Editing Breast cancer (section)

=== Metastatic disease ===

For around 1 in 5 people treated for localized breast cancer, their tumors eventually spread to distant body sites – most commonly the nearby bones (67% of cases), liver (41%), lungs (37%), brain (13%), and [[peritoneum]] (10%).{{sfn|Hayes|Lippman|2022|loc="Diagnostic Considerations"}}{{sfn|Harbeck|Penault-Llorca|Cortes|Gnant|2019|loc="Fig. 9: Common Metastatic Sites in Breast Cancer"}} Those with metastatic disease can receive further chemotherapy, typically starting with capecitabine, an anthracycline, or a taxane. As one chemotherapy drug fails to control the cancer, another is started. In addition to the chemotherapeutic drugs used for localized cancer, [[gemcitabine]], [[vinorelbine]], [[etoposide]], and [[epothilone]]s are sometimes effective.{{sfn|Hayes|Lippman|2022|loc="Systemic Treatments for Metastatic Breast Cancer"}} Those with bone metastases benefit from regular infusion of the bone-strengthening agents [[denosumab]] and the [[bisphosphonate]]s; infusion every three months reduces the chance of bone pain, fractures, and bone [[hypercalcemia]].{{sfn|Hayes|Lippman|2022|loc="Bone-Modifying Agents"}}

Up to 70% of those with ER-positive metastatic breast cancer benefit from additional endocrine therapy. Therapy options include those used in localized cancer, plus [[toremifene]] and [[fulvestrant]], often used in combination with [[CDK inhibitor|CDK4/6 inhibitor]]s ([[palbociclib]], [[ribociclib]], or [[abemaciclib]]). When one endocrine therapy fails, most will benefit from transitioning to a second one. Some respond to a third sequential therapy as well.{{sfn|Hayes|Lippman|2022|loc="Systemic Treatments for Metastatic Breast Cancer"}} Adding an [[mTOR inhibitor]], [[everolimus]], can further slow the tumors' progression.{{sfn|Hayes|Lippman|2022|loc="Systemic Treatments for Metastatic Breast Cancer"}}

Those with HER2-positive metastatic disease can benefit from continued use of trastuzumab, alone, in combination with pertuzumab, or in combination with chemotherapy. Those whose tumors continue to progress on trastuzumab benefit from HER2-targeted [[antibody drug conjugate]]s (HER2 antibodies linked to chemotherapy drugs) [[trastuzumab emtansine]] or [[trastuzumab deruxtecan]]. The HER2-targeted antibody [[margetuximab]] can also prolong survival, as can HER2 inhibitors [[lapatinib]], [[neratinib]], or [[tucatinib]].{{sfn|Hayes|Lippman|2022|loc="Systemic Treatments for Metastatic Breast Cancer"}}

Certain therapies are targeted at those whose tumors have particular gene mutations: [[Alpelisib]] or [[capivasertib]] for those with mutations activating the protein [[PIK3CA]].{{sfn|Hayes|Lippman|2022|loc="Systemic Treatments for Metastatic Breast Cancer"}}<ref name=ACS-Meta/> [[PARP inhibitor]]s ([[olaparib]] and [[talazoparib]]) for those with mutations that inactivate [[BRCA1]] or [[BRCA2]].{{sfn|Hayes|Lippman|2022|loc="Systemic Treatments for Metastatic Breast Cancer"}} The [[immune checkpoint inhibitor]] antibody [[atezolizumab]] for those whose tumors express [[PD-L1]].{{sfn|Hayes|Lippman|2022|loc="Systemic Treatments for Metastatic Breast Cancer"}}<ref name=ACS-Meta>{{cite web|url=https://www.cancer.org/cancer/types/breast-cancer/treatment/treatment-of-breast-cancer-by-stage/treatment-of-stage-iv-advanced-breast-cancer.html |accessdate=18 April 2024 |title=Treatment of Stage IV (Metastatic) Breast Cancer |publisher=American Cancer Society |date=28 November 2023}}</ref> And the similar immunotherapy [[pembrolizumab]] for those whose tumors have mutations in various [[DNA repair]] pathways.<ref name=ACS-Meta/>