Introduction: Pregnancy Associated Breast cancer (PABC) is associated with poor prognosis and a decreased overall survival. A retrospective review was conducted to review the experience and outcome in a tertiary care hospital, and to compare those seen in a matched group for year of diagnosis. Materials and Methods: This is a retrospective review of a prospectively collected breast cancer registry. The study was conducted in a tertiary care hospital in Riyadh, Saudi Arabia from January to Decamber 2014 . Female patients with PABC were identified and matched with similar cohort of non-pregnant breast cancer patients that were diagnosed between 2001-2010. Clinical data including age, tumor biology, clinical stage, follow up and outcomes (disease free survival, DFS) were analyzed and compared between the two groups using SAS 9.3 and R-2.14.1 Results: A total of 110 patients in Group 1 and 114 patients in Group II were analyzed. In both groups, the patient age ranged was between 20 to 45 years; the median follow up was 34 months in PABC and 54 months in non-pregnant cohort. PABC were statistically more likely to be triple negative (p value-0.05) and diagnosed at advanced stage (stage 3 and 4) (p value-0.02). There was no difference in the occurrence of Her-2 positive disease. In pregnant patients there was a 5-year survival rate of 65% compared to non-pregnant cohort of 82% with p value of 0.002 and DFS was also 47.5% versus 65.4% with a p value .002 which is statistically significant. Conclusion: Pregnancy associated breast cancer (PABC) is diagnosed at a more advanced stage and tends to be triple negative and they are associated with a worse DFS and overall survival. Early detection during pregnancy may improve outcome.

<b><i>Background:</i></b>There is a paucity of literature examining the impact of timing of surgery after neoadjuvant chemotherapy. <b><i>Objective:</i></b>This study aimed to analyze the impact of the time taken to initiate surgical treatment following completion of neoadjuvant chemotherapy on patients’ outcomes by evaluating their pathological response, overall survival (OS), and disease-free survival (DFS). <b><i>Methods:</i></b>This is a retrospective review of 611 patients diagnosed with stage II and III breast cancer that received neoadjuvant chemotherapy and surgery between January 2004 and December 2014. The data was collected from a prospectively gathered registry. The patients were stratified into three cohorts according to the time of surgery after neoadjuvant chemotherapy: &#x3c;4 weeks, 4–7 weeks, or ≥8 weeks. Outcomes were assessed using Kaplan-Meier curves, and the variables were compared using log-rank statistics. <b><i>Results:</i></b>The 5-year OS rate was 89.6% and the 5-year DFS rate was 74%. OS and DFS were not significantly different when stratified according to timing of surgery; however, the trends of OS and DFS were poor when surgery was delayed for ≥8 weeks. Median OS and median DFS have not yet been reached. Of the 17% of patients that had surgery after ≥8 weeks, 12.9% had pathological complete response (pCR), while among those that received surgery 4–7 weeks and &#x3c;4 weeks after neoadjuvant chemotherapy, 26% and 21% had pCR, respectively (<i>p</i> = 0.02). ER+/HER-2+ patients had a statistically significant decrease in pCR if surgery was performed after ≥8 weeks. <b><i>Conclusion:</i></b>Our patients showed improved pCR if surgery was performed within 8 weeks, especially for ER+/HER-2+ patients. All patients had better OS and DFS trends if surgery was performed between 4 and 7 weeks after neoadjuvant chemotherapy.

Therapeutic anti-PD-L1 antibodies are safe as a monotherapy, albeit with minimal efficacy in triple-negative breast cancer (TNBC). This trial aimed to test the safety and efficacy of Durvalumab and Paclitaxel in metastatic TNBC. In this open-label, one-arm trial, five cycles of weekly paclitaxel were delivered intravenously (IV) concurrent with Durvalumab that was given IV every 2 weeks. The combination was preceded by one cycle of paclitaxel alone, for immunological priming, followed by Durvalumab solo until disease progression or unacceptable toxicity. Between 2017 and 2019, 14 patients received at least one cycle of the combination therapy. The therapy was safe with no-dose limiting toxicity, except one case of skin lesions. Adverse events (AEs) were reported in 71% of patients, and there was no death due to the combination therapy. Regardless of grade, the most common AEs were headache and peripheral neuropathy, as each happened in four patients (29%), followed by fatigue and skin rash in three patients (21%) each. Grade 3/4 AEs were experienced by three patients (21%), with the most common being headache and anemia, which happened in two patients (14%). The confirmed objective response rate (ORR) was observed in five patients with a median duration of 10.0 months. Median Progression-free survival (PFS) and overall survival (OS) were 5 and 20.7 months, respectively. The combination of Durvalumab and Paclitaxel is safe, leaving room for additional agents. This is the first report on the combination of Durvalumab and Paclitaxel in the treatment of TNBC (NCT02628132).

Resistance to therapy is a persistent problem that leads to mortality in breast cancer, particularly triple-negative breast cancer (TNBC). MiRNAs have become a focus of investigation as tissue-specific regulators of gene networks related to drug resistance. Circulating miRNAs are readily accessible non-invasive potential biomarkers for TNBC diagnosis, prognosis, and drug-response. Our aim was to use systems biology, meta-analysis, and network approaches to delineate the drug resistance pathways and clinical outcomes associated with circulating miRNAs in TNBC patients. MiRNA expression analysis was used to investigate differentially regulated circulating miRNAs in TNBC patients, and integrated pathway regulation, gene ontology, and pharmacogenomic network analyses were used to identify target genes, miRNAs, and drug interaction networks. Herein, we identified significant differentially expressed circulating miRNAs in TNBC patients (miR-19a/b-3p, miR-25-3p, miR-22-3p, miR-210-3p, miR-93-5p, and miR-199a-3p) that regulate several molecular pathways (PAM (PI3K/Akt/mTOR), HIF-1, TNF, FoxO, Wnt, and JAK/STAT, PD-1/PD-L1 pathways and EGFR tyrosine kinase inhibitor resistance (TKIs)) involved in drug resistance. Through meta-analysis, we demonstrated an association of upregulated miR-93, miR-210, miR-19a, and miR-19b with poor overall survival outcomes in TNBC patients. These results identify miRNA-regulated mechanisms of drug resistance and potential targets for combination with chemotherapy to overcome drug resistance in TNBC. We demonstrate that integrated analysis of multi-dimensional data can unravel mechanisms of drug-resistance related to circulating miRNAs, particularly in TNBC. These circulating miRNAs may be useful as markers of drug response and resistance in the guidance of personalized medicine for TNBC.

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