Development of Genome-Derived Tumor Type Prediction to Inform Clinical Cancer Care.

Importance: Diagnosing the site of origin for cancer is a pillar of disease classification that has directed clinical care for more than a century. Even in an era of precision oncologic practice, in which treatment is increasingly informed by the presence or absence of mutant genes responsible for cancer growth and progression, tumor origin remains a critical factor in tumor biologic characteristics and therapeutic sensitivity.

Objective: To evaluate whether data derived from routine clinical DNA sequencing of tumors could complement conventional approaches to enable improved diagnostic accuracy.

Phase II Study of Paclitaxel and Dasatinib in Metastatic Breast Cancer.

Background: Overexpression and activation of tyrosine kinase Src has been linked to breast carcinogenesis and bone metastases. We showed the feasibility of combining the SRC inhibitor dasatinib with weekly paclitaxel in patients with metastatic breast cancer (MBC) and herein report the subsequent phase II trial.

Patients And Methods: Patients had received ≤ 2 chemotherapy regimens for measurable, HER2-negative MBC.

Canted Antiferromagnetism in Two-Dimensional Silver(II) Bis[pentafluoridooxidotungstate(VI)].

By slow reaction between colorless AgWOF and elemental F in liquid anhydrous HF, violet platelike single crystals of Ag(WOF) were grown. The crystal structure of Ag(WOF) consists of layers built from Ag cations bridged by [WOF] anions and not, as previously assumed, from infinite [Ag-F] chains and [WOF] anions. A majority (97%) of the disordered Ag cations are found with square-planar coordination of F/O ligands within the same layer, and they form additional long contacts with O/F atoms originating from the neighboring layers.

[Ag(OH ) ][Ag(SO ) ]: A Hydrate of a Silver(II) Salt.

When exposed to air at ambient conditions, AgSO slowly reacts with moisture, yielding AgSO ⋅H O. The crystal structure determination (powder data) shows that it may be described as [Ag(OH ) ][Ag(SO ) ], with some sulfate groups being shared between different Ag cations, resembling in that way its Cu analogue. [Ag(OH ) ][Ag(SO ) ], the first hydrate of a compound of Ag , was extensively characterized using many physicochemical methods.

AgSO meets AgSO: the second example of metal-ligand redox isomerism among inorganic systems.

Valence (redox) isomerism based on electron exchange between a metal and a ligand is immensely rare in purely inorganic systems, with only one documented case, that of PbS which adopts two polymorphic forms corresponding to Pb(iv)(S) and Pb(ii)(S). Here we have taken advantage of metathetic reactions using salts of weakly coordinating anions and we have prepared for the first time Ag(i)SO, silver(i) peroxydisulphate. The title compound crystallizes in the non-centrosymmetric Cc space group with partial disorder of the anionic sublattice.

Phase II study of paclitaxel given once per week along with trastuzumab and pertuzumab in patients with human epidermal growth factor receptor 2-positive metastatic breast cancer.

Purpose: The CLEOPATRA (Clinical Evaluation of Trastuzumab and Pertuzumab) study demonstrated superior progression-free survival (PFS) and overall survival when pertuzumab was added to trastuzumab and docetaxel. Paclitaxel given once per week is effective and less toxic than docetaxel. We performed a phase II study to evaluate the efficacy and safety of pertuzumab and trastuzumab with paclitaxel given once per week.

A phase II open-label study of ganetespib, a novel heat shock protein 90 inhibitor for patients with metastatic breast cancer.

Background: Ganetespib is a small molecule, nongeldanamycin HSP90 inhibitor with potent inhibitory effects on HSP90-dependent oncoproteins of relevance to breast cancer pathogenesis. We therefore tested ganetespib in an unselected cohort of patients with MBC.

Patients And Methods: Patients were treated with single agent ganetespib at 200 mg/m(2) once weekly for 3 weeks, on a 28-day cycle.

The joys and challenges of caring for patients.

Optimal care of patients involves the integration of both the scientific and humanistic aspects of medicine. However, the tremendous focus on technology can easily overshadow the personal effect of patient care. The complex relationship between the physician and the patient is a reciprocal one.

Encountering grief in patient care.

Grief is essentially unavoidable and is a normal reaction to loss. Grief may be experienced by patients and their loved ones as well as by physicians and members of the health care team in response to the consequences of illness or death. Grief is typified by certain indicators that may significantly effect one's emotional and physical well-being.

The oncologist as the patient with cancer or relative.

To an extent, physicians are familiar with the consequences of illness through their interactions with patients. However, when cancer becomes personal, the physician has an opportunity to gain greater insight into the intricacies of medical care, including its humanistic elements. Physicians who encounter cancer in themselves or in a relative may deepen their understanding of the patient experience.

A phase I study of dasatinib and weekly paclitaxel for metastatic breast cancer.

Background: SRC plays an important role in the pathogenesis of metastatic breast cancer (MBC). In preclinical models, paclitaxel and the oral SRC inhibitor dasatinib showed greater antitumor activity than either agent. To determine the maximum tolerated dose of this combination, we conducted a phase I study.

A feasibility study of bevacizumab plus dose-dense doxorubicin-cyclophosphamide (AC) followed by nanoparticle albumin-bound paclitaxel in early-stage breast cancer.

Purpose: Bevacizumab confers benefits in metastatic breast cancer but may be more effective as adjuvant therapy. We evaluated the cardiac safety of bevacizumab plus dose-dense doxorubicin-cyclophosphamide (ddAC) → nanoparticle albumin-bound (nab)-paclitaxel in human epidermal growth factor receptor 2 normal early-stage breast cancer.

Experimental Design: Eighty patients with normal left ventricular ejection fraction (LVEF) were enrolled.

Dose dense cyclophosphamide, methotrexate, fluorouracil is feasible at 14-day intervals: a pilot study of every-14-day dosing as adjuvant therapy for breast cancer.

Purpose: Cyclophosphamide/methotrexate/fluorouracil (CMF) is a proven adjuvant option for patients with early-stage breast cancer. Randomized trials with other regimens demonstrate that dose-dense (DD) scheduling can offer greater efficacy. We investigated the feasibility of administering CMF using a DD schedule.

A phase II trial of erlotinib in combination with bevacizumab in patients with metastatic breast cancer.

Purpose: To evaluate the efficacy and toxicity of erlotinib plus bevacizumab in patients with metastatic breast cancer (MBC), targeting the epidermal growth factor receptor (EGFR/HER1) and the vascular endothelial growth factor (VEGF) pathway.

Experimental Design: Thirty-eight patients with MBC were enrolled and treated at two institutions with erlotinib, a small molecule EGFR tyrosine kinase inhibitor (150 mg p.o.

Prolonged dose-dense epirubicin and cyclophosphamide followed by paclitaxel in breast cancer is feasible.

Purpose: We conducted a pilot study of dose-dense epirubicin/cyclophosphamide (EC) x 6 --> paclitaxel (P) x 6 with pegfilgrastim. A previous dose-dense trial of FEC (5-fluorouracil [5-FU]/EC) x 6 with filgrastim --> by weekly paclitaxel alternating with docetaxel x 18 was not feasible because of pneumonitis (with dose-dense FEC) and pericardial/pleural effusion (taxane phase). Dose-dense EC (without the 5-FU) is not associated with pneumonitis, and dose-dense paclitaxel (alone) is feasible.

The safety of dose-dense doxorubicin and cyclophosphamide followed by paclitaxel with trastuzumab in HER-2/neu overexpressed/amplified breast cancer.

Purpose: Dose-dense (dd) doxorubicin and cyclophosphamide (AC) followed by paclitaxel (P) is superior to every 3-weekly AC followed by P. Given the demonstrated cardiac safety for trastuzumab (T) with conventionally scheduled AC followed by P, we tested the safety of dd AC followed by P with T. The primary end point was cardiac safety, and the secondary end points were time to recurrence and overall survival.

Immunization of high-risk breast cancer patients with clustered sTn-KLH conjugate plus the immunologic adjuvant QS-21.

Purpose: To determine the clinical toxicities and antibody response against sTn and tumor cells expressing sTn following immunization of high-risk breast cancer patients with clustered sTn-KLH [sTn(c)-KLH] conjugate plus QS-21.

Experimental Design: Twenty-seven patients with no evidence of disease and with a history of either stage IV no evidence of disease, rising tumor markers, stage II (>or=4 positive axillary nodes), or stage III disease received a total of five injections each during weeks 1, 2, 3, 7, and 19. Immunizations consisted of sTn(c)-KLH conjugate containing 30, 10, 3, or 1 microg sTn(c) plus 100 microg QS-21.

Reevaluation of the cellular immune response in breast cancer patients vaccinated with MUC1.

Conjugation of antigens to a carrier protein like keyhole limpet hemocyanin (KLH) has proven effective in clinical trials for inducing antibodies against selected tumor antigens. The impact of this approach on T-cell immunity has not been previously tested. We utilized peripheral blood mononuclear cells (PBMC) obtained at leukapheresis from 6 breast cancer patients vaccinated 4 times each with a 106-amino acid-long MUC1 peptide conjugated with KLH plus immune adjuvant QS-21.

Doxorubicin followed by sequential paclitaxel and cyclophosphamide versus concurrent paclitaxel and cyclophosphamide: 5-year results of a phase II randomized trial of adjuvant dose-dense chemotherapy for women with node-positive breast carcinoma.

Purpose: We conducted a randomized Phase II trial to directly compare toxicity, feasibility, and delivered dose intensities of two adjuvant dose-intensive regimens containing doxorubicin, paclitaxel, and cyclophosphamide for patients with node-positive breast carcinoma.

Experimental Design: Forty-two patients with resected breast carcinoma involving one or more ipsilateral axillary lymph nodes, were randomized to receive two different schedules of adjuvant chemotherapy using 14-day dosing intervals: either (a) three cycles of doxorubicin 80 mg/m(2) as i.v.

The art of medicine: teaching oncology fellows about the end of life.

The artistry of medicine is important in any doctor-patient interaction, but becomes particularly meaningful at the end of life. In the US there has a been a recent acknowledgment by several medical organizations, including the American Medical Association and the American Board of Internal Medicine, that education of physicians regarding this aspect of medicine has been inadequate. Awareness of the importance of end of life issues must occur in training programs, such as oncology fellowships.

Weekly trastuzumab and paclitaxel therapy for metastatic breast cancer with analysis of efficacy by HER2 immunophenotype and gene amplification.

Purpose: This phase II study evaluated weekly trastuzumab and paclitaxel therapy in women with HER2-normal and HER2-overexpressing metastatic breast cancer. Efficacy was correlated with immunohistochemical and fluorescent in situ hybridization (FISH) assay results.

Patients And Methods: Eligible patients had bidimensionally measurable metastatic breast cancer.

Immunization of metastatic breast cancer patients with a fully synthetic globo H conjugate: a phase I trial.

The carbohydrate antigen globo H commonly found on breast cancer cells is a potential target for vaccine therapy. The objectives of this trial were to determine the toxicity and immunogenicity of three synthetic globo H-keyhole limpet hemocyanin conjugates plus the immunologic adjuvant QS-21. Twenty-seven metastatic breast cancer patients received five vaccinations each.

Effect of adjuvant tamoxifen on the endometrium in women with breast cancer: a prospective study using office endometrial biopsy.

Purpose: To determine the frequency of developing abnormal pathologic changes in the endometria of tamoxifen-treated women. To characterize the type of pathologic changes involved.

Patients And Methods: Between October 1991 and September 1998, 159 patients initiating tamoxifen therapy for breast cancer confined to the breast and axillary lymph nodes were entered in a prospective study.