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ImportanceNational Comprehensive Cancer Network guidelines currently recommend germline testing for high-risk genes in selected patients with breast cancer. The clinical utility of recommending testing all patients with breast cancer with multigene panels is currently under consideration.ObjectiveTo examine the implications of universal testing of patients with breast cancer with respect to clinical decision-making.Design, Setting, and ParticipantsPatients from a previously reported cohort were assessed as in-criteria or out-of-criteria according to the 2017 guidelines and underwent testing with a multigene germline panel between 2017 to 2018. Patients were women and men aged 18 to 90 years, with a new and/or previous diagnosis of breast cancer who had not undergone either single or multigene testing. Clinicians from 20 community and academic sites documented patient clinical information and changes to clinical recommendations made according to test findings. Association between prevalence of pathogenic or likely pathogenic germline variants and previously unreported clinical features, including scores generated by the BRCAPRO statistical model, was determined. Data were analyzed from April 2020 to May 2022.ExposureNew and/or previous diagnosis of breast cancer.Main Outcomes and MeasuresDisease management recommendations that were changed as a result of genetic testing results are reported.ResultsClinicians were asked to assess changes to clinical management as a result of germline genetic testing for 952 patients. Informative clinician-reported recommendations were provided for 939 (467 in-criteria and 472 out-of-criteria) of the patients with breast cancer (936 [99.7%] female; 702 [74.8%] White; mean [SD] age at initial diagnosis, 57.6 [11.5] years). One or more changes were reported for 31 of 37 (83.8%) in-criteria patients and 23 of 34 (67.6%) out-of-criteria patients with a pathogenic or likely pathogenic variant. Recommendations were changed as a result of testing results for 14 of 22 (63.6%) out-of-criteria patients who had a variant in a breast cancer predisposition gene. Clinicians considered testing beneficial for two-thirds of patients with pathogenic or likely pathogenic variants and for one-third of patients with either negative results or variants of uncertain significance. There was no difference in variant rate between patients meeting the BRCAPRO threshold (≥10%) and those who did not (P = .86, Fisher exact test). No changes to clinical recommendations were made for most patients with negative results (345 of 349 patients [98.9%]) or variants of uncertain significance (492 of 509 patients [96.7%]).Conclusions and RelevanceIn this cohort study, germline genetic testing was used by clinicians to direct treatment for most out-of-criteria patients with breast cancer with pathogenic or likely pathogenic germline variants, including those with moderate-risk variants. Universal germline testing informs clinical decision-making and provides access to targeted treatments and clinical trials for all patients with breast cancer.

Annals of Surgical Oncology seeks to cover the broad spectrum of multidisciplinary clinical cancer care and basic cancer research relevant to practicing surgeons. As the official journal of the Society of Surgical Oncology, this new journal publishes annual meeting papers and distributes news to its more than 1000 members. Rigorous competition for manuscript acceptance and peer review characterize the editorial process. The editors essentially comprise the "who's who" of surgical oncology in the United States. The editorial board consists of oncologists representing notable institutions. Quality contributions from the US community of surgical oncologists fill its pages.Surgical oncologists frequently coordinate all aspects of cancer care, which encompasses diagnosis, surgical or nonsurgical treatment, rehabilitation, and surveillance. Their educational, clinical, and research activities include a wide array of cancers spanning all organ systems and various anatomic sites. Although this journal has strong appeal and value for general surgical oncologists, other surgical specialists

This study was undertaken to determine whether the phorbol diester, phorbol 12-myristate 13-acetate (PMA), causes differentiation of the human colon carcinoma cell line, SW 48. Under routine growth conditions, the cells are round, have a high nuclear-to-cytoplasmic ratio, and lack cytoplasmic vacuoles. After treatment for 1 hour with 100 nmol/L of PMA at 37 degrees C, the cells assumed a spread-out, flasklike shape, displayed a low nuclear-to-cytoplasmic ratio, and exhibited cytoplasmic vacuoles. An inert but lipophilic phorbol diester, 4 phorbol 12,13-didecanoate, failed to induce these morphological changes. Cell kinetic studies showed that whereas SW 48 cells have a doubling time of 35 hours, those incubated with 100 nmol/L of PMA have a doubling time of 90 hours. Although the flow cytometry histograms were similar until 8 hours into the cell cycle, the PMA-treated cells ultimately spent proportionately less time in S and more in G2/M. Finally, under routine growth conditions, SW 48 cells express neither carcinoembryonic antigen nor G7 antigen. These antigens, which are present on the surface of well-differentiated cells, were expressed after treatment of SW 48 with PMA. The data suggest that PMA causes profound changes in structure, cell growth kinetics, and antigen expression, consistent with induction of differentiation of the cell line SW 48.

• An isolated axillary lymph node metastasis in a woman without an obvious clinical primary site most frequently originates from the breast. Mastectomy has been the historical treatment of choice. A retrospective study of 35 patients was undertaken to evaluate the roles of modern mammography, breast preservation, and adjuvant systemic therapy in the management of these patients. Twenty-eight patients underwent a mastectomy, while 7 were managed by a combination of limited resection and/or axillary dissection and radiation therapy. Twenty-two (67%) of the 33 breast specimens contained carcinoma. Comparison of the pathologic results with the preoperative mammograms showed a specificity of 73%, while the sensitivity was only 29%. Actuarial 5-year survival after mastectomy or breast preservation was similar (77% and 65%, respectively). Patients with more than one positive lymph node benefited from adjuvant therapy. Mammography does not locate the majority of occult stage II breast cancers, and both breast preservation and adjuvant therapy may have roles in the management of these patients. ( Arch Surg . 1990;125:210-215)