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Is this the most controversial issue in early breast cancer treatment?
Is this the most controversial topic in breast oncology? Quite likely: the results of a recent online poll show split votes and no consensus.
The topic is the use of chemotherapy for premenopausal women with early-stage hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer.
, as the other expert countered?
The debate was held during the recent San Antonio Breast Cancer Symposium (SABCS), at which new results were presented that increased the controversy.
The controversy had arisen the previous year over results from the RxPONDER trial.
Five-year follow-up data from RxPONDER showed that adding chemotherapy to endocrine therapy did not improve outcomes over endocrine therapy alone for postmenopausal women with low-risk, node-positive HR+, HER2- breast cancer. This suggests that older women with early-stage breast cancer may safely forgo chemotherapy.
However, the same trial included premenopausal women with the same disease profile, and the results in this subgroup showed that there was benefit from chemotherapy, with a 5-year invasive disease-free survival (IDFS) rate of 94.2%, versus 89.0% for endocrine therapy alone (P = .0004).
The results were immediately controversial.
Some experts suggested the effect was due to the chemotherapy incidentally causing ovarian suppression, not the cytotoxic effect of the drugs on cancer cells. These experts were skeptical about the suggestion that chemotherapy works differently in premenopausal women than it does in postmenopausal women.
Some clinicians feel the lack of clarity creates an opportunity for greater discussion with women when making the treatment decision.
“When I have this conversation with patients, it’s really nuanced,” Stephanie L. Graff, MD, director of breast oncology, Lifespan Cancer Institute, Providence, R.I., told this news organization.
“I would choose chemotherapy for myself, but I’m a chemotherapy doctor, so I’m very comfortable with these medications and their side effects, and I am also very familiar with the slow burn of the side effects of endocrine therapy,” she said.
But for patients who are hearing their options for the first time, the idea of chemotherapy “feels scary,” and there is “a lot of stigma” associated with it, she commented.
Ultimately, she believes in offering patients as much information as possible, inasmuch as “knowledge is power.”
For Dr. Graff, the message from RxPONDER was that, in premenopausal patients with lymph node positive, HR+ breast cancer, “all comers benefited from chemotherapy.”
“And so if the goal is to be maximally aggressive and optimally lower your risk of distant recurrence, which is a life-threatening event, chemotherapy should offered.”
But chemotherapy comes with side effects, so it’s an important conversation to have with patients; RxPONDER showed that the absolute difference in the rate of distant recurrence with chemotherapy was relatively minor, she added.
Debate rages on
The debate at SABCS was moderated by Harold J. Burstein, MD, PhD, from the Dana-Farber Cancer Institute, Boston, who commented that if this was “a compelling question last week in clinic, it has now become red hot.”
At the meeting, held in December 2021, new longer-term data from the SOFT and TEXT clinical trials were presented, showing that ovarian suppression with tamoxifen plus an aromatase inhibitor provides a greater reduction in long-term risk of recurrence than tamoxifen alone.
Moreover, updated results from RxPONDER presented at the same session revealed that chemoendocrine therapy was associated with longer IDFS and distant relapse-free survival than endocrine therapy alone for women with one to three positive lymph nodes and a recurrence score of 25 or lower on the Oncotype DX (Genomic Health) 21-gene breast cancer assay.
Dr. Burstein said the debate over the use of chemotherapy in premenopausal women “is the most interesting question right now in early-stage breast cancer.”
The debate focused on the effect of chemotherapy in these patients – was it all down to ovarian function suppression?
Yes, argued Michael Gnant, MD, from the Medical University of Vienna.
Data from “modern adjuvant chemotherapy trials” suggest that chemo offers a 2%-3% benefit in distant disease-free survival at 5 years for premenopausal women, he noted. But the effect is much larger with ovarian function suppression via endocrine therapy, which provides 5-year disease-free and overall survival benefits of 9%-13%.
Older studies have shown that the benefit with chemotherapy is seen only in women who experience amenorrhea with the cytotoxic drugs, Dr. Gnant noted.
“In short, if you give adjuvant chemotherapy and you induce amenorrhea, then there is going to be a survival difference,” he said. “But if you give adjuvant chemotherapy and there is no amenorrhea, there won’t be an outcome difference.”
The ABSCG-05 trial, which compared endocrine therapy with chemotherapy, showed that “in the presence of optimal endocrine adjuvant treatment, adjuvant chemotherapy doesn’t add anything, because you have already achieved the effect of treatment-induced amenorrhea.”
So Dr. Gnant argued that the effect of chemotherapy in RxPONDER was due to ovarian function suppression.
But the real question is: “What does it mean for clinical practice?”
Dr. Gnant asserted that for the “large group of lower-risk premenopausal patients, tamoxifen will be good enough,” while those at moderate or intermediate risk should receive ovarian function suppression with either tamoxifen or an aromatase inhibitor, with the choice dictated by their adverse effects.
Chemotherapy “is just a graceless method of ovarian function suppression and should only be given to high-risk patients and to patients with endocrine nonresponsive disease,” he argued.
On the other side of the debate, Sibylle Loibl, MD, PhD, from the Centre of Hematology and Oncology, Bethanien, Frankfurt, argued that the effect is not all due to ovarian function suppression and that chemotherapy also has a cytotoxic effect in these patients.
“We need chemotherapy” because “cancer in young women is biologically different,” she asserted.
Dr. Loibl pointed to data currently awaiting publication in the Journal of the National Cancer Institute that suggest that younger women have “higher immune gene expression” that may make them more chemotherapy sensitive, and lower expression of hormone receptor genes, which “could make them less endocrine sensitive.”
She also cited data from a study from her own group that showed that pathologic complete response rates to neoadjuvant chemotherapy were higher in younger women with HR+, HER2- breast cancer, indicating a direct effect of chemotherapy on the disease and that age was an important prognostic factor.
The data on the induction of amenorrhea by chemotherapy is also not as clearcut as it seems, she commented. Chemotherapy does not achieve 100% amenorrhea, and gonadotropin-releasing hormone analogues are unable to suppress ovarian function in 20% of women.
Dr. Loibl concluded that the “chemotherapy effect is there, it is higher in young women with HR+, HER2- breast cancer,” and that the effect has two components.
“There is a direct cytotoxic effect which cannot be neglected, and there is an endocrine effect on the ovarian function suppression,” she argued.
“I think both are needed in young premenopausal patients,” she added.
Audience responses
After the debate, the audience was polled on what effect they thought chemotherapy was having in lower-risk HR+, HER2- breast cancer patients. About two-thirds responded that it was all or mostly due to ovarian function suppression.
However, the next question split the audience. They were presented with a clinical scenario: a 43-year-old woman with a mammographically detected 1.4-cm, intermediate grade, HR+, HER2- breast cancer who also had metastatic disease in one of three sentinel lymph nodes and whose recurrence score was 13.
When asked about the treatment plan they would choose for this patient, the audience was split over whether to opt for chemoendocrine therapy or endocrine therapy alone.
A similar clinical question was posited recently on Twitter, when Angela Toss, MD, PhD, from the University of Modena and Reggio Emilia, Italy, asked respondents which they would chose from among three options.
From the 815 votes that were cast, 46% chose Oncotype DX testing to determine the likely benefit of chemotherapy, 48% chose chemotherapy, and 6% picked ovarian function suppression and an aromatase inhibitor.
In response, Paolo Tarantino, MD, from the Dana-Farber Cancer Institute, commented: “If you had any doubt of which is the most controversial topic in breast oncology, doubt no more. 815 votes, no consensus.”
Approached for comment, Eric Winer, MD, director of the Yale Cancer Center, New Haven, Conn., said that the data from RxPONDER “in many ways was helpful, but ... it created about as many questions as it answered, if not more.”
Because the results showed a benefit from chemotherapy for premenopausal women but not for postmenopausal women with breast cancer, Dr. Winer told this news organization that one of the outstanding questions is “whether premenopausal women are fundamentally different from postmenopausal women ... and my answer to that is that is very unlikely.”
Dr. Winer added that the “real tragedy” of this trial was that it did not include women with more than three positive nodes, particularly those who have a low recurrence score, he said.
Clinicians are therefore left either “extrapolating” data from those with fewer nodes or “marching down a path that we’ve taken for years of just giving those people chemotherapy routinely,” even though there may be no benefit, Dr. Winer commented.
Another expert who was approached for comment had a different take on the data. Matteo Lambertini, MD, IRCCS Ospedale Policlinico San Martino, Genoa, Italy, agreed with Loibl’s argument that chemotherapy has a cytotoxic effect in premenopausal women with HR+, HER2- breast cancer in addition to its effect on ovarian function suppression.
He did not agree, however, that there is a question mark over what to do for patients with more than three positive lymph nodes.
Dr. Lambertini said in an interview that he thinks “too much” trust is placed in genomic testing and that there is a “risk of forgetting about all the other factors that we normally use to make our treatment choices.”
A patient with five positive nodes will benefit from chemotherapy, “even if she had a very low recurrence score,” he said, “because there is a very high clinical risk of disease recurrence,” and chemotherapy “is of benefit” in these situations, he asserted.
Dr. Lambertini said that the RxPONDER results – and also studies such as TAILORx, which demonstrated the ability of Oncotype DX to identify which patients with early breast cancer could skip chemotherapy – show that “chemotherapy has a role to play” and that most patients should receive it.
He suggested, however, that “probably the benefit of chemotherapy is smaller” in real life than was seen in these trials, because in the trials, they did not use optimal adjuvant endocrine therapy.
Treating individual patients
When it comes to making treatment decisions for individual patients, Dr. Winer said he has a “conversation with people about what the results of the study showed and what [he believes] that they need.”
For patients whose Oncotype DX score is in the “very low range, I do not recommend chemotherapy,” he said, preferring instead to use endocrine therapy for ovarian function suppression.
For women with a more intermediate score, “I explain that I don’t think we have an answer and that, if they would want to take the most traditional and conservative path, it would be to get chemotherapy.
“But I’m certainly not rigid about my recommendations, and I’m particularly open” to ovarian function suppression for a premenopausal woman with an Onctyope DX score of 20 and two positive nodes who does not have “other adverse features.”
“Ultimately, what pushes me in one direction or another,” Dr. Winer said, aside from number of positive nodes or the size of the tumor, “is the patient’s preferences.”
This was a theme taken up by Kim Sabelko, PhD, vice-president of scientific strategy and programs at Susan G. Komen, Dallas.
The results from RxPONDER and similar studies are “really interesting,” as researchers are “working out how to individualize treatment,” and that it is not a matter of “one size fits all.”
“We need to understand when to use chemotherapy and other drugs, and more importantly, when not to, because we don’t want to overtreat people who don’t necessarily need these drugs,” she commented.
Dr. Sabelko emphasized that treatment decisions “should be shared” between the patient and their doctor, and she noted that there “will be some people who are going to refuse chemotherapy for different reasons.”
These clinical trial results help clinicians to explain the risks and benefits of treatment options, but the treatment decision should be taken “together” with the patient, she emphasized.
Dr. Gnant has relationships with Sandoz, Amge, Daiichi Sankyo, AstraZeneca, Eli Lilly, Nanostring, Novartis, Pierre Fabre, TLC Pharmaceuticals, and Life Brain. Dr. Loibl has relationships with AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Meyers Squibb, Celgene, Daiichi Sankyo, Eirgenix, GSK, Gilead, Lilly, Merck, Novartis, Pfizer, Pierre Fabre, Medscape, Puma, Roche, Samsung, Seagen, VM Scope, and GBG Forschungs.
A version of this article first appeared on Medscape.com.
Is this the most controversial topic in breast oncology? Quite likely: the results of a recent online poll show split votes and no consensus.
The topic is the use of chemotherapy for premenopausal women with early-stage hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer.
, as the other expert countered?
The debate was held during the recent San Antonio Breast Cancer Symposium (SABCS), at which new results were presented that increased the controversy.
The controversy had arisen the previous year over results from the RxPONDER trial.
Five-year follow-up data from RxPONDER showed that adding chemotherapy to endocrine therapy did not improve outcomes over endocrine therapy alone for postmenopausal women with low-risk, node-positive HR+, HER2- breast cancer. This suggests that older women with early-stage breast cancer may safely forgo chemotherapy.
However, the same trial included premenopausal women with the same disease profile, and the results in this subgroup showed that there was benefit from chemotherapy, with a 5-year invasive disease-free survival (IDFS) rate of 94.2%, versus 89.0% for endocrine therapy alone (P = .0004).
The results were immediately controversial.
Some experts suggested the effect was due to the chemotherapy incidentally causing ovarian suppression, not the cytotoxic effect of the drugs on cancer cells. These experts were skeptical about the suggestion that chemotherapy works differently in premenopausal women than it does in postmenopausal women.
Some clinicians feel the lack of clarity creates an opportunity for greater discussion with women when making the treatment decision.
“When I have this conversation with patients, it’s really nuanced,” Stephanie L. Graff, MD, director of breast oncology, Lifespan Cancer Institute, Providence, R.I., told this news organization.
“I would choose chemotherapy for myself, but I’m a chemotherapy doctor, so I’m very comfortable with these medications and their side effects, and I am also very familiar with the slow burn of the side effects of endocrine therapy,” she said.
But for patients who are hearing their options for the first time, the idea of chemotherapy “feels scary,” and there is “a lot of stigma” associated with it, she commented.
Ultimately, she believes in offering patients as much information as possible, inasmuch as “knowledge is power.”
For Dr. Graff, the message from RxPONDER was that, in premenopausal patients with lymph node positive, HR+ breast cancer, “all comers benefited from chemotherapy.”
“And so if the goal is to be maximally aggressive and optimally lower your risk of distant recurrence, which is a life-threatening event, chemotherapy should offered.”
But chemotherapy comes with side effects, so it’s an important conversation to have with patients; RxPONDER showed that the absolute difference in the rate of distant recurrence with chemotherapy was relatively minor, she added.
Debate rages on
The debate at SABCS was moderated by Harold J. Burstein, MD, PhD, from the Dana-Farber Cancer Institute, Boston, who commented that if this was “a compelling question last week in clinic, it has now become red hot.”
At the meeting, held in December 2021, new longer-term data from the SOFT and TEXT clinical trials were presented, showing that ovarian suppression with tamoxifen plus an aromatase inhibitor provides a greater reduction in long-term risk of recurrence than tamoxifen alone.
Moreover, updated results from RxPONDER presented at the same session revealed that chemoendocrine therapy was associated with longer IDFS and distant relapse-free survival than endocrine therapy alone for women with one to three positive lymph nodes and a recurrence score of 25 or lower on the Oncotype DX (Genomic Health) 21-gene breast cancer assay.
Dr. Burstein said the debate over the use of chemotherapy in premenopausal women “is the most interesting question right now in early-stage breast cancer.”
The debate focused on the effect of chemotherapy in these patients – was it all down to ovarian function suppression?
Yes, argued Michael Gnant, MD, from the Medical University of Vienna.
Data from “modern adjuvant chemotherapy trials” suggest that chemo offers a 2%-3% benefit in distant disease-free survival at 5 years for premenopausal women, he noted. But the effect is much larger with ovarian function suppression via endocrine therapy, which provides 5-year disease-free and overall survival benefits of 9%-13%.
Older studies have shown that the benefit with chemotherapy is seen only in women who experience amenorrhea with the cytotoxic drugs, Dr. Gnant noted.
“In short, if you give adjuvant chemotherapy and you induce amenorrhea, then there is going to be a survival difference,” he said. “But if you give adjuvant chemotherapy and there is no amenorrhea, there won’t be an outcome difference.”
The ABSCG-05 trial, which compared endocrine therapy with chemotherapy, showed that “in the presence of optimal endocrine adjuvant treatment, adjuvant chemotherapy doesn’t add anything, because you have already achieved the effect of treatment-induced amenorrhea.”
So Dr. Gnant argued that the effect of chemotherapy in RxPONDER was due to ovarian function suppression.
But the real question is: “What does it mean for clinical practice?”
Dr. Gnant asserted that for the “large group of lower-risk premenopausal patients, tamoxifen will be good enough,” while those at moderate or intermediate risk should receive ovarian function suppression with either tamoxifen or an aromatase inhibitor, with the choice dictated by their adverse effects.
Chemotherapy “is just a graceless method of ovarian function suppression and should only be given to high-risk patients and to patients with endocrine nonresponsive disease,” he argued.
On the other side of the debate, Sibylle Loibl, MD, PhD, from the Centre of Hematology and Oncology, Bethanien, Frankfurt, argued that the effect is not all due to ovarian function suppression and that chemotherapy also has a cytotoxic effect in these patients.
“We need chemotherapy” because “cancer in young women is biologically different,” she asserted.
Dr. Loibl pointed to data currently awaiting publication in the Journal of the National Cancer Institute that suggest that younger women have “higher immune gene expression” that may make them more chemotherapy sensitive, and lower expression of hormone receptor genes, which “could make them less endocrine sensitive.”
She also cited data from a study from her own group that showed that pathologic complete response rates to neoadjuvant chemotherapy were higher in younger women with HR+, HER2- breast cancer, indicating a direct effect of chemotherapy on the disease and that age was an important prognostic factor.
The data on the induction of amenorrhea by chemotherapy is also not as clearcut as it seems, she commented. Chemotherapy does not achieve 100% amenorrhea, and gonadotropin-releasing hormone analogues are unable to suppress ovarian function in 20% of women.
Dr. Loibl concluded that the “chemotherapy effect is there, it is higher in young women with HR+, HER2- breast cancer,” and that the effect has two components.
“There is a direct cytotoxic effect which cannot be neglected, and there is an endocrine effect on the ovarian function suppression,” she argued.
“I think both are needed in young premenopausal patients,” she added.
Audience responses
After the debate, the audience was polled on what effect they thought chemotherapy was having in lower-risk HR+, HER2- breast cancer patients. About two-thirds responded that it was all or mostly due to ovarian function suppression.
However, the next question split the audience. They were presented with a clinical scenario: a 43-year-old woman with a mammographically detected 1.4-cm, intermediate grade, HR+, HER2- breast cancer who also had metastatic disease in one of three sentinel lymph nodes and whose recurrence score was 13.
When asked about the treatment plan they would choose for this patient, the audience was split over whether to opt for chemoendocrine therapy or endocrine therapy alone.
A similar clinical question was posited recently on Twitter, when Angela Toss, MD, PhD, from the University of Modena and Reggio Emilia, Italy, asked respondents which they would chose from among three options.
From the 815 votes that were cast, 46% chose Oncotype DX testing to determine the likely benefit of chemotherapy, 48% chose chemotherapy, and 6% picked ovarian function suppression and an aromatase inhibitor.
In response, Paolo Tarantino, MD, from the Dana-Farber Cancer Institute, commented: “If you had any doubt of which is the most controversial topic in breast oncology, doubt no more. 815 votes, no consensus.”
Approached for comment, Eric Winer, MD, director of the Yale Cancer Center, New Haven, Conn., said that the data from RxPONDER “in many ways was helpful, but ... it created about as many questions as it answered, if not more.”
Because the results showed a benefit from chemotherapy for premenopausal women but not for postmenopausal women with breast cancer, Dr. Winer told this news organization that one of the outstanding questions is “whether premenopausal women are fundamentally different from postmenopausal women ... and my answer to that is that is very unlikely.”
Dr. Winer added that the “real tragedy” of this trial was that it did not include women with more than three positive nodes, particularly those who have a low recurrence score, he said.
Clinicians are therefore left either “extrapolating” data from those with fewer nodes or “marching down a path that we’ve taken for years of just giving those people chemotherapy routinely,” even though there may be no benefit, Dr. Winer commented.
Another expert who was approached for comment had a different take on the data. Matteo Lambertini, MD, IRCCS Ospedale Policlinico San Martino, Genoa, Italy, agreed with Loibl’s argument that chemotherapy has a cytotoxic effect in premenopausal women with HR+, HER2- breast cancer in addition to its effect on ovarian function suppression.
He did not agree, however, that there is a question mark over what to do for patients with more than three positive lymph nodes.
Dr. Lambertini said in an interview that he thinks “too much” trust is placed in genomic testing and that there is a “risk of forgetting about all the other factors that we normally use to make our treatment choices.”
A patient with five positive nodes will benefit from chemotherapy, “even if she had a very low recurrence score,” he said, “because there is a very high clinical risk of disease recurrence,” and chemotherapy “is of benefit” in these situations, he asserted.
Dr. Lambertini said that the RxPONDER results – and also studies such as TAILORx, which demonstrated the ability of Oncotype DX to identify which patients with early breast cancer could skip chemotherapy – show that “chemotherapy has a role to play” and that most patients should receive it.
He suggested, however, that “probably the benefit of chemotherapy is smaller” in real life than was seen in these trials, because in the trials, they did not use optimal adjuvant endocrine therapy.
Treating individual patients
When it comes to making treatment decisions for individual patients, Dr. Winer said he has a “conversation with people about what the results of the study showed and what [he believes] that they need.”
For patients whose Oncotype DX score is in the “very low range, I do not recommend chemotherapy,” he said, preferring instead to use endocrine therapy for ovarian function suppression.
For women with a more intermediate score, “I explain that I don’t think we have an answer and that, if they would want to take the most traditional and conservative path, it would be to get chemotherapy.
“But I’m certainly not rigid about my recommendations, and I’m particularly open” to ovarian function suppression for a premenopausal woman with an Onctyope DX score of 20 and two positive nodes who does not have “other adverse features.”
“Ultimately, what pushes me in one direction or another,” Dr. Winer said, aside from number of positive nodes or the size of the tumor, “is the patient’s preferences.”
This was a theme taken up by Kim Sabelko, PhD, vice-president of scientific strategy and programs at Susan G. Komen, Dallas.
The results from RxPONDER and similar studies are “really interesting,” as researchers are “working out how to individualize treatment,” and that it is not a matter of “one size fits all.”
“We need to understand when to use chemotherapy and other drugs, and more importantly, when not to, because we don’t want to overtreat people who don’t necessarily need these drugs,” she commented.
Dr. Sabelko emphasized that treatment decisions “should be shared” between the patient and their doctor, and she noted that there “will be some people who are going to refuse chemotherapy for different reasons.”
These clinical trial results help clinicians to explain the risks and benefits of treatment options, but the treatment decision should be taken “together” with the patient, she emphasized.
Dr. Gnant has relationships with Sandoz, Amge, Daiichi Sankyo, AstraZeneca, Eli Lilly, Nanostring, Novartis, Pierre Fabre, TLC Pharmaceuticals, and Life Brain. Dr. Loibl has relationships with AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Meyers Squibb, Celgene, Daiichi Sankyo, Eirgenix, GSK, Gilead, Lilly, Merck, Novartis, Pfizer, Pierre Fabre, Medscape, Puma, Roche, Samsung, Seagen, VM Scope, and GBG Forschungs.
A version of this article first appeared on Medscape.com.
Is this the most controversial topic in breast oncology? Quite likely: the results of a recent online poll show split votes and no consensus.
The topic is the use of chemotherapy for premenopausal women with early-stage hormone receptor–positive (HR+), human epidermal growth factor receptor 2–negative (HER2-) breast cancer.
, as the other expert countered?
The debate was held during the recent San Antonio Breast Cancer Symposium (SABCS), at which new results were presented that increased the controversy.
The controversy had arisen the previous year over results from the RxPONDER trial.
Five-year follow-up data from RxPONDER showed that adding chemotherapy to endocrine therapy did not improve outcomes over endocrine therapy alone for postmenopausal women with low-risk, node-positive HR+, HER2- breast cancer. This suggests that older women with early-stage breast cancer may safely forgo chemotherapy.
However, the same trial included premenopausal women with the same disease profile, and the results in this subgroup showed that there was benefit from chemotherapy, with a 5-year invasive disease-free survival (IDFS) rate of 94.2%, versus 89.0% for endocrine therapy alone (P = .0004).
The results were immediately controversial.
Some experts suggested the effect was due to the chemotherapy incidentally causing ovarian suppression, not the cytotoxic effect of the drugs on cancer cells. These experts were skeptical about the suggestion that chemotherapy works differently in premenopausal women than it does in postmenopausal women.
Some clinicians feel the lack of clarity creates an opportunity for greater discussion with women when making the treatment decision.
“When I have this conversation with patients, it’s really nuanced,” Stephanie L. Graff, MD, director of breast oncology, Lifespan Cancer Institute, Providence, R.I., told this news organization.
“I would choose chemotherapy for myself, but I’m a chemotherapy doctor, so I’m very comfortable with these medications and their side effects, and I am also very familiar with the slow burn of the side effects of endocrine therapy,” she said.
But for patients who are hearing their options for the first time, the idea of chemotherapy “feels scary,” and there is “a lot of stigma” associated with it, she commented.
Ultimately, she believes in offering patients as much information as possible, inasmuch as “knowledge is power.”
For Dr. Graff, the message from RxPONDER was that, in premenopausal patients with lymph node positive, HR+ breast cancer, “all comers benefited from chemotherapy.”
“And so if the goal is to be maximally aggressive and optimally lower your risk of distant recurrence, which is a life-threatening event, chemotherapy should offered.”
But chemotherapy comes with side effects, so it’s an important conversation to have with patients; RxPONDER showed that the absolute difference in the rate of distant recurrence with chemotherapy was relatively minor, she added.
Debate rages on
The debate at SABCS was moderated by Harold J. Burstein, MD, PhD, from the Dana-Farber Cancer Institute, Boston, who commented that if this was “a compelling question last week in clinic, it has now become red hot.”
At the meeting, held in December 2021, new longer-term data from the SOFT and TEXT clinical trials were presented, showing that ovarian suppression with tamoxifen plus an aromatase inhibitor provides a greater reduction in long-term risk of recurrence than tamoxifen alone.
Moreover, updated results from RxPONDER presented at the same session revealed that chemoendocrine therapy was associated with longer IDFS and distant relapse-free survival than endocrine therapy alone for women with one to three positive lymph nodes and a recurrence score of 25 or lower on the Oncotype DX (Genomic Health) 21-gene breast cancer assay.
Dr. Burstein said the debate over the use of chemotherapy in premenopausal women “is the most interesting question right now in early-stage breast cancer.”
The debate focused on the effect of chemotherapy in these patients – was it all down to ovarian function suppression?
Yes, argued Michael Gnant, MD, from the Medical University of Vienna.
Data from “modern adjuvant chemotherapy trials” suggest that chemo offers a 2%-3% benefit in distant disease-free survival at 5 years for premenopausal women, he noted. But the effect is much larger with ovarian function suppression via endocrine therapy, which provides 5-year disease-free and overall survival benefits of 9%-13%.
Older studies have shown that the benefit with chemotherapy is seen only in women who experience amenorrhea with the cytotoxic drugs, Dr. Gnant noted.
“In short, if you give adjuvant chemotherapy and you induce amenorrhea, then there is going to be a survival difference,” he said. “But if you give adjuvant chemotherapy and there is no amenorrhea, there won’t be an outcome difference.”
The ABSCG-05 trial, which compared endocrine therapy with chemotherapy, showed that “in the presence of optimal endocrine adjuvant treatment, adjuvant chemotherapy doesn’t add anything, because you have already achieved the effect of treatment-induced amenorrhea.”
So Dr. Gnant argued that the effect of chemotherapy in RxPONDER was due to ovarian function suppression.
But the real question is: “What does it mean for clinical practice?”
Dr. Gnant asserted that for the “large group of lower-risk premenopausal patients, tamoxifen will be good enough,” while those at moderate or intermediate risk should receive ovarian function suppression with either tamoxifen or an aromatase inhibitor, with the choice dictated by their adverse effects.
Chemotherapy “is just a graceless method of ovarian function suppression and should only be given to high-risk patients and to patients with endocrine nonresponsive disease,” he argued.
On the other side of the debate, Sibylle Loibl, MD, PhD, from the Centre of Hematology and Oncology, Bethanien, Frankfurt, argued that the effect is not all due to ovarian function suppression and that chemotherapy also has a cytotoxic effect in these patients.
“We need chemotherapy” because “cancer in young women is biologically different,” she asserted.
Dr. Loibl pointed to data currently awaiting publication in the Journal of the National Cancer Institute that suggest that younger women have “higher immune gene expression” that may make them more chemotherapy sensitive, and lower expression of hormone receptor genes, which “could make them less endocrine sensitive.”
She also cited data from a study from her own group that showed that pathologic complete response rates to neoadjuvant chemotherapy were higher in younger women with HR+, HER2- breast cancer, indicating a direct effect of chemotherapy on the disease and that age was an important prognostic factor.
The data on the induction of amenorrhea by chemotherapy is also not as clearcut as it seems, she commented. Chemotherapy does not achieve 100% amenorrhea, and gonadotropin-releasing hormone analogues are unable to suppress ovarian function in 20% of women.
Dr. Loibl concluded that the “chemotherapy effect is there, it is higher in young women with HR+, HER2- breast cancer,” and that the effect has two components.
“There is a direct cytotoxic effect which cannot be neglected, and there is an endocrine effect on the ovarian function suppression,” she argued.
“I think both are needed in young premenopausal patients,” she added.
Audience responses
After the debate, the audience was polled on what effect they thought chemotherapy was having in lower-risk HR+, HER2- breast cancer patients. About two-thirds responded that it was all or mostly due to ovarian function suppression.
However, the next question split the audience. They were presented with a clinical scenario: a 43-year-old woman with a mammographically detected 1.4-cm, intermediate grade, HR+, HER2- breast cancer who also had metastatic disease in one of three sentinel lymph nodes and whose recurrence score was 13.
When asked about the treatment plan they would choose for this patient, the audience was split over whether to opt for chemoendocrine therapy or endocrine therapy alone.
A similar clinical question was posited recently on Twitter, when Angela Toss, MD, PhD, from the University of Modena and Reggio Emilia, Italy, asked respondents which they would chose from among three options.
From the 815 votes that were cast, 46% chose Oncotype DX testing to determine the likely benefit of chemotherapy, 48% chose chemotherapy, and 6% picked ovarian function suppression and an aromatase inhibitor.
In response, Paolo Tarantino, MD, from the Dana-Farber Cancer Institute, commented: “If you had any doubt of which is the most controversial topic in breast oncology, doubt no more. 815 votes, no consensus.”
Approached for comment, Eric Winer, MD, director of the Yale Cancer Center, New Haven, Conn., said that the data from RxPONDER “in many ways was helpful, but ... it created about as many questions as it answered, if not more.”
Because the results showed a benefit from chemotherapy for premenopausal women but not for postmenopausal women with breast cancer, Dr. Winer told this news organization that one of the outstanding questions is “whether premenopausal women are fundamentally different from postmenopausal women ... and my answer to that is that is very unlikely.”
Dr. Winer added that the “real tragedy” of this trial was that it did not include women with more than three positive nodes, particularly those who have a low recurrence score, he said.
Clinicians are therefore left either “extrapolating” data from those with fewer nodes or “marching down a path that we’ve taken for years of just giving those people chemotherapy routinely,” even though there may be no benefit, Dr. Winer commented.
Another expert who was approached for comment had a different take on the data. Matteo Lambertini, MD, IRCCS Ospedale Policlinico San Martino, Genoa, Italy, agreed with Loibl’s argument that chemotherapy has a cytotoxic effect in premenopausal women with HR+, HER2- breast cancer in addition to its effect on ovarian function suppression.
He did not agree, however, that there is a question mark over what to do for patients with more than three positive lymph nodes.
Dr. Lambertini said in an interview that he thinks “too much” trust is placed in genomic testing and that there is a “risk of forgetting about all the other factors that we normally use to make our treatment choices.”
A patient with five positive nodes will benefit from chemotherapy, “even if she had a very low recurrence score,” he said, “because there is a very high clinical risk of disease recurrence,” and chemotherapy “is of benefit” in these situations, he asserted.
Dr. Lambertini said that the RxPONDER results – and also studies such as TAILORx, which demonstrated the ability of Oncotype DX to identify which patients with early breast cancer could skip chemotherapy – show that “chemotherapy has a role to play” and that most patients should receive it.
He suggested, however, that “probably the benefit of chemotherapy is smaller” in real life than was seen in these trials, because in the trials, they did not use optimal adjuvant endocrine therapy.
Treating individual patients
When it comes to making treatment decisions for individual patients, Dr. Winer said he has a “conversation with people about what the results of the study showed and what [he believes] that they need.”
For patients whose Oncotype DX score is in the “very low range, I do not recommend chemotherapy,” he said, preferring instead to use endocrine therapy for ovarian function suppression.
For women with a more intermediate score, “I explain that I don’t think we have an answer and that, if they would want to take the most traditional and conservative path, it would be to get chemotherapy.
“But I’m certainly not rigid about my recommendations, and I’m particularly open” to ovarian function suppression for a premenopausal woman with an Onctyope DX score of 20 and two positive nodes who does not have “other adverse features.”
“Ultimately, what pushes me in one direction or another,” Dr. Winer said, aside from number of positive nodes or the size of the tumor, “is the patient’s preferences.”
This was a theme taken up by Kim Sabelko, PhD, vice-president of scientific strategy and programs at Susan G. Komen, Dallas.
The results from RxPONDER and similar studies are “really interesting,” as researchers are “working out how to individualize treatment,” and that it is not a matter of “one size fits all.”
“We need to understand when to use chemotherapy and other drugs, and more importantly, when not to, because we don’t want to overtreat people who don’t necessarily need these drugs,” she commented.
Dr. Sabelko emphasized that treatment decisions “should be shared” between the patient and their doctor, and she noted that there “will be some people who are going to refuse chemotherapy for different reasons.”
These clinical trial results help clinicians to explain the risks and benefits of treatment options, but the treatment decision should be taken “together” with the patient, she emphasized.
Dr. Gnant has relationships with Sandoz, Amge, Daiichi Sankyo, AstraZeneca, Eli Lilly, Nanostring, Novartis, Pierre Fabre, TLC Pharmaceuticals, and Life Brain. Dr. Loibl has relationships with AbbVie, Amgen, AstraZeneca, Bayer, Bristol-Meyers Squibb, Celgene, Daiichi Sankyo, Eirgenix, GSK, Gilead, Lilly, Merck, Novartis, Pfizer, Pierre Fabre, Medscape, Puma, Roche, Samsung, Seagen, VM Scope, and GBG Forschungs.
A version of this article first appeared on Medscape.com.
False-positive breast cancer screening likely over 10-year period
Breast cancer screening modality has less effect on the probability of false-positive results than screening interval, patient age, and breast density according to a new study comparing digital breast tomosynthesis (DBT) with digital mammography.
Although DBT was associated with a modest improvement in recalls for false-positive results compared with mammography, about half of women in both groups received at least one false-positive result over a 10-year period of annual screening, reported senior author Diana L. Miglioretti, PhD, from the University of California, Davis, and colleagues.
By contrast, the authors reported “substantial reductions” in false-positive recalls with biennial screening. Specifically, while annual mammography and DBT resulted in cumulative 10-year false-positive recall rates of 56.3% and 49.6% respectively, biennial rates were 38.1% and 35.7%.
The comparative effectiveness study, published in JAMA Network Open, included 903,495 women who underwent 10 years of breast cancer screening at 126 radiology facilities in the Breast Cancer Surveillance Consortium. The mean age of participants was 57.6 years, and 46% of them had dense breasts. A total of 2,969,055 screening exams were performed (15% DBT), with each woman receiving a mean of 3.3 exams over 10 years. Most participants (71.8%) had annual exams, while 16.8% had biennial, with the remainder being performed at intervals of 3 years or more.
Investigators looked at the cumulative rate of three kinds of false-positive results over 10 years: false-positive recalls for further imaging, false-positive short-interval follow-up recommendations, and false-positive biopsy recommendations. A result was considered false positive if there was no diagnosis of invasive carcinoma or ductal carcinoma in situ within 1 year of the screening examination and before the next screening examination.
Overall, across all screening intervals, and after adjusting for age and breast density, the percentage of false-positive results was slightly lower for DBT vs. mammography: 7.6% vs. 9.0%, respectively, for false-positive recalls; 1.8% vs. 2.1%, respectively, for false-positive short-interval follow-up recommendations; and 1.1% vs. 1.2% for false-positive biopsy recommendations. “We did not observe consistent clinically meaningful differences in the cumulative probabilities of false-positive short-interval follow-up or biopsy recommendation by screening modality,” they noted, adding that, although DBT provided “modest” reductions in false-positive recalls, compared with mammography (2.4% less for biennial screening and 6.7% less for annual screening), “nonetheless, this percentage equates to many thousands of individuals in absolute numbers, especially for annual screening, which is the dominant practice in the U.S.”
The authors also noted that, regardless of screening modality, all three types of false-positive results were substantially lower for biennial versus annual mammograph, and depended on age and breast density. The highest cumulative rates of false-positive results occurred in women aged 40-49 years (68.0% with annual digital mammography and 60.8% with annual DBT). Women with extremely dense breasts had the highest probability of all three types of false positive, which “may be due to the lack of interspersed fat within dense fibroglandular tissue, with the contrast between the fat and tissue being a requirement for more accurate detection of suspicious features by interpreting radiologists.”
The study findings “offer new information about the potential harms of repeated screening, which may be used to inform screening guidelines and decision-making between individuals and their physicians. However, it is important to weigh these and other potential harms with potential benefits of earlier diagnosis. … Women at high risk of an advanced cancer under biennial screening, including some women with dense breasts, may reduce their risk with annual screening,” they suggested.
Although DBT is now widely used in the United States, amid growing optimism about its superiority over digital mammography, this study reminds clinicians to counsel patients appropriately, according to Lydia E. Pace, MD, from Brigham and Women’s Hospital in Boston. “Unfortunately, the growing availability of DBT does not substantially change the likelihood that women will experience a false-positive result over years of regular mammograms,” she wrote in an invited commentary published with the study. She noted that, although many women tolerate false-positive results, “they are associated with at least transient anxiety as well as time, inconvenience, and expense. More information is needed to understand the association of DBT with overdiagnosis, which is the more clinically important harm of screening.”
The study was funded by the National Cancer Institute. Dr. Miglioretti and Dr. Pace reported no conflicts of interest. One coauthor of the study is an unpaid consultant for Grail, for the STRIVE study, and another coauthor receives personal fees from Grail for work on a data safety monitoring board. No other disclosures were reported.
Breast cancer screening modality has less effect on the probability of false-positive results than screening interval, patient age, and breast density according to a new study comparing digital breast tomosynthesis (DBT) with digital mammography.
Although DBT was associated with a modest improvement in recalls for false-positive results compared with mammography, about half of women in both groups received at least one false-positive result over a 10-year period of annual screening, reported senior author Diana L. Miglioretti, PhD, from the University of California, Davis, and colleagues.
By contrast, the authors reported “substantial reductions” in false-positive recalls with biennial screening. Specifically, while annual mammography and DBT resulted in cumulative 10-year false-positive recall rates of 56.3% and 49.6% respectively, biennial rates were 38.1% and 35.7%.
The comparative effectiveness study, published in JAMA Network Open, included 903,495 women who underwent 10 years of breast cancer screening at 126 radiology facilities in the Breast Cancer Surveillance Consortium. The mean age of participants was 57.6 years, and 46% of them had dense breasts. A total of 2,969,055 screening exams were performed (15% DBT), with each woman receiving a mean of 3.3 exams over 10 years. Most participants (71.8%) had annual exams, while 16.8% had biennial, with the remainder being performed at intervals of 3 years or more.
Investigators looked at the cumulative rate of three kinds of false-positive results over 10 years: false-positive recalls for further imaging, false-positive short-interval follow-up recommendations, and false-positive biopsy recommendations. A result was considered false positive if there was no diagnosis of invasive carcinoma or ductal carcinoma in situ within 1 year of the screening examination and before the next screening examination.
Overall, across all screening intervals, and after adjusting for age and breast density, the percentage of false-positive results was slightly lower for DBT vs. mammography: 7.6% vs. 9.0%, respectively, for false-positive recalls; 1.8% vs. 2.1%, respectively, for false-positive short-interval follow-up recommendations; and 1.1% vs. 1.2% for false-positive biopsy recommendations. “We did not observe consistent clinically meaningful differences in the cumulative probabilities of false-positive short-interval follow-up or biopsy recommendation by screening modality,” they noted, adding that, although DBT provided “modest” reductions in false-positive recalls, compared with mammography (2.4% less for biennial screening and 6.7% less for annual screening), “nonetheless, this percentage equates to many thousands of individuals in absolute numbers, especially for annual screening, which is the dominant practice in the U.S.”
The authors also noted that, regardless of screening modality, all three types of false-positive results were substantially lower for biennial versus annual mammograph, and depended on age and breast density. The highest cumulative rates of false-positive results occurred in women aged 40-49 years (68.0% with annual digital mammography and 60.8% with annual DBT). Women with extremely dense breasts had the highest probability of all three types of false positive, which “may be due to the lack of interspersed fat within dense fibroglandular tissue, with the contrast between the fat and tissue being a requirement for more accurate detection of suspicious features by interpreting radiologists.”
The study findings “offer new information about the potential harms of repeated screening, which may be used to inform screening guidelines and decision-making between individuals and their physicians. However, it is important to weigh these and other potential harms with potential benefits of earlier diagnosis. … Women at high risk of an advanced cancer under biennial screening, including some women with dense breasts, may reduce their risk with annual screening,” they suggested.
Although DBT is now widely used in the United States, amid growing optimism about its superiority over digital mammography, this study reminds clinicians to counsel patients appropriately, according to Lydia E. Pace, MD, from Brigham and Women’s Hospital in Boston. “Unfortunately, the growing availability of DBT does not substantially change the likelihood that women will experience a false-positive result over years of regular mammograms,” she wrote in an invited commentary published with the study. She noted that, although many women tolerate false-positive results, “they are associated with at least transient anxiety as well as time, inconvenience, and expense. More information is needed to understand the association of DBT with overdiagnosis, which is the more clinically important harm of screening.”
The study was funded by the National Cancer Institute. Dr. Miglioretti and Dr. Pace reported no conflicts of interest. One coauthor of the study is an unpaid consultant for Grail, for the STRIVE study, and another coauthor receives personal fees from Grail for work on a data safety monitoring board. No other disclosures were reported.
Breast cancer screening modality has less effect on the probability of false-positive results than screening interval, patient age, and breast density according to a new study comparing digital breast tomosynthesis (DBT) with digital mammography.
Although DBT was associated with a modest improvement in recalls for false-positive results compared with mammography, about half of women in both groups received at least one false-positive result over a 10-year period of annual screening, reported senior author Diana L. Miglioretti, PhD, from the University of California, Davis, and colleagues.
By contrast, the authors reported “substantial reductions” in false-positive recalls with biennial screening. Specifically, while annual mammography and DBT resulted in cumulative 10-year false-positive recall rates of 56.3% and 49.6% respectively, biennial rates were 38.1% and 35.7%.
The comparative effectiveness study, published in JAMA Network Open, included 903,495 women who underwent 10 years of breast cancer screening at 126 radiology facilities in the Breast Cancer Surveillance Consortium. The mean age of participants was 57.6 years, and 46% of them had dense breasts. A total of 2,969,055 screening exams were performed (15% DBT), with each woman receiving a mean of 3.3 exams over 10 years. Most participants (71.8%) had annual exams, while 16.8% had biennial, with the remainder being performed at intervals of 3 years or more.
Investigators looked at the cumulative rate of three kinds of false-positive results over 10 years: false-positive recalls for further imaging, false-positive short-interval follow-up recommendations, and false-positive biopsy recommendations. A result was considered false positive if there was no diagnosis of invasive carcinoma or ductal carcinoma in situ within 1 year of the screening examination and before the next screening examination.
Overall, across all screening intervals, and after adjusting for age and breast density, the percentage of false-positive results was slightly lower for DBT vs. mammography: 7.6% vs. 9.0%, respectively, for false-positive recalls; 1.8% vs. 2.1%, respectively, for false-positive short-interval follow-up recommendations; and 1.1% vs. 1.2% for false-positive biopsy recommendations. “We did not observe consistent clinically meaningful differences in the cumulative probabilities of false-positive short-interval follow-up or biopsy recommendation by screening modality,” they noted, adding that, although DBT provided “modest” reductions in false-positive recalls, compared with mammography (2.4% less for biennial screening and 6.7% less for annual screening), “nonetheless, this percentage equates to many thousands of individuals in absolute numbers, especially for annual screening, which is the dominant practice in the U.S.”
The authors also noted that, regardless of screening modality, all three types of false-positive results were substantially lower for biennial versus annual mammograph, and depended on age and breast density. The highest cumulative rates of false-positive results occurred in women aged 40-49 years (68.0% with annual digital mammography and 60.8% with annual DBT). Women with extremely dense breasts had the highest probability of all three types of false positive, which “may be due to the lack of interspersed fat within dense fibroglandular tissue, with the contrast between the fat and tissue being a requirement for more accurate detection of suspicious features by interpreting radiologists.”
The study findings “offer new information about the potential harms of repeated screening, which may be used to inform screening guidelines and decision-making between individuals and their physicians. However, it is important to weigh these and other potential harms with potential benefits of earlier diagnosis. … Women at high risk of an advanced cancer under biennial screening, including some women with dense breasts, may reduce their risk with annual screening,” they suggested.
Although DBT is now widely used in the United States, amid growing optimism about its superiority over digital mammography, this study reminds clinicians to counsel patients appropriately, according to Lydia E. Pace, MD, from Brigham and Women’s Hospital in Boston. “Unfortunately, the growing availability of DBT does not substantially change the likelihood that women will experience a false-positive result over years of regular mammograms,” she wrote in an invited commentary published with the study. She noted that, although many women tolerate false-positive results, “they are associated with at least transient anxiety as well as time, inconvenience, and expense. More information is needed to understand the association of DBT with overdiagnosis, which is the more clinically important harm of screening.”
The study was funded by the National Cancer Institute. Dr. Miglioretti and Dr. Pace reported no conflicts of interest. One coauthor of the study is an unpaid consultant for Grail, for the STRIVE study, and another coauthor receives personal fees from Grail for work on a data safety monitoring board. No other disclosures were reported.
JAMA NETWORK OPEN
Clinical Edge Journal Scan Commentary: Breast Cancer April 2022
Studies have demonstrated inferior survival outcomes associated with delays in time to surgery and adjuvant chemotherapy for early breast cancer. The timing of adjuvant endocrine therapy is also notable because of the favorable effect on recurrence risk and survival with these agents in early HR+ breast cancer. A cohort study from the National Cancer Database including 144,103 women demonstrated a 31% increase in the risk for death (hazard ratio [HR] 1.31; P < .001) with a time to adjuvant hormone therapy (TTH) > 150 days (6.4% of patients) compared with those with TTH ≤ 150 days (93.6% of patients). Factors associated with delay in TTH included Black race, nonprivate insurance, metropolitan residence (vs. urban or rural), community hospital setting (vs. academic), higher comorbidity index, poorly differentiated tumors, higher stage, breast conservation surgery (vs. mastectomy), and radiation therapy. This study highlights the need to avoid unnecessary delays in adjuvant hormone therapy and encourages further exploration of barriers to timely initiation of breast cancer therapies to maximize outcomes for patients.
The role of reproductive hormones in breast cancer risk and carcinogenesis has been extensively studied and hormonal therapies are an essential component of the management of HR+ breast cancer. Lan and colleagues performed a retrospective analysis including 196 premenopausal and 137 postmenopausal women treated with neoadjuvant chemotherapy for breast cancer, investigating the correlation between pretreatment levels of reproductive hormone levels with pathologic and survival outcomes. Higher likelihood of achieving pathologic complete response was seen in premenopausal women with lower vs. higher testosterone levels (odds ratio [OR] 0.996; P = .026) and in postmenopausal women with higher vs. lower follicle-stimulating hormone levels (OR 1.045; P = .005). Furthermore, lower progesterone levels in premenopausal patients was associated with inferior overall survival (OS) (3-year OS 72.9% vs. 97.4% for lowest tertile progesterone vs. higher tertiles; P = .007). These data suggest a potential role of reproductive hormones in the preoperative evaluation for breast cancer patients. Also, the complex actions of progesterone and "crosstalk" between estrogen receptors and progesterone receptors continue to be elucidated and ongoing studies are evaluating progestin combined with endocrine therapy.
The CLEOPATRA trial has established the regimen of trastuzumab plus pertuzumab plus docetaxel as first-line therapy for metastatic HER2-positive (HER2+) breast cancer with an absolute survival benefit of 16.3 months vs. trastuzumab plus docetaxel. A retrospective study conducted in Ontario, Canada, explored real-world outcomes of pertuzumab plus trastuzumab plus chemotherapy among 1158 patients and demonstrated a similar magnitude of survival improvement with the addition of pertuzumab (14.9 months) (Dai et al). The median OS was higher among patients receiving pertuzumab compared with control (40.2 vs. 25.3 months), and although the median OS was shorter in the real-world setting than in the CLEOPATRA trial, they had similar HRs for mortality reduction (0.66 for real-world and 0.69 for trial). Furthermore, there was no increase in cardiotoxicity and lower cumulative incidence of hospitalization at 1 year with pertuzumab vs. control (11.7% vs. 19.0%; P < .001). This study adds to the existing body of data supporting first-line treatment with pertuzumab plus trastuzumab plus chemotherapy for metastatic HER2+ breast cancer. The treatment landscape for these patients is certainly dynamic with the development of novel therapies and combinations in this space and resultant shifts in the current algorithm.
Recommended Additional Reading:
Hortobagyi GN et al. LBA17 Overall survival (OS) results from the phase III MONALEESA-2 (ML-2) trial of postmenopausal patients (pts) with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB). Ann Oncol. 2021;32:S1290-S1291. Doi: 10.1016/j.annonc.2021.08.2090
Chavez-MacGregor M et al. Delayed initiation of adjuvant chemotherapy among patients with breast cancer. JAMA Oncol. 2016;2:322-329. Doi:10.1001/jamaoncol.2015.3856
Trabert B et al. Progesterone and breast cancer. Endocr Rev. 2020;41:320-344. Doi: 10.1210/endrev/bnz001
Swain SM et al; on behalf of the CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:519-530. Doi: 10.1016/S1470-2045(19)30863-0
Studies have demonstrated inferior survival outcomes associated with delays in time to surgery and adjuvant chemotherapy for early breast cancer. The timing of adjuvant endocrine therapy is also notable because of the favorable effect on recurrence risk and survival with these agents in early HR+ breast cancer. A cohort study from the National Cancer Database including 144,103 women demonstrated a 31% increase in the risk for death (hazard ratio [HR] 1.31; P < .001) with a time to adjuvant hormone therapy (TTH) > 150 days (6.4% of patients) compared with those with TTH ≤ 150 days (93.6% of patients). Factors associated with delay in TTH included Black race, nonprivate insurance, metropolitan residence (vs. urban or rural), community hospital setting (vs. academic), higher comorbidity index, poorly differentiated tumors, higher stage, breast conservation surgery (vs. mastectomy), and radiation therapy. This study highlights the need to avoid unnecessary delays in adjuvant hormone therapy and encourages further exploration of barriers to timely initiation of breast cancer therapies to maximize outcomes for patients.
The role of reproductive hormones in breast cancer risk and carcinogenesis has been extensively studied and hormonal therapies are an essential component of the management of HR+ breast cancer. Lan and colleagues performed a retrospective analysis including 196 premenopausal and 137 postmenopausal women treated with neoadjuvant chemotherapy for breast cancer, investigating the correlation between pretreatment levels of reproductive hormone levels with pathologic and survival outcomes. Higher likelihood of achieving pathologic complete response was seen in premenopausal women with lower vs. higher testosterone levels (odds ratio [OR] 0.996; P = .026) and in postmenopausal women with higher vs. lower follicle-stimulating hormone levels (OR 1.045; P = .005). Furthermore, lower progesterone levels in premenopausal patients was associated with inferior overall survival (OS) (3-year OS 72.9% vs. 97.4% for lowest tertile progesterone vs. higher tertiles; P = .007). These data suggest a potential role of reproductive hormones in the preoperative evaluation for breast cancer patients. Also, the complex actions of progesterone and "crosstalk" between estrogen receptors and progesterone receptors continue to be elucidated and ongoing studies are evaluating progestin combined with endocrine therapy.
The CLEOPATRA trial has established the regimen of trastuzumab plus pertuzumab plus docetaxel as first-line therapy for metastatic HER2-positive (HER2+) breast cancer with an absolute survival benefit of 16.3 months vs. trastuzumab plus docetaxel. A retrospective study conducted in Ontario, Canada, explored real-world outcomes of pertuzumab plus trastuzumab plus chemotherapy among 1158 patients and demonstrated a similar magnitude of survival improvement with the addition of pertuzumab (14.9 months) (Dai et al). The median OS was higher among patients receiving pertuzumab compared with control (40.2 vs. 25.3 months), and although the median OS was shorter in the real-world setting than in the CLEOPATRA trial, they had similar HRs for mortality reduction (0.66 for real-world and 0.69 for trial). Furthermore, there was no increase in cardiotoxicity and lower cumulative incidence of hospitalization at 1 year with pertuzumab vs. control (11.7% vs. 19.0%; P < .001). This study adds to the existing body of data supporting first-line treatment with pertuzumab plus trastuzumab plus chemotherapy for metastatic HER2+ breast cancer. The treatment landscape for these patients is certainly dynamic with the development of novel therapies and combinations in this space and resultant shifts in the current algorithm.
Recommended Additional Reading:
Hortobagyi GN et al. LBA17 Overall survival (OS) results from the phase III MONALEESA-2 (ML-2) trial of postmenopausal patients (pts) with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB). Ann Oncol. 2021;32:S1290-S1291. Doi: 10.1016/j.annonc.2021.08.2090
Chavez-MacGregor M et al. Delayed initiation of adjuvant chemotherapy among patients with breast cancer. JAMA Oncol. 2016;2:322-329. Doi:10.1001/jamaoncol.2015.3856
Trabert B et al. Progesterone and breast cancer. Endocr Rev. 2020;41:320-344. Doi: 10.1210/endrev/bnz001
Swain SM et al; on behalf of the CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:519-530. Doi: 10.1016/S1470-2045(19)30863-0
Studies have demonstrated inferior survival outcomes associated with delays in time to surgery and adjuvant chemotherapy for early breast cancer. The timing of adjuvant endocrine therapy is also notable because of the favorable effect on recurrence risk and survival with these agents in early HR+ breast cancer. A cohort study from the National Cancer Database including 144,103 women demonstrated a 31% increase in the risk for death (hazard ratio [HR] 1.31; P < .001) with a time to adjuvant hormone therapy (TTH) > 150 days (6.4% of patients) compared with those with TTH ≤ 150 days (93.6% of patients). Factors associated with delay in TTH included Black race, nonprivate insurance, metropolitan residence (vs. urban or rural), community hospital setting (vs. academic), higher comorbidity index, poorly differentiated tumors, higher stage, breast conservation surgery (vs. mastectomy), and radiation therapy. This study highlights the need to avoid unnecessary delays in adjuvant hormone therapy and encourages further exploration of barriers to timely initiation of breast cancer therapies to maximize outcomes for patients.
The role of reproductive hormones in breast cancer risk and carcinogenesis has been extensively studied and hormonal therapies are an essential component of the management of HR+ breast cancer. Lan and colleagues performed a retrospective analysis including 196 premenopausal and 137 postmenopausal women treated with neoadjuvant chemotherapy for breast cancer, investigating the correlation between pretreatment levels of reproductive hormone levels with pathologic and survival outcomes. Higher likelihood of achieving pathologic complete response was seen in premenopausal women with lower vs. higher testosterone levels (odds ratio [OR] 0.996; P = .026) and in postmenopausal women with higher vs. lower follicle-stimulating hormone levels (OR 1.045; P = .005). Furthermore, lower progesterone levels in premenopausal patients was associated with inferior overall survival (OS) (3-year OS 72.9% vs. 97.4% for lowest tertile progesterone vs. higher tertiles; P = .007). These data suggest a potential role of reproductive hormones in the preoperative evaluation for breast cancer patients. Also, the complex actions of progesterone and "crosstalk" between estrogen receptors and progesterone receptors continue to be elucidated and ongoing studies are evaluating progestin combined with endocrine therapy.
The CLEOPATRA trial has established the regimen of trastuzumab plus pertuzumab plus docetaxel as first-line therapy for metastatic HER2-positive (HER2+) breast cancer with an absolute survival benefit of 16.3 months vs. trastuzumab plus docetaxel. A retrospective study conducted in Ontario, Canada, explored real-world outcomes of pertuzumab plus trastuzumab plus chemotherapy among 1158 patients and demonstrated a similar magnitude of survival improvement with the addition of pertuzumab (14.9 months) (Dai et al). The median OS was higher among patients receiving pertuzumab compared with control (40.2 vs. 25.3 months), and although the median OS was shorter in the real-world setting than in the CLEOPATRA trial, they had similar HRs for mortality reduction (0.66 for real-world and 0.69 for trial). Furthermore, there was no increase in cardiotoxicity and lower cumulative incidence of hospitalization at 1 year with pertuzumab vs. control (11.7% vs. 19.0%; P < .001). This study adds to the existing body of data supporting first-line treatment with pertuzumab plus trastuzumab plus chemotherapy for metastatic HER2+ breast cancer. The treatment landscape for these patients is certainly dynamic with the development of novel therapies and combinations in this space and resultant shifts in the current algorithm.
Recommended Additional Reading:
Hortobagyi GN et al. LBA17 Overall survival (OS) results from the phase III MONALEESA-2 (ML-2) trial of postmenopausal patients (pts) with hormone receptor positive/human epidermal growth factor receptor 2 negative (HR+/HER2−) advanced breast cancer (ABC) treated with endocrine therapy (ET) ± ribociclib (RIB). Ann Oncol. 2021;32:S1290-S1291. Doi: 10.1016/j.annonc.2021.08.2090
Chavez-MacGregor M et al. Delayed initiation of adjuvant chemotherapy among patients with breast cancer. JAMA Oncol. 2016;2:322-329. Doi:10.1001/jamaoncol.2015.3856
Trabert B et al. Progesterone and breast cancer. Endocr Rev. 2020;41:320-344. Doi: 10.1210/endrev/bnz001
Swain SM et al; on behalf of the CLEOPATRA study group. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA): end-of-study results from a double-blind, randomised, placebo-controlled, phase 3 study. Lancet Oncol. 2020;21:519-530. Doi: 10.1016/S1470-2045(19)30863-0
Breast density linked to familial breast cancer risk
observed during mammography, according to a new study of two retrospective cohorts published online Feb. 17 in JAMA Network Open. The findings suggest that breast density measured during mammography may have a genetic component, and suggest the importance of initiating early mammography in premenopausal women with a family history of breast cancer.
“We know that mammographic breast density is a very strong risk factor for breast cancer, probably one of the strongest risk factors, and it’s also a surrogate marker for breast cancer development, especially in premenopausal women. We also know that family history of breast cancer is a strong risk factor for breast cancer as well. Surprisingly, we have very limited information on how these risk factors are related to each other. There have been only two studies that have been done in this field in premenopausal women, and the studies are conflicting. So, we felt that we need to really understand how these two factors are related to each other and whether that would have an impact on modifying or refining mammographic screening in high-risk women,” Adetunji T. Toriola, MD, PhD, MPH, said in an interview. Dr. Toriola is professor of surgery at Washington University, St. Louis.
Previous research identified risk factors for dense breast tissue. A genome-wide association study found 31 genetic loci associated with dense breast tissue, and 17 had a known association with breast cancer risk.
In the JAMA Network Open study, the researchers included data from women who were treated at Washington University’s Joanne Knight Breast Health Center and Siteman Cancer Center. The discovery group included 375 premenopausal women who received annual mammography screening in 2016 and had dense volume and non-dense volume measured during each screen. The validation set drew from 14,040 premenopausal women seen at the centers between 2010 and 2015.
In the discovery group, women with a family history of breast cancer had greater volumetric percent density (odds ratio [OR], 1.25; P < .001). The validation set produced a similar result (OR, 1.30; 95% confidence interval, 1.17-1.45). Subanalyses revealed similar associations in non-Hispanic White and Black or African American women.
The current study included a higher percentage of women with a family history of breast cancer than previous studies, and also controlled for more variables. This may have removed confounding variables that could have affected previous studies.
“It reinforces the need to start mammogram screening early in women who have a family history of breast cancer,” Dr. Toriola said.
The study had some limitations, including a higher percentage of women with a family history of breast cancer than the National Health Interview Survey (23.2% and 15.3%, versus 8.4%), explained by the fact that women with a family history of breast cancer are more likely to seek out screening. The average age of women was on average 47 years, making them closer to perimenopausal than premenopausal.
The study was funded by the National Institutes of Health.
observed during mammography, according to a new study of two retrospective cohorts published online Feb. 17 in JAMA Network Open. The findings suggest that breast density measured during mammography may have a genetic component, and suggest the importance of initiating early mammography in premenopausal women with a family history of breast cancer.
“We know that mammographic breast density is a very strong risk factor for breast cancer, probably one of the strongest risk factors, and it’s also a surrogate marker for breast cancer development, especially in premenopausal women. We also know that family history of breast cancer is a strong risk factor for breast cancer as well. Surprisingly, we have very limited information on how these risk factors are related to each other. There have been only two studies that have been done in this field in premenopausal women, and the studies are conflicting. So, we felt that we need to really understand how these two factors are related to each other and whether that would have an impact on modifying or refining mammographic screening in high-risk women,” Adetunji T. Toriola, MD, PhD, MPH, said in an interview. Dr. Toriola is professor of surgery at Washington University, St. Louis.
Previous research identified risk factors for dense breast tissue. A genome-wide association study found 31 genetic loci associated with dense breast tissue, and 17 had a known association with breast cancer risk.
In the JAMA Network Open study, the researchers included data from women who were treated at Washington University’s Joanne Knight Breast Health Center and Siteman Cancer Center. The discovery group included 375 premenopausal women who received annual mammography screening in 2016 and had dense volume and non-dense volume measured during each screen. The validation set drew from 14,040 premenopausal women seen at the centers between 2010 and 2015.
In the discovery group, women with a family history of breast cancer had greater volumetric percent density (odds ratio [OR], 1.25; P < .001). The validation set produced a similar result (OR, 1.30; 95% confidence interval, 1.17-1.45). Subanalyses revealed similar associations in non-Hispanic White and Black or African American women.
The current study included a higher percentage of women with a family history of breast cancer than previous studies, and also controlled for more variables. This may have removed confounding variables that could have affected previous studies.
“It reinforces the need to start mammogram screening early in women who have a family history of breast cancer,” Dr. Toriola said.
The study had some limitations, including a higher percentage of women with a family history of breast cancer than the National Health Interview Survey (23.2% and 15.3%, versus 8.4%), explained by the fact that women with a family history of breast cancer are more likely to seek out screening. The average age of women was on average 47 years, making them closer to perimenopausal than premenopausal.
The study was funded by the National Institutes of Health.
observed during mammography, according to a new study of two retrospective cohorts published online Feb. 17 in JAMA Network Open. The findings suggest that breast density measured during mammography may have a genetic component, and suggest the importance of initiating early mammography in premenopausal women with a family history of breast cancer.
“We know that mammographic breast density is a very strong risk factor for breast cancer, probably one of the strongest risk factors, and it’s also a surrogate marker for breast cancer development, especially in premenopausal women. We also know that family history of breast cancer is a strong risk factor for breast cancer as well. Surprisingly, we have very limited information on how these risk factors are related to each other. There have been only two studies that have been done in this field in premenopausal women, and the studies are conflicting. So, we felt that we need to really understand how these two factors are related to each other and whether that would have an impact on modifying or refining mammographic screening in high-risk women,” Adetunji T. Toriola, MD, PhD, MPH, said in an interview. Dr. Toriola is professor of surgery at Washington University, St. Louis.
Previous research identified risk factors for dense breast tissue. A genome-wide association study found 31 genetic loci associated with dense breast tissue, and 17 had a known association with breast cancer risk.
In the JAMA Network Open study, the researchers included data from women who were treated at Washington University’s Joanne Knight Breast Health Center and Siteman Cancer Center. The discovery group included 375 premenopausal women who received annual mammography screening in 2016 and had dense volume and non-dense volume measured during each screen. The validation set drew from 14,040 premenopausal women seen at the centers between 2010 and 2015.
In the discovery group, women with a family history of breast cancer had greater volumetric percent density (odds ratio [OR], 1.25; P < .001). The validation set produced a similar result (OR, 1.30; 95% confidence interval, 1.17-1.45). Subanalyses revealed similar associations in non-Hispanic White and Black or African American women.
The current study included a higher percentage of women with a family history of breast cancer than previous studies, and also controlled for more variables. This may have removed confounding variables that could have affected previous studies.
“It reinforces the need to start mammogram screening early in women who have a family history of breast cancer,” Dr. Toriola said.
The study had some limitations, including a higher percentage of women with a family history of breast cancer than the National Health Interview Survey (23.2% and 15.3%, versus 8.4%), explained by the fact that women with a family history of breast cancer are more likely to seek out screening. The average age of women was on average 47 years, making them closer to perimenopausal than premenopausal.
The study was funded by the National Institutes of Health.
FROM JAMA NETWORK OPEN
Avoiding delay in AHT may improve survival in HR-positive, ERBB2-negative early BC
Key clinical point: A delay in initiation of adjuvant hormone therapy (AHT) beyond 150 days was significantly associated with poor survival in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (ERBB2)-negative breast cancer (BC) not receiving chemotherapy.
Major finding: Time to AHT (TTH) >150 days vs. ≤150 days was associated with an increased risk for death in the overall population (hazard ratio 1.31; P < .001).
Study details: Findings are from a population-based retrospective study including 144,103 patients with HR-positive/ERBB2-negative early BC who received AHT without chemotherapy, of which 6.4% of patients experienced a delay in AHT initiation (TTH >150 days) and 93.6% initiated AHT on time (TTH ≤150 days).
Disclosures: This study was supported by the Natural Science Foundation of Fujian Province and the Fujian Provincial Health Technology Project. The authors declared no conflicts of interest.
Source: Fu F et al. Association of adjuvant hormone therapy timing with overall survival among patients with hormone receptor–positive human epidermal growth factor receptor-2–negative early breast cancer without chemotherapy. JAMA Netw Open. 2022;5(2):e2145934 (Feb 15). Doi: 10.1001/jamanetworkopen.2021.45934
Key clinical point: A delay in initiation of adjuvant hormone therapy (AHT) beyond 150 days was significantly associated with poor survival in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (ERBB2)-negative breast cancer (BC) not receiving chemotherapy.
Major finding: Time to AHT (TTH) >150 days vs. ≤150 days was associated with an increased risk for death in the overall population (hazard ratio 1.31; P < .001).
Study details: Findings are from a population-based retrospective study including 144,103 patients with HR-positive/ERBB2-negative early BC who received AHT without chemotherapy, of which 6.4% of patients experienced a delay in AHT initiation (TTH >150 days) and 93.6% initiated AHT on time (TTH ≤150 days).
Disclosures: This study was supported by the Natural Science Foundation of Fujian Province and the Fujian Provincial Health Technology Project. The authors declared no conflicts of interest.
Source: Fu F et al. Association of adjuvant hormone therapy timing with overall survival among patients with hormone receptor–positive human epidermal growth factor receptor-2–negative early breast cancer without chemotherapy. JAMA Netw Open. 2022;5(2):e2145934 (Feb 15). Doi: 10.1001/jamanetworkopen.2021.45934
Key clinical point: A delay in initiation of adjuvant hormone therapy (AHT) beyond 150 days was significantly associated with poor survival in patients with hormone receptor (HR)-positive/human epidermal growth factor receptor 2 (ERBB2)-negative breast cancer (BC) not receiving chemotherapy.
Major finding: Time to AHT (TTH) >150 days vs. ≤150 days was associated with an increased risk for death in the overall population (hazard ratio 1.31; P < .001).
Study details: Findings are from a population-based retrospective study including 144,103 patients with HR-positive/ERBB2-negative early BC who received AHT without chemotherapy, of which 6.4% of patients experienced a delay in AHT initiation (TTH >150 days) and 93.6% initiated AHT on time (TTH ≤150 days).
Disclosures: This study was supported by the Natural Science Foundation of Fujian Province and the Fujian Provincial Health Technology Project. The authors declared no conflicts of interest.
Source: Fu F et al. Association of adjuvant hormone therapy timing with overall survival among patients with hormone receptor–positive human epidermal growth factor receptor-2–negative early breast cancer without chemotherapy. JAMA Netw Open. 2022;5(2):e2145934 (Feb 15). Doi: 10.1001/jamanetworkopen.2021.45934
Pretreatment circulating reproductive hormones predict treatment response in breast cancer
Key clinical point: Pretreatment levels of testosterone and follicle-stimulating hormone (FSH) independently predicted pathological complete response (pCR) in premenopausal and postmenopausal women with breast cancer (BC) who received neoadjuvant chemotherapy (NAC).
Major finding: The likelihood of achieving pCR was higher in premenopausal women with lower vs. higher testosterone levels (odds ratio [OR] 0.996; P = .026) and in postmenopausal women with higher vs. lower FSH levels (OR 1.045; P = .005).
Study details: This was a retrospective study of 196 premenopausal and 137 postmenopausal women with invasive BC who received NAC.
Disclosures: This study was funded by National Natural Science Foundation of China. The authors declared no conflicts of interest.
Source: Lan A et al. Pre-treatment circulating reproductive hormones levels predict pathological and survival outcomes in breast cancer submitted to neoadjuvant chemotherapy. Int J Clin Oncol. 2022 (Mar 3). Doi: 10.1007/s10147-022-02141-9
Key clinical point: Pretreatment levels of testosterone and follicle-stimulating hormone (FSH) independently predicted pathological complete response (pCR) in premenopausal and postmenopausal women with breast cancer (BC) who received neoadjuvant chemotherapy (NAC).
Major finding: The likelihood of achieving pCR was higher in premenopausal women with lower vs. higher testosterone levels (odds ratio [OR] 0.996; P = .026) and in postmenopausal women with higher vs. lower FSH levels (OR 1.045; P = .005).
Study details: This was a retrospective study of 196 premenopausal and 137 postmenopausal women with invasive BC who received NAC.
Disclosures: This study was funded by National Natural Science Foundation of China. The authors declared no conflicts of interest.
Source: Lan A et al. Pre-treatment circulating reproductive hormones levels predict pathological and survival outcomes in breast cancer submitted to neoadjuvant chemotherapy. Int J Clin Oncol. 2022 (Mar 3). Doi: 10.1007/s10147-022-02141-9
Key clinical point: Pretreatment levels of testosterone and follicle-stimulating hormone (FSH) independently predicted pathological complete response (pCR) in premenopausal and postmenopausal women with breast cancer (BC) who received neoadjuvant chemotherapy (NAC).
Major finding: The likelihood of achieving pCR was higher in premenopausal women with lower vs. higher testosterone levels (odds ratio [OR] 0.996; P = .026) and in postmenopausal women with higher vs. lower FSH levels (OR 1.045; P = .005).
Study details: This was a retrospective study of 196 premenopausal and 137 postmenopausal women with invasive BC who received NAC.
Disclosures: This study was funded by National Natural Science Foundation of China. The authors declared no conflicts of interest.
Source: Lan A et al. Pre-treatment circulating reproductive hormones levels predict pathological and survival outcomes in breast cancer submitted to neoadjuvant chemotherapy. Int J Clin Oncol. 2022 (Mar 3). Doi: 10.1007/s10147-022-02141-9
HER2-negative early BC: Subset of patients may benefit from anthracycline-containing chemotherapy
Key clinical point: An anthracycline-containing chemotherapy (AC-T) regimen was not associated with a survival benefit compared with 6 cycles of docetaxel/cyclophosphamide (TC6) in an overall cohort of patients with human epidermal growth factor receptor 2 (HER2)-negative, high-risk, early breast cancer (BC); however, patients with lobular tumor and ≥3 affected lymph nodes may benefit.
Major finding: Although disease-free survival (DFS) was similar between AC-T and TC6 treatment arms in the overall cohort (P = .57), the subgroup of patients with lobular tumor and ≥3 affected lymph nodes showed improved DFS with AC-T vs. TC6 (hazard ratio 3.521; P = .003). The frequency of grade 3/4 adverse events was significantly higher in AC-T vs. TC6 treatment arm (P < .001).
Study details: Findings are from the pooled analysis of two phase 3 studies, SUCCESS-C and PlanB, including 5,924 patients with high-risk HER2-negative invasive early BC who were randomly assigned to receive TC6 or AC-T.
Disclosures: The study did not receive any funding. Some authors declared receiving financial and nonfinancial support from several sources.
Source: Gregorio AD et al. The impact of anthracyclines in intermediate and high-risk HER2-negative early breast cancer—a pooled analysis of the randomised clinical trials PlanB and SUCCESS C. Br J Cancer. 2022 (Feb 22). Doi: 10.1038/s41416-021-01690-6
Key clinical point: An anthracycline-containing chemotherapy (AC-T) regimen was not associated with a survival benefit compared with 6 cycles of docetaxel/cyclophosphamide (TC6) in an overall cohort of patients with human epidermal growth factor receptor 2 (HER2)-negative, high-risk, early breast cancer (BC); however, patients with lobular tumor and ≥3 affected lymph nodes may benefit.
Major finding: Although disease-free survival (DFS) was similar between AC-T and TC6 treatment arms in the overall cohort (P = .57), the subgroup of patients with lobular tumor and ≥3 affected lymph nodes showed improved DFS with AC-T vs. TC6 (hazard ratio 3.521; P = .003). The frequency of grade 3/4 adverse events was significantly higher in AC-T vs. TC6 treatment arm (P < .001).
Study details: Findings are from the pooled analysis of two phase 3 studies, SUCCESS-C and PlanB, including 5,924 patients with high-risk HER2-negative invasive early BC who were randomly assigned to receive TC6 or AC-T.
Disclosures: The study did not receive any funding. Some authors declared receiving financial and nonfinancial support from several sources.
Source: Gregorio AD et al. The impact of anthracyclines in intermediate and high-risk HER2-negative early breast cancer—a pooled analysis of the randomised clinical trials PlanB and SUCCESS C. Br J Cancer. 2022 (Feb 22). Doi: 10.1038/s41416-021-01690-6
Key clinical point: An anthracycline-containing chemotherapy (AC-T) regimen was not associated with a survival benefit compared with 6 cycles of docetaxel/cyclophosphamide (TC6) in an overall cohort of patients with human epidermal growth factor receptor 2 (HER2)-negative, high-risk, early breast cancer (BC); however, patients with lobular tumor and ≥3 affected lymph nodes may benefit.
Major finding: Although disease-free survival (DFS) was similar between AC-T and TC6 treatment arms in the overall cohort (P = .57), the subgroup of patients with lobular tumor and ≥3 affected lymph nodes showed improved DFS with AC-T vs. TC6 (hazard ratio 3.521; P = .003). The frequency of grade 3/4 adverse events was significantly higher in AC-T vs. TC6 treatment arm (P < .001).
Study details: Findings are from the pooled analysis of two phase 3 studies, SUCCESS-C and PlanB, including 5,924 patients with high-risk HER2-negative invasive early BC who were randomly assigned to receive TC6 or AC-T.
Disclosures: The study did not receive any funding. Some authors declared receiving financial and nonfinancial support from several sources.
Source: Gregorio AD et al. The impact of anthracyclines in intermediate and high-risk HER2-negative early breast cancer—a pooled analysis of the randomised clinical trials PlanB and SUCCESS C. Br J Cancer. 2022 (Feb 22). Doi: 10.1038/s41416-021-01690-6
Real-world evidence supports use of ribociclib+letrozole in males with HR-positive/HER2-negative BC
Key clinical point: Ribociclib plus letrozole was safe and effective in male patients with hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (BC) who did not receive prior endocrine therapy (ET).
Major finding: Male patients vs. overall population experienced fewer treatment-related adverse events (AE), especially neutropenia (all grade 53.8% vs. 74.5%; grade ≥3 41.0% vs. 57.2%). After a median follow-up of 25.4 months, median time to progression was 27.1 months for the overall cohort vs. not reached in males.
Study details: Findings are from an exploratory analysis of the phase 3b CompLEEment-1 trial including 39 males with HR-positive HER2-negative advanced BC who received ribociclib+letrozole but not prior ET for the advanced disease.
Disclosures: The study was supported by Novartis Pharmaceuticals. The authors declared serving as members of speakers’ bureau or receiving honoraria, advisory/consulting fees, expert testimony fees, research grants, or travel and accommodation expenses from several sources, including Novartis. Two authors declared being employees or shareholders of Novartis.
Source: Campone M et al. Ribociclib plus letrozole in male patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: subgroup analysis of the phase IIIb CompLEEment-1 trial. Breast Cancer Res Treat. 2022 (Feb 25). Doi: 10.1007/s10549-022-06543-1
Key clinical point: Ribociclib plus letrozole was safe and effective in male patients with hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (BC) who did not receive prior endocrine therapy (ET).
Major finding: Male patients vs. overall population experienced fewer treatment-related adverse events (AE), especially neutropenia (all grade 53.8% vs. 74.5%; grade ≥3 41.0% vs. 57.2%). After a median follow-up of 25.4 months, median time to progression was 27.1 months for the overall cohort vs. not reached in males.
Study details: Findings are from an exploratory analysis of the phase 3b CompLEEment-1 trial including 39 males with HR-positive HER2-negative advanced BC who received ribociclib+letrozole but not prior ET for the advanced disease.
Disclosures: The study was supported by Novartis Pharmaceuticals. The authors declared serving as members of speakers’ bureau or receiving honoraria, advisory/consulting fees, expert testimony fees, research grants, or travel and accommodation expenses from several sources, including Novartis. Two authors declared being employees or shareholders of Novartis.
Source: Campone M et al. Ribociclib plus letrozole in male patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: subgroup analysis of the phase IIIb CompLEEment-1 trial. Breast Cancer Res Treat. 2022 (Feb 25). Doi: 10.1007/s10549-022-06543-1
Key clinical point: Ribociclib plus letrozole was safe and effective in male patients with hormone receptor (HR)-positive human epidermal growth factor receptor 2 (HER2)-negative advanced breast cancer (BC) who did not receive prior endocrine therapy (ET).
Major finding: Male patients vs. overall population experienced fewer treatment-related adverse events (AE), especially neutropenia (all grade 53.8% vs. 74.5%; grade ≥3 41.0% vs. 57.2%). After a median follow-up of 25.4 months, median time to progression was 27.1 months for the overall cohort vs. not reached in males.
Study details: Findings are from an exploratory analysis of the phase 3b CompLEEment-1 trial including 39 males with HR-positive HER2-negative advanced BC who received ribociclib+letrozole but not prior ET for the advanced disease.
Disclosures: The study was supported by Novartis Pharmaceuticals. The authors declared serving as members of speakers’ bureau or receiving honoraria, advisory/consulting fees, expert testimony fees, research grants, or travel and accommodation expenses from several sources, including Novartis. Two authors declared being employees or shareholders of Novartis.
Source: Campone M et al. Ribociclib plus letrozole in male patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer: subgroup analysis of the phase IIIb CompLEEment-1 trial. Breast Cancer Res Treat. 2022 (Feb 25). Doi: 10.1007/s10549-022-06543-1
Family history of breast cancer increases likelihood of dense breast in premenopausal women
Key clinical point: A family history of breast cancer (FHBC) was positively associated with mammographic breast density in premenopausal women, highlighting the role of heredity and the need for initiating early annual screening in women with an FHBC.
Major finding: The volumetric percent density was 25% higher among premenopausal women with vs. without FHBC (odds ratio [OR] 1.25; 95% CI 1.12-1.41) in the discovery cohort, and the odds of having a dense breast was 30% higher in premenopausal women with vs. without FHBC in the validation cohort (OR 1.30; 95% CI 1.17-1.45).
Study details: This study evaluated two retrospective cohorts, a discovery set of 375 premenopausal women and a validation set of 14,040 premenopausal women without any history of cancer, including breast cancer, or breast augmentation/reduction.
Disclosures: This study was supported by US National Institutes of Health (NIH)/National Cancer Institute and the National Institute on Minority Health and Health Disparities of the NIH. The authors declared no conflicts of interest.
Source: Han Y et al. Family history of breast cancer and mammographic breast density in premenopausal women. JAMA Netw Open. 2022;5(2):e2148983 (Feb 17). Doi: 10.1001/jamanetworkopen.2021.48983
Key clinical point: A family history of breast cancer (FHBC) was positively associated with mammographic breast density in premenopausal women, highlighting the role of heredity and the need for initiating early annual screening in women with an FHBC.
Major finding: The volumetric percent density was 25% higher among premenopausal women with vs. without FHBC (odds ratio [OR] 1.25; 95% CI 1.12-1.41) in the discovery cohort, and the odds of having a dense breast was 30% higher in premenopausal women with vs. without FHBC in the validation cohort (OR 1.30; 95% CI 1.17-1.45).
Study details: This study evaluated two retrospective cohorts, a discovery set of 375 premenopausal women and a validation set of 14,040 premenopausal women without any history of cancer, including breast cancer, or breast augmentation/reduction.
Disclosures: This study was supported by US National Institutes of Health (NIH)/National Cancer Institute and the National Institute on Minority Health and Health Disparities of the NIH. The authors declared no conflicts of interest.
Source: Han Y et al. Family history of breast cancer and mammographic breast density in premenopausal women. JAMA Netw Open. 2022;5(2):e2148983 (Feb 17). Doi: 10.1001/jamanetworkopen.2021.48983
Key clinical point: A family history of breast cancer (FHBC) was positively associated with mammographic breast density in premenopausal women, highlighting the role of heredity and the need for initiating early annual screening in women with an FHBC.
Major finding: The volumetric percent density was 25% higher among premenopausal women with vs. without FHBC (odds ratio [OR] 1.25; 95% CI 1.12-1.41) in the discovery cohort, and the odds of having a dense breast was 30% higher in premenopausal women with vs. without FHBC in the validation cohort (OR 1.30; 95% CI 1.17-1.45).
Study details: This study evaluated two retrospective cohorts, a discovery set of 375 premenopausal women and a validation set of 14,040 premenopausal women without any history of cancer, including breast cancer, or breast augmentation/reduction.
Disclosures: This study was supported by US National Institutes of Health (NIH)/National Cancer Institute and the National Institute on Minority Health and Health Disparities of the NIH. The authors declared no conflicts of interest.
Source: Han Y et al. Family history of breast cancer and mammographic breast density in premenopausal women. JAMA Netw Open. 2022;5(2):e2148983 (Feb 17). Doi: 10.1001/jamanetworkopen.2021.48983