How I treat metastatic triple-negative breast cancer

Abstract

Triple-negative breast cancer (TNBC) is associated with a high risk of recurrence and generally a bad prognosis. More than one-third of patients with TNBC will present distant metastases during the course of their disease. Although chemotherapy has been the main treatment option for metastatic TNBC for a long time, this scenario has changed recently with the advent of the polyadenosine diphosphate-ribose polymerase inhibitors (PARPis) for patients harbouring a mutation in the BRCA genes (BRCAmut) and also with the results of immunotherapy in patients with PD-L1-positive tumours. The present manuscript proposes a treatment algorithm for patients with metastatic TNBC based on the currently available, most relevant literature on the topic. For patients with a BRCAmut and able to tolerate chemotherapy, we recommend initiating treatment with platins (carboplatin/cisplatin) and to start PARPis at disease progression. For patients with PD-L1-positive tumours (PD-L1 expression on tumour-infiltrating immune cells ≥1%), we recommend first-line treatment with nab-paclitaxel and atezolizumab, when available. In patients without a BRCA mutation and with PD-L1-negative tumours, we recommend single-agent chemotherapy with taxanes (paclitaxel or docetaxel) as a first-line treatment. In patients with a high disease burden or who are very symptomatic, combinations such as anthracyclines plus cyclophosphamide or platins with taxanes are valid options. Chemotherapy should be maintained until the occurrence of disease progression or limiting toxicities. After progression to first-line chemotherapy, anthracyclines are an option for patients who received taxanes and vice versa. For patients who progressed to taxanes and anthracyclines, or who present contraindications to these agents, fluorouracil/capecitabine, eribulin, gemcitabine, cisplatin/carboplatin, vinorelbine and ixabepilone are alternatives. The treatment of TNBC is constantly evolving, and the inclusion of patients in ongoing trials evaluating new targeted agents, immunotherapy and predictive biomarkers should be encouraged, in an attempt to improve metastatic TNBC treatment outcomes.

53BP1 Accumulation in Circulating Tumor Cells Identifies Chemotherapy-Responsive Metastatic Breast Cancer Patients

“…Among the MBC patients recruited during the baseline and the 1st treatment visits, more than one fourth had suffered from an HR-primary tumor (Supplementary Figure S2). None of these TNBC patients participated in the trial until the final visit, which was mostly due to adverse events or disease progression, illustrating the poor prognosis of this breast cancer subtype [27]. Similar to the pattern seen with all MBC patients (Supplementary Figure S1), mean CTC numbers in MBC patients with primary HR+ breast cancer declined from the baseline to the 2nd treatment visit and then increased again until the final visit (Figure 2a).…”

“…Present treatments of MBC patients include conventional chemotherapeutics such as anthracyclines and taxanes, but hopefully in the near future, more effective and/or better tolerable drugs will be available [27,39]. Though not addressed in our present study, monitoring 53BP1 in CTCs may also identify resistance to PARP inhibitors as previously suggested from preclinical investigations [40].…”

Exploiting the internalization feature of an antibody against the glycosphingolipid SSEA‐4 to deliver immunotoxins in breast cancer cells

“…We next evaluated the potential effect of the MC‐813‐70 + Mab‐ZAP immunotoxin complex in combination with chemotherapeutic drugs frequently used in breast cancer treatment. In the case of TNBC, first‐line chemotherapy uses taxanes (paclitaxel, sold under the brand name Taxol®) as a single agent or in combinations . To study the effect of a combination of chemotherapeutic drugs with the immunotoxin, we first selected an appropriate cytotoxic dose for paclitaxel (30 nm; not shown), which does not affect cellular endocytosis of the immunotoxin (Figure a).…”

“…In the case of TNBC, first-line chemotherapy uses taxanes (paclitaxel, sold under the brand name Taxol â ) as a single agent or in combinations. 27,28 To study the effect of a combination of chemotherapeutic drugs with the immunotoxin, we first selected an appropriate cytotoxic dose for paclitaxel (30 nm; not shown), which does not affect cellular endocytosis of the immunotoxin (Figure 10a). Under this treatment condition (30 nm paclitaxel), we observed that MDA-MB-231 cellular viability remained at 50% after 3 days of treatment (Figure 10b).…”

Pegylated liposomal doxorubicin in patients with metastatic triple-negative breast cancer: 8-year experience of a single center

“…When indicated, the immunotherapy and polyadenosine diphosphate-ribose polymerase inhibitors (PARPis) are the most active agents in the treatment of metastatic triple-negative breast cancer (TNBC) [4]. The immunotherapy with atezolizumab is indicated in combination with nab-paclitaxel in the treatment of patients with advanced TNBC.…”