Inflammation is implicated in triple negative breast cancer (TNBC) progression. TNBC carries a worse prognosis than other breast cancer subtypes, and with the clinical and molecular heterogeneity of TNBC, there is a lack of effective therapeutic targets available. Identification of molecular targets for TNBC subtypes is crucial towards personalized patient stratification. Inducible nitric oxide synthase (iNOS) has been shown to induce p53 mutation accumulation, basal-like gene signature enrichment and transactivation of the epidermal growth factor receptor (EGFR) via s-nitrosylation. Herein we report that iNOS is associated with disease recurrence, distant metastasis and decreased breast cancer specific survival in 209 cases of TNBC. Employing TNBC cell lines representing normal basal breast, and basal-like 1 and basal-like 2 tumors, we demonstrate that nitric oxide (NO) induces EGFR-dependent ERK phosphorylation in basal-like TNBC cell lines. Moreover NO mediated cell migration and cell invasion was found to be dependent on EGFR and ERK activation particularly in basal-like 2 TBNC cells. This occurred in conjunction with NF-κB activation and increased secretion of pro-inflammatory cytokines IL-8, IL-1β and TNF-α. This provides substantial evidence for EGFR as a therapeutic target to be taken into consideration in the treatment of a specific subset of basal-like TNBC overexpressing iNOS.

PurposeThe rate of pathological complete response (pCR) for patients with triple negative breast cancer (TNBC) is increased when carboplatin is added to neo-adjuvant chemotherapy (NACT). However, while phase III trial data showing a survival benefit are awaited, carboplatin is not yet standard-of-care for TNBC. The aim of this study was to examine the rate of pCR and the outcome for those treated with carboplatin and to examine the predictors of response to therapy.MethodsThe retrospective series comprised 333 consecutive patients with TNBC (median follow-up time, 43 months). Adjuvant chemotherapy was given to 51% (n = 168) of patients and 29% (n = 97) received anthracycline–taxane NACT with carboplatin given to 9% (n = 31) of patients.ResultsOverall, 25% (n = 78) of patients experienced a breast cancer recurrence and 22% (n = 68) died from disease. A pCR breast and pCR breast/axilla was more common in those who received carboplatin (n = 18, 58% and n = 17, 55%, respectively) compared those who did not (n = 23, 36% and n = 18, 28%, respectively) (p = 0.041 and p = 0.011, respectively). By multivariable analysis, carboplatin and high tumor grade were independent predictors of pCR breast/axilla (ORnon-pCR = 0.17; 95% CI 0.06–0.54; p = 0.002; and ORnon-pCR = 0.05, 95% CI 0.01–0.27; p < 0.001, respectively). pCR breast/axilla was an independent predictor of DFS (HRnon-pCR=6.23; 95% CI 1.36–28.50; p = 0.018), metastasis-free survival (HRnon-pCR = 5.08; 95% CI 1.09–23.65; p = 0.038) and BCSS (HRnon-pCR = 8.52; 95% CI 1.09–66.64; p = 0.041).ConclusionCarboplatin therapy and high tumor grade are associated with a significant increase in the rate of pCR, which is an independent predictor of outcome. These data support the use of carboplatin in NACT for TNBC, while results from phase III studies are awaited.Electronic supplementary materialThe online version of this article (10.1007/s10549-018-5066-6) contains supplementary material, which is available to authorized users.

A 35-year-old primigravida presented with significant anxiety symptoms at 26 weeks’ gestation. Symptoms were preceded by a nightmare about her upcoming labour. She developed repetitive intrusive thoughts of being trapped emotionally and physically in her pregnancy. Her symptoms were suggestive of new-onset claustrophobia associated with pregnancy, which has not been previously reported on. Her symptoms ameliorated with a combination of cognitive–behavioural therapy and pharmacotherapy (sertraline and low dose quetiapine). The later stages of pregnancy were associated with minimal symptoms and the resolution of her subjective ‘entrapment’. A subsequent pregnancy resulted in similar although less severe symptomatology. No postpartum anxiety symptoms were demonstrated on both occasions. Anxiety symptoms can adversely impact both the mother and fetus, and thus correct identification and management of pregnancy-related claustrophobia improved symptomatology and functioning and allowed for earlier detection and reduced symptomatology in a subsequent pregnancy.