Breast cancer is the most commonly diagnosed malignancy in women, with triple-negative breast cancer (TNBC) accounting for 10–20% of cases. Historically, fewer treatment options have existed for this subtype of breast cancer, with cytotoxic chemotherapy playing a predominant role. This article aims to review the current treatment paradigm for curative-intent TNBC, while also reviewing potential future developments in this landscape. In addition to chemotherapy, recent advances in the understanding of the molecular biology of TNBC have led to promising new studies of targeted and immune checkpoint inhibitor therapies in the curative-intent setting. The appropriate selection of TNBC patient subgroups with a higher likelihood of benefit from treatment is critical to identify the best treatment approach.

Immune checkpoint blockade (ICB) is becoming an increasingly prevalent strategy in the clinical realm of cancer therapeutics. With more patients being administered ICB for a host of tumor types, the scope of adverse events associated with these drugs will likely grow. Here we report a case of aplastic anemia (AA) in a patient with metastatic melanoma secondary to dual ICB therapy. To our knowledge, this is only the second case of AA secondary to dual ICB in the literature, and the first to have a positive patient outcome. A 51-year old male with metastatic melanoma was started on dual immune checkpoint blockade, in the form ipilimumab (3 mg/kg) and nivolumab (1 mg/kg). Two weeks following the second cycle, he presented to the emergency department with profound polypipsia, polyuria and fatigue. The patient was diagnosed with diabetic ketoacidosis secondary to immune therapy induced type-1 diabetes and was admitted to the ICU. While in hospital the patient developed a symptomatic anemia and neutropenia. A bone marrow biopsy revealed a markedly hypocellular marrow with trinlineage hypoplasia with no evidence of myelodysplasia, neoplasm or excess blasts. Flow cytometry revealed an inverted CD4+:CD8+ ratio and an absence of hematogones. Taken together the presumed etiology was AA secondary to immunotherapy. The patient was subsequently started in IV methylprednisone 70 mg/day for 8 days, followed by a prednisone taper. This intervention rectified the bicytopenia and to date the patient has shown stable blood counts. With the use of ICBs becoming increasingly prevalent in the clinical arena, the number of patients presenting with immune-related adverse events will likely increase. The current case illustrates the need to be vigilant when managing cancer patients receiving ICB. The resolution of this patient’s AA with corticosteroids highlights the value of early detection and appropriate treatment of these rare immune-mediated adverse events.

Primary febrile neutropenia (FN) prophylaxis with ciprofloxacin or granulocyte-colony stimulating factors (G-CSF) is recommended with docetaxel-cyclophosphamide (TC) chemotherapy for early-stage breast cancer (EBC). A pragmatic randomised trial compared the superiority of G-CSF to ciprofloxacin and a cost-utility analysis were conducted. EBC patients receiving TC chemotherapy were randomised to ciprofloxacin or G-CSF. The primary outcome was a composite of FN and non-FN treatment-related hospitalisation. Secondary outcomes included; rates of FN, non-FN treatment-related hospitalisation, chemotherapy dose reductions/delays/discontinuations. Primary analysis was performed with the intention to treat population. Cost-utility analyses were conducted from the Canadian public payer perspective. 458 eligible patients were randomised: 228 to ciprofloxacin and 230 to G-CSF. For the primary endpoint there was non-statistically significant difference (Risk difference = -6.7%, 95%CI = -13.5%-0.1%, p = 0.061) between ciprofloxacin patients (46,20.2%) and G-CSF (31,13.5%). Patients receiving ciprofloxacin were more likely to experience FN (36/228, 15.8% vs 13/230, 5.7%) than patients receiving G-CSF (p < 0.001). Non-FN treatment-related hospitalisation occurred in 40/228 (17.5%) of ciprofloxacin patients vs 28/230 (12.2%) of G-CSF patients (p = 0.12). There were no differences in other secondary outcomes. G-CSF was associated with an incremental cost-effectiveness ratio of C$1,760,796 per one quality-adjusted life year gained. The primary endpoint of superiority of G-CSF over ciprofloxacin was not demonstrated. While there were reduced FN rates with G-CSF, there were no differences in chemotherapy dose delays/reductions or discontinuations. With the commonly used willingness to pay value of C$50,000/QALY, G-CSF use was not cost-effective compared to ciprofloxacin and deserves scrutiny from the payer perspective.

Patients with hormone receptor (HR)-positive, human epidermal growth factor receptor-2 (HER2)-negative, node negative (NN) breast cancer may be offered a gene expression profiling (GEP) test to determine recurrence risk and benefit of adjuvant chemotherapy. We developed a clinical-pathologic (CP) model to predict genomic recurrence risk and examined its performance characteristics. Patients diagnosed with HR-positive, HER2-negative, NN breast cancer with a tumour size < 30 mm and who underwent a GEP test [OncotypeDX or Prosigna] in Alberta from October 2017 through March 2019 were identified. Patients were classified as low or high genomic risk. Multivariable logistic regression analysis was performed to examine the associations of CP factors with genomic risk. A CP model was developed using coefficients of regression and sensitivity analyses were performed. A total of 366 patients were eligible (135 were tested using OncotypeDX and 231 with Prosigna). Of these, 64 (17.5%) patients were classified as high genomic risk. On multivariable logistic regression, tumour size > 20 mm (odds ratio [OR], 3.58; 95% confidence interval [CI], 1.84-6.98; P<0.001), low expression of progesterone receptor (OR, 3.46; 95% CI, 1.76-6.82; P<0.001), and histological grade III (OR, 7.24; 95% CI, 3.82-13.70; P<0.001) predicted high genomic risk. A CP model using these variables was developed to provide a score of 0-4. A CP cut-point of 0, identified 56% of genomic low risk patients with a specificity of 98.4%. A CP model could be used to narrow the population of breast cancer patients undergoing GEP testing.