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It’s okay to consider breast-conserving therapy in breast cancer patients with high-risk hereditary genetic mutations, according to guidelines published in the Journal of Clinical Oncology.
The presence of a germline BRCA1 or BRCA2 mutation shouldn’t preclude breast-conserving therapy as long as the patient is otherwise eligible for the procedure, according to the guidelines, which were developed by an expert panel convened by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society for Surgical Oncology.
Nadine M. Tung, MD, of Beth Israel Deaconess Medical Center in Boston and the rest of the expert panel reviewed evidence from 58 published articles to create the guidelines.
In addition to supporting use of breast-conserving therapy, the guidelines suggest that radiation shouldn’t be withheld because of mutation status, except in patients with TP53 mutations. Furthermore, BRCA1/2 mutation carriers with metastatic HER2-negative disease can receive the poly (ADP-ribose) polymerase (PARP) inhibitors olaparib and talazoparib as an “alternative to chemotherapy” for first-, second-, or third-line therapy.
However, it’s the “license to consider breast-conserving therapy” for high-risk individuals that is one of the most noteworthy points in the guidelines, and the one that may surprise some readers, according to William J. Gradishar, MD, of Northwestern University in Chicago, who was not involved in developing the guidelines.
“We don’t have to be as dogmatic with these patients with respect to local therapies as we were in the past,” Dr. Gradishar said in an interview. “That’s a good thing for patients, but you also have to understand the nuances that go into recommending [breast-conserving surgery] to a patient. Other variables, like the age at which the patient develops breast cancer, family history, etc., all go into it.”
Weighing options for surgery
The guidelines emphasize that, for patients with germline BRCA1/2 mutations, health care providers need to discuss treatment options for the breast cancer at hand. However, patients should also be made aware of their increased risk of contralateral and new ipsilateral breast cancer as compared with noncarriers.
When weighing breast-conserving therapy versus mastectomy in light of contralateral breast cancer risk, the guidelines recommend considering not only age at diagnosis – the strongest predictor of a later contralateral breast cancer – but also family history, comorbidities, life expectancy, ability to undergo MRI, and prognosis from breast or other cancers, such as ovarian cancer.
If a bilateral mastectomy isn’t performed in a BRCA1/2 mutation carrier, an annual mammogram and MRI are warranted thereafter for screening of the remaining breast tissue, according to the guidelines.
The guidelines say breast-conserving therapy should be offered to patients with mutations in moderate-penetrance genes, including PALB2, CHEK2, and ATM. However, there’s not much data regarding the risk of ipsilateral breast cancer after breast-conserving therapy in these patients.
Likewise, there’s limited evidence on contralateral breast cancer risk for patients with mutations in moderate-penetrance genes aside from CHEK2. The guidelines say the risk should be discussed with patients “in the context of shared decision making.”
Nipple-sparing mastectomy is “reasonable” to consider in certain newly diagnosed patients with BRCA1/2 mutations, as well as in newly diagnosed patients with moderate-risk mutations, the guidelines state.
Women with breast cancer and a deleterious BRCA1/2 mutation who are undergoing unilateral mastectomy should be offered contralateral risk-reducing mastectomy. Likewise, women with moderate-risk mutations should be offered contralateral risk-reducing mastectomy, but not solely based on mutation status, according to the guidelines. Data are limited on contralateral breast cancer risk related to those mutations.
Considerations for radiation
Radiation therapy in the context of breast-conserving therapy or mastectomy should not be withheld because of hereditary mutations, except in the case of TP53 mutations, according to the guidelines.
There’s no evidence that radiotherapy increases toxicity or contralateral breast cancer risk for most BRCA1/2 or moderate-penetrance gene mutations. However, the intact breast shouldn’t be irradiated in germline TP53 mutation carriers, the guidelines say, because of the important role that TP53 plays in the ability to repair DNA damage after cellular stress.
“Carriers of a TP53 mutation would be expected to be unable to repair tissue damage from DNA damaging radiotherapy and be at risk for significant [radiotherapy]-associated sequelae,” the guidelines state.
Chemotherapy and PARP inhibitors
For women with metastatic breast cancer harboring germline BRCA1/2 mutations, the guidelines say platinum chemotherapy should be preferred over taxanes for platinum-naive patients.
Provided the breast cancer is HER2 negative, the PARP inhibitors olaparib or talazoparib “should be offered as an alternative to chemotherapy in the first- to third-line settings,” the guidelines state.
The guidelines confirm that PARP inhibitors are a “valid starting point” for treatment of BCRA1/2–associated metastatic breast cancer, Dr. Gradishar said.
“When a patient progresses on a PARP inhibitor, assuming they’re not going on some other investigational drug or clinical trial, they’re going to get chemotherapy,” he said. “So the argument is that, if you have something that’s at least as good or maybe a little bit better and has fewer side effects, why not start with that and then move on to other things?”
By contrast, there’s not enough evidence to recommend PARP inhibitors for germline BRCA mutation carriers with nonmetastatic breast cancers, according to the guidelines, and there’s “no robust data” for using PARP inhibitors in patients with breast cancers with mutations in moderate-penetrance genes.
The guideline authors disclosed relationships with AstraZeneca, Myriad Genetics, Pfizer, Lilly, and other companies. Dr. Gradishar has relationships with AstraZeneca, Celltrion, Genentech, MacroGenics, Merck, Pfizer, and Seattle Genetics.
SOURCE: Tung NM et al. J Clin Oncol. 2020 Apr 3;JCO2000299. doi: 10.1200/JCO.20.00299.
It’s okay to consider breast-conserving therapy in breast cancer patients with high-risk hereditary genetic mutations, according to guidelines published in the Journal of Clinical Oncology.
The presence of a germline BRCA1 or BRCA2 mutation shouldn’t preclude breast-conserving therapy as long as the patient is otherwise eligible for the procedure, according to the guidelines, which were developed by an expert panel convened by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society for Surgical Oncology.
Nadine M. Tung, MD, of Beth Israel Deaconess Medical Center in Boston and the rest of the expert panel reviewed evidence from 58 published articles to create the guidelines.
In addition to supporting use of breast-conserving therapy, the guidelines suggest that radiation shouldn’t be withheld because of mutation status, except in patients with TP53 mutations. Furthermore, BRCA1/2 mutation carriers with metastatic HER2-negative disease can receive the poly (ADP-ribose) polymerase (PARP) inhibitors olaparib and talazoparib as an “alternative to chemotherapy” for first-, second-, or third-line therapy.
However, it’s the “license to consider breast-conserving therapy” for high-risk individuals that is one of the most noteworthy points in the guidelines, and the one that may surprise some readers, according to William J. Gradishar, MD, of Northwestern University in Chicago, who was not involved in developing the guidelines.
“We don’t have to be as dogmatic with these patients with respect to local therapies as we were in the past,” Dr. Gradishar said in an interview. “That’s a good thing for patients, but you also have to understand the nuances that go into recommending [breast-conserving surgery] to a patient. Other variables, like the age at which the patient develops breast cancer, family history, etc., all go into it.”
Weighing options for surgery
The guidelines emphasize that, for patients with germline BRCA1/2 mutations, health care providers need to discuss treatment options for the breast cancer at hand. However, patients should also be made aware of their increased risk of contralateral and new ipsilateral breast cancer as compared with noncarriers.
When weighing breast-conserving therapy versus mastectomy in light of contralateral breast cancer risk, the guidelines recommend considering not only age at diagnosis – the strongest predictor of a later contralateral breast cancer – but also family history, comorbidities, life expectancy, ability to undergo MRI, and prognosis from breast or other cancers, such as ovarian cancer.
If a bilateral mastectomy isn’t performed in a BRCA1/2 mutation carrier, an annual mammogram and MRI are warranted thereafter for screening of the remaining breast tissue, according to the guidelines.
The guidelines say breast-conserving therapy should be offered to patients with mutations in moderate-penetrance genes, including PALB2, CHEK2, and ATM. However, there’s not much data regarding the risk of ipsilateral breast cancer after breast-conserving therapy in these patients.
Likewise, there’s limited evidence on contralateral breast cancer risk for patients with mutations in moderate-penetrance genes aside from CHEK2. The guidelines say the risk should be discussed with patients “in the context of shared decision making.”
Nipple-sparing mastectomy is “reasonable” to consider in certain newly diagnosed patients with BRCA1/2 mutations, as well as in newly diagnosed patients with moderate-risk mutations, the guidelines state.
Women with breast cancer and a deleterious BRCA1/2 mutation who are undergoing unilateral mastectomy should be offered contralateral risk-reducing mastectomy. Likewise, women with moderate-risk mutations should be offered contralateral risk-reducing mastectomy, but not solely based on mutation status, according to the guidelines. Data are limited on contralateral breast cancer risk related to those mutations.
Considerations for radiation
Radiation therapy in the context of breast-conserving therapy or mastectomy should not be withheld because of hereditary mutations, except in the case of TP53 mutations, according to the guidelines.
There’s no evidence that radiotherapy increases toxicity or contralateral breast cancer risk for most BRCA1/2 or moderate-penetrance gene mutations. However, the intact breast shouldn’t be irradiated in germline TP53 mutation carriers, the guidelines say, because of the important role that TP53 plays in the ability to repair DNA damage after cellular stress.
“Carriers of a TP53 mutation would be expected to be unable to repair tissue damage from DNA damaging radiotherapy and be at risk for significant [radiotherapy]-associated sequelae,” the guidelines state.
Chemotherapy and PARP inhibitors
For women with metastatic breast cancer harboring germline BRCA1/2 mutations, the guidelines say platinum chemotherapy should be preferred over taxanes for platinum-naive patients.
Provided the breast cancer is HER2 negative, the PARP inhibitors olaparib or talazoparib “should be offered as an alternative to chemotherapy in the first- to third-line settings,” the guidelines state.
The guidelines confirm that PARP inhibitors are a “valid starting point” for treatment of BCRA1/2–associated metastatic breast cancer, Dr. Gradishar said.
“When a patient progresses on a PARP inhibitor, assuming they’re not going on some other investigational drug or clinical trial, they’re going to get chemotherapy,” he said. “So the argument is that, if you have something that’s at least as good or maybe a little bit better and has fewer side effects, why not start with that and then move on to other things?”
By contrast, there’s not enough evidence to recommend PARP inhibitors for germline BRCA mutation carriers with nonmetastatic breast cancers, according to the guidelines, and there’s “no robust data” for using PARP inhibitors in patients with breast cancers with mutations in moderate-penetrance genes.
The guideline authors disclosed relationships with AstraZeneca, Myriad Genetics, Pfizer, Lilly, and other companies. Dr. Gradishar has relationships with AstraZeneca, Celltrion, Genentech, MacroGenics, Merck, Pfizer, and Seattle Genetics.
SOURCE: Tung NM et al. J Clin Oncol. 2020 Apr 3;JCO2000299. doi: 10.1200/JCO.20.00299.
It’s okay to consider breast-conserving therapy in breast cancer patients with high-risk hereditary genetic mutations, according to guidelines published in the Journal of Clinical Oncology.
The presence of a germline BRCA1 or BRCA2 mutation shouldn’t preclude breast-conserving therapy as long as the patient is otherwise eligible for the procedure, according to the guidelines, which were developed by an expert panel convened by the American Society of Clinical Oncology, American Society for Radiation Oncology, and Society for Surgical Oncology.
Nadine M. Tung, MD, of Beth Israel Deaconess Medical Center in Boston and the rest of the expert panel reviewed evidence from 58 published articles to create the guidelines.
In addition to supporting use of breast-conserving therapy, the guidelines suggest that radiation shouldn’t be withheld because of mutation status, except in patients with TP53 mutations. Furthermore, BRCA1/2 mutation carriers with metastatic HER2-negative disease can receive the poly (ADP-ribose) polymerase (PARP) inhibitors olaparib and talazoparib as an “alternative to chemotherapy” for first-, second-, or third-line therapy.
However, it’s the “license to consider breast-conserving therapy” for high-risk individuals that is one of the most noteworthy points in the guidelines, and the one that may surprise some readers, according to William J. Gradishar, MD, of Northwestern University in Chicago, who was not involved in developing the guidelines.
“We don’t have to be as dogmatic with these patients with respect to local therapies as we were in the past,” Dr. Gradishar said in an interview. “That’s a good thing for patients, but you also have to understand the nuances that go into recommending [breast-conserving surgery] to a patient. Other variables, like the age at which the patient develops breast cancer, family history, etc., all go into it.”
Weighing options for surgery
The guidelines emphasize that, for patients with germline BRCA1/2 mutations, health care providers need to discuss treatment options for the breast cancer at hand. However, patients should also be made aware of their increased risk of contralateral and new ipsilateral breast cancer as compared with noncarriers.
When weighing breast-conserving therapy versus mastectomy in light of contralateral breast cancer risk, the guidelines recommend considering not only age at diagnosis – the strongest predictor of a later contralateral breast cancer – but also family history, comorbidities, life expectancy, ability to undergo MRI, and prognosis from breast or other cancers, such as ovarian cancer.
If a bilateral mastectomy isn’t performed in a BRCA1/2 mutation carrier, an annual mammogram and MRI are warranted thereafter for screening of the remaining breast tissue, according to the guidelines.
The guidelines say breast-conserving therapy should be offered to patients with mutations in moderate-penetrance genes, including PALB2, CHEK2, and ATM. However, there’s not much data regarding the risk of ipsilateral breast cancer after breast-conserving therapy in these patients.
Likewise, there’s limited evidence on contralateral breast cancer risk for patients with mutations in moderate-penetrance genes aside from CHEK2. The guidelines say the risk should be discussed with patients “in the context of shared decision making.”
Nipple-sparing mastectomy is “reasonable” to consider in certain newly diagnosed patients with BRCA1/2 mutations, as well as in newly diagnosed patients with moderate-risk mutations, the guidelines state.
Women with breast cancer and a deleterious BRCA1/2 mutation who are undergoing unilateral mastectomy should be offered contralateral risk-reducing mastectomy. Likewise, women with moderate-risk mutations should be offered contralateral risk-reducing mastectomy, but not solely based on mutation status, according to the guidelines. Data are limited on contralateral breast cancer risk related to those mutations.
Considerations for radiation
Radiation therapy in the context of breast-conserving therapy or mastectomy should not be withheld because of hereditary mutations, except in the case of TP53 mutations, according to the guidelines.
There’s no evidence that radiotherapy increases toxicity or contralateral breast cancer risk for most BRCA1/2 or moderate-penetrance gene mutations. However, the intact breast shouldn’t be irradiated in germline TP53 mutation carriers, the guidelines say, because of the important role that TP53 plays in the ability to repair DNA damage after cellular stress.
“Carriers of a TP53 mutation would be expected to be unable to repair tissue damage from DNA damaging radiotherapy and be at risk for significant [radiotherapy]-associated sequelae,” the guidelines state.
Chemotherapy and PARP inhibitors
For women with metastatic breast cancer harboring germline BRCA1/2 mutations, the guidelines say platinum chemotherapy should be preferred over taxanes for platinum-naive patients.
Provided the breast cancer is HER2 negative, the PARP inhibitors olaparib or talazoparib “should be offered as an alternative to chemotherapy in the first- to third-line settings,” the guidelines state.
The guidelines confirm that PARP inhibitors are a “valid starting point” for treatment of BCRA1/2–associated metastatic breast cancer, Dr. Gradishar said.
“When a patient progresses on a PARP inhibitor, assuming they’re not going on some other investigational drug or clinical trial, they’re going to get chemotherapy,” he said. “So the argument is that, if you have something that’s at least as good or maybe a little bit better and has fewer side effects, why not start with that and then move on to other things?”
By contrast, there’s not enough evidence to recommend PARP inhibitors for germline BRCA mutation carriers with nonmetastatic breast cancers, according to the guidelines, and there’s “no robust data” for using PARP inhibitors in patients with breast cancers with mutations in moderate-penetrance genes.
The guideline authors disclosed relationships with AstraZeneca, Myriad Genetics, Pfizer, Lilly, and other companies. Dr. Gradishar has relationships with AstraZeneca, Celltrion, Genentech, MacroGenics, Merck, Pfizer, and Seattle Genetics.
SOURCE: Tung NM et al. J Clin Oncol. 2020 Apr 3;JCO2000299. doi: 10.1200/JCO.20.00299.
FROM THE JOURNAL OF CLINICAL ONCOLOGY