Conventional preoperative chemotherapy regimens have only limited efficacy in hormone receptor positive (HR+) breast cancer and new approaches are needed. We hypothesized that capecitabine, which is ...effective in metastatic breast cancer, may be an active preoperative treatment for HR+ breast cancer. Women with HR+, HER2‐negative operable breast cancer received capecitabine, 2000 mg/m2 daily in divided doses for 14 days, followed by a 7‐day rest period. Treatment was repeated every 21 days for a total of four cycles. The primary endpoint of the study was to determine the rate of pathological complete response (pCR). Because of slow accrual, the study was closed after 24 patients were enrolled. Three patients had a complete clinical response, and eight patients had a partial clinical response, for an overall clinical response rate of 45.8%. There were no cases of pCR. Of the 22 patients who had pathological response assessment by the Miller–Payne grading system, there were six grade 3 responses, and no grade 4 or 5 responses. Toxicity was manageable: the only grade 3 toxicities observed were one case each of diarrhea, palmar plantar erythrodysesthesia, hypokalemia, and mucositis. There was no association between baseline levels, or change in level from baseline to cycle 1, or from baseline to time of surgery, of thymidine phosphorylase (TYMP), thymidylate synthase (TYMS), dihydropyrimidine dehydrogenase (DPYD), or Ki67 and pathological, clinical, or radiographic response. Preoperative capecitabine is a well‐tolerated regimen, but appears not lead to pCR when used as monotherapy in HR+ breast cancer.
Conventional preoperative chemotherapy regimens have only limited efficacy in hormone receptor positive (HR+) breast cancer and new approaches are needed. This study examines the use of preoperative capecitabine for HR+ breast cancer.
The ability to assay large numbers of low-frequency mutations is useful in biomedicine, yet, the technical hurdles of sequencing multiple mutations at extremely high depth, with accuracy, limits ...their detection in clinical practice. Low-frequency mutations can typically be detected by increasing the sequencing depth, however this limits the number of loci that can be probed for simultaneously. Here, we report a technique to accurately track thousands of distinct mutations with minimal reads, termed MAESTRO (minor allele enriched sequencing through recognition oligonucleotides), which employs massively-parallel mutation enrichment to enable duplex sequencing to track up to 10,000 low-frequency mutations, yet requiring up to 100-fold less sequencing. We show that MAESTRO could inform the mutation validation of whole-exome sequencing and whole genome sequencing data from tumor samples, enable chimerism testing, and is suitable for the monitoring of minimal residual disease via liquid biopsies. MAESTRO may improve the breadth, depth, accuracy, and efficiency of sequencing-based mutational testing.
Massively-parallel mutation enrichment enables the tracking of up to 10,000 low-frequency mutations, via duplex sequencing, requiring up to 100-fold less sequencing depth.
Abstract In the US, over 200,000 new cases of invasive breast cancer are diagnosed each year, with an additional 60,000 cases of ductal carcinoma in situ. The majority of these women will never ...experience a recurrence of their disease, and most will survive more than 5 years. Follow-up care for these women is focused on addressing long-term complications of therapy, and early detection of new primary cancers and locoregional recurrences. There is no evidence that early detection of distant metastases will lead to an increase in survival, and currently routine imaging studies are not recommended. With the growing number of breast cancer survivors, further studies should be undertaken to study the cost-effectiveness of surveillance strategies.
Differential diagnosis can be extensive in immunocompromised patients who present for evaluation of apparent community-acquired pneumonia. In addition to the usual pathogens seen in the general ...population, many opportunistic organisms of widely differing classes may require consideration. Here, the authors have chosen to focus on four pathogens that may be overlooked in the primary care setting. Epidemiologic, clinical, and therapeutic points are highlighted.
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