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First-Line ER-Positive MBC Treatments

Insight From: Joanne L. Blum, MD, PhD, Texas Oncology; Adam Brufsky, MD, Pittsburgh; Harold J. Burstein, MD, PhD, Dana-Farber
Published: Monday, Aug 18, 2014
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Treatment of estrogen receptor (ER)-positive breast cancer can be complicated and depends on many factors, such as disease burden and the duration of a patient’s disease-free interval from the original diagnosis. For example, a patient with lymph node soft tissue, such as pleural or bone metastatic disease, would be treated differently than a patient with highly proliferative, liver-predominant, extensive visceral disease. Joanne Blum, MD, notes that the patient in the latter scenario who is symptomatic would receive chemotherapy up front to control the extensive burden of disease, usually with 2 agents to achieve a rapid response.

In patients who are less symptomatic with more limited disease burden, clinicians may give endocrine therapy for as long as possible. In this setting, aromatase inhibitor therapy would be first-line. Blum explains that if the patient has a history of relapsing on an aromatase inhibitor, it is presumed the patient has endocrine-resistant disease, and clinicians usually implement an everolimus-containing regimen under such circumstances. If the patient relapsed without aromatase inhibitor therapy, however, clinicians then consider an aromatase inhibitor, particularly if the patient had tolerated therapy well.

Individuals who have ER-positive disease with bone metastases require an osteoporosis medication to protect the bone and prevent fracture and other skeletal-related events. Adam Brufsky, MD, PhD, explains his practice uses either zoledronic acid or denosumab. He frequently uses denosumab, not because of the efficacy data, but because it is easily administered as an injection instead of an infusion; unlike other medications, intravascular access is not needed with denosumab. Brufsky notes that denosumab is not associated with many serious adverse events, but he is cautious of its hypocalcemia risk, and advises patients to be careful with their teeth. Patients who need a tooth extraction are instructed to inform their clinicians so that denosumab therapy can be held to reduce risk of osteonecrosis of the jaw.

Brufsky adds the majority of people who come in with ER-positive metastatic disease will have had an adjuvant regimen or continue to be on adjuvant therapy. In these settings, Brufsky assesses the circumstances of each individual; if a postmenopausal woman is already on an aromatase inhibitor, fulvestrant is considered, but if a patient has not yet had an aromatase inhibitor, they may be started on tamoxifen. If a patient has received an aromatase inhibitor or are pre- or postmenopausal and have not yet had their estrogen suppressed, Brufsky begins by suppressing estrogen with an LHRH agonist or an oophorectomy. Whether it is optimal to administer an aromatase inhibitor alongside this particular treatment is still uncertain among clinicians, he says.
 
Harold J. Burstein, MD, PhD, adds that aromatase inhibitors are usually the first drug of choice in woman who have not yet received an aromatase inhibitor. For most women, the side effects—hot flashes, night sweats, bone and joint stiffness—are relatively minor. Burstein also notes that a new class of drugs, CDK 4/6 inhibitors, are being studied in combination with aromatase inhibitors. 
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Treatment of estrogen receptor (ER)-positive breast cancer can be complicated and depends on many factors, such as disease burden and the duration of a patient’s disease-free interval from the original diagnosis. For example, a patient with lymph node soft tissue, such as pleural or bone metastatic disease, would be treated differently than a patient with highly proliferative, liver-predominant, extensive visceral disease. Joanne Blum, MD, notes that the patient in the latter scenario who is symptomatic would receive chemotherapy up front to control the extensive burden of disease, usually with 2 agents to achieve a rapid response.

In patients who are less symptomatic with more limited disease burden, clinicians may give endocrine therapy for as long as possible. In this setting, aromatase inhibitor therapy would be first-line. Blum explains that if the patient has a history of relapsing on an aromatase inhibitor, it is presumed the patient has endocrine-resistant disease, and clinicians usually implement an everolimus-containing regimen under such circumstances. If the patient relapsed without aromatase inhibitor therapy, however, clinicians then consider an aromatase inhibitor, particularly if the patient had tolerated therapy well.

Individuals who have ER-positive disease with bone metastases require an osteoporosis medication to protect the bone and prevent fracture and other skeletal-related events. Adam Brufsky, MD, PhD, explains his practice uses either zoledronic acid or denosumab. He frequently uses denosumab, not because of the efficacy data, but because it is easily administered as an injection instead of an infusion; unlike other medications, intravascular access is not needed with denosumab. Brufsky notes that denosumab is not associated with many serious adverse events, but he is cautious of its hypocalcemia risk, and advises patients to be careful with their teeth. Patients who need a tooth extraction are instructed to inform their clinicians so that denosumab therapy can be held to reduce risk of osteonecrosis of the jaw.

Brufsky adds the majority of people who come in with ER-positive metastatic disease will have had an adjuvant regimen or continue to be on adjuvant therapy. In these settings, Brufsky assesses the circumstances of each individual; if a postmenopausal woman is already on an aromatase inhibitor, fulvestrant is considered, but if a patient has not yet had an aromatase inhibitor, they may be started on tamoxifen. If a patient has received an aromatase inhibitor or are pre- or postmenopausal and have not yet had their estrogen suppressed, Brufsky begins by suppressing estrogen with an LHRH agonist or an oophorectomy. Whether it is optimal to administer an aromatase inhibitor alongside this particular treatment is still uncertain among clinicians, he says.
 
Harold J. Burstein, MD, PhD, adds that aromatase inhibitors are usually the first drug of choice in woman who have not yet received an aromatase inhibitor. For most women, the side effects—hot flashes, night sweats, bone and joint stiffness—are relatively minor. Burstein also notes that a new class of drugs, CDK 4/6 inhibitors, are being studied in combination with aromatase inhibitors. 
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