The patient in this scenario has presented with visceral metastases suggestive of an aggressive phenotype of HER2-positive metastatic breast cancer. I would administer trastuzumab in combination with pertuzumab and weekly paclitaxel. Because pertuzumab has been shown to provide a survival benefit, I would want to include it in my treatment approach. My recommendation would be the same if the patient were asymptomatic or symptomatic at presentation.

For an asymptomatic patient, I would consider either endocrine therapy and trastuzumab or the combination of trastuzumab and pertuzumab with weekly paclitaxel. The driving consideration would be how strongly I believe the tumor to be endocrine sensitive. If relapse occurs years after endocrine therapy, then I would opt for endocrine therapy and trastuzumab. If the patient experiences relapse early while receiving adjuvant endocrine therapy, then I would recommend trastuzumab and pertuzumab with weekly paclitaxel. I often follow that with endocrine therapy.

Conflicting issues are at play, however. First, no data indicate that higher response rates or increased progression-free survival is achieved with the inclusion of chemotherapy for hormone receptor-positive tumors. The old dogma that chemotherapy produced faster, more frequent responses likely reflected the comparison of hormone receptor-negative to hormone receptor-positive biology. In Stage IV breast cancer, as in Stages I through III, I believe that responses are as likely with endocrine therapy as they are with chemotherapy if the tumor is truly hormone receptor-positive and without acquired resistance. Second, hormone receptor assessments are often incorrect and do not always reflect endocrine sensitivity. Therefore, if I suspect this is not a luminal tumor (eg, borderline ER) or the tumor is not endocrine sensitive (eg, early relapse on adjuvant endocrine therapy), I would opt for trastuzumab in combination with pertuzumab and a taxane. The fact that the frequency of nonluminal subtype is higher in the case of visceral involvement would make me lean toward this option.

I would have the same recommendation for a symptomatic patient in the same situation. The crux of the question is whether a response is more likely to occur with an endocrine approach versus a chemotherapy approach. I would consider the combination of trastuzumab, pertuzumab and a taxane if it is questionable whether the tumor is a luminal tumor or is endocrine sensitive. The visceral involvement is another factor that would make me favor this option.

For this asymptomatic patient with liver and lung metastases, I would lean toward administering trastuzumab in combination with pertuzumab and weekly paclitaxel. I would follow this initial treatment with endocrine therapy. The degree of response would determine when I make the switch to endocrine therapy. I would likely continue trastuzumab with the maintenance endocrine therapy.

If the patient was symptomatic and in the same situation, I would recommend trastuzumab with pertuzumab and weekly paclitaxel with or without follow-up endocrine therapy and maintenance trastuzumab.

I would offer an asymptomatic 60-year-old patient with liver and lung metastases endocrine therapy. This treatment would be associated with the least toxicity, and if it does not work I could change to trastuzumab, pertuzumab and weekly paclitaxel.

In the case of the 60-year-old patient who is symptomatic and has visceral disease, I would offer trastuzumab in combination with pertuzumab and weekly paclitaxel first. If she has a good response, maintenance with hormone therapy might be an option later.

I would consider treatment with trastuzumab in combination with pertuzumab and a taxane for this patient. I believe this therapy is highly likely to reduce the size of the tumor and provide a survival benefit. I would continue with trastuzumab and pertuzumab after a plateau response. Because this patient has visceral disease, I would not feel comfortable with an up-front endocrine therapy approach.

My choice of treatment for a symptomatic patient in the same scenario would be the same. The combination of trastuzumab with pertuzumab and a taxane would be likely to cause tumor reduction, reduce symptoms of the disease and provide an overall survival benefit. After a plateau response, I would continue treatment with trastuzumab and pertuzumab without the chemotherapy.

For this asymptomatic 60-year-old patient with liver and lung metastases, I would consider endocrine therapy and trastuzumab. The goal would be to have the patient live as long as possible with a good quality of life. It is unlikely that she will become highly symptomatic or experience a decrease in organ function that precludes switching to chemotherapy while receiving therapy with close observation.

For a symptomatic 60-year-old patient with liver and lung metastases, I would administer trastuzumab and pertuzumab with a taxane initially and follow that with endocrine therapy with trastuzumab and pertuzumab.

My choice of therapy for an asymptomatic or symptomatic patient with liver and lung metastases would be the combination of pertuzumab, trastuzumab and nab paclitaxel. This patient needs optimal cytoreduction given the widespread visceral metastases. I would stop the taxane at the time of maximal response and continue with the 2 antibodies and an aromatase inhibitor. I believe her best chance for a prolonged response is with maximal cytoreduction of all tumor sites with pertuzumab, trastuzumab and a taxane followed by primary breast cancer surgery and then treatment with pertuzumab, trastuzumab and an aromatase inhibitor.

For an asymptomatic or symptomatic patient with liver and lung metastases, I would opt for trastuzumab, pertuzumab and a taxane. The CLEOPATRA study showed that this treatment increased overall survival without excessive toxicity. I would also consider T-DM1 for a patient in this setting, if feasible.