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Case Vignettes in Metastatic Breast Cancer

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Community Oncologist’s Perspective

Hussein Ali-Ahmad, MD, is a clinical assis­tant professor of oncology at Rosewell Park Cancer Institute in Jamestown, NY. He is board certified in oncology. He completed an internship and residency in internal medicine at the Bronx-Lebanon Hospital, and a fellowship in hematology/oncology at Okla­homa University Health Sciences Center.

In cases where I suspect metastatic disease based on laboratory results, physical examination, or radiographs, I always recommend that the metastatic site be biopsied to confirm that the lesion is con­sistent with breast cancer rather than another primary malignancy or some other benign process. Repeat biopsy when metastatic dis­ease is diagnosed is also important in order to reassess receptor status prior to the initiation of therapy.

Before I initiate therapy for metastatic breast cancer (MBC), I assess the extent of the disease with imaging studies, specifically, a computed tomography (CT) scan of the chest and abdomen and a bone scan. A positron emission tomography (PET) scan coupled with a CT scan is another option, but it is costlier and does not provide any more information than a CT scan and bone scan may provide. Brain magnetic resonance imaging (MRI) should also be performed in any patient with focal neurologic signs that suggest central nervous system involvement, such as headaches, seizures, cognitive changes, or focal neurologic weakness.

Laboratory studies are also necessary. These include a complete blood count to assess the bone marrow reserve, blood chemistry tests to assess renal and hepatic function and electrolyte levels, and testing for tumor markers, such as CA 15-3 and CA 27-29. El­evations in tumor marker levels at the time of MBC diagnosis yield helpful information for monitoring the response to treatment.

To control pain, I recommend local therapy for metastatic breast lesions. In the event of cord compression or unstable bone lesions, I recommend palliative surgery of the primary tumor, although this will not impact the clinical outcome.

For patients with bone metastasis, I add bisphosphonates (pami­dronate and zoledronic acid) or denosumab in combination with calcium and vitamin D. Due to the risk of osteonecrosis of the jaw, I recommend dental clearance before starting bisphosphonate treat­ment. When possible, dental procedures should be avoided.

When choosing therapy for MBC, I take many factors into con­sideration. My goal is to select the treatment regimen that is most likely to yield clinical response with the least amount of toxicity and side effects. It is critical to assess the hormonal status from the original breast biopsy or from a metastatic site. It is also very important to assess HER2 status early on in order to determine whether or not HER2-targeted therapy is a viable option.

In patients with hormone receptor-positive tumors, I recommend endocrine therapy as a first-line treatment if there is no evidence of visceral metastatic disease or rapid disease progression. I choose the type of endocrine therapy based on the patient’s menopausal status and comorbidities, as well as what agents she has received in the adjuvant setting.

For premenopausal women with no prior adjuvant tamoxifen therapy or who discontinued it more than 12 months prior to di­agnosis, I treat with tamoxifen and ovarian suppression. I always inform patients about the different options of ovarian suppression that are available, namely, medical suppression with a luteinizing hormone-releasing hormone analogue, surgery, or ovarian irradia­tion. Most patients prefer medical suppression. Further treatment in patients with ovarian ablation or suppression does not differ from that in postmenopausal women. 

 In postmenopausal women with no prior adjuvant hormonal therapy, or if it was discontinued more than 12 months prior to di­agnosis, I recommend an aromatase inhibitor, such as anastrozole, letrozole, or exemestane. To lower the risk of accelerated bone loss, I add calcium and vitamin D supplements. Patients whose disease displays resistance to upfront endocrine therapy should proceed to chemotherapy.

Patients with hormone-refractory or triple-negative disease should receive chemotherapy. I select the first-line chemotherapy regimen based on the patient’s performance status, comorbidities, and the presence or absence of visceral metastasis. I recommend taxane-based regimens as first-line therapy for patients progress­ing after adjuvant anthracycline-based, non-taxane-containing chemotherapy regimens. There are many single agents from which to choose; these include anthracyclines (doxorubicin, epirubicin, and doxil); taxanes (paclitaxel, docetaxel, and albumin-bound pa­clitaxel); antimetabolites (capecitabine and gemcitabine), and mi­crotubule inhibitors (eribulin and vinorelbine).  I usually select eribulin in the third-line setting after 2 failed chemotherapy regi­mens, one of them including an anthracycline.

I treat patients with triple-negative breast cancer with cytotoxic agents.  Combination therapy is more often required in triple-neg­ative breast cancer because of its aggressive course and frequent visceral involvement. However, triple-negative histology alone is not sufficient reason to give combination chemotherapy.

I reserve combination chemotherapy for highly symptomatic pa­tients or for those with high tumor burden. There are several com­bination chemotherapy regimens from which to choose. The most common regimens that I use are doxorubicin and cyclophospha­mide, gemcitabine and paclitaxel, or docetaxel and capecitabine. Ixabepilone and capecitabine are used in the third-line setting.

In patients with HER2-positive MBC, I generally recommend pertuzumab plus trastuzumab in combination with a taxane as the first-line treatment. Other possible regimens include trastuzumab in combination with any of the following agents: paclitaxel with or without carboplatin, docetaxel, vinorelbine, or capecitabine. Lapa­tinib and capecitabine are options for treatment in patients with HER2-positive disease following progression on a trastuzumab­containing regimen.

Finally, I monitor patients with MBC with examination and labo­ratory studies every 2 to 3 months for those on endocrine therapy and prior to each cycle in those on chemotherapy. I order a CT scan and bone scan every 3 to 6 months in patients on endocrine thera­py, and every 3 to 4 cycles in patients on chemotherapy.

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