To determine the long-term prognosis in each phenotypic subset of breast cancer related to residual cancer burden (RCB) after neoadjuvant chemotherapy alone, or with concurrent human epidermal growth factor receptor 2 (HER2)-targeted treatment. MethodsWe conducted a pathologic review to measure the continuous RCB index (wherein pathologic complete response has RCB = 0; residual disease is categorized into three predefined classes of RCB index [RCB-I, RCB-II, and RCB-III]), and yp-stage of residual disease. Patients were prospectively observed for survival. Three patient cohorts received paclitaxel (T) followed by fluorouracil, doxorubicin, and cyclophosphamide (T/FAC): original development cohort (T/FAC-1), validation cohort (T/FAC-2), and independent validation cohort (T/FAC-3). Another validation cohort received FAC chemotherapy only, and a fifth cohort received concurrent trastuzumab (H) with sequential paclitaxel and fluorouracil, epirubicin, and cyclophosphamide (FEC; H+T/FEC). Phenotypic subsets were defined by hormone receptor (HR) and HER2 status at diagnosis, classified as HR-positive/HER2-negative, HER2-positive (HR-negative/HER2-positive or HR-positive/HER2-positive), or triple receptor-negative. Relapse-free survival estimates were determined from Kaplan-Meier analysis and compared using the log-rank test. Results Five cohorts (T/FAC-1 [n = 219], T/FAC-2 [n = 262], T/FAC-3 [n = 342], FAC [n = 132], and H+T/FEC[n = 203]) had median event-free follow-up of 13.5, 9.1, 6.8, 16.4, and 7.1 years, respectively. Continuous RCB index was prognostic within each phenotypic subset, independent of other clinicalpathologic variables. RCB classes stratified prognostic risk overall, within each phenotypic subset, and within yp-stage categories. Estimates of 10-year relapse-free survival rates in the four RCB classes (pathologic complete response, RCB-I, RCB-II, and RCB-III) were 86%, 81%, 55%, and 23% for triple receptor-negative; 83%, 97%, 74%, and 52% for HR-positive/HER2-negative in the combined T/FAC cohorts; and 95%, 77%, 47%, and 21% in the H+T/FEC cohort. ConclusionRCB was prognostic for long-term survival after neoadjuvant chemotherapy in all three phenotypic subsets of breast cancer. Our institutional findings should be externally validated.

We analyzed 5 features on 12-core transrectal ultrasound-guided prostate needle biopsy (TRUS) to predict the extent of cancer at radical prostatectomy (RP). In 388 TRUS-RP pairs, number of positive cores (NPC), percentage of each core involved (%PC), perineural invasion (PNI), Gleason score (GS), distribution of positive cores (DPC), and preoperative prostate-specific antigen (PSA) were correlated with extraprostatic extension (EPE), seminal vesicle invasion (SVI), positive surgical margin (R1), positive lymph nodes (N1), and tumor volume. All features predicted EPE and SVI. NPC, GS, %PC, and PNI strongly predicted R1 status. RP tumor volume was directly proportional to the NPC and %PC. PSA alone and with selected biopsy findings correlated with tumor volume, stage, SVI, and N1 (P < .0001). Contiguous DPC was a significant risk for EPE and SVI (P < .0001) compared with isolated positive cores. Findings at 12-core TRUS along with preoperative PSA reliably predict advanced local disease and have practical value as guides to effective planning for surgical resections.

Performance characteristics of breast ultrasound associated with RCB vary by cancer subtype, whereas the performance characteristics of axillary ultrasound associated with RCB are consistent across cancer subtype. Breast and axillary ultrasound may be valuable in monitoring response to neoadjuvant therapy. 2017;22:394-401 IMPLICATIONS FOR PRACTICE: The differential performance characteristics of breast ultrasound by molecular subtype and the consistent performance characteristics of axillary ultrasound across molecular subtypes can have clinical utility in monitoring response to neoadjuvant therapy.

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Histology plays an essential role in therapeutic decision-making for lung cancer patients. However, the molecular determinants of lung cancer histology are largely unknown. We conduct whole-exome sequencing and microarray profiling on 19 micro-dissected tumor regions of different histologic subtypes from 9 patients with lung cancers of mixed histology. A median of 68.9% of point mutations and 83% of copy number aberrations are shared between different histologic components within the same tumors. Furthermore, different histologic components within the tumors demonstrate similar subclonal architecture. On the other hand, transcriptomic profiling reveals shared pathways between the same histologic subtypes from different patients, which is supported by the analyses of the transcriptomic data from 141 cell lines and 343 lung cancers of different histologic subtypes. These data derived from mixed histologic subtypes in the setting of identical genetic background and exposure history support that the histologic fate of lung cancer cells is associated with transcriptomic features rather than the genomic profiles in most tumors.