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Abstract Background: Doxorubicin is used in several chemotherapy regimens for many breast cancer subtypes, including triple-negative breast cancer (TNBC) and HER2-positive breast cancer before surgery (neoadjuvant). Doxorubicin can also be used in early-stage breast cancer in adjuvant therapy, after surgery, or in metastatic breast cancer. Patients refer to this drug as the “red devil.” It earns this moniker not just for its harsh red color, but for its side effects: fatigue, nausea, hair loss, and, far worse, permanent heart damage. Some patients die from neoadjuvant treatment itself. TNBC is an aggressive breast cancer subtype that affects 420,000 women worldwide and 56,000 in the US. Patients agree to intense neoadjuvant immunochemotherapy (Keynote-522), hoping to achieve a pathologic complete response (pCR), which means no cancer left at the time of surgery. Achieving pCR is strongly linked to an increase in event-free survival (EFS) and can serve as an endpoint to expedite FDA drug approvals. The SCARLET phase III trial, led by the National Cancer Institute, is studying whether an anthracycline-free regimen (NeoPACT) can remove doxorubicin in early-stage TNBC. While this trial gives patients hope, the EFS results are not expected until 2033 or 2034. Many patients are unable to wait so long, especially in the adjuvant or metastatic settings. Current Research Objectives and Rationale: INT230-6 is a new drug consisting of two potent cytotoxic chemotherapy agents (cisplatin and vinblastine sulfate) formulated with a diffusion and cell penetration enhancer (SHAO) in a single vial. The product candidate is designed for intratumoral injection. INT230-6 kills cancer cells locally and stimulates the immune system to recognize and attack cancer systemically. The drug, after being injected into the tumor, attacks the entire tumor. In early studies, the drug has been shown to cause up to 95% tumor necrosis in tumors as large as 4.4 cm. The ongoing INVINCIBLE-4 trial (NCT06358573) is a two-cohort randomized controlled study testing INT230-6 dosed before the standard Keynote-522 regimen, which includes doxorubicin (cohort A), and the KN-522 regimen alone (cohort B). The goal of INVINCIBLE-4 is to enhance initial tumor destruction and immune priming, thereby improving pathological complete response (pCR) rates over KN-522. With higher pCR rates and strong immune activation, a regimen without anthracyclines may become possible. Phase 3 Study Design and Rationale: If the results from the Phase 2 INVINCIBLE-4 study show a clinically meaningful increase in pCR using INT230-6 before KN-522, the next step would be a pivotal phase III trial design with three treatment arms in neoadjuvant TNBC: 1. INT230-6 followed by full KEYNOTE-522 regimen 2. INT230-6 followed by KEYNOTE-522 without anthracycline. 3. Standard KEYNOTE-522 regimen alone (with anthracycline) With pCR as the first primary endpoint for accelerated approval and enrolling sufficient TNBC patients for the endpoint of EFS, the three-arm 1:1:1 randomized study design comparing cohorts 1 or 2 separately to cohort 3 could enable a significantly faster approval pathway (for cohort 2). pCR results could be available years before the SCARLET study data. However, EFS will be required for full approval of INT230-6 with an anthracycline-free regimen. Citation Format: C. W. Handy, J. R. Rodrigues, K. A. Guedes, I. B. Walters, L. H. Bender. Accelerating an Anthracycline-Free Future: A New Drug in Clinical Testing Offers Patients Hope for Safer, More Effective Breast Cancer Therapy Combinations [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-10-15.

In 1980 the American Academy of Periodontology published the results of its first major survey of practice characteristics in the Journal of Periodontology. That first study arose from membership concerns about the lack of knowledge about career patterns of periodontists and, more specifically, about employment opportunities for graduating periodontists. Three years later, the Committee on Practice Styles and Opportunities in Periodontics was appointed to replicate the earlier study in order to provide information on recent changes in the practice of periodontics. This decision is commendable since few dental specialty organizations collect data from their membership which can be systematically compared to data from an earlier study. The Academy's Committee contacted David O. Born, PhD, a dental manpower specialist at the University of Minnesota and a technical advisor on the earlier study, for assistance in conducting a replication in 1984. Based on feedback on the first survey and on comments and suggestions from committee members, a revised questionnaire was developed. This questionnaire was, for the most part, a replication of the earlier survey instrument, although several problematic items were deleted or modified and new items, reflecting more recent concerns, were added. The revised questionnaire was distributed in the Spring of 1984 through two mailings to 2937 Active members and 798 Affiliate members. After unusable and undeliverable questionnaires were deleted from the returns, an effective response rate of 55% (N = 2082) was obtained. This report is based on the information supplied by those 2082 members. In the tables and text which follow, the figures reported at the national level refer to "Private practice" periodontists responding to the survey; Academy members who are a part of the Federal services (e.g., Military, Veterans' Administration, Indian Health Service, etc.) are tabulated separately as "District 8" data. While several members from foreign countries responded to the survey, their data have not been included since the information was too dispersed to permit conclusions to be drawn.

John Humphrey of Massachusetts Bay Colony Get access Henry S. Baldwin Henry S. Baldwin 1Swampscott, Massachusetts Search for other works by this author on: Oxford Academic Google Scholar Notes and Queries, Volume CLXV, Issue jul15, 15 July 1933, Page 27, https://doi.org/10.1093/nq/CLXV.jul15.27 Published: 15 July 1933

THE Institute, meeting here in convention on the “stern and rock bound coast” of New England, finds itself on historic ground. In this region are located many battle fields, of arms and of intellect, that have left their deep impress on our civilization. The battle fields of arms are marked by monuments that are now shrines of an appreciative people. The battles of the intellect, though often accompanied by bloodshed, are not so well remembered. Bunker Hill is fresher in our minds than are Salem and Roger Williams, yet Williams' heroic struggle for freedom of thought paved the way for that later struggle marked by the shaft on Bunker Hill.

A. P. Thoms: I do not see why so much stress should be placed on the dielectric loss in a joint. E. S. Lee, in a paper before the A. I. E. E. Midwinter Convention <sup xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink">2</sup> , stated that the dielectric-strength test is the most important and the best test available at the present time; that indications are that the present standardized voltages should be increased and that increasing the application of the test two or three minutes is of doubtful value. The authors of this paper have used the standardized dielectric-strength test with the application increased a few minutes, and this test, according to Lee, is of doubtful value.

H. W. Oetinger: Reference is made to the checking of instrument transformers with equivalent secondary burdens. The usual procedure in determining this secondary burden is to calculate it from the published data of the instrument coil constants and the size and length of leads. Where test wiring is used exclusively, there can be no question regarding this procedure but where the test instruments are inserted in conjunction with station instruments and wiring, there is some question as to what is actually in the circuit. In one case it was found that coils of unknown and variable volt-ampere characteristics were left in circuit. In such cases it seems desirable to actually measure the secondary burden and include all connections and instruments to be used during the test. A voltmeter, ammeter and wattmeter can be used in conjunction with a load box. The disconnection is made at the terminals of the instrument transformers and voltage applied to the leads at this point.