr Melisko discusses how the 2021 FDA approval of abemaciclib plus endocrine therapy in the adjuvant setting mandates that patients have a Ki-67 score of 20%. This is a more restrictive patient population than those who saw benefit in the monarchE clinical trial and presents a challenge for physicians selecting therapy for their patients.

Dr Melisko concludes by sharing 3-year data from the OlympiA trial supporting the use of olaparib in patients with BRCA1 and BRCA2 mutations, as well as findings from the SOFT/TEXT trials that demonstrated the benefit of ovarian suppression in younger patients.

--

Michelle E. Melisko, MD, Associate Clinical Professor, Department of Medicine, Division of Hematology-Oncology, University of San Francisco Medical Center; UCSF Bakar Precision Cancer Medicine, San Francisco, California

Michelle E. Melisko, MD, has disclosed no relevant financial relationships

Many patients with early-stage HR+/HER2- breast cancer are at high risk for disease recurrence within just a few years of first-line treatment. In this ReCAP, Michelle Melisko, MD, of the University of San Francisco Medical Center, discusses strategies for reducing recurrence rates in these patients.

Dr Melisko begins by identifying the traditional criteria for selecting treatment, including age, comorbidities, tumor size, and nodal status, along with proper utilization of genomic assays. She notes that the RxPONDER and TAILORx trials have demonstrated benefits of chemotherapy plus endocrine therapy in premenopausal patients on the basis of Oncotype DX recurrence scores between 0 and 25.

Next, Dr Melisko discusses how the 2021 FDA approval of abemaciclib plus endocrine therapy in the adjuvant setting mandates that patients have a Ki-67 score of 20%. This is a more restrictive patient population than those who saw benefit in the monarchE clinical trial and presents a challenge for physicians selecting therapy for their patients.

Dr Melisko concludes by sharing 3-year data from the OlympiA trial supporting the use of olaparib in patients with BRCA1 and BRCA2 mutations, as well as findings from the SOFT/TEXT trials that demonstrated the benefit of ovarian suppression in younger patients.

--

Michelle E. Melisko, MD, Associate Clinical Professor, Department of Medicine, Division of Hematology-Oncology, University of San Francisco Medical Center; UCSF Bakar Precision Cancer Medicine, San Francisco, California

Michelle E. Melisko, MD, has disclosed no relevant financial relationships

Many patients with early-stage HR+/HER2- breast cancer are at high risk for disease recurrence within just a few years of first-line treatment. In this ReCAP, Michelle Melisko, MD, of the University of San Francisco Medical Center, discusses strategies for reducing recurrence rates in these patients.

Dr Melisko begins by identifying the traditional criteria for selecting treatment, including age, comorbidities, tumor size, and nodal status, along with proper utilization of genomic assays. She notes that the RxPONDER and TAILORx trials have demonstrated benefits of chemotherapy plus endocrine therapy in premenopausal patients on the basis of Oncotype DX recurrence scores between 0 and 25.

Next, Dr Melisko discusses how the 2021 FDA approval of abemaciclib plus endocrine therapy in the adjuvant setting mandates that patients have a Ki-67 score of 20%. This is a more restrictive patient population than those who saw benefit in the monarchE clinical trial and presents a challenge for physicians selecting therapy for their patients.

Dr Melisko concludes by sharing 3-year data from the OlympiA trial supporting the use of olaparib in patients with BRCA1 and BRCA2 mutations, as well as findings from the SOFT/TEXT trials that demonstrated the benefit of ovarian suppression in younger patients.

--

Michelle E. Melisko, MD, Associate Clinical Professor, Department of Medicine, Division of Hematology-Oncology, University of San Francisco Medical Center; UCSF Bakar Precision Cancer Medicine, San Francisco, California

Michelle E. Melisko, MD, has disclosed no relevant financial relationships

Key clinical point: Pyrotinib-based therapy could prolong survival in patients with lapatinib-resistant, human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer, including those with brain metastases and those who benefitted from prior lapatinib.

Major finding: The overall survival was not reached, and the median progression-free survival (PFS) was 8 months (95% CI 5.1-10.9) in the overall cohort and 7.1 (95% CI 5.6-8.6) months in patients with brain metastases. Patients who benefitted from lapatinib therapy ≥6 vs. <6 months prior had a longer PFS after pyrotinib treatment (P = .034). Diarrhea was the most common grade 3-4 adverse event (14.5%).

Study details: This real-world study included 76 patients with HER2+ metastatic breast cancer who received pyrotinib-based therapy after lapatinib progression.

Disclosures: This work was financially supported by the National Key Research and Development Program of China, High-level Innovation Team of Nanjing Medical University, and other sources. The authors declared no conflicts of interest.

Source: Hua Y et al. Treatment with pyrotinib-based therapy in lapatinib-resistant HER2-positive metastatic breast cancer: a multicenter real-world study. Ther Adv Med Oncol. 2022;14 :1-9 (Mar 24). Doi: 10.1177/17588359221085232

Key clinical point: Pyrotinib-based therapy could prolong survival in patients with lapatinib-resistant, human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer, including those with brain metastases and those who benefitted from prior lapatinib.

Major finding: The overall survival was not reached, and the median progression-free survival (PFS) was 8 months (95% CI 5.1-10.9) in the overall cohort and 7.1 (95% CI 5.6-8.6) months in patients with brain metastases. Patients who benefitted from lapatinib therapy ≥6 vs. <6 months prior had a longer PFS after pyrotinib treatment (P = .034). Diarrhea was the most common grade 3-4 adverse event (14.5%).

Study details: This real-world study included 76 patients with HER2+ metastatic breast cancer who received pyrotinib-based therapy after lapatinib progression.

Disclosures: This work was financially supported by the National Key Research and Development Program of China, High-level Innovation Team of Nanjing Medical University, and other sources. The authors declared no conflicts of interest.

Source: Hua Y et al. Treatment with pyrotinib-based therapy in lapatinib-resistant HER2-positive metastatic breast cancer: a multicenter real-world study. Ther Adv Med Oncol. 2022;14 :1-9 (Mar 24). Doi: 10.1177/17588359221085232

Key clinical point: Pyrotinib-based therapy could prolong survival in patients with lapatinib-resistant, human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer, including those with brain metastases and those who benefitted from prior lapatinib.

Major finding: The overall survival was not reached, and the median progression-free survival (PFS) was 8 months (95% CI 5.1-10.9) in the overall cohort and 7.1 (95% CI 5.6-8.6) months in patients with brain metastases. Patients who benefitted from lapatinib therapy ≥6 vs. <6 months prior had a longer PFS after pyrotinib treatment (P = .034). Diarrhea was the most common grade 3-4 adverse event (14.5%).

Study details: This real-world study included 76 patients with HER2+ metastatic breast cancer who received pyrotinib-based therapy after lapatinib progression.

Disclosures: This work was financially supported by the National Key Research and Development Program of China, High-level Innovation Team of Nanjing Medical University, and other sources. The authors declared no conflicts of interest.

Source: Hua Y et al. Treatment with pyrotinib-based therapy in lapatinib-resistant HER2-positive metastatic breast cancer: a multicenter real-world study. Ther Adv Med Oncol. 2022;14 :1-9 (Mar 24). Doi: 10.1177/17588359221085232

Key clinical point: In patients with pT1aN0M0, human epidermal growth factor receptor 2 positive (HER2+) invasive breast cancer adding systemic therapy after surgical excision had clinical outcomes similar to local therapy alone.

Major finding: Overall survival was similar in all patients with pT1aN0M0 HER2-positive breast cancer who received local therapy+systemic therapy or only local therapy (P = .206), including the matched cohort of patients with hormone receptor positive (P = .107) and negative (P = .369) breast cancer.

Study details: This retrospective cohort study included 8948 patients with HER2+, pT1aN0M0 breast cancer, of which 4026 patients received local therapy only and 4922 patients received local therapy+adjuvant chemotherapy/HER2 therapy.

Disclosures: This study did not report any source of funding. CW Towe declared serving as consultant, providing expert testimony, and receiving research funding from several sources.

Source: Cao L et al. A comparison of local therapy alone with local plus systemic therapy for stage I pT1aN0M0 HER2+ breast cancer: A National Cancer Database analysis. Cancer. 2022 (Apr 1). Doi: 10.1002/cncr.34200

Key clinical point: In patients with pT1aN0M0, human epidermal growth factor receptor 2 positive (HER2+) invasive breast cancer adding systemic therapy after surgical excision had clinical outcomes similar to local therapy alone.

Major finding: Overall survival was similar in all patients with pT1aN0M0 HER2-positive breast cancer who received local therapy+systemic therapy or only local therapy (P = .206), including the matched cohort of patients with hormone receptor positive (P = .107) and negative (P = .369) breast cancer.

Study details: This retrospective cohort study included 8948 patients with HER2+, pT1aN0M0 breast cancer, of which 4026 patients received local therapy only and 4922 patients received local therapy+adjuvant chemotherapy/HER2 therapy.

Disclosures: This study did not report any source of funding. CW Towe declared serving as consultant, providing expert testimony, and receiving research funding from several sources.

Source: Cao L et al. A comparison of local therapy alone with local plus systemic therapy for stage I pT1aN0M0 HER2+ breast cancer: A National Cancer Database analysis. Cancer. 2022 (Apr 1). Doi: 10.1002/cncr.34200

Key clinical point: In patients with pT1aN0M0, human epidermal growth factor receptor 2 positive (HER2+) invasive breast cancer adding systemic therapy after surgical excision had clinical outcomes similar to local therapy alone.

Major finding: Overall survival was similar in all patients with pT1aN0M0 HER2-positive breast cancer who received local therapy+systemic therapy or only local therapy (P = .206), including the matched cohort of patients with hormone receptor positive (P = .107) and negative (P = .369) breast cancer.

Study details: This retrospective cohort study included 8948 patients with HER2+, pT1aN0M0 breast cancer, of which 4026 patients received local therapy only and 4922 patients received local therapy+adjuvant chemotherapy/HER2 therapy.

Disclosures: This study did not report any source of funding. CW Towe declared serving as consultant, providing expert testimony, and receiving research funding from several sources.

Source: Cao L et al. A comparison of local therapy alone with local plus systemic therapy for stage I pT1aN0M0 HER2+ breast cancer: A National Cancer Database analysis. Cancer. 2022 (Apr 1). Doi: 10.1002/cncr.34200

Key clinical point: Imaging can be dependably used for estimating the size of clinical T1 tumors to plan lumpectomy; however, overestimation by preoperative imaging size (PIS) should be considered for larger tumors.

Major finding: Significant correlation was observed between PIS and postoperative pathology size (PPS), highest when estimated with ultrasound (correlation coefficient [r] 0.628) followed by mammography (r 0.571; both P < .001). Although ultrasound underestimated T1 (mean difference between PIS and PPS [MD] −3.47 mm; 95% CI −4.02 to −2.91 mm) and T2 (MD −2.20 mm; 95% CI −3.39 to −1.02 mm) tumors, mammogram underestimated T1 tumors (MD −2.91; 95% CI −3.51 to −2.32) and overestimated T2 tumors (MD 0.90; 95% CI −0.44 to 2.24), all within the range of concordance.

Study details: This study identified 1512 tumors in 1502 patients with invasive breast cancer who underwent their first surgery.

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

Source: Kapur H et al. Accuracy of preoperative imaging estimates: Opportunities to de-escalate surgery for early invasive breast cancer. Am J Surg. 2022 (Mar 30). Doi:  10.1016/j.amjsurg.2022.03.053

Key clinical point: Imaging can be dependably used for estimating the size of clinical T1 tumors to plan lumpectomy; however, overestimation by preoperative imaging size (PIS) should be considered for larger tumors.

Major finding: Significant correlation was observed between PIS and postoperative pathology size (PPS), highest when estimated with ultrasound (correlation coefficient [r] 0.628) followed by mammography (r 0.571; both P < .001). Although ultrasound underestimated T1 (mean difference between PIS and PPS [MD] −3.47 mm; 95% CI −4.02 to −2.91 mm) and T2 (MD −2.20 mm; 95% CI −3.39 to −1.02 mm) tumors, mammogram underestimated T1 tumors (MD −2.91; 95% CI −3.51 to −2.32) and overestimated T2 tumors (MD 0.90; 95% CI −0.44 to 2.24), all within the range of concordance.

Study details: This study identified 1512 tumors in 1502 patients with invasive breast cancer who underwent their first surgery.

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

Source: Kapur H et al. Accuracy of preoperative imaging estimates: Opportunities to de-escalate surgery for early invasive breast cancer. Am J Surg. 2022 (Mar 30). Doi:  10.1016/j.amjsurg.2022.03.053

Key clinical point: Imaging can be dependably used for estimating the size of clinical T1 tumors to plan lumpectomy; however, overestimation by preoperative imaging size (PIS) should be considered for larger tumors.

Major finding: Significant correlation was observed between PIS and postoperative pathology size (PPS), highest when estimated with ultrasound (correlation coefficient [r] 0.628) followed by mammography (r 0.571; both P < .001). Although ultrasound underestimated T1 (mean difference between PIS and PPS [MD] −3.47 mm; 95% CI −4.02 to −2.91 mm) and T2 (MD −2.20 mm; 95% CI −3.39 to −1.02 mm) tumors, mammogram underestimated T1 tumors (MD −2.91; 95% CI −3.51 to −2.32) and overestimated T2 tumors (MD 0.90; 95% CI −0.44 to 2.24), all within the range of concordance.

Study details: This study identified 1512 tumors in 1502 patients with invasive breast cancer who underwent their first surgery.

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

Source: Kapur H et al. Accuracy of preoperative imaging estimates: Opportunities to de-escalate surgery for early invasive breast cancer. Am J Surg. 2022 (Mar 30). Doi:  10.1016/j.amjsurg.2022.03.053

Key clinical point: Increased stromal tumor-infiltrating lymphocytes (sTIL) were associated with improved survival in young patients (<40 years old) with early-stage, node-negative (N0), triple negative breast cancer (TNBC) who were naive to systemic therapy.

Major finding: At 15 years, the cumulative incidence of distant metastasis or death was only 2.1% (95% CI 0%-5.0%) in patients with high sTIL (≥75%) compared with 38.4% (95% CI 32.1%-44.6%) in patients with low sTIL (<30%), with an increase in overall survival by 19% for every 10% increase in sTIL (adjusted hazard ratio 0.81; 95% CI 0.76-0.87).

Study details: The study evaluated prospectively collected population-based cohort data of 441 patients aged <40 years who had N0 TNBC and had not received neoadjuvant systemic therapy.

Disclosures: This study was supported by The Netherlands Organization for Health Research and Development, A Sister’s Hope, De Vrienden van UMC Utrecht, and other sources. The authors declared serving as consultants, advisors, or in speaker’s bureaus or receiving research grants or travel and accommodation expenses from several sources.

Source: de Jong VMT et al. Prognostic value of stromal tumor-infiltrating lymphocytes in young, node-negative, triple-negative breast cancer patients who did not receive (neo)adjuvant systemic therapy. J Clin Oncol. 2022 (Mar 30). Doi: 10.1200/JCO.21.01536

Key clinical point: Increased stromal tumor-infiltrating lymphocytes (sTIL) were associated with improved survival in young patients (<40 years old) with early-stage, node-negative (N0), triple negative breast cancer (TNBC) who were naive to systemic therapy.

Major finding: At 15 years, the cumulative incidence of distant metastasis or death was only 2.1% (95% CI 0%-5.0%) in patients with high sTIL (≥75%) compared with 38.4% (95% CI 32.1%-44.6%) in patients with low sTIL (<30%), with an increase in overall survival by 19% for every 10% increase in sTIL (adjusted hazard ratio 0.81; 95% CI 0.76-0.87).

Study details: The study evaluated prospectively collected population-based cohort data of 441 patients aged <40 years who had N0 TNBC and had not received neoadjuvant systemic therapy.

Disclosures: This study was supported by The Netherlands Organization for Health Research and Development, A Sister’s Hope, De Vrienden van UMC Utrecht, and other sources. The authors declared serving as consultants, advisors, or in speaker’s bureaus or receiving research grants or travel and accommodation expenses from several sources.

Source: de Jong VMT et al. Prognostic value of stromal tumor-infiltrating lymphocytes in young, node-negative, triple-negative breast cancer patients who did not receive (neo)adjuvant systemic therapy. J Clin Oncol. 2022 (Mar 30). Doi: 10.1200/JCO.21.01536

Key clinical point: Increased stromal tumor-infiltrating lymphocytes (sTIL) were associated with improved survival in young patients (<40 years old) with early-stage, node-negative (N0), triple negative breast cancer (TNBC) who were naive to systemic therapy.

Major finding: At 15 years, the cumulative incidence of distant metastasis or death was only 2.1% (95% CI 0%-5.0%) in patients with high sTIL (≥75%) compared with 38.4% (95% CI 32.1%-44.6%) in patients with low sTIL (<30%), with an increase in overall survival by 19% for every 10% increase in sTIL (adjusted hazard ratio 0.81; 95% CI 0.76-0.87).

Study details: The study evaluated prospectively collected population-based cohort data of 441 patients aged <40 years who had N0 TNBC and had not received neoadjuvant systemic therapy.

Disclosures: This study was supported by The Netherlands Organization for Health Research and Development, A Sister’s Hope, De Vrienden van UMC Utrecht, and other sources. The authors declared serving as consultants, advisors, or in speaker’s bureaus or receiving research grants or travel and accommodation expenses from several sources.

Source: de Jong VMT et al. Prognostic value of stromal tumor-infiltrating lymphocytes in young, node-negative, triple-negative breast cancer patients who did not receive (neo)adjuvant systemic therapy. J Clin Oncol. 2022 (Mar 30). Doi: 10.1200/JCO.21.01536