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Breast cancer is commonly staged using the American Joint Committee on Cancer (AJCC) staging system. The 7(th) edition of the AJCC Staging Manual, was a purely anatomic staging method, which uses primary tumor size (T), nodal involvement (N), and metastasis (M) based on clinical and pathological evaluations. Advancements in tumor biology and prognostic biological markers, such as estrogen receptor (ER)/progesterone receptor (PR), HER2/neu, and Ki-67, have allowed clinicians to understand why similarly staged patients had significantly different outcomes. The most recent update to the staging system integrates molecular markers with disease extent for more optimal estimation of prognosis. This change improves the prognosis of breast cancer patients and better informs physicians in the planning of treatments. This review summarizes the changes in the AJCC Staging Manual, 8(th) edition and their impact on practicing radiologists in breast cancer management.

Two novel inhibitors of isocitrate dehydrogenase (IDHi), ivosidenib and enasidenib, significantly improve survival for AML patients with an IDH1 or IDH2 mutation, respectively; however, rash has been reported as a toxicity of IDHi. The objective of our study is to determine the incidence, grade, clinical, and histopathologic features of dermatologic adverse events (DAEs) secondary to IDHi. This study is a retrospective analysis of 169 patients who were treated with either ivosidenib or enasidenib as single agent or in combination with induction chemotherapy at Memorial Sloan Kettering Cancer Center from January 1, 2013 to April 1, 2021. DAEs thought to be possibly, probably, or definitely related to IDHi occurred in 55 of 169 patients [0.32, 95 % CI: 0.25 - 0.40]. Of a total 81 DAEs observed, the most common DAE types were inflammatory dermatoses (27 %); cutaneous vascular manifestations (8%); cutaneous infections (7%); and pruritus (2%). Notably, 50% of infections and 15.5% of rashes were high grade. Knowledge of these findings is critical to optimize the treatment and quality of life of patients with AML on IDHi.

Truncating mutations in the terminal exon of protein phosphatase Mg2+/Mn2+ 1D (PPM1D) have been identified in clonal hematopoiesis and myeloid neoplasms, with a striking enrichment in patients previously exposed to chemotherapy. In this study, we demonstrate that truncating PPM1D mutations confer a chemoresistance phenotype, resulting in the selective expansion of PPM1D-mutant hematopoietic cells in the presence of chemotherapy in vitro and in vivo. Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein-9 nuclease mutational profiling of PPM1D in the presence of chemotherapy selected for the same exon 6 mutations identified in patient samples. These exon 6 mutations encode for a truncated protein that displays elevated expression and activity due to loss of a C-terminal degradation domain. Global phosphoproteomic profiling revealed altered phosphorylation of target proteins in the presence of the mutation, highlighting multiple pathways including the DNA damage response (DDR). In the presence of chemotherapy, PPM1D-mutant cells have an abrogated DDR resulting in altered cell cycle progression, decreased apoptosis, and reduced mitochondrial priming. We demonstrate that treatment with an allosteric, small molecule inhibitor of PPM1D reverts the phosphoproteomic, DDR, apoptotic, and mitochondrial priming changes observed in PPM1D-mutant cells. Finally, we show that the inhibitor preferentially kills PPM1D-mutant cells, sensitizes the cells to chemotherapy, and reverses the chemoresistance phenotype. These results provide an explanation for the enrichment of truncating PPM1D mutations in the blood of patients exposed to chemotherapy and in therapy-related myeloid neoplasms, and demonstrate that PPM1D can be a targeted in the prevention of clonal expansion of PPM1D-mutant cells and the treatment of PPM1D-mutant disease.

To compare the outcomes of microcalcifications recalled on full-field digital (FFDM) and FFDM and combined tomosynthesis (Combo) to synthetic (SM) screening mammograms.We reviewed medical records, radiology, and pathology reports of all patients found to have abnormal calcifications requiring further evaluation on mammography screening at our institution between 11/1/2016-11/1/2018 and collected patient demographics, calcification morphology and distribution, and mammography technique (SM, FFDM, or Combo). We used biopsy pathology or at least 1-year imaging follow-up to establish overall diagnostic outcome (benign or malignant). Fisher's exact test was used to compare validation rates at diagnostic work-up, BI-RADS category, and final outcome of calcifications identified on each screening technique. T-test was used for continuous variables.Of 699 calcifications in 596 women recalled, 176 (30%) of 596 were from SM and 420 (70%) FFDM/Combo. There was a significantly higher rate of calcifications unvalidated at diagnostic work-up for SM compared to FFDM/Combo (0.8% vs. 10%, p0.0001). SM calcifications were more likely to receive BI-RADS 2/3 at diagnostic work-up compared to FFDM/Combo ones (55% vs. 42%, p = 0.003). Of 346 (49%) calcifications that underwent biopsy, 88 (25%) were malignant (36% of SM vs. 22% of FFDM/Combo, OR:0.5 [95% CI: 0.3, 0.8] p = 0.01). Of 622 lesions with established diagnostic outcome, there was no difference between having an overall benign or malignant outcome between SM and FFDM/Combo (17% vs. 13%, OR: 0.8 [95% Cl: 0.5, 1.2] p = 0.27).Synthetic tomosynthesis screening results in a higher rate of false positive and unvalidated calcification recalls compared to FFDM/Combo.