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NCCN Guidelines for HR+ HER2 Metastatic Breast Cancer

Insights From: Debu Tripathy, MD, MD Anderson Cancer Center; Sara Hurvitz, MD, UCLA Jonsson Comprehensive Cancer Center; Hatem Soliman, MD, H. Lee Moffitt Cancer Center & Research Institute
Published: Thursday, Jul 26, 2018



Transcript: 

Debu Tripathy, MD: The management guidelines for hormone receptor–positive and HER2-negative cancers have evolved a lot over the past several years. It used to be maybe 10, 15 years ago that most patients with metastatic breast cancer, even though it was hormone receptor–positive, were treated with chemotherapy. There was a sense that it was a stronger agent, that it led to better outcomes, but we’ve learned really that comparisons between chemotherapy and hormonal therapy as initial therapy really lead to equivalent results, maybe even slightly better with hormonal therapy, and certainly from a quality-of-life standpoint, it’s better tolerated.

So, the guidelines now state that if you have hormone receptor–positive and HER2-negative breast cancer, hormonal therapy should generally be the first type or class of treatment that you use. The exceptions to that, the patient factors that might lead you otherwise, would be patients who have very rapidly progressing cancers, those who have what we call visceral crisis—they have organ involvement, such as lung and liver, to the point that it’s affecting organ function or causing significant symptoms. Those patients should get chemotherapy first, and then if they have a response, get converted over to endocrine therapy. Whereas the rest of the patients, which is most of the patients, should get hormonal therapy first.

Now, I would add my own commentary that if the estrogen receptor is very low, because the new classification for hormone receptor–positive is 1% or higher, we know that the 1% to 10% probably don’t respond very well to hormonal therapy. So that, I would say, should be added to the consideration.

But then if endocrine therapy is used, the first-line recommendation, now based on the data I mentioned with fulvestrant, really calls for either an aromatase inhibitor or fulvestrant for postmenopausal patients. And for premenopausal patients, it calls for ovarian suppression, along with either an aromatase inhibitor or fulvestrant. There may be some patients who have very low disease burden whom you may not want to treat with ovarian suppression and maybe use tamoxifen.

Now, the use of biological agents in combination is somewhat optional, according to the current guidelines because at the current time, there isn’t a difference in overall survival. And even though the studies weren’t powered to detect an overall survival, the latest NCCN guidelines really call for first-line therapy being an aromatase inhibitor alone or with a CDK4/6 inhibitor. You sort of have the option there. And for second-line therapy, now fulvestrant or exemestane alone or with an mTOR inhibitor—the only one being approved really is everolimus—would be an option as well. So, that’s generally how the endocrine pathways are.

After that, one might move on to chemotherapy. But there are some patients who could respond to additional hormonal therapies, really apart from the ones I mentioned. The only other one that really has clinical testing is megestrol acetate, which isn’t used as much today. But the point at which you might switch someone over to chemotherapy, whether it’s after first- or second-line therapy, also depends on the tempo of the disease and factors such as those.

Hatem Soliman, MD: There are multiple factors that we would consider in determining which first-line therapy we would choose for a patient. Often it hinges on what prior treatments they’ve had and what they’ve been exposed to—so things that they’ve already seen, an aromatase inhibitor in the adjuvant setting, and possibly having relapsed or potentially that they’ve had no therapy prior to their being diagnosed with metastatic disease, and this is their truly first line of therapy for their metastatic breast cancer. Sometimes also patient preference and discussions about what kind of therapies they’re willing to undertake are also important factors we have to consider.

Transcript Edited for Clarity 
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Transcript: 

Debu Tripathy, MD: The management guidelines for hormone receptor–positive and HER2-negative cancers have evolved a lot over the past several years. It used to be maybe 10, 15 years ago that most patients with metastatic breast cancer, even though it was hormone receptor–positive, were treated with chemotherapy. There was a sense that it was a stronger agent, that it led to better outcomes, but we’ve learned really that comparisons between chemotherapy and hormonal therapy as initial therapy really lead to equivalent results, maybe even slightly better with hormonal therapy, and certainly from a quality-of-life standpoint, it’s better tolerated.

So, the guidelines now state that if you have hormone receptor–positive and HER2-negative breast cancer, hormonal therapy should generally be the first type or class of treatment that you use. The exceptions to that, the patient factors that might lead you otherwise, would be patients who have very rapidly progressing cancers, those who have what we call visceral crisis—they have organ involvement, such as lung and liver, to the point that it’s affecting organ function or causing significant symptoms. Those patients should get chemotherapy first, and then if they have a response, get converted over to endocrine therapy. Whereas the rest of the patients, which is most of the patients, should get hormonal therapy first.

Now, I would add my own commentary that if the estrogen receptor is very low, because the new classification for hormone receptor–positive is 1% or higher, we know that the 1% to 10% probably don’t respond very well to hormonal therapy. So that, I would say, should be added to the consideration.

But then if endocrine therapy is used, the first-line recommendation, now based on the data I mentioned with fulvestrant, really calls for either an aromatase inhibitor or fulvestrant for postmenopausal patients. And for premenopausal patients, it calls for ovarian suppression, along with either an aromatase inhibitor or fulvestrant. There may be some patients who have very low disease burden whom you may not want to treat with ovarian suppression and maybe use tamoxifen.

Now, the use of biological agents in combination is somewhat optional, according to the current guidelines because at the current time, there isn’t a difference in overall survival. And even though the studies weren’t powered to detect an overall survival, the latest NCCN guidelines really call for first-line therapy being an aromatase inhibitor alone or with a CDK4/6 inhibitor. You sort of have the option there. And for second-line therapy, now fulvestrant or exemestane alone or with an mTOR inhibitor—the only one being approved really is everolimus—would be an option as well. So, that’s generally how the endocrine pathways are.

After that, one might move on to chemotherapy. But there are some patients who could respond to additional hormonal therapies, really apart from the ones I mentioned. The only other one that really has clinical testing is megestrol acetate, which isn’t used as much today. But the point at which you might switch someone over to chemotherapy, whether it’s after first- or second-line therapy, also depends on the tempo of the disease and factors such as those.

Hatem Soliman, MD: There are multiple factors that we would consider in determining which first-line therapy we would choose for a patient. Often it hinges on what prior treatments they’ve had and what they’ve been exposed to—so things that they’ve already seen, an aromatase inhibitor in the adjuvant setting, and possibly having relapsed or potentially that they’ve had no therapy prior to their being diagnosed with metastatic disease, and this is their truly first line of therapy for their metastatic breast cancer. Sometimes also patient preference and discussions about what kind of therapies they’re willing to undertake are also important factors we have to consider.

Transcript Edited for Clarity 
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