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Case Vignettes in Metastatic Breast Cancer

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Conclusions

MBC remains an incurable disease, such that the main goals of treatment focus on prolongation of survival while maintaining or improving QOL. For women with HR-positive MBC, who constitute the vast majority of patients with MBC, current guideline recom­mendations strongly advocate endocrine therapies as first-line intervention unless the disease is immediately life threatening.4,7 Main benefits of endocrine therapy are lower toxicity and better QOL. It is also recommended to extend the duration of hormonal therapy before advancing to cytotoxic CT, with sequential use of endocrine agents.Resistance to endocrine agents is common; however, because of multiple mechanisms that may cause resis­tance, patients may still benefit from other endocrine therapies with different mechanisms of action.37 The optimal sequence for use of the available single-agent therapies—including tamoxifen, nonsteroidal AI (anastrozole, letrozole), the steroidal AI exemes­tane, and fulvestrant—is not established. Fulvestrant and exemes­tane represent equivalent therapies for patients with recurrence during treatment with AI, a frequent scenario due to the extensive use of AI in earlier stages of the disease.Among potential ap­proaches to restore endocrine resistance by blocking complemen­tary pathways, mTOR inhibition has entered clinical practice, and everolimus can be offered in combination with exemestane follow­ing treatment with a nonsteroidal AI.56 The oral CDK 4/6 inhibi­tor palbociclib has recently become available for the treatment of MBC in postmenopausal patients, in combination with letrozole,65 and 2 inhibitors of CDK kinases are in advanced clinical evalua­tion in combination with an AI or fulvestrant as first- and second-line therapy. 

Chemotherapy should be considered for patients with rapidly progressing or life-threatening disease, and for those with resis­tance to multiple endocrine therapies.4,7 Multiple CT agents with proven activity in HR-positive MBC are available, and the se­quential use of single agents is recommended over combination regimens unless the disease is immediately life threatening, such that the need for a response outweighs the disadvantages of in­creased toxicity.Although combination regimens increase ORR and PFS compared with sequential single-agent therapies, they do not provide benefits in duration of response and OS.Agent selection should be based on previous exposure, differential toxicity, comorbid conditions, and patient preferences. First-line recommendations include taxanes and anthracyclines, for which efficacy data are strongest, as well as capecitabine, gemcitabine, platinum compounds, vinorelbine, and ixabepilone.7 As long as it is tolerated, CT should be continued until progression of dis­ease; however, interruptions and scheduling changes need to be considered to maintain QOL, and palliative strategies should be incorporated into treatment early on. Second- and later-line CT treatments are recommended because they can provide clinical benefit. Again, the choice of agent depends on previous treatment, toxicity, comorbidities, and patient choice; efficacy data suggest a survival benefit with eribulin.92 Participation in clinical trials, in­cluding earlier stages such as targeted phase I and II, is strongly encouraged. With intense research into treatment modalities for MBC, clinical trial data are evolving rapidly, and continuing incor­poration of novel strategies into clinical practice is essential to al­low for best patient care. The palliation of symptoms, both medical and psychosocial, remains a major aspect of the management of patients with MBC.

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